273 ‒ Prostate health: common problems, cancer prevention, screening, treatment, and more

I always talk about ancestry and I talk about all cancer risks right when I'm taking a family history I say what's your personal history of prostate cancer and if you have a personal history of prostate cancer you're meaning a father uncle or brother so first degree relative father uncle brother okay the number of individuals and the age that they were diagnosed and we'll put a link in the show note for the table it increases your full risk of being diagnosed with prostate cancer significantly it doesn't mean you need to chant you shouldn't have a prophylactic prostatectomy but you should just have intensive intensive monitoring hey everyone welcome to the drive podcast I'm your host Peter attia Ted awesome to uh to be sitting down with you to talk about all things prostate related it's been probably four years since we did this yeah thanks for having me so um I think probably it's worth assuming that there are a lot of people who didn't hear that first podcast and those that did probably don't remember much anyway and also a lot has changed in four years so um I think never a bad idea to to sort of start from the beginning um so let's start with talking about what the prostate gland is what it does before we get into any of the pathology associated with it yeah so the prostate's an exocrine gland and it's part of the reproductive system it sits just below the bladder in men so it's a dimorphic organ it does not exist in women it develops in utero in response to fetal androgens and so it produces basically most of the components are about 50 to 60 percent of the components of semen so it's used in reproduction in all mammals and where a mammals so we use it too and um I guess when you sort of think about things that start to go wrong in the prostate I'm guessing that most men listening to this the first thing that they might think of is you know prostatitis certainly and age-wise right before you get into prostate cancer which of course we're going to talk at length about so when I think what just as a lay person thinking about the prostate gland I sort of think about inflammation infection I think about benign enlargement that leads to obstruction and then obviously we'll talk about neoplasm is that how you sort of think about the problems associated with it it's a it's an organ that sits in line with the urinary tract and it and so the urinary tract in men has a dual purpose General urinary tract is a dual purpose one it's used for reproduction the other is used to kind of eliminate all the urine and so because of that shared functionality you can you can develop problems in one or the other of those two disease systems and they result in symptomatic issues and a lot of the problems that men even at a young age but particularly as they age will experience are related to the prostate so in some ways it's kind of the Nexus of the lower urinary tract so yes it's absolutely true that in younger men you can develop infections in the urinary tract they can be very problematic and difficult to solve and address if it's involving the prostate additionally if you develop an infection classic bacterial or potentially viral or other kinds of causes you can get inflammation in the prostate which can result in long-standing long-term pain so that's one of the things I see when young men come in with prostatitis then as men evolve in age as the prostate evolves and changes as we get older different issues arise and they can result in an impact your urinary function because this is shared kind of it's a shared system of elimination of semen and of urine and so as we get older 50 50 to 60 percent of men at age 50 and and and older will have you know issues with lower urinary tract dysfunction and those almost always directly relate to the prostate in some way or another so um some of this some of the stats are pretty staggering so at age 50 it's probably 50 to 60 percent of men have low urinary tract dysfunction but by age 60 it's 75 to 80 percent of men will have lower urinary tract symptoms so let's talk about what those are typical urine lower urinary tract symptoms weak stream hesitation or slowness in getting your urinary stream started urgency to go to the bathroom increase frequency to go to the bathroom and they're related to two things one functional disruption functional obstruction of the urethra that's the tube that we urinate through the tube that comes out of the tip of the penis and that tube the first part of it passes right through the middle of the prostate so as the prostate enlarges it can compress that channel and that result in Weak stream it can result in dribbling and straining Additionally the muscle behind above the prostate is the is the bladder the bladder is a is a a bag a storage device that is is muscular and so that muscle as the uh as the diameter of the tube Narrows with increasing size for example that muscle will have to work harder compliance will go down and when the compliance of the bladder goes down the capacity can go down and the increased urgency to go to the bathroom will go up because it's less stretchy so again as we get older the prostate parts of the prostate will grow oftentimes that growth of the prostate results in narrowing of the channel that can concomitantly lead to thickening of the bladder wall and then that results in the whole constellation of urinary symptoms which can be managed but many many men have them and it's certainly something that we talk a lot about with almost all of our patients so maybe let's talk a little bit about um what the medical management is for those things because this is an area where the surgeon does both the medical management and the surgical management right typically yeah urologists are it's one of the more unique Specialties in that we do a lot of diagnosing and then managing medically and treating surgically and then survivorship for almost all the conditions that we take care of so what are the first steps in the medical management of lower urinary symptoms yeah so behavioral modifications so um if you're an executive at a water company and all you do is drink water all the day all day long you're going to urinate a lot so a lot of it is just education and behavioral modifications so educating people that a lot of what you take in will come out that you know that the idea that you know the kidneys are designed to maintain our body's fluid status in a kind of homeostasis if you increase your fluid intake you're going to have increased urinary outputs and so just basic educational things about that is really really helpful in addition to regulating what you drink it's when you drink it and what's in what you're drinking so a lot of people will come and and and come in with symptoms of nighttime urinary frequency and a lot of that is just you can modify with education saying hey don't you know don't drink you know two glasses of water right before you go to bed and if you get up in the middle of the night because you have to urinate don't drink another glass of water right when you get up to urinate so so that kind of component of the education timing of when you take in those fluids and then what's in the fluids specifically caffeine and there are some fluids that have natural diuretic properties and so if you are taking or drinking uh something that's a diuretic you're going to produce more urine and that will result in more urinary symptoms within two to four hours after taking that fluid in so caffeine for example is a natural diuretic and it will cause you to produce more urine over a certain amount of time than you would have if you didn't if you took in iced tea with no caffeine in it for example so a lot of educational things a lot of um a lot of Education about what to do when to do it we often will have people do avoiding Diaries but really it's a diary of what you're taking what you're drinking and then when you're urinating and actually just having the patients just walk that walk through that with them will will be quite helpful right so they're measuring their input in timing and volume yeah and output in timing and volume yeah and that simple task which is you know easy easy to do will result in a a realization that hey I'm drinking you know 130 you know ounces of water a day like what you know and it's it's all excessive it's unnecessary because you can show them that yeah you're urinating out the same basic amount of volume because we also get in our Foods obviously water too or fluids so so mapping out mapping out kind of Behavioral modifications is the first step I always do if it persists and they're bothered by it then we'll talk about doing avoiding diary particularly if their symptoms are a little bit unusual for example if you're sensing that they're maybe urinating much more at night than you would anticipate after they've done these different behavioral modifications there are hormonal hormonal um you know hormonal deficiencies that can result in increased urinary production at night for example so if we're suspicious of any of those things or if patients are still bothered by their urinary symptoms and they um there they want to not go on a medication we'll do avoiding diarrhea we'll map out when they're drinking when they're urinating and then we'll kind of go from there now now what if a guy comes to you and and is sort of upset about the frequency with which he's waking up to pee at night the medical term for that of course is nocturia is there a norm right so you and I are 50 years old um I would say five nights a week I don't get up to pee two nights a week I get up to pee once and obviously that's probably more tied to the timing of my fluid intake and what it was than you know necessarily prostate specific symptoms but what's normal if there's such a thing as normal for a 50 year old a 60 year old Etc yeah great question because there's a lot of variability in terms of what you can expect based on on the age of the individual so there are there's a there's a naturally secreted hormone anti-diuretic hormone and it in younger Decades of life it has a surge of release around seven or eight o'clock at night anti-diuretic hormone prevents you from diuresing or producing more fluid alcohol by the way inhibits this hormone which is why alcohol before bed is a great recipe for having to get up and pee for two reasons you get the fluid in the drink and then you get a molecule that inhibits the release of antidiuretic hormone absolutely and and so the classic one for that is beer because it's a higher volume high volume high volume yeah intake so yeah so we have natural diurnal release of antidiuretic hormone and that diurnal variation is attenuated kind of per decade as we get older so that peak of anti-didirect hormone goes down per decade and that can then kind of normalize your 24-hour urine production whereas when you're in your 20s or 30s you would produce let's just say 80 or 90 percent of your urine during waking hours during the night time when you'll have high levels of antidiuretic hormone you're not going to produce as much urine and your kidneys and your body will save that extra fluid for the morning when you get it so is there a biologic explanation for the attenuation of that hormone as we age you know it's a good question I don't know the I don't know the answer that to as to why that could be but certainly we see it in general in aging populations men and women I see so because I did after we had got through this I wanted to ask the exact same set of questions around female symptoms yeah but so right now you're saying there's an equalizer both men and women experience this reduction yes in uh and yeah in in anti-diuretic hormone as we age and then there are other factors that are also similarly consistent among aging individuals male or female like the resiliency of the tight junctions in your capillaries and of your vascular system right so it's you know less resilient and less tight as we get older right so you have even if it's subtle and not fully appreciable you have some capillary leak and as you lie down when you're sleeping at night you know that fluid will leave the extracellular space into the intravascular space and your kidneys will read that as increased fluid so you know I'm a very I have a very focused Urology practice but when I have people with urinary symptoms I try to do a really full body assessment because one of the main drivers of uh nighttime urinary frequency or one of them that's particularly tracks with age is you know just peripheral edema so are you are you developing edema and so forth so meaning people who have a lot of peripheral edema at the at night time you get uh basically reverse some of the third spacing yes and it's almost like they have an IV drip that's taking fluid from the interstitial space into their vasculars it's like they're drinking at night yeah so one of my behavioral modifications it's not really behavioral but non-medical modifications is you know knee-high Ted stockings for people who are having symptoms who if I see them at eight or nine or ten o'clock in the morning they had any edema any kind of ringing around their socks or something like that then I definitely strongly encourage them to to do that because it you know I tell people if you're getting up twice a night and you have a little bit of Edema you do some behavioral modifications we can reduce your nocturnal urinary frequency by kind of one so you can go from Two Times a night to one time at night just by changing one you drink and wearing Ted stockings and that's a it's a maybe not true for everybody but it certainly encourages people to do simple things without doing the polypharmacy the other thing that is a main issue related to nocturnal urinary frequency is sleep apnea and I'm sure you've talked a lot about sleep apnea on a variety of your different uh your shows it is a driver of a lot of just bad pathology and one of them is nocturnal urinary frequency and and we'll talk about it later but in the post-prostatectomy space it can actually result in profound nighttime urinary incontinence but it will produce a really symptomatic profound nocturnal urinary urine production and nocturnal urinary frequency and individuals why is that it's I think it's also related to the the regulation of your anti diuretic hormones and um really there's profound you know whole body side effects from it so you know in many ways if there's a there's a subset of men who this is a good way to encourage them to get their sleep apnea a diagnosed and then treat it okay so that's so that's behavioral yeah so then let's talk about the pharmacologic tools so you've already kind of alluded to one and it's one that we use in our practice um which is when we have a guy who otherwise we don't have a clear explanation for why he's getting up to pee um then he doesn't appear to have a particularly enlarged prostate and we're going to talk about of course all those things a very low dose of desmopressin which is this I get is the synthetic version of the antidiuretic hormone uh typically 2.2 milligrams before bed uh has profound effects yeah um so talk a little bit about that and then maybe some of the other things and also are there any contraindications to the use of that I know certainly theoretically a contraindication or a concern would be hyponatremia as you would sort of increase plasma volume and therefore dilute sodium but maybe just talk a little bit about how you would use that yeah so there there are very straightforward you know Front Line Medical Management you know pharmacologic agents to manage slower urinary tract symptoms and generally speaking the front line ways that we manage it would be with an alpha blocker so there are um that's a a class of compounds that are nowadays very very specific to prevent activation of a set of smooth muscles that are really is isolated mostly in the prostate and somewhat in the seminal vesicles and so if you just take a step back and look at the embryology of the prostate it obviously is a um it develops from urogenital sign your genital sinus and there's mesenchymal and epithelial components of that so there's a lot of smooth muscle within the prostate the smooth muscle exists within the prostate in part to help with ejaculation it's a effectively like it's a pump it's a pump so once you have when you're having an orgasm the the pump squeezes the prostate will squeeze and that will result in emission of the fluid so what you can do for individuals who have lower urinary tract symptoms is that while you have this channel this tube going right through the middle of it you can relax the smooth muscle within the prostate and that will relax a little bit and and theoretically it enhances the diameter of the of the uh of the prosthetic urethral Channel That's the thought for how it works and that could then result in relaxation and Improvement in urinary symptoms and it works quite well for most people now originally this was noted because of the kind of first class of of of Alpha blackers are used for blood pressure control and so one of the side effects of the first generation of these medications was just profound hypotension until you kind of titrated up the dose and so forth but the more modern meta more modern ones um really effectively treat specifically the so they're selective in that they relax those muscles without dropping blood pressure and in the newest generation of ones will actually be more are even selective to the smooth muscle within the prostate and not the seminal vesicle so the seminal vesicles in the prostate kind of grow up right next to each other for example when you do a radical prostatectomy you take out both organs they're attached to each other the seminal vesicles dump into the prostatic urethra so the second generation third generation anti-muscarinics or I'm sorry alpha blockers would paralyze or prevent contraction of the prostatics with muscle right so you would have improved urinary symptoms but would also have to do it doesn't impede ejaculation it would they would impede a jacket the kind of the first more targeted ones would because they would in fact paralyze both paralyze both the newest generation of the newest classes of these uh of these medications really focus only on prostate and so the impact on volume of emission of seminal emission or or semen is actually much less impacted and so I usually will just reach for those they're great so what how many of those are there out on the market today there's there's three typically today you would only use these third generation alpha blockers what are they what are they called yeah so how fusison is the one I usually go to but there's another uh you know 3.5 generation medication called sildenafin Rapaflo is what that goes by and then Al Fusion goes by um I don't know Al fusion and sildenafen are the two newest medications that are third generation that result in less impact on sexual dysfunction specifically less impact on semen production but have really really outstanding uh efficacy in terms of relaxing the prostate and improving urinary symptoms got it now when I was in med school and I remember doing Urology rotations and even in residency doing Urology rotations a common drug that was used to treat this was um a drug that blocked the conversion of testosterone to DHT so proscar was the name of that drug uh the brand name of that drug finasteride was the the generic name and um I you know we're going to talk I want to come back and talk about finasteride specifically so we can punt on the discussion of of that syndrome that we're going to discuss but strategically whether we're talking about finasteride or dutasteride drugs that block the conversion of testosterone to DHT which again will bracket for a moment that will come back and explain why are those drugs still in use today to treat this particular condition yeah so there are specific indications where you would think about utilizing a five Alpha reductase inhibitor for men with low urinary tract symptoms it's second line so if you have uh urinary symptoms you've kind of failed behavioral modifications then we would do an alpha blocker if an alpha blocker is working but not to the extent that the patient's satisfied and the individual patient has a large prostate over 70 or so grams and that you can easily diagnose that on an ultrasound or MRI yes you you would typically you know be able to size that no problem can a good urologist size that on a rectal exam a good urologist can I personally kind of think about things like small medium large in general for people in a relatively high quality Urology practices you're going to know the patient's volume of their prostate based on a variety of things you're kind of monitoring for but if you have a large prostate and you're having progression on Alpha blocker you can reach for a five Alpha reductase inhibitor finasteride or dutasteride and they have been shown to reduce the likelihood of urinary retention and reduce the need for surgical procedures in prospective randomized trials but in general they're recommended for really the big beefy prostates but remember the symptoms uh that they would treat that is they result in the the um the decrease in the kind of size of the prostate by between 20 and 30 percent over the long haul it doesn't happen immediately when you take an alpha blocker you feel better within a week when you take a a five outproductus inhibitor it will take six plus months to a feel better B see the size reduction in your in your in the prostate and then of course most importantly you'll have an impact on the PSA levels in the serum and so it's critical that patients are aware that your PSA is artificially depressed it's I mean it's you could be masking pathology potentially is that yes the PSA value will decline because PSA is a proportion regulated products and so when you reduce the amount of that potent Androgen you'll reduce the value of PSA it goes down by about half so it's a very um it's that useful drug but it is not something that I usually reach for because it requires a lot of very active monitoring has limited effect limited kind of uh you know efficacy in my opinion and um and there's a downside we'll talk about there's a lot of potential issues that one can experience while taking it so I'm very cautious about doing that so for me I reach for an alpha blocker if the alpha blocker is working in terms of improving the kind of Outlet obstruction symptoms that's strength of the stream how fast can you empty but patients still have a significant urinary bother increased urinary frequency urgency to go to the bathroom then you can either do a anti-muscarinic or an M3 Agonist which is the newest class in that kind of category which really helps relax the muscles in the bladder and really significantly impact the symptomatology for people with those kind of predominantly what we would call Storage symptoms you can have obstructive symptoms alpha blockers are great for those you can have storage symptoms and and storage symptoms are frequency frequency urgency just think about it if you have a thick flat bladder is impeded the compliance is poor it doesn't stretch well it's hard it's just always kind of feels full then those are things that can be very nicely addressed with these agents the anti-muscarinics are dangerous or you need to be careful when using those because in aging individuals they can they are associated with worsening of dementia and other kinds of neurologic cognitive well um you know Acuity so the M3 agonists which is is has the same net effect um are much cleaner so much much less side effects and so and the anti-muscarinics were just older drugs they were and it was the first line so the the so we kind of put those in the same categories maybe the five Alpha reductase Inhibitors which is it's yeah that's right you always look for a better option first um are women as susceptible to urgency and frequency from the same underlying pathology obviously women when they go through menopause estrogen withdrawal alone can produce those symptoms and there the treatment is clear it's estrogen replacement um so given that women don't have a prostate and therefore don't have something abutting their bladder in the same way um is there a role to use these M3 agonists in their frequency and urgency symptoms yeah I mean most of those medications and the prescription frequencies is much much higher in women so that would be the kind of classic overactive bladder got it and so women will have bladder symptoms that are also similar in men the men have uh have uh you know a thousand to one more often you know obstructive symptoms because the urethra in a woman is very short it's four centimeters long the urethra in a man is you know 25 centimeters long on average or something like that so the obstructive symptoms are much more prevalent in men and so that's why Frontline is always an alpha blocker but if they're having a good response with an alpha blocker um but still bothered and you can reach for an a uh an M3 Agonist for me personally though it's always a balance because at some point you have to start saying well okay how old is the patient how significant are those symptoms because there are highly effective ways to manage these issues surgically these days they can most of the time be done just as a simple outpatient and so then you start saying I usually begin to introduce the idea of okay well if you're still bothered we have Outpatient Surgical procedures that can basically fix this for life with no medications and so I that's kind of my stepwise process that I kind of lead patients through in terms of thinking about their urinary symptoms for men let's talk about let's talk about the surgical procedure so again I'm just kind of going back to my where I what I learned about 25 years ago that the terp right the trans urethral resection of the prostate yes uh uh kind of a Roto-Rooter job yeah so the prostate develops from the urine identical sinus the prostate as we mature in response to androgens and estrogens too for that matter will it develops into different zones or different regions the peripheral Zone which is outlying the prostate think about a orange and the orange peel and the pulp of the Orange is the transitional zone of the prostate that gets bigger actually it's not just a testosterone driven thing it's actually when there's more estrogens around that actually with testosterone that can result in hypertrophy increasing in the size of the transition zone that is what causes all the urinary symptoms in individuals with rare exceptions with an aggressive cancer that's what's causing it in those situations you can do what they call there's a variety of missed procedures so minimally invasive surgical procedures that can address these urinary symptoms so you can do a variety of things you can introduce steam into the transitional Zone tissue that can then you know kill that and effectively kill all the smooth muscle and reduce to some extent the kind of hypertrophy of the epithelial cells you can surgically resect it you can Trends urethrally transurethrally so no incisions so what we would you could call a natural orifice procedure uh you could suspend it surgically so there's kind of tethers that you can put in place that kind of tent open the urethra but the Mainstay the gold standard is to remove the tissue which can result in profoundly improved urinary symptoms it is and is that done with like laser electrocautery I mean what is the gold standard today for the the the means by which you remove the tissue so the gold standard has always been the terp procedure which is what you describe now that procedure itself has evolved in that it can now be done with irrigation that is with normal saline so traditionally to maintain a monopolar current you had to use water because you would not want the sodium to disrupt that current so now a modern terp is a bipolar terp a bipolar where you have you you the the the explain to folks why you need an arrogant when you're doing this procedure so you're effectively um as you described that this is a kind of Roto-Rooter procedure but you're technically removing bulky tissue in the urethra that's kind of circumferentially surrounding the prosthetic urethra yeah so you sort of have as you know you've got this thing here and you you using the natural orifice of itself you have to expand the diameter of this thing by actually getting rid of prostatic tissue in the transitional Zone yeah so you scrape out small portions usually one or two gram size little scoops of tissue you do that with effectively a hot knife it's shaped like a loop so you kind of core out little Loops of tissue and when you do that you a have bleeding and B the tissue collapses on you it's like it's like a cave so it keeps falling in on you so you have to suspend it open with the arrogant and you have to use the Arrogant to better visualize what you're doing that's a traditional terp that was always done with water and when you did it with water and you were tenting open the tissue putting it under pressure you could have water move into the intravascular system and you could get something called post-tur syndrome which is basically where you made the patient profoundly hyponatremic you diluted their sodium too much and that's very dangerous yes and you'd have significant neurologic issues and so forth so that particular procedure there's lots of kind of advances in urology in this particular space that procedure 15 years ago they started basically redesigning the devices so you could do it with saline so therefore if you were if there was flow of fluid from the procedure into the intervascular space you could it was just like giving them intravenous fluid it's like isotonic exactly so that really prevented the um that prevented any issues that you could have with this tur syndrome and terp is a very effective and it Remains the gold standard that all these new Mists these minimally invasive surgical techniques compare themselves to in terms of efficacy now I have the pleasure of having a partner at Northwestern Dr Amy crambeck she has in mind we've actually sent a couple patients yeah Amy is Amy does a procedure called holep which is a homium laser enucleation of the prostate so the terp basically is is effectively scraping out little one gram chunks of tissue so if you have a 100 gram prostate you'd have to scrape out let's just say your goal is to get that down to 50. your goal is to get it down to 15 15. so even less than like normal we would say might be 30 right and yeah so normal prostates increase in size as we get older so the a normal prostate for a man who's 40 or 50 is between 20 and 30. yeah but people can have profound urinary symptoms with prostates that are as small as 35 grams so people often assume because you have urinary symptoms that you actually have this gigantic and large prostate that's not always true but the smaller prostates typically can be well managed with medications and Only We will we be moving to surgical treatment when the prostates get larger so you've got sort of of a selection bias going on you do so front line gold standard historical is terp it's now a bipolar terp so it can be done safely and the reason you go from a hundred if you're starting there down to 15 as opposed to 30 or 40 is you want to be one and done you never want to be back again yes a good a good surgical procedure is effective for life now they're not all like that and so the ones that the less tissue remove if you don't remove any tissue for example you're more likely to have a secondary treatment okay my partner Amy cranback is really one of the Pioneers in modern whole Lab surgery so this is different so again if you think about the orange analogy a terp or any of those other procedures is basically trying to scrape out the pulp one one little chunk at a time Amy will go in and she'll get in the plane between the peel or the Rind of the orange and she'll take out all the poultry take it all out in one piece she pushes it into the bladder and then there's a more Slater that then Chomps it into little tiny pieces that you then remove through the urethra so there the beaut the benefits of whole so just let's make sure people are saying because I love that I think that I think your orange analogy makes this so much easier to understand yeah if you're doing a terp you're sticking a pen you've got a pencil hole going through the orange you got to put that you got to put a hollow pencil into that pencil hole and literally one tiny tiny thimble at a time yeah pull out little sacks of Pulp one by one by one by one by one by one by one yes additionally remember that when you're doing that you're disrupting the kind of architecture of the orange and there's lots of blood vessels that exist within the transition zone itself yeah and so it's now it's bleeding like a sieve bleeds a lot when when Dr krambach when Amy does her procedures she gets in that natural tissue into that natural plane and it's not bleeding as much and she somehow manages to take that whole pulp minus the peel shove it into the bladder and when it's in the bladder now isolated you can break it apart Yes and she'll more slate it apart so she'll she is spectacular so um whole app was a procedure developed originally described in New Zealand I Believe by a New Zealand urologist and it was limited for a long time based on the technology that existed within the lasers but the Laser Technology in Amy really helped develop the latest versions of these lasers that are just higher energy more precise take that and then you can then you know couple that with an experienced surgeon the outcomes for it are spectacular so what are the what are the um patients who would not be considered candidates for that procedure is there a is there a contraindication to that no if you're talented enough you you can do it in anybody which she can now the smaller the prostate the less distinct there the the differentiation is between the peripheral Zone the the skin of the orange the peel of the orange and the pulp and so it actually requires more skill to do a whole lap in a smaller gland than in a bigger gland when the prostate's really really big the adenomas very well formed it's easier to get into that plane so a large prostate would be something over 80 grams that's where you would really say in let's say a general urologist practice the threshold for doing a terp-like procedure goes down it's really long to do a terp it takes a long long time to do it yeah if you're a talented whole Lab surgeon you know Amy can do a 200 gram prostate in about 20 minutes I mean it's just spectacular tell me about what that patient goes through post procedure they go home that day obviously they go home procedure they have a catheter in place no no catheter yeah so that's the other thing I remember Ted from when we were little spring chickens is how many the the catheter Management on that patient with a blood bag full of bloody water and urine coming out for days and days and days and again it's a relatively small price to pay I think for the ultimate relief you're gonna get but how is it that this patient just literally leaves the office without a catheter yeah so it has to just do with you know what you do at the end of the procedure so how well you're controlling the bleeding and I think the big difference in Holub as I mentioned is when you're in that distinctive plane it separates paranoma in peripheral Zone you it's just the vessels are much more discreet whereas in a terp there's these sinuses and so forth so but the analogy again to the Orange is perfect right yeah if you try to peel an orange from the inside ripping apart yes you're going to get orange juice all over your hands whereas if you're taking the skin off it's actually it's less elegant you remove less tissue it's bloodier Etc so big picture if people um are on medication and they have progression you can start talking about minimally invasive surgical procedures there are in office minimally invasive procedures and there are they're quick the in general a take-home message though is the the less you do the less durable and the less effective it is over time so there are procedures where you can tent up the the prosthetic urethral Channel they work with basically temporary relief I would only even consider those an individual who could not tolerate the medications but why would you if you're going to go to the trouble of actually putting a probe in the urethra yeah to go through the tenting up procedure why wouldn't you just do the procedure Amy does I I do I'm just saying for your general audience that maybe offer for somebody I don't I never recommend it because it never works it can cause a lot of pain you put these clips and you're tethering things up it prevents an effective high quality MRI there's lots of limitations but people may who listen to your show may be offered these things so it's called eurolift yeah then secondary or Next Step Up would be to basically use steam to ablate the prostatic cells when you do steam you're killing and just desiccating the cells and that can result in pretty good symptomatic Relief by the way did the patients require general anesthesia for this I've forgotten no for the Euro left you can do it in the office for this procedure called resume you can do that in the office with local anesthesia it's uncomfortable for patients but it can be done there okay or it can be done under like you know uh Twilight um that works it is a step more in terms of intensity and what you feel those individuals go home with the cathe there's lots of Edema and lots of swelling when you do that procedure so they require a catheter for several days to a week right because that steam creates inflammation even though it's cauterizing and if you don't leave that catheter and they're going to get urinary obstruction they're not going to close their exactly urethra so resume would be the next step up in terms of invasiveness then you can always go to this traditional by terp or bipolar terp that's all those are all effective therapies to think about or talk about with the patient when your prostate's less than let's say 70 or 80 grams whole up was originally developed to just handle the bigger prostates which traditionally you and I when we were training at Hopkins we would do an open Simple prostatectomy that's where you open the patient up from above just below their belly button you will open up the bladder and then you manually with your finger kind of carve out that inner pulp of the orange leaving the peel of the orange behind and the reason you leave the peel behind in that procedure is because it's not a cancer you don't need to risk injuring the neurovascular bundle on the outside which is up you see what we're going to talk about when we get to prostate cancer yeah everything around the outer um peel of the oranges all the important you know real estate so the urinary sphincter muscle and all the nerve tissue that goes to the sphincter and also goes to the cavernosa bodies that trigger erection so when you that was what we used to do now that procedure is evolved that can be done minimally and basically with a robotic procedure and that was really kind of emerging as a standard of care and then the peop you know super talented surgeons like Amy cranback came along and can do a 200 400 600 gram prostate first of all can you just show me what a 400 gram prostate looks like physically what is it 400 gram prostate is a large grapefruit I mean it's massive what's amazing to me is whereas a normal prostate is a golf ball so a normal prostate it's a golf ball and orange would be a hundred grams a big grapefruits 400 grams that used to be a procedure that was technically very difficult to handle with an open Simple prostate robotic simple prostatectomy Amy cranbeck can you know do do three of those in a day and be done by noon she's you know so it's spectacular a couple of other just questions on the on the the size of that prostate so when a guy has a two to four hundred gram prostate how much of that is genetic is that virtually all genetic yes a lot of the you know you see that a lot where it's runs in families so what it is that is underlying that overgrowth um you know not well studied frankly should the NIH be putting their research dollars behind like why do men get big prostates probably not so but yes definitely any correlation with prostate size and cancer yeah so the bigger the prostate the less your chance of developing aggressive cancer is why is that not sure and it may have to do with variations in the balance of hormones for example there's definitely a large prostates grow in response to kind of a not an increase in testosterone actually but but a more of a even ratio of T to e so testosterone estrogens so actually as your testosterone declines as you know as you get older the T can go down estrogens remain pretty stable or can go up obviously with especially if you're metabolic syndrome rise so as men age their prostates grow and I believe that that's more hormonal so in other words if you're saying that you know again classic thinking that has clearly been proved false is that testosterone is causing prostate cancer you're saying it's way more nuanced than that and it's maybe if the endocrine component of prostate cancer may be more related to the relationship of testosterone and estrogen yes and a declining testosterone in the presence of a rising estrogen would be a more favorable endocrine milieu for prostate cancer than the younger phenotype Which is higher testosterone to estrogen well let's just take that back a second so when you're when you're as you're aging your testosterone and you let's say as you're aging and if you have metabolic syndrome your testosterone levels will go down your estrogen levels will go up and that can result in prostatic growth but it's typically more adenoma growth in the transition zone causing lower urinary tract symptoms so benign growth benign growth that somehow is protective either the size or just the ratio that difference in ratio of T to e is somehow productive for developing kind of later onset prostate cancer remember in my mind yeah you're you're locked in and your code is is effectively set in stone in your 30s and 40s in my opinion for for developmental processing cancer wow right when your estrogen levels are very low your T levels are higher now we'll talk a lot about testosterone what it's doing in prostate cancer later but in my opinion um it's the T to e ratio that attributes is responsible for prosthetic enlargement much more than the development of any prostate cancer and just to kind of close the loop on the surgical procedures for lower urinary tract symptoms two two final thoughts one is what is the floor for the uh what's it called the whole whole app laser nucleation of the prostates so what what is the in the hands of as someone as talented as Amy what is the smallest prostate she would do that procedure on somewhere on let's just call it 25 or 30 grams oh wow so basically there's no limit in the hands of a talented she does hold UPS on anybody who needs a surgical procedure that's her go-to technique now below that there's not a lot of transitional Zone tissues so the other key take-home message for the listeners are if you develop if you're developing profound urinary symptoms and you have a small prostate you have to start looking for other sources and and by definition you're not responding to two classes of drugs yes you have to worry about cancers not prostate cancer but you have to worry about urothelial carcinoma urothelial carcinoma which is a cancer in the lining of the bladder but also can even get into the urethra yeah the urethra has urethral aligning oftentimes people particularly young women will it's a classic kind of board exam you know younger woman comes in with urgency frequency you neglect to look at their urine for cancer cells and they can have a a aligning a cancer in the lining of their urothelium that's causing all those urinary symptoms so I see so so small prostate unresponsive to medical management persistent symptoms you better be doing urinary cytology in my opinion you need to do a workup to rule that out for sure and there can be other you know central nervous system uh you know diseases that can result in urinary symptomatology but in general as a urologists you have someone coming in with those symptoms you really want to start understanding well what else could be going on because as we mentioned you may have those individuals may have had a history of prostate infection like a bacterial infection or may have had a viral infection they can result in prostatitis and inflammation in the in the in the pelvic floor itself and that can result in all those symptoms and so the so yes you can have as your kind of canary in that coal mine that you have urgency frequency but it's not at all attributed to a large prostate it's not attributed to drinking too much fluid if you if you take away the attribution of a urothelial carcinoma then you have to start saying well what are the other causes and there's a lot of uh potential issues that can be addressed that can cause that inflammation that has a unknown etiology to what incited it causing that urgency frequency urinary bother now given the success of this procedure I mean obviously Northwestern is probably top five Urology institutions in the United States uh approximately would you how many people does every city have an Amy like is what's the frequency of surgeons of that skill I would say that in the U.S uh well I'm biased I think there's only one Amy out there but there's very few people who are as talented as she is I would say that there's probably 10 whole Lab surgeons that are on her part her level that could basically go all the way down to a 20 30 gram it's not the it's not the small process yes it requires a lot of skills there's a small prostate but handling um handling these very very large prostates in individuals who are incredibly frail and older who were told look you're too old for a surgery I was just on call a couple weeks ago and we had a 95 year old gentleman came in from another major Hospital in the in our city who was having bleeding from their prostate that was more than one unit of blood a day transfusion what yes and was told we can't do anything for you you're too old and you're too frail so I go around in this guy on a Saturday Amy had done a whole up it was a hospital hospital transfer coronary care to coronary Care Center Hospital right just so speaks to her skill level transfer in she does the hold up it was a 450 gram prostate she takes out 400 grams of tissue and the guy we left at Catherine because you know we just weren't sure we took his catheter on Saturday morning he went back home aged 95. so amazing like really a talented surgeon like Amy and there are other Amy's out there but talented surgeons like Amy which are hard to find really can transform people's quality of life let's before we get into some of the pathophysiology of how the hormones impact the prostate which is a good lead and I think to to cancer let's go back and talk a little bit about prostatitis because I I would guess that for many men that is their first brush with pelvic floor discomfort and uh you know a symptom associated with uh with this gland so so I I remember you probably don't remember this but I remember having a brush with this about six years ago and of course you you help me out and so what this is part of the problem when you start to play doctor to yourself right so all of a sudden I start having some you know discomfort when I'm peeing and um you know I I do all the usual stuff I you know check oh is it an infection none of the above right so it's not like I have a urinary tract infection or you know an STD or anything like that um and boy does it and it's not unbearable pain to be I don't wanna I don't want to over dramatize this it's not like razor blades are coming out which I've heard people describe you know that might be certain infections no no it's none of that it's just not comfortable it's really uncomfortable to void and um I gave you a call I remember exactly where I was when I called you by the way and and you were the one that said no no look you know and you started asking me a bunch of questions hey you've been traveling a lot are you a little constipated and one thing led to another in the diagnosis in your mind was look playing doctor over the phone at least I'm actually more likely thinking this is prostatic inflammation yeah so walk us through the the pathology of that yeah I mean I wish I could tell you in in the next five minutes what the pathology was because we did the short answer is we do not know we call this kind of constellation of symptoms chronic pelvic pain syndrome so what that really ends up meaning is it's a bucket that you really we put a lot of different things into so you can have pelvic pain and discomfort if you have a large prostate and it's obstructing your urinary tract okay that one we talked about you can manage that that's pretty easy to do but there are other things that can cause pelvic pain and discomfort one would be acute bacterial infection and That's a classic frankly if we find that I feel good because I know we have a solution that we can address it and so forth you can address the infection now the inflammation and the discomfort and pain that results after that may take much much longer to resolve you can have a a non-bacterial inflammation that could be viral although no one's really ever isolated specific viral viruses that are you know an individual man tracks with that pain but viral and then there's pelvic floor you know dysfunction that is outside of the urinary tract that pelvic floor function could be in the in the anus and in the rectum having to do with dysfunctional voiding or elimination in the rectum it could have to do with dysfunctional elimination between the bladder and the urinary or urethral sphincter those are common yeah because the other thing anatomically that maybe we failed to mention was the proximity of the rectum to the prostate yeah so the rectum and the prostate are adjacent to each other the rectum and the prostate effectively develop from the cloaca the cloaca is the embryonic kind of sewer that's where all the waste in a fetus would go into and out of and then it's divided anteriorly and posteriorly into the urogenital sinus and then the what we comes to anus and the rectum and so yes they're they're intimately um they're intimately associated with each other and the innervation between the two of them is actually there's a lot of cross innervation so if you have inflammation in the gut in the rectum and the anus you can result in irritation and inflammation in the prostate there also can be translocation of bacteria between the rectum and the prostate so when we when we are talking about your individual situation I said are you traveling are you constipated we think that that can result in maybe some increased transmural translocation of bacteria but by the way to this day we don't really know what it was but but that said like any for reason I go to Great Lengths to make sure my bowel habits are regular when I travel it's still difficult like it's yeah like I'm out of routine I don't know if it's dehydration I don't know what it is uh it also might be parasympathetic sympathetic balance I think there are lots of reasons why a lot of most people I talk to you know as patients obviously I don't have this discussion at parties but but we'll say yeah I just get constipated when I travel a lot that almost always seems to produce some change in voiding quality 100 so there's a huge correlation number one it's just physically the pressure on the prostate and and and so forth can just make it much more difficult so the classic the classic presentations for a man with urinary retention um obviously post procedural so if you have a hip or knee anesthesia can shut your your gut down and you can get constipated and you can do that or um you know some of the different uh cough and cold medications can can do the same thing but in general I think of travel constipation from changing in your bowel function that will be a a big one and even if you doesn't make you frankly go into urinary attention it affects how you urinate and and so forth so so let's say you rule out the common stuff yes your father wrote a very important paper in New England Journal of Medicine has it been 20 years now 15 years ago yeah um that I refer back to that paper quite a bit yeah um and it was actually following the algorithm of that paper that when I got back to New York from when I back in whenever this was going on Circa 2016 that um we went through that diagnostic procedure yeah walk through that procedure which again I think for most people seems like a lot it's a that's a long run but when you're dealing with something so complicated um it is important to get some diagnostic specificity because the treatments do differ yeah and once in my case the treatment was identified the fix was on yeah so the there's a workup that you can do and you implement if you're concerned about a word that someone has an infection in their prostate or potentially their seminal vesicles that you would have to go through to distinguish that type of infection from an infection in the bladder which is right next to the prostate and so that is basically was described by a Stanford urologist Tom Stamey and that effectively um was that you would capture urine as it comes out the urethra in different phases and therefore you could track where that urine came from so it's actually a four-step process so the first step would be to capture urine immediately after you start voiding that would then capture and wash out any bacteria within the urethra the long Channel between the bladder and the tip of your penis right so that first few CC of urine that comes into the it gives you a sense for is there any bacteria growing in the urethra urethritis then the second phase would be you'd wait a couple seconds and then capture urine Midstream coming out from the bladder this is you know if and then you could then determine is there an infection in the bladder then what you would do is you'd tell the patient to pause you would do then a rectal examination and you would press on the prostate pressing on the prostate vigorously so that you could effectively in some ways replicate what you what happens in an orgasm that is where the smooth muscle squeezes the fluid out of the prostate when you do a vigorous rectal exam you're trying to push the fluid into the urethra you can sometimes just actually capture that prosthetic secretion by itself we call that EPS or expressed prosthetic secretion you can send that off for an evaluation for any bacteria in it that is not always the case that you can get um you know that fluid out so then what you would do is to send the patient back to the washroom have them then capture a urine coming out of the urethra and the the kind of the final the the beginning of the flow okay right after a vigorous exam that will capture the fluid that may be still in the prostatic and the other parts of the urethra but it was in the prostate yes and that would be the kind of essence of the step and then you can just kind of complete the void so then therefore what you can do is look for where are the cultures showing any bacteria and the cultures that would be let's say for example clean in the initial void that would be vb1 the initial void and clean in vb2 that would be the bladder but having bacteria in the EPS the prostatic fluid itself or vb3 then that would tell you that there's an infection within the prostate now the key thing is that standard Labs will call an infection if they see bacteria that's growing more than 10 to the fifth so more than ten thousand plus bacteria in that sample but if you're worried about having a infection in the prostate for example you need to lower that thresh threshold more like are you having hundreds or thousands of bacteria so 10 to the 2 or 10 to the three so whenever that should be a completely sterile it should be completely sterile the bacteria is a Haas the prostate is a hostile environment for bacteria to persist it's very acidic it's actually thought when people say like well what's the point of the prostate right it's used for reproduction but it's also thought that it can be somehow a barrier to developing an infection in a man in the bladder so the the the Hostile acidic environment of the prostate is thought people speculate to somehow prevent a bladder infection because remember pre-modern medicine if you as a man would develop an infection in your bladder it's life-threatening yeah especially if it goes up with the kidneys if it goes into the kidneys or it goes into the blood you get urosepsis and you often will die so people think okay what's the prostate for well it's used for reproduction but it's also may be used for helping to prevent as a bear natural barrier for bacteria to go all the way do women have any such thing I mean women are so much more susceptible to YouTube because of the short urethra yes they're they're susceptible to UTIs but remember if you have a infection in the bladder of a woman yes it can also attract to the kidney but in general this there's limited stasis of urine in a in a woman's bladder because the urethra is so short and you can evacuate or empty the bladder so effectively in a woman whereas in a man as you get older and your prostate gets larger you don't empty all the way more Francis of urine in the bladder if you have if you retain urine that's infected with bacteria you're you're gonna so women so all things equal women are less likely to develop urosepsis or uh you know kidney infections based on the fact that they're more it's easier for them to evacuate the bladder if there's an infection it's by Aid by decade yeah right so young men they're the least likely to get any urinary tract infection period but as men get older their chances of developing a urinary attraction infection equal that of a woman but you could argue because of the urinary stasis Etc that that infection in a man is much more life-threatening early on in their disease course than a woman the the probability that you wouldn't develop an infection in the kidneys is probably the same between a man and a woman but remember if you have a man who's older who has a bladder infection that can go into the blood but it also can go into the prostate and as we are alluding to in our discussion of working up somebody for a prosthetic infection clearing an infection in the prostate it's very very difficult and very challenging so you have to do these specific Stamey floor glass test that's the different phases of the urinary avoiding you have to rule out that there's any infection in the prostate it's rare that we would pick that up but it's possible and the other place that you want to look for in the kind of very unusual cases is in somebody who has maybe an infection in their seminal vesicles maybe we can put a picture up for the for the audience but the seminal vesicles they produce about 50 percent of your semen you can get a bacterial infection in your seminal vesicles and unless you're looking for that infection you'll never you'll never clear that person because it's kind of very isolated from any continuity of the urinary tract but can result in pelvic pain can result in persistent issues with infection in general we do that very specific test to rule out infections in the urinary tract um that are related to the prostate or the seminal vesicles the other way you could do it a poor man's version is to actually send off a semen for a bacterial testing we like to do this this uh you know Express secretion kind of setup but you could do that too if you have an infection in the prostate or in the seminal vesicles or the genital tract then yes we know how to treat that it's with directed antibiotics that in many ways will address the infection and most of the time address the pain and discomfort that's associated with those symptoms now the issue is that there are many people who have discomfort that is not associated with bacterial infection it could be viral it could just be inflammation it's not necessarily within the urinary or genital tract so I see a lot of patients and when I do a rectal exam on somebody who's complaining of of of uh prosthetic pain I always want to feel the muscles in the pelvic floor and just like and how do you do that on the rectal is it just a broader exam so when you do a rectal exam and you feel kind of straight posterior you're feeling just the prostate if you just move your finger laterally you're into the floor if you're in the pelvic muscle for sure and so oftentimes you won't feel much of anything but in a man who has pelvic pain syndrome I I feel all the time like I mean it's just locked up it feels like a guitar string yeah you'll feel bands of muscle so you know think about when you when you tweak your traps yep you have those bands of muscle you can feel with your hands but the good thing about that is you can go get a massage and you can work it out and and that same thing happens the pelvic floor muscles so when I'm dealing with the patient who has chronic pelvic pain syndrome or pelvic pain I should say maybe not chronic but oftentimes we'll see them after a while this discomfort and pain I try to be I try to treat their symptoms based on whether where the pain is coming from so is it prostatic if it's prostatic I try to do things like um you know alpha blockers potentially Cialis is another one to treat the symptoms that are associated with that discomfort if I pick up that they have a lot of tightness in their pelvic floor I send them for myofascial release so it's trans rectal myofascial release it sounds barbaric but yeah I've seen this make like change a guy's life 100 and so I feel and the same for women yes true so I feel you know um great when I can when I if I'm examining somebody and they have that it makes me feel good because I have a solution the ones that are difficult are the ones that we just don't know what's causing it can be related to food too so if somebody has pelvic discomfort pelvic pain you do a very thorough kind of diary of what they're eating and and it's more classic in women with what the kind of female equivalent of this would be Interstitial cystitis where you'd say well what foods trigger it for you because it can be triggered and irritate the bladder and that's causing the pelvic discomfort so again you you take a thorough history the NIH has a very good online questionnaire to help you kind of tease out where the symptoms are coming from then once you that's that's under nih's website or is it under specific if you Google an NIH chronic pelvic pain syndrome questionnaire we'll get into it in the show notes and then and then you can take it and you can delineate that and so yes is it common in young men no but it's more common for if a young man's seeing a urologist to have that then let's say BPH or something obviously the most common thing for a young man to come see us for is Ed but yes it's definitely something that we can address and I've seen a number of men who go through the diagnostic workup there is is no infectious agent whatsoever but simple prostatic massage yep just like you describe as a massage to an you know an ailing muscle alleviates the problem it's it's an end it's a very anti-inflammatory process yes that's that's a great point so a why that works for some people we don't know but it works and hey we'll take it the other classic thing I hear about and and you you know you'll hear about in medicine is um well I have chronic prostatitis again that's a that's a very specific diagnosis it's a bacterial infection you can't clear so it's almost impossible to have that but I have chronic prostatitis and I take an antibiotic and I'll go on 30 days or 60 days of this stuff and it makes me feel better that scares me a lot because as you know going on anything like a potent antibiotic has a lot of Downstream consequences that you just got to be careful of changing your gut Flora tendon you know all these different issues why is it that they work and if you ask the patient they'll say as soon as I get this discomfort I'll take a sipro I'll take a Levaquin I'll take a bactrim and I feel better it's because these powerful anti-microbial agencies anti-antibiotics they are profoundly anti-inflammatory too so if that's what they're telling me I try to transition them out of popping these you know month-long runs of antibiotics and get them on an anti-inflammatory yeah so strong particular NSAID that you find works better or is it like does Celebrex even work even though it's you know I don't find it to be necessarily as potent as yeah you know I try to stick with the more potent ones and I think naproxen is what I like it's bid dosing it can be a little hard on your stomach but I find that to be you know ibuprofen is incredibly potent but at taking the right dose three times or four times a day can be hard so I use what about meloxicam do you which one I haven't I haven't you know gone to it but it theoretically should work and people you know there have different sensitivities or efficacies with these different ones so I started I start generally with naproxen and I'll do that with a little bit of an anxiolytic because some of the energy analytics help just relax the pelvic they relax a lot of your muscles and they'll help relax the pelvic floor muscles because although you want to treat that particular symptom it's causing inflammation in all the structures around it rectum bladder prostate and pelvic floor muscles so I usually will try to do that for a limited time I don't like people taking long-term antibiotics for it unless they have a difficult infection no I think you're absolutely right I mean I I have a friend who I sent to you recently in that boat right where kind of has prostatitis you know or believed to be bacterial prostatitis once a year and that sort of triggered my thinking that maybe that's not what this is and yeah and maybe we need to go down a different path so now there are individuals who you know we can't put our finger on what's causing the symptoms but my father still has an active research lab he is the worlds of Floridian kind of prostatitis and pelvic pain and one of the things and he's still at Northwestern he's still at Northwestern he has an ongoing clinical trial for people he can pick up uh he believes that a lot of the discomfort and pain has to do with Mast Cell dysfunction and so he'll actually do he has a clinical trial where he'll actually see individuals he'll do an EPS he'll look at their voided uh fluid he'll assess them for different markers for mast cells if they're high he'll put them on Mast Cell Inhibitors in a clinical trial and it's quite effective so if folks are interested listening to this uh presumably this is a trial only for men of course um where can they find more information about the trial yeah on the Northwestern Feinberg School of Medicine under the department of urologies webpage my father and his um Anthony J Shafer and Praveen tumakat are the he's my my father's scientific partner they are so we'll link to that as well for folks who will so there is hope for these individuals because there is a subset of men we do see that it really is sad because it has a huge impact on the quality of their life yeah Okay so we've talked now at length about two of the big problems associated with the prostate and while both of these can be an enormous threat to the quality of a man's life um they're they're not often a threat to the length of life though I guess one point I'd make before we leave these is one of the questions I get asked a lot is how does somebody actually die from Alzheimer's disease and you know what I usually explain to people is they usually don't die from Alzheimer's disease they usually die from something else that is brought on by the Alzheimer's disease and one of the classic sad tragic cases you see is urosepsis yeah so you see it a man with Alzheimer's disease and he is simply so one he might have a catheter in him because he's unable to void on his own and that dramatically increases his risk but even if he doesn't he's simply less responsive to the signs of an infection he's not attentive to the fact that it's burning when he pees and because of his age and his immunologic reserve what starts out as a urinary tract infection on day one is a lethal case of urosepsis on day four and so you know I do think of this as kind of one of the Grim Reapers uh of of older men yeah I mean um as men age and particularly if you have con you know concomitant other significant medical issues your Frailty goes way up and so any little insult to your body can do it and obviously classic things are aspiration aspiration pneumonia smallest cellulitis if you're not moving around exactly yeah yeah and so I think it's a lack of awareness and and absolutely it requires a very astute kind of caregiving family or or cohort of individuals to notice subtle changes because obviously if you can pick up an infection early then it doesn't necessarily have to spread and it won't be so symptomatic if you could speak to someone listening to this who's caring for an elderly patient male or female who is in the throes of dementia what can a caregiver do on this particular front is there anything they can do to minimize the risk of a kidney infection or a bladder infection turned into systemic sepsis is there anything they can do yeah good hygiene is obviously key and I think in general if you're monitoring the individual uh they're they're avoiding you know they're avoiding history so we we obviously would prefer for people to void on their own and many people can many times people have catheters in place for convenience of the caregiver right and so if you can keep Hardware out of somebody that's obviously very effective and if you if the individual can't void and they're having trouble with that then intermittent catheterization is what we obviously endorse and recommend where you just place a catheter temporarily and any different catheterization poses less of an infectious than constant catheterization a little counter-intuitive right you would think gosh if three times a day you have to Cath somebody that's three times you're introducing it but you're saying if it's done with Duality sterile technique dwell time right so three times a day for 60 seconds each for so that's 180 seconds versus 24 7 for the bacteria to be there and we know if you leave a catheter in place by 48 Hours the bacteria has colonized crawled up the the tubing and is in the bladder so yes if you can minimize the dwell time of the foreign body the better so yes it is a little counterintuitive but for men and for women if you can do intermittent catheterization that's a profound way to reduce the chances that you develop any you know Euro sepsis will you develop or will you have bacteria in the urine if you do intermittent cancer stations possible does that mean that you've failed with that Technique No because if you're continuously emptying the bladder you never can get overgrowth and you can never get enough urine with bacteria in it to cause or pose a problem and that leads to another point which I often see which is an individual's as they're aging you know I think dehydration is a key under appreciated contributor to all these medical conditions so remember especially because older people lose their relationship between thirst and hydration status that that's another one of those things that yeah and if you have Alzheimer's you forget to drink frankly and so if you have bacteria in the urine but you keep the concentration at 10 you know 10 bacteria per ml well that's not going to be a problem but if you're dehydrated and you have more concentrated urine and there's the same amount of bacteria with less urine then you're going to have you could really have significant issues so yeah I mean it's very you know the you know as we age and you have these comorbidities a good caregiver is critical and that's the you know oftentimes in medicine they're paid the least you know and it's really an important role that you have so I think if you can maintain any kind of Hardware in an individual get them out walking around and just remind them to drink if they have a catheter you want to get that catheter change every month or three weeks and generally a good caregiver and a good Urology practice we have a whole team of nurses that do this for our cohort of patients um they'll get an idea of the Cadence for that individual but we try to stay away from it if at all possible okay so Ted let's let's let's kind of put those two aside and now pivot to the third uh major source of pathology associated with the prostate which is prostate cancer so so prostate cancer is the second leading cause of cancer death uh for men uh behind only lung cancer um and so in order right it goes for men uh it's it's lung prostate colon pancreas um the thing that kind of stands out to me is we have great tools of detection for prostate cancer and based on that I guess it's a little surprising to me that it is still the second leading cause of cancer death in men so one of the things I hope to be able to do by the end of this final part of our discussion is get a better sense of what an individual can do to flip the odds in their favor because you've probably heard me say this before I don't think anybody should ever die of colon cancer right for the same reason we have remarkable tools of detection and um and we also have a very predictable pathogenesis where we must go from a polyp we must go from an adenoma to a carcinoma yes and we can detect the presence of the adenoma because it is outside the body effectively so just to bring it back old school to where we first met obviously that would be the halsteadian theory for how cancer would spread right and that would be a step Wise from a localized non-invasive to an invasive tumor to a regionally advanced and then medicine and colon follows the that algorithm pretty well there are obviously always you know the cases that you can't you know that that are sure they're assess all polyps that are very difficult to detect but in general I would say that yes I agree with everything you're saying and I would agree that on average prostate cancers follow a similar halsteadian spread how steadian theory of spread as opposed to Bernard Fisher and the fisherian spread which I think is the breast cancer breast cancer exactly so yes 100 agree with you that prostate cancer is on average um 250 to 260 000 new diagnoses this last year so a lot we'll follow a a more of a halsteadian spread now remember um if you keep that in mind and you're the math guy not me if you do this just model it 250 to 260 000 new diagnoses 34 000 deaths so yes on average we are picking up cancers but on average if you look at the ratio of cancers diagnosed to cancer deaths that ratio is pretty it's much better yes than the other cancers conversely to put pancreatic cancer in terms like that of the people diagnosed with adenocarcinoma of the pancreas about 95 percent of those people will experience lethality within five years exactly so we have that in our favor and so yes what keeps me up that gets me up in the morning and excited is to understand and identify what it is about the individuals who develop prostate cancer that is you know localized and you know does it have a lethal potential and how do we better attack those subset of individuals that will ultimately die from their prostate cancer so lots of progress even since when we last talked but yes big picture it is still a real issue okay we've already touched on um testosterone we touched on estrogen we peripherally discussed dihydrotestosterone let's explain how androgens work where are Androgen receptors what are these hormones doing and for the purpose of this discussion how do they factor into the pathogenesis of this condition yeah so if you go back and I actually think it's a really good exercise for for an individual to go back and understand where the prostate actually comes from it comes from the urogenital sinus this is a sexually dimorphic organ and in the response to androgens around week 10 or 11 in uh developing fetus human fetus there's a surge of testosterone from the gonad and that surge of testosterone results in the development of this ductal Network it's an extra conglan and it develops in out of the structure and it turns out by the way how big a surge in testosterone I know that it's much more significant than the levels that a little boy is boy a little boy is born with very low testosterone but he did experience a lot of it in utero right yeah lots in utero Lots in in really at Birth and then puberty those are the Three Peaks and they're um similar I think to obviously pewterbury is the highest but it's enough to impact a change and we'll talk a little bit about that because it's not just testosterone levels of course that matter but it's what what the intracellular dihydro testosterone levels are so in the urogenital sinus the mesenchyme those are the things that eventually turn into muscle and kind of connective tissue they contain Androgen receptors that then send a paracrine signal to the epithelium let's even back up for a moment to make sure people understand this so testosterone complicated molecule derived from testosterone derived from cholesterol so picture a cholesterol molecule with all of its rings testosterone is very comparable what is an androgen receptor explain what it is and where it sits yeah so the Androgen receptor is a um it's a very fluid molecule that basically um sits in the cytosol of a cell and in outside the nucleus outside the nucleus and the Androgen receptor is a transcription Factor so it turns on a variety of different uh genes within a cell so think about when in your house if you have a circuit breaker and you turn on the circuit breaker and every light in the house goes on that's what a transcription Factor does in my mind that's how I think about and explain to people patients Androgen receptor is a transcription factor and needs to be in the nucleus of the cell to flip those switches and it sits in in the cytoplasm and it needs to translocate to the nucleus and then bind to the DNA of our cells to have its effect and it only does that once testosterone or dihydrotestosterone binds to it cytoplasm so it's signal it has a conformational change that permits it to enter the nucleus when it's bound to testosterone or dihydrotestosterone now dihydrotestosterone has a much stronger higher affinity for the Androgen receptor and enables it to be it's about 10 times more potent so one molecule of DHT is the equivalent of 10 molecules of testosterone now that conversion of testosterone to dihydrotestosterone does not occur anywhere in your body and just for the listeners by the way women have an equal distribution of Androgen receptor as do men okay but they don't typically have androgens around now to add one more layer of specificity I mean they have I guess let's do the math a woman will have probably five percent of the androgens right yes you'll have about five percent of the testosterone that a man will have but theoretically at Earth or in utero they have the equal distribution of Androgen receptor and they don't but they don't have dihydrotestosterone so they'd men have five Alpha reductase in their hair follicles and in their prosthetic tissue predominant those are the two main areas where it exists so if you have the same amount of testosterone floating around in your blood um it will have one effect let's say on your skin because it is never converted to to DHT um but if if that same testosterone molecule hits a hair follicle or hits the prostate it's converted into a very potent Androgen um DHT through five Alpha reductase and that can then have a much more potent effect in terms of the subsequent you know effect of the of the Androgen receptor so just make sure I understand um if if if a if a male has a normal testosterone level yes but he's taking a 5-alpha reductase inhibitor which I want to talk about that now which lowers the conversion of testosterone to DHT and this is young guys will take this all the time to prevent hair loss these are the most common drugs that are used to prevent hair loss because the part of the story I guess we didn't finish here was DHT uh in the hair will damage the follicle it's it's leading to baldness early death yeah yep so so it seems to me like he's shortchanging his Androgen receptor potential he's he's shortchanging the ability to experience testosterone it's almost like he's taking a testosterone haircut without taking the testosterone haircut yes what you end up with is less intraprostatic DHT more intra prostatic tea actually right because you can't convert any so you're pulling it in there you normally would convert it that's true in the hair follicle also but as we'll talk about because there's there's significant pathology associated with taking finasteride and so we we used to think that it was predominantly in those main structures follicles under hair prostate Etc but now we know it actually has there's profound potential impact of of that neural you know centrally in your nerve system right and it can affect your sex drive it can affect your sex performance Etc so so let's talk about this because I had never heard of this until a few months ago post finasteride syndrome yeah so we talked earlier about finasteride when it's taken in a drug called proscar five milligrams a day it has a cousin called dutasteride or Avodart I think that's 0.5 milligrams per day yep that one theoretically is more potent because it blocks five Alpha reductase one and two okay but but their effect the efficacy is equivalent in the human body okay and then lower dose finasteride so not lower dose one milligram per day is called Propecia yeah and that's the Branded version that's used for hair loss yes okay the first thing I remember you telling me about this was it's a little bit of a scam that these drugs are taken daily because their Half-Life is quite long right yeah they all have a very long Half-Life so if you took a single uh finasteride five milligram dose it's generic so it costs nothing anyway yeah but if you took that it would hang around in your system for a week or two okay so so the idea that that you know the reason it was reformulated at one milligram versus five milligrams was for a new patent new indication of course uh but you could take you could I I haven't worked it out you could probably just take a single five milligram of finasteride once a week and that would be the same as one milligram of the other stuff every day it's it has a much longer Half-Life than anyone appreciates um and um it's you know that's the least of the problems that I think so let's get to let's get to the issues because this is also a very controversial topic right there are people that get up in arms on both sides of this discussion so describe what post-finesteride syndrome is well it's a variety of symptoms that men will complain of after taking either you know uh the BPH dosing or the kind of hair loss dosing of these medications decreased sex drive impotence um and ejaculation inability to ejaculate the inability to ejaculate depress more those are obvious and apparent things for any young man trying to do it but there's a lot of other Associated uh findings with it like depression you know deep you know just general uh change in your affects so those are harder in my mind to attribute to the medication but patients do complain about it but when you have a patient who's young healthy has a great interest in sex Etc and they take this medication for hair loss and they can't get an erection they have no interest in sex they can't have any orgasm those are real and those are directly in my opinion definitely related to the drug and what do you think is the approximate frequency of this post finasteride syndrome yeah that's probably where there's more debate right I think and some people would say five percent some people would say fifteen percent I mean it depends on where you look but I you know I think about like one in ten guys will have appreciable issues with it and it's not just the young men it's an older men too it's just that there may be on average less interested in sex or less sexually active it's less apparent than an older guy but you definitely I definitely see it so it's why I never really use it in my practice I mean it's just such a limited drug in part because the efficacy is limited in my opinion in terms of managing lower urinary tract symptoms and then the side effects from it this post finasteride syndrome are are real the duration of these symptoms can be uh highly variable so some people will stop the medication and they'll have resolution within a couple weeks once the drug washes out but there are people that I know uh who have it you know permanently yeah there are case reports and that's the really scary stuff which is the case report of the guy who goes to see the hair doctor they put them on finasteride he experiences all of these symptoms they're horrible and they're very noticeable because he's 25 or 30. he stops taking the drug and it never comes back yeah so those are rare like you say but they're real and they are associated with the drug and there's no doubt in my mind um I guess the obvious question here is let's assume that the frequency of this is one in ten and we want to avoid it at all costs because we never know if it's reversible is there any sense of what predicts susceptibility to this it's a good question you know it's a post-hoc diagnosis I haven't seen a grade paper that really took a hundred or a you know 500 men and really tried to evaluate what it was that would predict it so not I'm I'm not aware of any high quality study that can help predict that Association would you be comfortable then and feel free to say no uh but but would you be comfortable recommending to a patient who's considering using a five Alpha reductase inhibitor for hair loss that they might be better off looking at other medical and non-medical therapies for hair loss yeah I mean I don't recommend it in for use in any any man if it's one pH or otherwise yeah why if you're taking it for hair loss which I experience at a very young age so I know what that feels like and it can have a real impact on a young individual's life there's a lot of really effective Therapies that you can do I mean hair transplant works very well it's very precise and I know people who've done it and you know they're very satisfied with it so I think there's Alternatives I think understanding what that spectrum of Alternatives is is really important because when young guys go to these kind of pop-up shop clinics they're not given the full kind of um they don't have a consent with this yes and they don't understand what the long-term effects are because in addition to um the post-synasteride syndrome as a prostate cancer you know biologist and and and individual it treats people with prostate cancer the other big thing has to do with what its effect is on your PSA value so it it halves your PSA value if you take the medication for one to two or two to three years and after five years of on being on the medication it reduces your PSA number by about 2.5 x so if that does not come back if you stop the medication your PSA will rise but the biggest issue is not whether or not it suppresses your PSA or not it's lack of awareness that it does yeah amongst the patients and the providers because if you're going to some Men's Health clinic for your finasteride or your you know your your finasteride for your head hair loss you may not mention it to your internist and and usually when you start that for hair loss you maintain it for life and so you'll I a classic case I see it probably every other week of a guy whose PSA is rising on finasteride if your PSA begins to rise on finance we'll talk about PSA in general a sec if your PSA Rises on finasteride you have a problem that is a warning sign that there is a Cancer and likely an aggressive cancer growing in your prostate wow and guys aren't aware of it and there'll be guys who's PSA and that's just guys it might be that Physicians are that's right so if you're a man you take finasteride starting at age 25 um you start at age 25 and it's uh your PSA is 0.5 think about this you may it may begin to rise and it goes between let's say now you're 50. so 20 years later it goes between 0.5 to 1 to 2 to 4. that's four years where your PSA is doubling which tells you you got a really bad problem before it's even anywhere near being on the radar of the patient or their internist so in my opinion it's just you got to be very very careful with these medications particularly taking them that long and this says nothing about the other issue which is not having DHT probably isn't a good thing if you're in the business of taking advantage of your Androgen receptors right you're taking away the most potent Androgen in the body and androgens do really good things yeah I mean I I think uh absolutely I mean the the impact on a man I mean if you the extreme examples are those individuals with no testosterone we induce that in individuals with Advanced prostate cancer and there are rare cases for men who are born with no testosterone at all but in general yes I mean for a healthy man you know it's absolutely imperative in my opinion that you maintain a you know eugan adult State and that's debatable what that means but I think in my opinion you can titrate to a functional Hugo natal state in almost all men if their testosterone levels are low but having testosterone around is just critical for for everything for metabolic metabolic health is structural Health everything really for everything probably mood and a whole bunch of others all that exactly okay now let's talk about the relationship between testosterone and DHT and the development of prostate cancer over a man's lifetime so one of the you know obvious statements is when a man has the most testosterone and presumably DHT in his body so let's just take out the case of guys who are taking five alpharetto case Inhibitors so when a man is in his 20s you know call it 18 to 20 18 to 30. his testosterone and DHT are through the roof we don't see guys getting prostate cancer yes um similarly by the way we don't see women getting breast cancer when their estrogen is at their highest either so so we know there's we know that the story is more complicated than the caricature is yes which is not to say that these hormones don't matter because to your point a moment ago when you have men with metastatic prostate cancer or untreatable prostate cancer hormone deprivation therapy is a core treatment yes so how do we reconcile those two observations well it has to just there's a Time dependent covariable here right so you you will when you have there's lots of things that testosterone does at a cellular level right it impacts damage to the DNA repair of that damage to the DNA all these different things that people I don't think really fully appreciate but um I think when you have when you go through your surge of testosterone whatever that may be if you're puberty you know your peak in in is age 18 or age 25 wherever your Peak is I think you begin to reset um the functional code right so you're born with your DNA but it's not really for the most part what's in your DNA that matters it's the epigenetic you know changes that result in this RNA trans trans you know location transition that really is the most important thing so I think that you begin to Mark and see differences in terms of the epigenetics of different genes within a test an androgen responsive organ that then sets the stage for your potential risk for developing prostate cancer right so I think that there's a correlation between testosterone and and subsequent you know future diagnosis of prostate cancer but it's just one of the many factors that plays a role so if you don't have any testosterone you're not going to get prostate cancer because you won't have a prostate right that's the obvious one yeah but I do think that there's a correlation between T and A being a healthy male and part of being a healthy male is a potential risk for developing prostate cancer does that does that make sense I mean it does and then there's this other very interesting observation and I don't know if this has been subsequently refuted but I remember this probably when we were in Residence he Ted that there was that paper that came out that found that men with lower testosterone this was in the New England Journal of Medicine yeah we're at risk for higher grade prostate cancers yes the the sort of teleologic explanation was at least this was my teleologic explanation if you are developing prostate cancer in the presence of low androgens you have a very sensitive you have a cancer that's very sensitive and therefore is probably much higher grade is that still kind of a thinking or has the thinking evolved significantly yeah so we just published a paper on this we we looked at 100 000 prostate cancer transcriptomes and where did you get so much we did this in partnership with the company originally it was called decipher now it was it's owned by a company called verisite okay and I did this with uh the the founder of the company Eli DaVinci and uh we looked at their database of now they now have 140 000 plus prostate cancer transcriptomes wow so if you just we we just asked a simple question if you take prostate Cancers and you do AI based hierarchical clustering just looking for patterns do you see different types of cancer not you know grade or stage but different types from the perspective of the transcriptome of prostate cancer and you do so you see two general themes one you see luminal like prostate Cancers and basal like prostate cancers and then within that sub classification of luminal basal there are kind of effectively aggressive luminals explain to people that are between the luminal and basal side so so so you can see aggressive luminals and and then aggressive basals and then less aggressive ones so where is this all coming from so if you take a look back at embryonic development and you people have done this I did this in my postdoc study what happens to the prostate in a mouse or a rat when you begin to take away testosterone and give it back you can see that the prostate as we mentioned before grows in response in parts of testosterone and the estrogens around but if you castrate a mouse all of the luminal cells post maturity yes you develop a normal prostate and you castrate a mouse or a rat with the prostate it will regress and think about it like just like a plant in the middle of a drought right it looks dead but there's roots that are still alive okay those roots that are still alive in the prostate are predominantly basal cells if you give that prostate back its growth uh fuel testosterone or DHT then it will regrow a new prostate and the basal cells will begin to repopulate and you'll get also a proliferation of these luminal cells that will then form the big bulky meaty prostate that we think about let's say just think like a beep the BPH part portion of the prostate so you have luminal cells and the luminal cells in development and we believe in prostate cancer are exquisitely sensitive to testosterones androgens okay the basal cells the cells that survive the drought the cell that survived in the absence of effectively any testosterone or law at all those are the ones that form more basal-like tumors which are very very aggressive okay so when I look at somebody with prostate cancer yes I look at the grade yes I look at their stage but I also look at the genomics of their tumor and what's the biology of their tumor because they may have a big bulky luminal proliferating aluminal tumor but I know it's exquisitely sensitive to testosterone suppression which is something that I have in my back pocket and B it's less likely to start spreading to other parts of the body why is that no if it's aluminal if it's a luminal type tumor think about it it's more dependent on that testosterone-rich microenvironment with the DHT around it doesn't do as well theoretically living in the bone marrow when it metastasizes to the Bone or the lymph nodes this is very counterintuitive on the one hand you're saying it's a more aggressive tumor locally bulky but on the other hand you're saying less likely to survive medicine yeah if you look which we've done wow the distribution of aluminal differentiated tumor in a localized state is about 40 percent okay if you look at how many metastatic lesions so you take tumors that are metastatic it's only it's less than 10 percent are luminal differentiated because they they just don't have the capacity to survive and spread to other parts of the body whereas a basal tumor which is by nature able to survive in the absence of testosterone and or uses alternate growth Pathways to testosterone because it doesn't have it's not it's not dependent on it those tumors are more capable of spreading to other parts of the body so this is kind of a great tragedy it means that the cancers the prostate cancers that are most likely to kill you which by definition are the ones that spread are also the most capable of thriving a low testosterone environments right and therefore are least hurt by Androgen deprivation yes but I mean this is just you know things that we've been working on this thesis Eli and I for now a decade but we have this data now that is we just published this year and lots of other interesting studies coming out that really kind of support this idea so that's why in my opinion I am very comfortable with a patient who is have who has a low testosterone being on testosterone supplementation if they have a low T either during the process of being diagnosed with their cancer or in their their recovery phase because I know that if they were to develop a recurrent disease a recurrence of their cancer it's most likely a luminal type and we can exquisitely modulate that tumor with testosterones so it's a big step it's a big step in a different direction it takes a lot to think about it but it in my opinion it really helps us understand the biology not so much of localized prostate cancers but rather when you have a localized cancer that has the capacity to spread so a localized cancer with lethal potential and what's the nature of that of that tumor how do you begin to attack it and understanding the molecular underpinnings of it is key that's Precision medicine yeah absolutely so you've got these hundred thousand transcriptomes they've given you this insane amount of insight yes how often can you now predict based on a man's genetics or do you need a tissue biopsy to map to the transcriptome to say yeah let's talk about the transcriptome of the tumor so once a patient has a diagnosis you can get the transcriptome information it's provided to the providers it's not commercially available and the reason that we it's not provided commercially because we you have to be cautious about how you interpret that data and what you pre you advise the patient until we have more information from clinical trials about well what is a particular molecular phenotype mean for the a how you treat their new new diagnosed localized or potentially if they have a recurrent disease how you should better treat it but those trials are now in process or are just being built based on some of this work now that's the transcriptome sorry just to be clear Ted does that mean that someone listening to this who has a biopsy of their prostate their physician will get this information back but won't necessarily know how to interpret it if if a patient gets a biopsy of their tumor and they have genomic testing with decipher verocyte which I don't have any conflicts with by the way they will then get a simple readout of how aggressive is their tumor it's a molecular Gleason score okay but on the back end in addition to measuring those 21 different genes that consist of the decipher score they capture the whole transcriptome or that tumor and you can get access to what they call the grid report which gives you this whole Deep dive into what's the biology in nature and phenotype of that particular tumor which for me I look at and I will then look at that and then say okay this patient on paper perhaps has an X or Y or Z but the the molecular phenotype of the tumor is favorable or it's not favorable I'm going to alter what I recommend to the patient based on that so that's how I interpret it it's kind of experimental use only so to speak but but it is the direction of precision it's the future of it and so based on these papers and many many others not just the one I I did this one but many many other papers with really great scientists they are the platform for through which all clinical trials in prostate cancer are now reliant on so the decipher score as a as an entry criteria as a predictor for intensification or deintensification of therapy um is part of almost all clinical trials going through the the National Institute of Health right now which is exciting yeah so let's let's talk a little bit more about the pathogenesis um you talked earlier about the transition zone in the peripheral Zone the orange analogy I'm assuming that most prostate cancers develop in the peripheral Zone correct and the reason for that is it we didn't State this earlier but you would think or hope I suppose that any man who's undergoing uh prostate cancer or prostate tissue removal for BPH would have a lower risk of prostate cancer because hey you just shed 80 of your prostate that doesn't seem to be the case correct well it doesn't necessarily change their risk for developing prostate cancers in the future however it changes your ability to monitor them for the development of prostate cancer because remember the PSA blood test is you know it it's um it's been often criticized but it's a very powerful tool and it just depends on how you use that blood test to identify people at risk for potentially having prostate cancer yeah I want to really talk about this in a minute because there are a few things that annoy me more than people who harp on how bad the PSA is which to me means no it's how bad you are at using it like the PSA is a remarkable test so the issue arises from this overlap in the test because it's not prostate cancer specific it's prostate specific so the beauty of having my partner Amy cranback do a hole up and take out 90 of your prostate is that reduces 90 percent of the PSA producing cells the PSA should be below one but it makes the test way more sensitive for me to follow for a future potential risk of developing prostate cancer so in general I would say that yes the specificity of the tool changes based on how much prostate tissue you have so the PSA test is actually exquisitely sensitive in young men to their future risk for developing prostate cancer because they have such limited amounts of transition zone tissue and the bulk of their prostate is just peripheral zone so why is it that the that the cells in the peripheral zone are susceptible to becoming neoplastic as opposed to the cells in the transition it's a great question because under the microscope there are some subtle differ for instance is how they look but people don't know why that particular zone or that zonal Anatomy is such that you have a higher risk of developing it there it's obviously very unfortunate because the real estate problem as the name implies it's in the periphery and what's just outside of the prostate is the high high price real estate of the nerves for erection the nurse for for urinary continence and the muscles for urinary content so that has a big impact on how we manage prostate cancer and it's been a result that's what results in a lot of the potential side effects that occur but in general yes in young men PSA is a very potent way for us to initially screen someone for their prostate cancer risk and your PSA if you're young good numbers remember for the listeners median PSA for a 40 year old 0.5 median PSA for a 50 year old one so if your numbers over those medians those age-adjusted medians then you need to just take action do you have to have a prostatectomy no but here's the problem we talked earlier a lot of those guys are going to be on five Alpha reductase Inhibitors these days and now those numbers become very difficult to interpret yes they do they become difficult to interpret and difficult to follow so if your numbers are over those then any you should just consider a kind of annual or twice in every other year kind of intensive follow-up it doesn't mean that you have prostate cancer but it means if you're over that median that you have a much higher risk in your future next 20 or 30 years of developing it again the issue is in young men who are on five Alpha reductase Inhibitors or PSAs are going to be very very low and you may miss early blip and actually there's a great as a somewhat sidebar there's a great paper published out of the group at UCSD looking at finasteride and dutasteride use in veterans so it's a closed access system and they ask the question is use of dutasteride and finasteride associated with more prostate cancer lethalities and it's highly hotly debated about whether or not the drugs actually induce more aggressive Cancers and result in in that but if you just take that as a side as a more Public Health kind of issue the answer was glaringly yes there was a huge increased risk of death from prostate cancer in men on finasteron and asteroid why for the reason we talked about neglect you don't realize you're on it you don't know your numbers are rising your internist has no idea that your PSA of four isn't really four it's ten because you've been on the meds for 10. so it's not necessarily we certainly don't know if five Alpha reductase inhibition impacts prostate cancer biology but to our point about detection it impedes detection yes and you know I think I think that there may be an impact on on the actual subtly on the biology but that's less of a real you know kind of General issue it's really being a lack of awareness of the biomarker that you use to screen for prostate cancer and the effect that do tests right or faster I have on that biomarker how many uh cases of prostate cancer are associated with germline Gene that you know germline genes that we know are drivers you know for example the equivalent of a bracha mutation in breast cancer or is it virtually all somatic mutation it is very limited so there are a class of of proteins molecules that affix homologous recombination uh defects and those um hrd classes of of molecules include block Bronco one and bronca two the actual protein complex that fixes double strand DNA breaks is really really big so there's lots of different genes that fit within that kind of protein complex that fixes a double strand break that's what that's what Bronco one and Bronco two do classically but the most potent of the different genes in that grouping of hrd molecules is bronchit II for men so individual men it's about one percent or less of the general population have a broca to deficiency Baraka one broccoli deficiency those men are at increased risk for developing breast cancer and prostate cancer and in case of prostate cancer if you develop prostate cancer it's a more aggressive disease course and you have to be very very careful with individuals who have that deficiency and have prostate cancer but on average it's very rare probably less than two percent of prostate cancer cases localized prostate cancers diagnosed are attributable to a germline genetic alteration there are mutations in those same Pathways somatically seen within the tumor right not in the germline but in the tumor that are attributed and related to cancer aggressiveness and progression of cancer the classic one in my opinion so so the way I think about prostate cancer in very general terms is you can have localized prostate cancers these are these lower grade lesions on average localized prostate cancers with lethal potential so lclp right you got to localize cancer or lethal potential and in my mind the general genetic trait associated with that transition from localized to localized with lethal potential is an is something to do with the P10 akt pathway sure and that doesn't mean that you have a lethal tumor if you have P10 loss but it in my mind it begins to open up the book to say lots of other mischief and nonsense can go on within the tumor we know from lots of studies that if you have loss of p53 for example of course that that's associated with lethal prostate cancer amplification of Mick lethal cancer in general yes exactly amplification of Mick is another one too it's the end okay so it's interesting so basically between Mick and P P 53 and all of k-ras I mean I'm sure k-ras is less so less okay wraps but yes those are classic markers of lethal Cancers and so prostate is not you know you know immune to that as well got it okay let's talk a little bit about uh non-genetic risk factors or at least non um we can include sort of polygenic stuff that's embedded so one of the things I always remember from training African-American men at a higher risk why no one knows um I like to think there's a great paper published by this scientist at USC Chris Heyman and they looked at genomic risk you know through Snips for individuals who did or did not develop prostate cancer was like 235 000 guys ton a ton of individuals how did they know what Snips to look at well they did they they there's a there's been lots of work in in in single nucleotide polymorphisms and risk for prostate cancer and then this paper was a refreshed look at saying how many Snips are actually out there associated with risk of developing prostate cancer and it's somewhere around 250 or 260 I don't know the exact number but there's a certain amount so what they did was they developed a genomic risk score based on how many Snips you had and your likelihood or probability of developing prostate cancer and what they showed was that that although there's no difference between snip profiles in men of African ancestry because they could look genomically where their ancestry was and Caucasians are non-black men there was an enrichment for that same group of of snips in Black Men and an enrichment in men who were diagnosed with prostate cancer at a young age so why is it that there's an enrichment of these different portfolio of of snips in black men and why is there an enrichment in the younger men we don't know but we it doesn't appear as though the tumors are profoundly different from a genomic perspective and we've looked ourselves we had a series of Grants to look at again you know somatic alterations and prostate tumors between black and white men with lethal tumors we found a difference in in a cell cycle Gene pathway but again these are single percentile differences so what exactly is driving the development of more prostate cancers in black men than white men is thought to be at this point kind of environmental so you know what is their exposure to um you know epigenetic changes what's their exposure to smoking it's in general in urban you know populations of of black individuals there's more smoking it asks it correlates with the food deserts all these different kinds of epigenetic factors let's see so it may not actually be hardwired it's not hardwired and most of the kind of that's great news it is good news and so yes I think people would bundle that under this kind of umbrella of social determinants of Health but you can actually begin to really begin to connect those two ends of what are the social determinants and then what is the impact on the Snips and the epigenetic changes that occur so I think a great future project would be to take that and look at exposures in think about it like your exposures in an environment with high smoke High pollution poor Foods and the epigenetic changes that occur when you're having a surge in your testosterone in your 20s that begins to hardwire that person's cells for future development of prostate cancer yeah and that's kind of how I think about it now because we did I spent a decade looking for The Smoking Gun the heritable germline change there are some out there but they're not very they're not big enough they're not big enough to be you know associated with that change and so this paper that Chris did and his team of you know there's like 150 authors to spectacular work really begins to provide more insight so this is the UCSD group that led this USC uh USC USC um Chris Heyman is the last author and um liking on the first author's name great publication to that paper yeah so it gives you a sense of you know so then why are there different sub populations of individuals that have different risks it's likely not just enrichments for these single nucleotide polymorphism changes which by the way if you look at that paper if you had the highest let's say decile or quartile of snips you had about a five-fold increased risk of developing prostate cancer compared to the average man which is the same fold increase as if you're bracha too deficient wow so having a poor genomic risk score is just as potent as having deficiency in Baraka 2 which we know is not good and the penetrance of bracha 2 and Bronco one for prostate cancer or how high like 80 percent ish no lifetime risk is is less than that a lifetime risk is somewhere on the order of um 60 to 70 so penetrant enough that you treated enough we would keep we would definitely do intensive screening for them but it's not a guarantee but it's are you do it you know obviously women that are highly penetrated and at a very young age that's not true for men but yeah average but but you know it's not unreasonable for a woman to undergo a prophylactic mastectomy if she is uh if she has a deficient copy of the broca gene are any men considering prophylactic prostatectomy not at this point because we the difference is we have very powerful screening tools those tools work to Halstead versus Fisher and those screening tools work just as well in individuals who are broca deficient so their tumors may be more aggressive when they're diagnosed but we have very powerful tools to a identify them early and B monitored them once they're picked up and so it doesn't necessarily change that Paradigm which is different for breasts because you have to wait till you have a visible lesion which a visible lesion on mammogram is what 40 or 50 million cells you know you know I mean yes closer to a billion I don't think it's a centimeter well we'll we'll try to find something for the show notes but yes it's it's a ton of cells whereas we have much better deals to look at that with the blood test and hopefully with breast cancer we're going to see liquid biopsies and cell free DNA adding more to that um as a biomarker it's definitely you know shows promise I mean there's lots of those liquid things it's not essential for our space because we have a very good one yep um another esoteric risk I kind of vaguely remember and I don't know if I'm remembering it correctly is there an inverse relationship between the frequency of ejaculation and the development of prostate cancer yeah there's an epidemiologic study that shows that men who are ejaculating more than 20 times a month that there was a lower risk of developing prostate cancer it's never you know that the state the paper you're remembering is the really the paper on that topic it still exists and so how big was the hazard ratio is it worth paying attention to and that's a good question I don't remember because it's so old I mean I certainly don't you know I I don't you know to be honest I've never thought about encouraging you know uh increased ejaculation from the as a preventative strategy I mean it's it's not a bad idea but I've never it's never occurred to me to kind of encourage that so so that's not the idea isn't that prostatic stasis in the absence of ejaculation allows something to occur in the prostate that that leads the development either through the micro environment or other genetic issues I mean point is we have no further Insight than that logic study but it's not a bad one I think the converse would be horrific for men like don't ejaculate because you'll lower your risk of cancer so it's not it's like a kind of a win-win right that's how I think about it okay so so let's now get into the nuts and bolts so let's talk about a couple other risk factors um besides you know ancestry which is huge which is of course bigger than many cancers yes um so it's not just black patients you know you have to think about um are not just African Americans but there's a you know there's anybody with at West African ancestry is really what is the most significant in that risk factor and then there's um other ones so Ashkenazi Jewish individuals have a much higher chance of harboring you know Foundry mutations in Bronco one and bronca two so I always talk about ancestry and I talk about all cancer risks right when I'm taking a family history I say what's your personal history of prostate cancer and if you have a personal history of prostate cancer you're meaning a father uncle or brother so first degree relative father uncle brother okay the number of individuals and the age that they were diagnosed and we'll put a link in the show note for the table it increases your full risk of being diagnosed with prostate cancer significantly it doesn't mean you need to chant you shouldn't have a prophylactic prostatectomy but you should just have intensive intensive monitoring that's what you write what about grandfather grandfather is not it's for shifts the generation it doesn't matter so your grandfather has prostate cancer but none of your brother it's not considered to be a family history of of interesting okay what about grandfather and father is that worse than just father father's the driver for that okay so family history so ancestry um right and then family history and then individual patients so smoking it is classically linked with breath with lung cancer and classically linked with bladder cancer urothelial carcinoma but smoking is associated with more the development of more aggressive prostate cancer so so not necessarily more prostate cancer but when you get it it's worse yes and at a younger age so the the correlation is younger age onset more aggressive cancer what's the youngest patient you've ever seen with prostate 34. that is staggering to me I would have never guessed that I'll never forget that that gentleman's you know I I have his picture in my brain he didn't survive he we treated him um and he he lived he's still alive now but still when you have a 34 year old and the and his wife sitting there going like what you know so I've I've subsequently diagnosed young men with prostate cancer and then subsequently treated their fathers so they had their cancer before their father which is also mind-boggling right tell me a little bit about this guy's case what was there was there just some freak Gene thing that you know the the youngest man the 34 year old was early in my career at Hopkins where we had such a lack of understanding of the genetic risks and so forth so I would love to go back and pull his tumor and you know just sequence the whole thing he just presented with the rising he went in for uh he wanted to get a 250 discount on his health insurance for the year so he got a routine screening through his work and they picked up a PSA that was like 10 and he's 34. he wasn't from an infection so but anything below what is freakish 50. so the median age of diagnosis for prostate cancer 68. we would consider early prostate cancer which would be a criteria for doing genetic screening at around 50. so hereditary could be young age of onset so 50. uh I I if I am if I'm not mistaken I believe type 2 diabetes and metabolic disease also increase the risk of they do prostate cancer as it does breast cancer and endometrial cancer absolutely number of cancers and also the aggressiveness and likelihood and probability of recurrence okay all the other things really have never been you know fully supported with any decent follow-up studies so these different products in the skin of grape you know broccoli tomato um Oh you mean it's preventive yeah there really haven't been linked with any real increase or decreased risk for developing prostate cancer so let's talk about the PSA a little bit because we've alluded to it a number of times so let's explain what it is where it comes from and more importantly of course how we use it yeah so PSA is a is a protein it exists to Aid in the liquefication of semen so it's produced by the prostate and if one were to measure PSA in semen it would be very very high I always tell people if you looked at PSA and the semen it would be I don't know 100 000 nanograms from a liter of PSA and semen it's designed to be there and it exists there to liquefy the semen to help in the process of fertilization it is not designed and it should not exist in the blood but a certain percentage of PSA made in prostatic epithelial cells leaks into the bloodstream and when we do a PSA blood test we're measuring the PSA that has leaked into the bloodstream from a prostatic epithelial cell now most of the PSA that leaks into the bloodstream is bound to other proteins a certain percentage is that like albumin mostly or sexism Alpha chymotryptin oh so it's its own a separate binding protein yeah it has that's the most common protein that PSA binds to but it can bind to a family of three or four or four or five but these are prostatic proteins yeah yep it's bound now how much it's processed because as you know protein soaps don't come out finished they grow into their final State and they grow by shrinking right they get things snipped off of them as they're maturing and going through that process as PSA is evolving in the normal kind of development of its exocrine function it gets snipped into smaller and smaller States fully fully processed PSA can float around in the bloodstream freely that's free PSA so if you have a benign prosthetic epithelial cell a lot of its PSA will be fully processed and ready to go in the ejaculate let's just say and if it leaks into the bloodstream it can float around freely you can measure it in an assay and it's what we call free PSA a lot of the unprocessed or incompletely processed PSAs bound to protein Alpha chymotryptin is the most common one and that is what we would consider to be when we do a measurement of when we're looking at total PSA you're measuring mostly bound PSA and some free PSA and that ratio we use you and I use in our practices to help discriminate against PSA that's in the bloodstream that may have leaked from a cancer cell or may have leaked from a benign epithelial cell now there are other siblings of PSA that are also produced in prosthetic epithelial cells of course all in response to androgens they're produced in those cells and they can also leak into the bloodstream and we use those in some Advanced psa-based blood testing as well but in general when we are measuring PSA we are measuring the amount of PSA this Protein that's leaked from a prosthetic epithelial cell into the bloodstream we can refine that value by saying how much of it is how much is there and how much is free if we have high amounts of free PSA 30 for example then we can have good reassurance that most of the PSA in the blood that you're detecting is from benign cells when most of the PSA that you have in your blood is um bound very limited amounts of free PSA that's a strong marker that there's something going on I.E that cancer cells are leaking the PSA into the bloodstream now as I mentioned you can also measure other byproducts other other types of free PSA or other sibling molecules to PSA PSA is called hk3 or human calkine three you can measure for example how much of human calicrine two is in the blood and these are part of it more advanced PSA tests like the 4K score or for example the prostate health index these are both mathematical equations that predict probability of aggressive cancers but they're built off of looking at not just the PSA itself but the PSA and how much other types of process PSA exist as well let's go back and talk a little bit about the free PSA um does the amount of free PSA that we would want to see to be more assured of a benign nature of the PSA vary by age and absolute PSA level yes it does so we begin to use the kind of free PSAs and the free PSA ratios and all those things when PSAs have crossed over a certain threshold right because yeah typically a lab if you have your PSA is one we can't even get a lab to check a free TSA that's right because we know if your P if you're screening someone in your PSA is one then the chances you the probability of a prostate cancer that's lethal is incredibly low right so that's why they they just don't they don't have the assay set up to check it and oftentimes or some Labs will not do that you know secondary default testing unless it's over four for example or over 2.5 we our lab set up to do everything at low levels as low as two so you can get them at lower levels but in general the idea is well if your PSA is below two the probability you have a lethal prostate cancer is you know less than one in a million so we don't have to worry about that individual and we really want to use the percent free PSA to discriminate yep individuals who have elevated essays and having to discriminate between elevated because of BPH and elevated because of a cancer so yes and as you get older your prostate enlarges as we talked about metabolic syndrome causes your prostate in large part to grow all you know just because of the T to e ratios um as it gets as you get older your prostate gets bigger so you we begin to use that in in as you get older and your prostate gets bigger you can have a proportional rise in total PSA in your bloodstream just because your prostate is bigger and it's leakier but you can easily tease that out by looking at the percent free PSA so if the percent free PSA is over 18 to 20. then you can be rest pretty well assured that that's likely not coming from some aggressive bulky tumor what about with prostatitis when we see these huge spikes everything goes up in those in those cases but but does the free still remain disproportionately high to well it's a good question I don't use free PSA and people because you're tracking etiology I'm tracking it I'm literally looking for trends for coming back down to a new Baseline yeah so yeah okay um let's talk about two other ways we use the PSA the density and the velocity how do those work yeah so um as I mentioned as you get older your prostate on average gets bigger not for all men but for many men and when that happens your PSA can concordantly rise because it's just your prostate gets bigger and gets equal it's equally leaky so the PSA can kind of go up now what we look at is the ratio of the prostate the PSA value to the prostate volume and then as you alluded to is called PSA density and in general when I when I educate patients I tell them well we want a a PSA to be about 10 of the volume of the prostate or less to kind of be in a safe range so if your PSA is four and your prostate's 40 grams which is about average size for 60 65 year old guy that's a PSA density of 0.1 we know that that is correlated with the low risk of having an aggressive prostate cancer so when when I'm looking at someone's case I want to know what their PSA density is if the PSA density in a young man frankly he's more than 0.1 I get a little worried if on an average age person if the PSA density is more than 0.15 I also get I start saying let's do some additional testing so I put every you put everything together but yes PSA density predicts likelihood that you'd ever be diagnosed with prostate cancer it predicts aggressiveness of a cancer If you're diagnosed with it and it actually predicts your outcome if you have a prostate cancer so the higher your PSI density the more significant your disease will be So the faster it increases and the faster that your PSA Rises it is a canary in the coal mine to say hey you need to do some additional evaluation now it doesn't mean you have prostate cancer because I often have and we share patients for their PSA went from one to five but they had we we tracked it and it came back down because it had a flare-up or inflammation in their prostate that made their PSA go sometimes we don't know why often we don't know why but if you track it you can see that so whenever somebody in general comes to see me with an elevated PSA the first thing I always do is just recheck it because there can be transient rises in the PSA now as you know we have very similar practice I don't just recheck the PSA I always order Advanced psa-based testing what does that mean that is testing that involves looking at the percent free PSA and then other things like minus two pro PSA for the prostate health index test or the 4K score which basically looks at different calicrines in their ratios so and you and I discussed these tests in great detail in the first podcast so we can also refer people back to those um so that I won't make you re-explain them but um it does surprise me that the official screening guidelines for prostate cancer uh don't make any recommendation on the use of PSA testing other than something benign like discussed every patient should discuss this with their physician which is a real cop-out in my view of what we should be doing is that still is that well it depends on which guideline you're looking at so the American urologist this was the this is the guideline U.S preventative this is the U.S preventative task force and the CDC um and there's one other that is yeah the American Cancer Society uh the American urologist Society in the National Comprehensive Cancer Network they're a little bit more Progressive they really suggest that you should talk about the risks and the benefits of screening they kind of screw it around the idea of well how do you properly screen for well AUA and and and and American Cancer Society don't get into details up front they say start the discussion with like what's your potential risk for developing prostate cancer you can ascertain that with the family history again if you're reading the AUA guidelines of the American Cancer Society guidelines you already have a leg up on the average internist because an average internist is just looking at General things they learned in med school or the U.S preventative Services Task Force which is too General and too vague so I totally agree with you I like and personally reference everybody to the National Comprehensive Cancer networks prostate cancer screening guideline that basically says that every man at age 45 should have a baseline PSA because as you mentioned changes over time are key they're critical and you want to know where you are in relationship to the median right so a 45 year old man's medium PSA between 0.5 and 0.7 somewhere around there understand your median PSA and then if your PSA is below one you could just get reached you can get rechecked in two to four years if your PS but Ted isn't I mean the test is free it doesn't cost anything to do a PSA why wouldn't we do this every single year you I guess the argument against it is that um there can be natural variations in P again if you're a smart physician you're going to pick up that hey there's natural variations and if it goes up from 0.7 to 1.5 I'm going to recheck it and it's still in a safe range et cetera et cetera I think that but that's isn't that all the more reason to do frequent testing if there's natural variation because it also means that if you're testing infrequently you're more likely in the presence of natural variation to miss what the actual trend is like think of the following thought experiment right so I love doing the thought experiment so my thought experiment with colorectal cancer is imagine you had a low-cost zero risk colonist you know colonoscopy that you could do on somebody every month yep would you eliminate colorectal cancer yes there'd be no such thing as colorectal cancer yes right the third leading cause of cancer death is gone if you have that now the reason we don't do that is they're not free and they're not risk-free okay well similarly imagine you had just like we have a continuous glucose monitor a continuous PSA monitor you could slap on somebody's arm and you could for free basically measure their PSA over their lifetime I would argue there would be no such thing as lethal prostate cancer because provided you had the AI engine and the physician to monitor this you would you would know oh you know Johnny rode his bike Johnny had sex Johnny you know had a urinary had a prostate infection but you would you would very quickly be able to pick up signal from noise yeah well I think I don't disagree with you it's just a matter of how frequent what what is considered to be intensive PSA testing right and so and let's just say annually right well annual PSA testing is very intensive so all the trials that showed that screening for prostate cancer with the PSA test those trials had tested whether or not that reduced deaths which they showed it did by 20 to 25 percent was PSA testing every two to four years so that's the Baseline so what we do in the U.S is can we do better is my point because to your point still the second leading cause of cancer death it is it is and the the real question is um which we don't know the answer to was which were those men that ended up dying of their prostate cancer offered early screening or not yeah and that's we don't know that and then the other thing is with a little bit more of an invent with a little bit more of an investment in knowing prostate size if you could now get that prostate density so now if you have from one blood measurement that costs less than a pack of gum you know your PSA you know your free PSA you know your PSA density yep that's really powerful yeah by the way a 4K test is a thousand dollar test you don't need to do it if you know PSA free PSA and PSA density and many would argue that hack a gum Chiclets those three things Chiclets those three they're cheaper than a pack of Comb but yes I think well the PSA density is the more expensive but you could but you can get that off an ultrasound you can which is free basically free I mean time for that you don't need to do anymore bottom line people what are you do that percent free PSA gives you some a strong correlation between PSI the size so yes I I totally agree with you I'm just pushing back Ted because I mean look you and I want the same thing but I view this as a I don't I've look there are certain things that I don't see a clear step on the horizon for the elimination right like I don't see an immediate step on the horizon for people not dying of pancreatic cancer I don't see sadly an immediate step on the horizon for people not dying women specifically of breast cancer but I sure as hell see with the existing technology a reason for people not to be dying of colorectal cancer and men not to be dying of prostate cancer I mean the deaths from prostate cancer with PSA screening have plummeted so that's the one thing but it's still 35 000 men died last year and so the question question is when they would they have not how many of them would have been saved with a traditional screening yeah yeah yeah and and trust me I'm trying to defend the rule makers that made these rules so that that I was uninvolved with but I would say that the this idea of Baseline PSA testing at age 40 on a population Health level where that all came about was from from Bank serum out of you know Sweden and so they were able to model that pretty well to understand what's your overall lifetime risk for developing or dying from prostate cancer if you're PSA at age 40 or 50 is below the median then your lifetime risk is very low remember so we have some information about it and the modelers this is the best that they could come with I'm not disagreeing with you I don't there's no Pro there's no reason in my mind why you should not get your PSA tested at an early age understand your Baseline and track it over time the other lesson you and I have both witnessed personally is the patients need to take ownership of this yeah we have both seen tragic cases where individuals who have no medical training but who like listen to this podcast for example uh have diagnosed their own prostate cancer even when their Physicians have said there's nothing wrong with you yes based on Advanced metrics such as PSA velocity and PSA density and and that to me is infuriating and heartwarming at the same time yeah I agree with you and it's and um and many of those cases that we share are are not like the subtle you know one of the thousand cases they're like the ones that are like obvious so I I do think that patients can own this and this is a key part of their overall health 100 agree with that and I think that you you know I mean it's and it's the it's the mindset of the of the individual patient that also matters because there are some patients that don't want to be proactive and Progressive about how they they they monitor their health now those are people who probably don't take care of at all but I I know sometimes I'll see them yeah and so yes we have to balance knowing early with overreaction and kind of over treatment of potential issue that may arise so there's subtlety to it can it be done well I believe it can be done well well let's now talk about that because I think that if you look at people on the other side of this discussion who are saying come on this PSA test I mean there are a lot of people out there saying PSA should never be done it's an awful test it leads to a bunch of unnecessary misery for men because they're getting unnecessary biopsies now let's sort of squash that nonsense yeah that might have been true 50 years ago but in the year 2023 in the hands of a competent physician One Step Above the parking lot attendant that's categorically untrue right yeah so today let's talk about what we can do with an MRI to check if we have suspicion based on these other blood-based biomarkers what can we do to increase the probability that if we actually go to the step of a biopsy the probability is sufficiently high that it was worth it yeah I mean it's you just said it you order an MRI which which is up is frankly like surprising and appalling to me that I see second opinions in my office weekly that they never had any pre-diagnostic I.E pre-biopsy MRI it's absurd to me like when I leave work I check on my Google Map if there's an accident on the expressway and I changed my course if there was it's a test that's approved by all insurances it should be done before any biopsy in my opinion there's really no case sure if the patient's PSA is a thousand and you just need a tissue diagnosis okay that's not let's not bait that but for every man who's undergoing routine screening for their prostate cancer if they have an elevated PSA they should get a reflex test which includes for sure percent free PSA prostate health index or 4K or other tests depending on the cost if those are abnormal and by the way typically insurance will approve those if the PSA is over about five right PSA over PSA over four uh for 4K score okay but we can we get Phi testing in our lab they do it for us it's covered by Insurance okay yep we it's very well calibrated over two yeah so we do it over two and by the way what I'm telling you is based off of a prospective randomized trial published in the New England Journal where they use Advanced PSA testing they did not use 4K or or Phi they use Stockholm 3 which is a European only test abnormal Advanced PSA testing do an MRI if the MRI has a suspicious lesion we'll talk about that in a second perform a biopsy not just of the lesion but of the whole prostate reduce prostate biopsies by 50 percent enhanced detection of clinically significant Disease by 11 percent so hello like why are you not doing that I don't know but frankly it happens all the time so what is it okay the blood test we talked about that provides more specificity to someone with an elevated PSA who may have a problem that's all I tell people it tells us we need to do the next step that next step is a high resolution Google map of their prostate that is a typically a 3T MRI or three tests lessons three tests moderate power yes and it doesn't need any like Endo rectal coil or any so a 3T magnet doing a prostate MRI because they're specific sequences and it's multi-parametric the key um you know parameters that we look at T2 images you look at diffusion weighted Imaging and dynamic contrast enhancement those are the three components of a multi-parametric MRI however there are great Radiologists scientists you're friends with one of them Raj who have and others have shown that you don't necessarily need for contrast right and that a on average a T2 uh and the Dynam the diffusion weighted Imaging are nearly as good not identical but nearly as good at evaluating the prostate for any risky lesions now is an MRI perfect no it misses prostate cancers it will miss small low-grade prostate cancers but like we'll talk about a sec that's not necessarily a bad thing but that's how the test works it's done and it's a screening tool to help us identify bulky higher grade higher risk tumors now when you look at your MRI report because as part of the 21st century cures act every patient can look at their entire medical record you'll see that they'll give they'll give you a good well done MRI the report should contain the size of the prostate and I it's baked into our reports because when I came to Chicago I said we're going to do PSA density so you get the density and then it tells you if there's a suspicious lesion and there's this degree of Suspicion it's called the rad score the pi RADS for prostate Imaging rad score and it goes between one and five one and two are considered to be BPH lesions they're not cancer so really we worry about RADS threes RADS fours and Rad's fives and in general most recommendations would be if you have a RADS three four five lesion in your prostate that and you've never had a biopsy before that you should consider biopsy that samples the spot and systematically that would be what we call Target and systematically samples the areas around the target I.E the peripheral Zone in the area kind of mapped around that lesion how easy is it for you to see this and make this determination for example when you look at the MRI and you see the lesion in presumably the peripheral Zone yeah how easy is it for you to then go and actually physically do the biopsy and know that you've hit it as opposed to miss it yeah there's skill involved with with doing an MRI Target are you doing it under some sort of ultrasound guidance yes so yeah you have an ultrasound so you use an ultrasound and ultrasounds are not great traditional standard ultrasounds which are very high resolution are not great at identifying lesion with the efficiency that a MRI is and granted they have time to think about and look at the images so what we typically do is we take the MRI images and you either cognitively I.E with your brain or with the computer assistance overlay the MRI and the suspicious area on the MRI with the real-time ultrasound and is this a trans rectal MRI you're doing it's a trans rectal ultrasound I'm sorry I'm sorry trans rectal ultrasound yes and then your biopsying right beside the well so that is how you overlay and you associate the suspicious area on the MRI is with the transact ultrasound overlay now you can do the prostate biopsy one of two ways one way is to to again pass the needle right alongside the um ultrasound probe that's a trans rectal biopsy that then you'll you can follow the track of the needle as it goes in alongside the ultrasound probe through the rectal mucosa into the prostate it's a very effective way to pick up prostate cancers and the trial I talked about that's the Stockholm 3 trial that's the technique that they used now the limitation of doing that is you you always introduce a small amount of rectal rectoflora bacteria from your rectum into the prostate when the needle passes from the rectum into the prostate and there's men prophylactically take an antibiotics so it's a prep for that procedure you'll do an enema to just decrease the volume of stool and bacteria in the rectum and then you also will take an antibiotic and with modern you know antimicrobial prophylaxis you can reduce infection after prostate biopsy to around depending on the series between one and four percent wow so still pretty high yeah it it it can be real I mean if you're the one in 100 or the four out of 100 guys you know that's a real issue now that's all types of infections so urosepsis where you have as we talked really severe with bacteria in your bloodstream that's very rare you know but infections in general between one and four percent the other approach that you can use is you can do a percutaneous biopsy so the ultrasound probes and the rectum is looking up at the prostate but the needle is inserted percutaneously in the space in the skin through the skin in the space between the rectum and the scrotum okay okay so that's usually around four out of five centimeters of space and in that space you can actually place a guide percutaneous needle guide and then from that you can then actually Target the biopsy in other words you're not pulling the needle in and out each time you have you are oh you are so you you have a short needle guide a trocar that goes through the skin so you can establish your trajectory yeah and then from there you can on with ultrasound guidance put the needle exactly into the suspicious lesion but you keep you the trocar stays in one time and you just yeah okay so you do one pass on them so what's the drawback of that approach is it more difficult one yeah so one pass on the right and one pass on the left now the original way that we did prostate biopsies was was with a percutaneous approach so back in the old days over 100 years ago if you had a suspicious bump on your prostate you'd make an incision there and you'd cut it out that was the original one that they did prostatectomies as well that's right exactly so that approach the prostate has been um long appreciated however doing the prostate biopsy in a way that you could systematically sample the prostate with that approach has historically been very morbid because what they would do is they would place a grid like every two millimeters two millimeter right two millimeter grid along the perineum and they would make between let's say 20 and 30 individual pokes into the perineum and into the prostate that was how you can deliver radioactive seeds or radioactive pellets yeah but that approach was also used to do biopsies that results in significant edema and swelling on the prostate and significant bleeding and urinary retention rates after that approach are very high fifteen twenty percent wow and it's very painful you can't do it awake yep okay so there's a guy Matt Alloway he's a Shafer family friend he is a urologist in Western Maryland very Innovative guy and he said there has to be a better way than doing trans rectal bringing bacteria into the prostate and there has to be a less painful way than doing this grid so he created this percutaneous approach where you can basically have a single troll car on the right go through the skin single crochet on the left go through the skin and you can navigate and Sample all areas of the prostate so he's been doing this for a decade now but you know and Nod to him he's an entrepreneurial guy he created a company with his product and it's the kind of gold standard for how you do that today so wow your biopsies are done with the trocar versus trans rectally I like the trans perennial approach but um in a nod to just not adopting things without with closed eyes and saying it's better we are in the midst of completing a 16 institution randomized trial that explores whether or not transperineal prostate biopsy is actually quote unquote better than trans rectal prostate biopsy and the primary endpoint is infection so as I mentioned modern contemporary infections with transfectal between one and four percent we think our approach to prevent infections transactional is very good and we're probably more on the one percent range when we do a transparental approach in Matt Alloys published a lot on this you can do that without any antibiotics and the infection rate is less than one in a thousand well so really we're trying to say you know so you'll obviously I mean you're presumably powered to show a difference in that direction it's a lot the power is hard so we we had a power calculation the NCI reviewed our power calculations and they gave they said this is the appropriate power to detect a difference um so I think what will end up happening and we're looking at the data right now so I'm not gonna I'm not gonna say but my sense is we're going to have zero percent infections in TP transperineal prostate biopsy but will we have done enough trans rectals to just to really statistically show a difference however it might be secondary outcomes that you look at detection yes so in my mind if you have an approach at a zero percent infections I don't care if it's one percent or you know point you know two percent unless you're losing detection yes so the other endpoints for the study are pain and side effects as I mentioned transperrineal biopsy with the old grid approach was 15 retention you know it's terrible so we're looking at side effects I think it's done properly they're minimal and then we use a lot of medication to do our blocks so I'll tell you a little nerve block yeah we do a potential nerve block and we use lidocaine and we don't just use any lidocaine we use buffered like it came because lidocaine when it comes out of the vial is a pH of about five yep so you know when you went to the little bicarbon yeah you know how you go to the doctor they go pinching a burn yeah well what's the burn the PA pH yeah there's no more burner so you buffered Lidocaine with the transparently approach we're gonna we're looking at the data now but it's I mean there's some discomfort but it's it's tolerable in the office awake and then the most important thing of course is cancer detection so we have 16 centers um there's two other ongoing trials not to just say that we're the only one there's a trial out of a limited number of centers out of Syracuse they finish their study um they're looking to get their paper published and then there's a large paper publication large study in the UK but we're going to be the first to publish a multi-center large prospective trial and it'll be interesting I I think that it will show that a um TP biopsies is zero percent it will show that um they're slightly more uncomfortable um and that and then the cancer detection we have yet to fully analyze but excited to do that okay so let's talk about the different types of results that one gets from the biopsy you've already mentioned the word Gleason let's talk about what that means and what the score is uh how the scores are determined and what the implications are yeah so you when you do a biopsy you systematically you first sample the targeted part let's let's just do one thing before we talk about this so who needs a prostate biopsy yeah but who needs a prostate biopsy somebody who has abnormal blood testing they go on to get an MRI now that's our regular pathway who do we say you don't need an MRI men who have bilateral hip replacements and MRIs effectively useless so we don't do an MRI for those individuals we can calculate PSA density with an ultrasound it's fast it's cheap it's effective otherwise people are go we we have everyone go to an MRI it's worth it even with a single hip replacement single hip our Radiologists are really good and a good radiologist can read an MRI effectively with a single hip if somebody has profound anxiety and they need general anesthesia for something will be nuanced about whether or not we think an MRI makes this but for the average person 99.5 percent of people you know you get an MRI now MRI shows a suspicious lesion three four or five on the right three four five you need a biopsy MRI shows sorry independent of PSA density independent of PSA density okay if your MRI shows um no lesion but a high PSA density so a young man let's say under 60 that's a PSA density of more than 0.1 or 0.12 yeah if you're older I'll give you a little bit more of a longer leash and it will say 0.15 over 65 or 70. if you have a PSA density that's below that threshold and you have a high PSA low percent free et cetera you need a biopsy in my opinion okay we're going to include Ted the slide that you shared with me a couple months ago that I still have I still look at it all the time now which shows buy pyrads by PSA density yes the outcome of biopsies that's right it's mind-boggling yes so PSA density is a huge variable in terms of impacting probability of having cancer when you sample a suspicious lesion yep and or the volume or bulk of that particular aggressiveness of that particular lesion so rats345 you need to you need a biopsy unless your PSA density is incredibly low like 0.02 yeah yeah which by the way patient we they sometimes they have it yes so there's there's that there's never always and there's never never as in medicine right but in general that was what we would say if you have a negative MRI in a in a high PSA density you we will often suggest a biopsy for you and if you have and if you have a negative MRI and a low PSA density we'll say you're likely can be monitored yep now we'll put in the Show links a nice figure that illustrates that from a large group of about 10 institutions pooling all their MRI and biopsy data together however I have the four Good Fortune having a partner who's a brilliant guy he analyzed this is Ashley Ashley Ross he analyzed and built a neural network real-time predictor for all patients not just Northwestern Medicine patients but we used all the Northwestern Medicine patients in her system who had had Phi MRI and a biopsy and looked at all their outcomes so there's some selection by us because we didn't include people who didn't have a biopsy but in general we took all these people and we created a neural network real-time predictor for what's your absolute risk for having prostate cancer in general but more specifically prostate cancers that would require treatment and that will put in the Show links that is a super powerful this is the model this is the my NM risk calculator okay so we'll make sure we learn so the figure is great because it just gives you an idea of a framework but the actual risk calculator gives the individual patient their individualized risk so he built it off around 16 1700 MRI biopsy linked cases but now that has grown because it's it's always learning now if you undergo a prostate biopsy it's not just the answer is not just cancer yes or no there's a lot of subtlety and a lot of things have changed about how we think about these different cancers so I always explain to patients that it's basic effectively when a pathologist looks at a biopsy sample under the microscope they're describing the pattern of the of the cancer gland we talked about this at the beginning the prostate is an exocrine gland that produces semen and there's an architecture of the gland or the duct that a normal prostate has so think about like a branching tree when you develop a cancer it's an abnormal developed branch and so the pathologist will score how abnormally developed that duct or that branch is and that score is what ends up being the Gleason score now the pathologist tells us if you have a cancer what is the individual Branch look like what's the pattern that would be the Gleason pattern and then the patterns today are pattern three pattern four and pattern 5. but what we get in the summation report is well how much pattern three cancer do you have how much pattern four cancer do you have and how much pattern 5 cancer do you have and that's the Gleason sum or what we now call it was all served through the Gleason score so the common ones would be three plus three equals six that means that the pathologist only saw abnormal glandular patterns that were pattern three so the pathologist is always reporting the highest scores that they see they're reporting the most common pattern they see first that's the first number okay and then the second most common pattern of cancer that they see as number two okay okay and this is on both sides they once they're looking at they take the every single sample they tell you the score okay so typical number of samples that should be done in a decent biopsy it's 12 systematics okay so that's right side left side kind of every five millimeters kind of approach plus you sample the Target and the recommendation number of samples of a Target is usually three so two is inadequate because the needle can bend it can deflect sometimes the needle is going in 20 centimeters beyond your hand so you have to account for the deflection and you can track it but the idea is you do it three times I mean talk about user error potential right like think about the difference between you and me doing a prostate biopsy it's like I mean I know you could do it better than me no but but like it requires within the field of Urology like there has to be a difference in skill yeah and that's what the training is part of and and Ashley and I actually host a course where we put on and train anybody who's interested in how to do a proper good transparental prostate biopsy for example because that's what hopefully this is a new technology Physicians yeah so it'll it'll be helpful and obviously um you know there is a skill involved with and and you can tell there's a skill involved with doing the biopsy and there's a skill involved by the pathologist when they report it out so the requirements or the recommendations are that you declare the Gleason score that's the sum of the most common and the second most common cancer now presumably um some of these core samples come back with no cancer in them and is that just reported as nothing they report no cancer okay got it so it's no cancer or at at best 3-3 yes well they'll so no cancer so there's some rare variants that are not cancer and they're not benign they'll tell us about them that would be like prosthetic atipia but that's uncommon especially in the era of MRI targeted biopsies only and and so I wouldn't worry about that too much and you're biopsying only the peripheral Zone you well we biopsy where the lesion is but most prostate cancers originate in the peripheral Zone they can invert the 12 systematic biopsies how big is that by the way it depends on the size of the prostate so in a young man it's about [Music] um four to five millimeters thick and a guy who has a big prostate let's say a hundred gram prostate the total peripheral Zone volume does not change in a man over time so does that mean it actually gets thinner it gets compressed and thinned out particularly if you have benign prostatic overgrowth wow so it's harder to biopsy it makes it harder to biopsy absolutely so that's where a skill definitely plays a role so you have to really understand what you're doing I mean you know not any you know it's not like anybody can I mean this is not to take away from breast biopsies and things like that but this or a thyroid biopsy but this is totally different totally different this is much more complicated in my opinion yes for sure because it's not like you're just you know sure a fly right or breast you're trying to Target the abnormal but we're yes there's a lot of subtlety to it you have to know what you're doing and yes the total peripheral Zone volume Remains the Same over time so if your prostate size increases the air the actual the thickness of that peripheral Zone goes way down yeah in other words another way to just get this back to our analogy is you're having to biopsy the skin of the orange yes and if it's a small orange the skin is a certain thickness which is relatively thin the bigger the orange gets you have to preserve the amount of skin so the skin gets thinner and thinner and thinner that's right yeah okay so now what do you do with these Gleason scores so you take a look at them and you say what is the score and then what's the distribution and that's the volume of the score because the two things matter in terms of determining what the next steps for the patient are in general the way I talk through this with patients is you know did your biopsy demonstrate prostate cancer and if it demonstrated prostate cancer is it the kind of prostate cancer that we need to treat right now or is it the kind of prostate cancer that we can safely follow or monitor over time okay so let's start with patient comes in both the lesion and the periphery are three three yeah so if somebody is a Gleason six prostate cancer that's Gleason three plus three equal six prostate cancer is the least aggressive type of prostate cancer when you look at it under the microscope and it has a very favorable prognosis meaning those prostate cancers the thought process should be I need to find some data that will convince me that this cancer requires treatment because the recommendation on average is that these cancers can be monitored now what are the variables that affect whether or not we think someone should have their cancer treated sorry just make sure I understand that Ted does that mean a three plus three can't spread or metastasize unless it progresses to a three four for example good excellent question and that's been explored um with one major caveat that is that they've been explored in surgical Series so in Indiana there's a there's a there's a bias already introduced huge bias yeah but if you look at radical prostatectomy Series in men who had Gleason 6 prostate cancer there's a large series by John Epstein at Hopkins and also Scott eggner at University of Chicago they both showed that there was no lymph node metastasis in men with Gleason 6 prostate cancer so just make sure we understand that any man who underwent a prostatectomy with a Gleason three plus three had lymph node negative disease and therefore by extension presumably they never went on to get metastatic they never had a recurrence they they never had at the time of their surgery injury never had so what's the longitudinal data on those folks do we know that they're free well they do very well they're like the probability that they would die from prostate cancer is very very low but they could have a local recurrence for example and that could result in subsequent problems a need for additional secondary therapy but on average we know that a Gleason 6 prostate cancer that is of low volume can be safely monitored because why did those men have cancer surgery then because we have evolved how we manage them I see so based on those data we now would be less that was the person that I operated on WE operated on Hopkins when I was training where One Core Gleason six we thought because they had a cancer that they required immediate treatment okay so this is so this is now very different very the colorectal cancer model yeah in colorectal cancer you have an adenomatous polyp it comes out you have a carcinoma in situ it comes out yeah the difference is because in the colorectal model you can easily resect the adenomenous polyp with minimum or no side effects I see so done with the coldest yeah it's the morbidity of the prostatectomy similarly in the breast right dcis it's coming out you know debate whether we should radiate or not yes we treat pre-cancer so so aggressively in these other organs yes and here but in that in that way in the positive light of things urologists have been very Progressive and have been at the Forefront of doing surveillance for tumors that have not yet established or declared that they have lethal potential so how often do you get a Man Ted or maybe let me reframe it this way for every hundred men who you see who have a Gleason three plus three how many say Dr Schaefer I understand what you just said about the data I don't want this thing in me take it out yeah I mean it's rare that I will offer my surgical services to that person because um there's a lot of new and sometimes the patients don't fully understand what the potential ramifications for their side effects may be meaning the surgical risks yeah or radiation risks so what I will do is I will do it I will jump jump through a lot of Hoops to look for reasons to reassure that that patient that they do not have an aggressive lethal situation and most of the time we're successful now so a man is diagnosed with Gleason 6 prostate cancer if it is of low volume let's call that between one and four course which is the most common thing that we would find okay and that one or four samples of a systematic biopsy or if you target a lesion on the MRI we consider just be one region so if you did five samples of an MRI suspicious RADS four lesion and all five samples came out Gleason six we would just call that one area of visible cancer in those situations we we generally would say you are somebody who is a candidate who can have their prostate cancer followed because at this time your tumor does not have the lethal potential to spread to your lymph nodes or other parts of your body and all kinds of therapy to treat it carry more morbidity than just leaving it in place and just monitoring it yeah it's amazing and you're right it's really Precision medicine well yeah but you have to be both as the patient and the physician you have to have a very high degree of certainty that you didn't miss a four yeah three plus four so patients will often say that to me and I will tell them so for the average patient uh look we don't just assume that you only had six although remember with MRI targeted biopsies yeah we know that chances of reclassification or change in the grade of the tumor at the time a prostatectomy's low like 10 percent historically when you and I are residents at Hopkins you'd have a guy like the Gleason six and you come out with the Gleason eight because there was no MRI and there was no MRI targeting so the Precision that's a very interesting point the physiologist when he gets to slice and dice the thing is yeah so the Precision of the biopsy today is much better and therefore we can provide much better Assurance to the patient that hey we think we the biopsy shows us six we got a pretty good idea you just got a six okay now that again doesn't mean that that patient's um we just assume that they're going to be fine for the rest of their life we do active intensive monitoring that's PSA testing every six months I still believe that like you were mentioning before following that PSA and if it changes closely is helpful and then we do do you repeat the MRI independent of a change in PSA in those patients once there are three plus three I do my general frequency would be um that if they've had an MRI pre-biopsy then I'll track them depending what their their PSA stable I will not repeat the biopsy and we recommend we recommend a confirmatory biopsy at one year okay so you have low volume low-grade prostate cancer we check your PSA at six months it's stable everything looks good your MRI was not concerning we'll do a biopsy free at one year if you come in with low grade prostate cancer like the patients we took care of 25 years ago at Hopkins and you have not had an MRI before your biopsy you immediately get an MRI because I want to know what else is going on in there I want to know your density and I want to know if there's a lesion that was missed if on that by that MRI right that I get after your initial diagnosis has a RADS four or five you go to immediate biopsy if the MRI shows that you have a rad 3 but let's say a really really high PSA density like again I have concerns that the biopsy quality was poor you go to immediate biopsy so again you want to do confirmation to establish that you your your North is your true north before you tell a patient yes 100 I endorse active surveillance okay yeah so we do a lot a lot a lot of testing in these individual patients to make sure that when we're recommending surveillance we're recommending it for low volume low-grade prostate cancer okay again if you can answer this all things equal for a hundred patients who show up with suspicious enough PSA that they buy a MRI suspicious enough RADS three four five that they buy a biopsy but now High degree of confidence they're three plus three meaning they're down the active surveillance pathway what percentage of those men and I'm sure it's age dependent will go the rest of their life without a prostatectomy I can't tell you the answer to that but I can tell you data that's 10 or 15 years out okay so and five years out so if you have Gleason 6 prostate cancer and you enroll in active surveillance the question of course is well what would be the trigger to recommend a treatment yep okay so it's effectively like your cancer is becoming more aggressive or you are just have a proliferation of a very your tumor becomes bulky okay so think about it that those two ways the chances that you would have a more aggressive cancer develop in the first five years of surveillance is 12.5 percent okay okay by the way is that independence of whether you're RADS three four five we didn't really talk about Commerce okay all comers this is Valentine Carter's active surveillance cohort from John's house from Hopkins 1996 he started it yep 12.5 chance in the first that you'd have a change in the grade of your cancer overall about 30 to 35 percent of men in the first five years of entering surveillance will go on to subsequently have definitive treatment Okay so about 12.5 percent of guys is because there's a change in the grade it becomes more aggressive looking and the other guys a variety of factors they have increasing bulkiness of their tumor they may develop concomitant urinary symptoms and they want it all addressed at one time Etc et cetera in general I tell people it's 12.5 chance that you have a really need to do something because there's a change in the grade that's pretty steady and pretty consistent it's around two three percent risk annually and that that holds for 10 years as well okay meaning you add two or three percent per year after five yeah so you're up to twenty two twenty five but overall if I told people there's a one in five chance that your tumor will become more aggressive over the next 10 years of your life and you need treatment yeah most people sit on that I think that's fair to I think it's a fair I think that's a reasonable frequency well especially because you're not saying Go away and we'll only see you again when you're in trouble it's like we're going to watch that progress right and what's the chance that a cancer progresses in survey wants to be uncurable it's one it's point one percent so one in a thousand guys who you're monitoring would have a fisherian event okay so wow okay that's that's Bell Carter's data Valentine Carter out of Johns Hopkins it is changed how we treat and think about prostate cancer from when we were training there to now so let's talk about the Gleason sevens yeah so again a pathologist um a pathologist will tell us what they see under the microscope how much pattern three do you have how much pattern four you have and if you have pattern five you have it so a Gleason seven as you said again the Gleason score is a Gleason sum and it tells how much pattern three and how much pattern four do you have so it is a blended Scotch not a single malt or whatever they call it okay and the blend is what matters the most how much pattern four you have particularly is the most important factor so you can have as little as less than five percent pattern four and as much as much as 99 pattern for if you have 100 pattern four you don't have a Gleason seven you're up to eight you have an eight okay so when I look at a pathology report I look at what is the percentage of pattern for there right it tells me two things one how good was the pathologist when he who read it because if he's not telling me percent pattern four I don't believe anything he's telling me right and two if it's there how much percent pattern for you have not just by percentage but millimeters right so I'll look at how long is the tumor remember our biopsy needles 15 millimeters long gauge it's a true cut biopsy around a 18 16 gauge it's not a small it's decent sized sample length of the tumor and then I translate well how much of that length is percent pattern for okay so if I have a patient who has a single biopsy core that has 10 percent prostate cancer that's 1.5 millimeters of prostate cancer and that that and he has five percent pattern four think about how little disease that is that has potential issues with lethality what I do with that sample is I send it off to verisight for decipher testing and I have them look because about 70 percent of the time those small volume Gleason 7 tumors genomically are minimally aggressive but I wanted to I want to delineate that so they behave more like the sixes they behave like a six but if you have more millimeters of pattern four the more millimeters of pattern for you have on your biopsy in total in some the more that would push you to do treatment so big picture if you're exclusively patterns free disease on average we think surveillance until proven otherwise if you have a smidge of pattern four I'm talking about one millimeter two millimeters in total we think okay maybe surveillance would work for this person we have a very thorough detailed discussion age other issues in their life Etc et cetera and we determine okay life expectancy so if you're 75 and you have two millimeters of pattern four and you you know your average US male maybe you don't need to aggressively treat at that time you need to aggressively monitor but don't need aggressive treatment yeah so that that's the subtlety to it but the higher the percentage of pattern four you have and therefore on average the more millimeters of pattern four you have the more I'm you're going to be talking about active treatment so that's the essence of how much prostate cancer management has changed in the last five years and a Gleason 7 that needs treatment is a perfect surgical candidate yes okay what about a Gleason eight now by definition every single thing that is looked at is four yeah I guess is there such a thing as a three five there is a three five and it's been well you know the the science Geeks have looked at it effectively it behaves like a four four eight okay so let's just talk about you treat them all the same and you treat anything that's an eight or higher the same way so you can have a only pattern four you can have a um only pattern four you can have a pattern four plus pattern five that would be a Gleason nine okay you can have a ten that's pretty rare but pretty bad and actually if your pattern 437 okay so if you're more than fifty percent pattern four your Gleason four plus three equals seven we generally bundle those together with the eights and the nines you have a lot of pattern four you need treatment okay and then the discussion becomes whether or not single modality treatment is effective at treating and curing that individual man of their prostate cancer we're talking about the Gleason 8 on average yes why because the analogy I always use is like a dandelion weed on your front lawn the higher the Gleason score the higher the probability that that person can have deep roots in their tumor extending outside the prostate potentially into the perirectal fat and Beyond and additionally you have a higher probability that that dandelion can go to seed and those seeds can float off to the lymph nodes okay so when you have a higher grade prostate cancer you need to do a couple different things in your workup the thing that you need to do the one key thing is to do a PET psma scan psma is a prostate specific antigen prostate specific membrane antigen specific particularly that is enriched in its expression in prostate cancer cells and it is the most sensitive and specific way to determine the extent of a person who has high grade prostate cancers disease so you need to Stage them so in other words it's a pet scan but instead of using fdg it uses psna specific radio ligand because prostate tumors are not fdg Avid okay okay so you do a pen it's a functional metabolic test as well you stage somebody's uh prostate cancer with the psma scan and then from there you develop a treatment plan on average if you have prostate area only let's just call it prostate only could be extra prosthetic but prostate only or prostate plus lymph nodes then you have to start thinking about your initial definitive therapy and potentially multimodal therapies to um more uh more aggressively treat an aggressive lesion so depending on the patient their age the bulk of their tumor Etc I will talk to people about radical prostatectomy as an option for them there are a select group of people let's call it 20 to 25 percent of my surgical practice that presents with very bulky potentially you know super bulky aggressive lesions in those individuals I'll have an upfront conversation that I don't think that surgery alone will be effective at completely curing you of your prostate cancer but vis-a-vis breast cancer treatment colorectal cancer treatment surgery is an important component of your initial therapy and will do surgery and we'll follow that up with the radiation based approach and that patient that you're describing they have bulky tumor but the Pet Scan doesn't reveal any activity in the bone correct does prostate cancer metastasize to places outside of the bone besides the local Invasion lymph nodes is the most common place it would metastasis within the Basin and in the yes it follows a halsteadian trajectory most of the time aortic lymph nodes yeah so it can go to lung it can be in the thoracic cavity yes mediastinum I see yeah okay it's you know superclavicular so so yeah and then it will go to Bone that's the uh White bone there's a lot of the micro environment of the bone that's thought to mimic the micro environment of the uh of the prostate and so that's one type are there Androgen receptors there no but the meal you that the other growth factors that prostates may need to grow are there number one number two as you know the bone marrow filters all your blood so if you have circulating tumor cells you know they're going to be trapped in the but isn't it interesting how how few cancers do that besides breast and prostate breast and prostate uh you know like think about colon cancer uh prostate you know pardon me pancreatic cancer I mean all these other cancers yeah I mean the the colon one I think is that we just pick up Advanced colon cancers while they're you know they're trapped in their kind of mesenteric blood spread right so you're picking them up regionally more right yeah yeah you're right it might just be that but colon is so concentrated towards the liver yeah I mean the the the the the the load of circulating tumor cells in Colon and are filtered by the liver yeah but again it's not uncommon to see colon go to lung too yeah I mean prostate goes along prostate goes just everywhere else but yes it is true lymph node is the most common side of metastasis and then effectively equivalent or just in a close second is bone from a staging perspective do we use typical tnm staging for prostate cancer and if so the if it's only in the lymph nodes is it considered uh considered white and N1 oh it is for tnm it's for ajcc that would be stage four at diagnosis if it's in pelvic lymph nodes I got it so even though it's m0 is that considered m0 or M1 we call that Regional yeah but it's stage four yeah okay and it's scary to have someone have stage four but prostate cancer in the pelvic lymph nodes is still curable how how curable the devils and the details it depends on again the big differences in prostate cancer overall for the listers 96 95 96 of prostate cancers are diagnosed when they're localized okay then there are people who have N1 disease and M1 disease and you can have M1A m1b it's just the extent of the metastasis if you have lymph node only disease it's rare but if it's picked up at the time of your initial diagnosis it's less curable than if you're you subsequently develop lymph node disease as a in your follow-up in your survivorship monitoring in general I would say that um yeah a vast majority of people who have lymph node only disease can live 10 years and are they cured or not that's debatable we have this blood test that tells us exactly what's going on but they can live 10 years and the treatment is prostatectomy plus radiation typically well the treatment at the best treatment if you look at the data there's never been a randomized trial that explores which one's better but the best way to control lymph node disease is probably with radiation now I think about what's the role of surgery in this space the role of surgery is to de-bulk the bulky tumor as we talked about a lymph node Med is probably 40 or 50 million cells at a minimum and so why not enable the radiation to be more effective by just debulking it but on average radiation is more effective at controlling the local that local disease extent than his surgery the morbidity of radiation is not trivial not just from the nausea and the sickness that can come from the treatment but at least in the few cases I've seen of patients many years out the rectal bleeding uh yeah that the normally gets better but not always right yeah so they're the main side effects when you're considering treatment with radiation would be urinary sexual and then kind of GI okay and GI meaning rectal rectal irritation rectal bleeding the urinary side effects with radiation on average are kind of you know you're burning the prostate so you're going to have these lower urinary tract symptoms that we talked about at the beginning of the podcast they're always intensified and Amplified they typically persist for the duration of the treatment plus about a two month lag after that the um the rectal side effects that you're describing I think are mostly historical why there are there's a lot of new technologies that have been used to really minimize that so you can put in place with the percutaneous approach like we talked about for the biopsies you can percutaneously deposit the radiation's gel no gel hydrogel when it warms up it thickens you put it in the plane between the prostate and the rectum and you elevate the prostate between 5 and 10 millimeters off the rectal wall and it gives the radiation oncologist this window clear Target to radiate the prostate effectively without um damaging the rectum and it reduces side effects substantially now the other newest and most exciting kind of way to deliver radiation is with MRI guidance so remember historically you are placing fiducial little gold seeds and you kind of line up the radiation and you just assume it was going to hit the prostate most of the time and then we've developed kind of CT guided radiation where you do a quick CT scan and for that day you line up the radiation Fields with the CT scan but it's not real time now there is MRI guided prostate radiation so again we do MRIs to see prostate cancers because it's way more resolution not CT scans so you can theoretically resolve to the prostate much better and now there's a single MRI guided a linear accelerator that does intra fractional modifications of the dosage based on subtle movements right so if you take a deep breath or there's a little rectal gas it will capture it within between the fractions of radiation delivered and alter the trajectory of the beam and that trial there's a trial called The Mirage study it was done at UCLA and they showed that there was you know there's almost zero rectal side effects from it that's the other really really cool thing about radiation is that when you have an a um when you have an MRI and you have a big Rad's lesion let's say you got a RADS four RADS five you theoretically can boost that lesion with tremendous Precision if you have MRI guided a linear accelerator because it's so visible on MRI so the field of radiation oncology is evolving and they're doing a lot of spectacular things one this kind of real-time gating is huge two using and boosting the MRI visible lesions is I think huge from a cancer control perspective and then from a patient morbidity perspective because the MRI linear accelerators are very expensive they're not we have one but they're not widely available you can do this uh space Oar that's the gel that basically separates the prostate from the rectum and that's been shown to reduce the toxicity of radiation treatment a lot it's good you know what it raises the field and the competition for us to think about ways to do better less morbid prostatectomies I guess to close the loop on that let's talk about systemic therapy yeah the Mainstay of this is Androgen deprivation therapy uh we've already kind of talked about the morbidity of that yes um are there other synthetic agents are there any things that are looking promising on the immunotherapy front we're seeing an enormous uh surge of that on the on the side of other epithelial tumors yeah so um so let's talk about let's talk about the first thing which is when you're doing localized therapy we do we do think about utilizing um Androgen deprivation therapy as a radiation sensitizer okay so it is known that when you have a higher grade tumor let's just say you have a Gleason eight or nine like we talked about that radiation alone is not going to effectively cure that patient of their prostate cancer so you need to get you need to deliver and we know you can deliver radiation sensitization with Androgen deprivation Androgen deprivation induces double-strand DNA breaks that's the whole purpose of radiation itself is to induce those breaks so you can in other words Androgen deprivation makes the cells even more susceptible to the radiation treatment so we use that routinely and one of the things that the radons have to work on and they're doing there's a series of Trials right now exploring this is either intensifying the Androgen deprivation in cases that are very aggressive or de-intensifying Androgen deprivation in cases that maybe that the patient would not benefit from it and the way that they're determining that is with the decipher test so so we use Androgen deprivation therapy typically uh in two spaces one to augment or enhance the results of radiation-based treatments and two in individuals who have more advanced prostate cancers so for individuals who are considering are going to have radiation for their localized or locally aggressive prostate cancers they will often get that with a course of Anderson deprivation and the course of Androgen deprivation typically ranges between 6 and 24 months depending on the bulk of the tumor and the aggressiveness or Gleason score of the tumor that ADT was typically delivered with an lhrh Agonist okay so you would give an lhrh Agonist it would eventually first you get a surgeon testosterone then it shuts the system down the problem with that is that it is very very durable it lasts it's given as a Depot that lasts a long time that's helpful for the patient but the probability that the patient would ever recover normal testosterone is very low less than 50 percent of men who do uh why is that because of the long-term effects on the hypothalamic pituitary axis it just gets shut down and or because as you know in the Aging male that that that whole you know fragile to begin with yeah so the good news for men who are getting ADT short course is that there are oral lhrh antagonists that are out there and so they're a pill so their Half-Life is much shorter and they have been shown to effectively suppress testosterone to the same levels as the lhrh um Agonist but their Half-Life is so short that people can have a rapid testosterone recovery and they do so for people who are going to get radiation treatment who need in radiation sensitizer with ADT we will typically use an oral an oral lhrh antagonist because it's wrap it on and wrap it off so good news for those individuals now for individuals who are diagnosed with prostate cancer that progresses to a metastatic state or individuals who are diagnosed with prostate cancer that's metastatic at the time of diagnosis those individuals need to go on systemic therapy and the Mainstay of systemic therapy is Androgen deprivation or ADT and that that is based off of Nobel prize winning work from Charles Huggins out of University of Chicago that Mainstay of therapy has not changed what has changed is the other alternate you know synthetic molecules that we use in addition to traditional lhrh agonists or antagonists to further suppress testosterone levels and the two main classes of those are sip 17 Inhibitors that's a molecule called aberratorone so as you alluded to androgens are made from cholesterol molecules and you can you can inhibit a specific enzyme in the anergenic pathway sip 17 and you can then prevent production of not just testosterone but other androgens not just in the testicle but within the adrenal glands and systemically and it results in a more profound deeper suppression of testosterone Androgen production that is now recommended as first line therapy for people with metastatic prostate cancer what what is the five-year survival for men with metastatic prostate cancer at diagnosis with and without ADT well if you're metastatic at diagnosis The Five-Year survival is probably let me ask that a better way what's the median survival for men diagnosed with metastatic cancer to Bone let's talk about distant metastases with and without ADT what I'm really getting at is given the morbidity of ADT are there men who say okay my median survival if I do nothing is 12 months versus my median survival is 16 months if I do ADT it might not be worth an extra four months of life if I have to live Sons androgens the median survival for someone with newly diagnosed prostate cancer that refuses treatment is probably on the order of two to three years okay the median survival for somebody who goes on traditional ADT only lhrh Agonist antagonist is between 48 and 50 months so you can double it so four years yeah yeah so you can add a year to two years of life yes but it's also the quality of the life of the individual there are effects that occur in terms of the impact on metabolic syndrome and overall health but remember when prostate cancer is metastatic it starts taking over your bone marrow you can develop aplastic anemia I mean it's it's brutal so if you can mitigate that I still think how do men die what what are the final stages of Life pathologic fracture aplastic anemia because of bone marrow placement so it's other organ dysfunction because the tumor takes over for it renal failure is classic one too yeah from local tumors so and tumor lysis and things like that you can take you can extend you ballpark you can effectively extend the life of a patient when if they're diagnosed with metastatic cancer two years by about two to three years by going on ADT the new agents um meaning aberratorone or this other class of Agents which are um they're competitive uh binders of of uh Androgen receptors so they will binder receptor tether it in the cytosol and prevent it the the ligand binding domain from binding the the DNA in the in the nucleus among other meth uh other mechanisms those are things like enzolutamide apollutamide and derulutamide they're related they're much more evolved cousins to finasteride and do testeride okay but they're very potent so there's aberratorone and then there's another class of of Novel hormonal therapies the amides enza Darrow and APA they will effectively extend the life of a patient an additional 24 months on average compared to just traditional ADT alone and they're done in concert they're done together yeah correct so now if you have someone with newly diagnosed metastatic prostate cancer median survivals are seven to eight years which is good now it depends a little bit on the situation that they're diagnosed with cancer in so if you're newly diagnosed de novo metastatic versus you had your prostate cancer treated and then you develop metastatic those two men have different outcomes the men who are newly diagnosed de novo they have a much shorter life expectancy three to five years compared to somebody who is um already had their cancer treated it progressed to the Bone or the or the lymph nodes they have a much longer life expectancy on average probably because of bulk of disease and you know somewhat lead time bias in terms of the detection yeah so those are so traditional Androgen deprivation then you have novel hormonal therapies they're always evolving newer ones the amides they have some toxicities enzolutamide and apollutamide they have kind of issues with seizures they have issues with um kind of overall um sleepiness and and kind of alertness and so they're real app uh they're a lot of my which is the newest agent in that family is much cleaner there's less kind of cognitive effect of it and there's since it doesn't cross The Blood Vein very very well no seizure side effects aberratorone is pretty well tolerated but it has an effect on aldosterone production so you have to monitor people's blood pressures while you have them on those drugs so there are toxicities with the treatment but on average people can have a longer lifespan and a relatively good health span while on these medications okay so let's talk a little bit about surgical therapy yeah um last time we spoke we spoke in great length about the evolution of this operation from the way you learned it which was an open procedure to the way you did it at the very very tail end of your residency which was transitioning to a robot um I don't you don't know when was the last time you did an open procedure two thousand sixteen Okay so it would be almost unheard of today that a patient would have a prostatectomy that has done anything other than through a robot correct what is different today in the surgical practice in your surgical practice than say four years ago how has it evolved what are you doing today to make that operation better yeah lots of things um and you know surgery is always this balance of maximal exposure so that you can see everything with minimal exposure to preserve all the structures around whenever you're removing whether it's the heart the colon the lung whatever and so prostate cancer surgeries evolved in a similar way historically the robotic procedure was developed and really mimicked the open surgical procedure which which basically maximally exposed the prostate within the Deep pelvis it's in a very small tube so for the tennis players out there the Deep pelvis is like the inside of a tennis ball you know case the kit where you get the three balls it's very narrow very small space and you enter that space at the top of that case and you're operating at the bottom that's why it's such a hard procedure to do now we used to expose all the structures around the prostate to see it and delineate it from those structures we've the way that my technique has evolved is that now I maximally preserve all those structures around the prostate and basically operate in even smaller hole what do I mean by that well there's fascia which for the average listener is effectively like the Kevlar or the Gore-Tex of our entire body it provides resiliency and strength to the structures it keeps them in place and the prostate is surrounded by a tremendous amount of fascia and when fascia gets really really thick we refer to that as a ligament or a tendon so the prostate has a fascia it has ligaments and they support the prostate in the Deep pelvis and we historically open and robotically always would open up and disassemble that fascia take it apart to expose the prostate and then we would just sew it back together and hope that people were okay we would preserve the structures around the prostate but we'd hope they were okay since that time we now have evolved not just me but you know I think the elite prostate surgeons in the world in the country have developed techniques to do pelvic fascial sparing surgery leaving all the fascia that surrounds the prostate top bottom right and left alone and again the purpose for this is not to enhance the removal of cancer it's to mitigate the that's right very real side effects of the surgery namely around erectile function incontinence yes so you have to always balance and weigh are you getting all the cancer out because you can maximally preserve all these structures in the fashion the tissues but leave a lot of cancer behind and then what's the point of the procedure so you're always balancing your outcomes functionally with your outcomes from a cancer control perspective so they a hundred years ago getting all the cancer out was doable the problem is the morbidity of the operation was I mean you were guaranteed to be incontinent and impotent yes I would say 60 years ago that was the case 100 years ago we could we could we were we were not picking up early enough anyway yeah but remember 100 years ago or 100 plus years ago the first prostatectomy was a pelvic fascial sparing prostatectomy because it was because it was unretroperative it was done in the perineum where all the fascia that supports the prostate was left in place it's just that no one had it was Bloody you couldn't see what you're doing so the robot enables you to have no bleeding and enables you to see what you're doing remind us just where the ports are where do you gain access yeah you gain access to the prostate typically through the abdominal compartment so you have a you have a central port at the belly button and then typically a couple ports around at the level the belly button more lateral to it that you insert your instrumentation usually the procedure is done trans peritoneal meaning you put the ports into the peritoneum where the intestines live and then you kind of exit the peritoneum and you do the procedure extra peritoneally outside of the peritoneum outside of the peritoneum and the Deep pelvis is where all the fascia is there supporting the prostate and the structures around it so now when I do the procedure I do pelvic fascial sparing I've been doing it for two and a half years now and that has when I look at my results I have not impacted at all my cancer control so some of the early surgeons who did pelvic fascial sparing they left a lot of cancer behind you don't want to do that that's the whole point of the procedure when I track my my data I'm able to have excellent cancer control numbers or data margin rates Etc while maximally preserving the structures around the prostate so as we mentioned before you have your orange the pulp of the Orange is not cancer but the outer peel is cancer and just adjacent to that outer peel our nerves for erectile function nerves for you know innervation of the urethral sphincter and the urethral sphincter itself all of those structures are supported by pelvic fascia we now leave all those structures in place and do the procedure through an even smaller space requires a learning curve to adapt to it but with that approach you can really effectively eliminate urinary incontinence in almost everybody and more importantly the the the rapidity with which urinary control comes back is outstanding so so what do you tell a patient today I tell the patients my data so I tell them that um there's about a four to five percent chance that if we do your procedure you you know you'd have a positive margin if the cancer is contain what's in the prostate which is what I was doing beforehand okay I tell the patients no meaning meaning it's a 95 to 96 chance that this operation will be successful from a cancer perspective four to five percent chance we'd have to go back in to get some of the cancer out I tell patients that it's a little bit more subtle than that so A measure of surgical skill is are you taking out the prostate and all the prostate cancer if the cancer is contained within the prostate right because you can see the process you should take it out so about four to five percent of the time I make a little Nick or I poke a little hole in the side of the process and expose some cancer it doesn't mean that they're going to have a recurrence yep but it's a sign of technical skill an average in an average you know surgical series is more like 15 or 20 percent so we do a good job then I tell patients it's 55 chance that when I take your catheter out after the procedure which is around 10 days that you'll be dry no leakage I tell them that at one month it's a 66 percent chance you'll be dry with no leakage and at three months and your first kind of in-person follow-up 95 chance you'll be dry no leakage whoa okay now when we're doing that I always tell patients that's no leakage but you can still wear a pad or liner a day because people will often just do that for insurance or for protection so that's what anterior fascial sparing surgery has done what about on erectile function yeah it's transformed that space urinary recovery substantially now when you do anterior fascial sparing you can also potentially less you know you can damage the nerve tissue less when you do it meaning you're not just fully moving and dissecting it free you kind of can leave it in sight to it kind of stays attached to the rectum and the fascia around it there's still neural trauma and the biggest hurdle that we have in urology and in Urologic oncology is really optimizing our neural preservation so we really are reliant on our neuroscientists to help us find those neuroprotective agents that we could deliver pre-surgery to minimize that trauma the nerves that we use that are are utilized for erection are unmyelinated and they don't really exist in a cable or bundle they're kind of individual nerve fiber so they're very sensitive to stretch pulling and tugging so that's what I explained to people now the likelihood or probability that people would recover erectile function is much better when you do anterior fascial or pelvic fascial sparing surgery but overall the probability that they recover erectile function is highly dependent on the Gleason score I.E the aggressiveness of the tumor and the extent of the tumor because if you have a high grade prostate cancer there's a 60 to 80 percent chance that that cancer is growing into the nerve tissue on the side that the tumor exists on already so we don't often think an absolutes like 100 percent resection of nerve or zero percent resection of nerve but we have to titrate the dissection surgically to incorporate any potential nerve tissue that may have cancer in it the nice thing and the exciting thing is that we are moving into a space where there are going to be Imaging agents in real time so think about pet psma there are now linking psma to near-infrared based tracers so you can actually flip a switch and do near infrared Imaging in real time during a prostatectomy to look for residual cancer maybe so if you maximally neurospare you can look at the tumor and look at the nerve and say hey is there any tumor left behind so lots of things that are evolving in surgery that will help Advance Us in identifying precisely where the tumor is and where it is not which are going to be you know those trials are kind of evolving and starting soon which would be really exciting stuff so if a Gleason three plus four patient comes into you and you're you know it's a high enough forward that you're going to operate on them what are you telling him is his uh on Cialis erectile because I assume most these patients will be on Cialis post-operatively age of the patient yeah so what's your sexual function before you start the procedure 65 year old guy who doesn't even require Cialis before surgery yeah I would tell him it's a 65 to 75 chance to recover erection sufficient for intercourse with Cialis on board within how long 24 months okay because that neuropraxia is a 24 to 30 month process wow so for the guys who don't get it back they're going to be looking at other therapies for erectile function pumps and things of that nature well there's uh injectable medications for prostaglandins they're very effective they bypass the nerves and or implantable devices okay now 65 year old guy who's on Cialis before surgery what's his recovery on Cialis it's going to be 10 or 20 percent less good okay same guy but he's a Gleason four plus four it depends on where the tumor is okay so the nerve bundles are in that kind of posterior lateral portions of the prostate let's let's think about like five and seven o'clock the bulk of them so if you have an anterior tumor at one o'clock so this is the kind of nuance that again comes into the the diagnosis yeah so the prostaglandins have also been a game changer here because it sort of lessens the the the the the the need for perfect uh recovery of erectile function post-operative well we use prostaglandins and injectable medication in that kind of one to two or you know two year period of time where the nerve function is recovering because and this is an injection at the base of the penis right at the vascular bundle at the base of the penis into the cavern also bring to the cavernos yeah okay and that will trigger uh an erection uh and what prevents that patient from getting priapism the dosage of the medication so you start out low and you titrate High got it so that you know reoxygenates the penis helps maintain penile length um if you're attempting intercourse uh it would prevent any kind of potential micro fracture like you had talked about with mokira with with um you know with potential scarring and plaque formation so I mean I I strongly advocate for it um for all the patients that helps with their recovery it helps them with their sexual you know function sexual activity in the meantime so I mean obviously a lot of people listen to this podcast and some of them at some point in their lives are gonna maybe require prostate surgery not everybody can come to see you um what are the questions that they should be asking their urologists as they're considering prostatectomy for cancer yeah a lot of key points we talked about through the whole thing so when the urologist you know did their biopsy did you do an MRI beforehand because that means he's just like up to date with modern medicine when the pathologist read the specimen did they do things like percent pattern four that means that the pathologist at that institution is up to date and then frankly you know what is the urologist practice that's offering them a radical prostatectomy I firmly believe and there's strong data to suggest that if you are a prostatectomy only practice like mine that you're dedicated to and focus and thinking about the operation and all the subtleties we've talked about over the last couple hours that are related to the surgical outcome so if you're a jack of all trade then I don't recommend that you go to that person for their prostatectomy so when my patients have uh kidney stones I don't treat them I send them to my partners because they do a better job all I do is prostatectomy so for me it's what's the scope of your practice are you prostatectomy only or you do everything and if you're process and then on top of that what are your outcomes so what's your surgical margin rate and what's your rate of recovery of functional recovery and just understanding what that numbers are sometimes I tell people numbers that they're not happy with I try to set appropriate expectations for them after their procedure um but just by you know they'll say well like that's not what my you know my physician told me those some Physicians will say 100 chance of erectile recovery well that's not accurate so that just tells me that they're trying to oversell having the procedure with that particular person yeah um you mentioned that there's maybe only a dozen people that are doing the fascial sparing procedure that I hear you correctly well it certainly is a limited number I mean it's always evolving in terms of how many people are out there doing it there is a learning curve too so when you're and you did say you off yesterday when you and I went for a rock you mentioned to me it's added time to your procedure it's a it's a harder procedure and it takes longer to do yeah there's a new learning curve so if you if you can do a prostatectomy um you can't just suddenly flip and do a fascial sparing so what how long did it take you to do it without fascial sparing and how long does it take you now it takes me about 45 minutes longer with fascial sparing so my average surgical time was maybe 92 120 minutes before and I had 45 minutes now but you know it's worth it um to do that we have a bunch of videos on our Northwestern Medicine Urology YouTube channel that show we'll link to these how you can learn the procedure for those surgeons out there and then there's other approaches to doing anterior fascial sparing done the way it then my Approach that I show but though there are there are numerous videos for those as well all right one last question Ted um what are you most excited about in the next five years in the field of prostate cancer and this could be anything from the Diagnostics to the surgical treatment of to the post-operative care and management of anything what what are you most excited about integration of precision medicine I've been passionate about and Incorporated in my practice for over a decade Precision medicine but like we talked about understanding the molecular subtypes and phenotypes of an individual's tumor is going to be incredibly powerful and I think it's going to change how we think about and manage these individual patients not only recommending you know treatment for the local licensees like I think we're going to discover that they're exquisitely radiation sensitive tumors and those that are radio resistant and we know that there are exquisitely tumors that are exquisitely sensitive to androgens and those that are inherently Androgen resistant and it's going to change a lot we've never ever looked or thought about it before but now we have in our hands the power to do that and that's going to change everything in my opinion it's changing now and we'll see the benefits of that those studies in the next five years awesome well I think that means we'll probably have to sit down again in five years and talk about it sounds good all right Ted thanks so much I really appreciate it thanks for having me Peter [Music] thank you

Channel: Peter Attia MD

Views: 716,828

Keywords: Peter Attia MD, Dr. Peter Attia, Early Medical, The Drive Podcast, The Drive, Longevity, Zone 2

Id: poTcAm_rknw

Length: 226min 39sec (13599 seconds)

Published: Mon Oct 02 2023