Information Session: Prostate Cancer and Men’s Health

Corporate Speakers 

• James Eastham; Memorial Sloan Kettering; Chief of the Urology 
• Sean McBride; Memorial Sloan Kettering; Radiation Oncologist 
• Dana Rathkopf; Memorial Sloan Kettering; Oncologist 
• John Mulhall; Memorial Sloan Kettering; Urologist, MD Director, Male Sexual and Reproductive Medicine Program 
• Claudia Derico; Memorial Sloan Kettering; Nurse 

Presentation

Operator:  Good afternoon and welcome to the Memorial Sloan Kettering Information Session Prostate Cancer and Men's Health.   

Our host and moderator for today's call is Dr. James Eastham, Chief of the Urology Service at MSK.  I will now turn the call over to Dr. Eastham.  Please, go ahead.   

James Eastham:  Thank you very much and thanks to everyone on the call today.  We do appreciate your participation and the question that were sent in.  As many of you know, September is Prostate Cancer Awareness Month and this does provide us with an opportunity to address some key issues regarding diagnosis of prostate cancer and also management of the disease.   

We have arranged what to I believe is an outstanding panel whom I will introduce during the session as various you questions are addressed.  As all of us know, COVID has taken over the headlines the last six months or so.  And certainly, that can provide many of us with a feeling of being vulnerable and just wanting to stay away and lock ourselves in a room to some extent.   

But it's important to understand that many health issues continue despite of the COVID virus and it's important to keep in touch with your physicians and to continue with your medical care even if that medical care is simply screening.   

Most medical centers including Memorial are back and operational.  Certainly, screening issues like for prostate cancer should be addressed.  Telemedicine is certainly something that is being used far more frequently and is proven to be very effective in terms of being able to reach out to patients.   

If a blood test or some other procedure is required, most centers have very good procedures in place that are safe and allow you to have excellent medical care despite the ongoing issues with COVID.  So, I do encourage everyone on this call whether it's for your blood pressure, your cholesterol or for screening for cancers and addressing cancer issues to do continue to seek the appropriate medical care.   

And with that, again, most of the questions, if not all of the questions we will try to address today came in from folks on this call.  We certainly can't address every single question.  We've tried to select those that are most appropriate for a general audience rather than specific fine details but hopefully this will prove beneficial to at least most of you, if not all of you, on the call.   

So, the first topic we're going to discuss his PSA.  And PSA, as most of you know is prostate-specific antigen and I'll call on Dr. Sean McBride who is one of our on stellar radiation oncologists, simply outstanding internationally and nationally recognized as a leader in the field.   

And, Sean, if you could address simply how do we use PSA in terms of screening for prostate cancer?  Let's start with that topic.   

QUESTIONS AND ANSWERS 

Sean McBride:  So, typically PSA is used as a screening test, it's a blood test.  And when the PSA is elevated above a certain value and that value can depend on how old the man is when he's getting this PSA, the PSA will be used to determine whether any additional investigation like an MRI or a biopsy is necessary.  That’s ort of the -- that’s sort of very broadly how PSA is used.   

James Eastham:  Right.  So, as I think you're saying, PSA certainly doesn't diagnose prostate cancer.  It basically tells us that something is going on in the prostate and usually additional testing is needed to determine whether or not that PSA test needs to be evaluated at all.   

And one of the tests you mentioned is prostate MRI.  How is MRI used in terms of a man has an elevated PSA test?  And he may be recommended to undergo an MRI, what would the MRI help with?   

Sean McBride:  That’s a great question.  So, I think the first point you make is a critical one to remember that just because the PSA is elevated does not mean that the guy has prostate cancer.  There's multiple other reasons why a man can have an elevated PSA.   

But if a guy does have an elevated PSA, oftentimes that MRI is the first type of investigation for -- one of the first types of investigation that we do and what you're looking at is you're -- the MRI gives you a very detailed exquisite picture of the prostate and it can -- there are certain pictures that come with the MRI that can help a guy's urologist to determine whether there is likely to be a tumor in the prostate or cancer in the prostate.  And it can help guide, if that is seen, it can help guide the biopsy give you a more accurate assessment of that potential cancer.   

James Eastham:  Right.  So, it used to be that if any man had even a slight elevation in his PSA, test he was almost immediately recommended to have a prostate biopsy and that proved problematic in terms of too many men getting unnecessary biopsies.  And so, now there are typically second line screening test, imaging like an MRI is one of the things we do.   

There are some alternative blood tests, people on the call may have heard of something called a 4K score, something called Prostate Health Index, which are two-second generation, if you will, screening tests to better assess a man's risk of having prostate cancer rather than just the PSA alone.   

There's some urine tests that are available as well such as PCA3.  There's a newer one called SelectMDx.  But ultimately, if these studies do show a worrisome enough situation, a prostate biopsy is typically recommended.   

Now, if a biopsy is performed and that biopsy does show prostate cancer, one of the important aspects of prostate cancer is something called a Gleason Score.  A Gleason Score is a number system which I'll ask Dr. Dana Rathkopf who's one of our, again, stellar medical oncologist that works with men who have more advanced prostate cancer.  But if Dana, if you could address what is the Gleason Score and how would you use it in practice?   

Dana Rathkopf:  Thank you, James.  So, Dr. Gleason, actually, was a pathologist from Minnesota who back in sort of the 1950s-'60s, developed a grading system to determine how aggressive prostate cancer is.   

We know that close to 200,000 men can be diagnosed with prostate cancer each year in the United States, but not everybody has the same type of cancer.  They're not all the same type of the aggressiveness.  And so, we need to need to figure out ways to tailor treatments appropriately.   

And so, this Gleason grading system is a way of looking at the actual cancer cells that come from the prostate biopsy and giving them a number to determine how aggressive they are or how risky the cancer is.   

And typically speaking, a Gleason Score of 6 is considered low risk, meaning low risk of growing quickly, low risk of metastasizing which means spreading to other parts of the body.  Gleason 7 would be intermediate risk, suggesting that maybe it will behave quietly but it does have potential to become more aggressive.   

And then the high-risk patients are Gleason 8, 9, and 10 with 10 being the most aggressive Gleason-graded possible and those are the patients that as a medical oncologist, I typically worry about the most because they tend to be the patients with high risk disease.  And again, speaking about risks suggesting that their cancer my group quickly or might even spread outside the prostate to other parts of the body which could render them not curable.   

James Eastham:  Thanks.  That’s a great summary.  So, the Gleason scoring basically gives those us, as Dr. Rathkopf said, an assessment of risk.  And risk is important because that will guide how a man is treated or at least what his options for treatment are.  So, not all prostate cancers require immediate treatment, those that are considered to be a low risk can actually be monitored which is a whole process of what's called active surveillance and active surveillance means rather than using any kind of treatment, we basically monitor patients.   

And we monitor PSAs, we monitor MRIs.  Occasionally, we will repeat biopsy.  And as long as risk stays low, we do not have to intervene.  Now, that ends up being at least a third of the patients that we diagnosed with prostate cancer.   

So, again, risk in this concept of Gleason scoring which is the most important aspect of assessing risk is critically important when making decisions.  So, that’s a brief summary of Gleason scoring and active surveillance.   

Now, Gleason Score can also guide management of prostate cancer that does require treatments.  So, I'll go back to Dr. McBride, Sean, and what about radiation therapy?  There have been -- there are questions related to brachytherapy, questions related to newer developments in proton beam radiation.  How do you evaluate a man at diagnosis that you recommend treatment for, so not an active surveillance patient, how do you guide that man into the type of radiation therapy that he might best be suited for?   

Sean McBride:  Thanks.  That’s a great question.  So, there are multiple -- there are two dominant types of radiation for prostate cancer.  One, as Dr. Eastham mentioned, it's brachytherapy or seed implantation in the prostate.  And the other is external beam radiation therapy where robotic arm, rotates around the prostate and delivers the radiation in 15-minute sessions.   

In terms of -- and occasionally, for men with slightly more aggressive prostate cancers, we'll recommend a combination of the seed implant and external beam radiation.   

How do we determine what sort of factors go into determining?  Which radiation treatment type is best for a particular man?  In part, it is the extent of any urinary symptoms he's having.  If he's getting up a lot at night to urinate, if he's having to go somewhat urgently during the day, those types of urinary symptoms may suggest that he's better served by external radiation or obviously, prostatectomy.   

Brachytherapy is a single treatment for prostate cancer.  We tend to reserve that for men with less aggressive prostate cancers.  These are men with the so-called favorable intermediate risk prostate cancer.  We tend to use it in younger men and we tend to use it in men with normal-sized prostates who don’t have a lot of urinary issues.   

For guys with slightly more aggressive prostate cancer, unfavorable intermediate risk or high-risk prostate cancer if they -- if they have good urinary function, if they have normal-sized prostates.  Oftentimes, we'll recommend the combination of brachytherapy to seed implants and external radiation.   

One of the newer types of radiation therapies that we have is called SBRT or SABR treatment.  This is external beam radiation therapy that can be delivered in five treatments, typically over a week and a half.   

We can utilize this for men with intermediate risk prostate cancer.  We're starting to use it even in men with higher risk prostate cancer.  Most men will qualify for this type of radiation treatment and in addition to being logistically easier for most guys, they com in for five treatments as opposed for the multi-week treatment regimen that we would frequently employ years ago.   

It also may be a bit more effective than the more traditional radiation.  Now, in terms of proton, obviously, this gives a lot of billing.  I think proton potentially have a role in the treatment of prostate cancer.  Certainly, protons are a type of radiation that may spare your normal healthy tissue more effectively than traditional radiation.   

But there are still -- but we don’t have what's called -- we haven't run what’s called a randomized controlled trial to demonstrate that.  Meaning, a coin is flipped and half the guys in the trial gets standard radiation and half the guys get proton radiation.  And those trials haven't -- have accumulated enough men, but we don’t have the data yet to say whether protons offer truly significant benefit for guys compared to the more standard radiation.   

James Eastham:  So, as I think everyone on the call can imagine, there are lots of issues with radiation therapy in terms of what is the appropriate type of radiation to deliver to a particular patient.  And there's lots of nuances.  And speaking with the radiation oncologist to review these is certainly critical in making decisions about radiation therapy.   

Certainly, seeds are appealing, but they're not appropriate for every patient.  The same with SBRT or stereotactic radiation therapy, Cyberknife it sometimes referred to, again, that's a wonderful way to deliver radiation therapy but it's certainly not for everyone.   

So, radiation is certainly a curative appropriate treatment for most men diagnosed with prostate cancer.  And certainly, resulting in excellent outcome.   

Now, now one of the things that the Dr. McBride alluded to during his discussion of radiation is that, unfortunately, all treatments do carry side effects.   

And one of the side effects that can happen with any treatment for prostate cancer is a change in sexual function.  And I'd like to bring on the or bring in to the conversation, at this point, Dr. John Mulhall, who runs our Sexual Medicine Department and is an expert in management of erectile dysfunction amongst other things.   

And, John, what do you tell patients who initially before treatment, whether the treatment of surgery or radiation therapy, are there things that they can do to try to better their outcomes in terms of sexual function?  And what can be done after treatment to try to maximize there either maintaining or recovering their best sexual function?   

John Mulhall:  Thank you, James.  So, first of all, I would like to congratulate all of you as potential patients attending this and gaining information.  I think information is critically important in your decision making for what treatment you will pursue for your prostate cancer.   

I think the first thing to do is communication to your physical or physicians, how important your sexual function is.  All treatments in prostate cancer, perhaps with the exception of Active Surveillance have some potential negative effects on your erectile function which is the most common sexual dysfunction.   

Most of that is temporary, after radical prostatectomy, but there are certain types of patients who will be left with long-term ED.  The time course of erectile function recovery after prostatectomy typically optimize over an 18-24 months' time period.   

So, it's very common that men have problems in the first year and then overtime, there is an improvement.  Radiation, on the other hand, is quite the opposite.  Like, you'll see very little negative effects within the first 12 months and then over the course of the ensuing 24 months, years two and three, there is a reduction in erectile function.   

Typically, for radiation and therapy, the classic predictors of long-term problems would be older man tend to struggle to have recovery to baseline.  Nerve sparing is very important in the prostatectomy group.  The better the degree of nerve sparing, the more lucky men are to have a good recovery.   

The dose of radiation, the use of androgen deprivation therapy will have some negative impact upon the erectile function recovery.  And generally speaking, the baseline erectile function, how healthy a man is and how good his erections are going into treatment.   

We are blessed at Memorial that -- I'm a urologist but we have the luxury having the urologist who all he does for a living is sexual medicine.  So, myself and my nursing staff and our psychologists work very carefully to maximize recovery.   

We understand that the goal is to treat and cure prostate cancer.  So, we're very cognizant of that.  But at the same time, we're focused on your quality of life.   

The whole concept of rehabilitation which is protecting your erectile tissue, if you put your hand around your penis, most of what's inside your hand is a muscle and what we're really trying to protect during the early stages of after prostatectomy and radiation is keeping that muscle healthy and that concept is called penile rehabilitation, which mostly, revolves around the use of the drug class called PDE5 inhibitors which is the Viagra and the Cialis drugs.   

And I think I'll leave it at that for the moment, James, unless there are more detailed questions later.   

James Eastham:  OK.  That’s great.  And one of the other aspects of recovery after surgery, not so much after radiation therapy is continence.  And there are things that we certainly discuss with patients regarding urinary continence.  And the last but certainly not least of the panelist we have today is Claudia Derico, who is one of our nurse leaders in terms of our prostate cancer program.   

So, Claudia, welcome number one.  And number two, what do you discuss with patients regarding, again, what can they do to try to improve their outcomes in terms of recovery of continence after surgery and what should their expectations be?  We heard from Dr. Mulhall that erectile function can take many months to recover after surgery, what about with urinary function?   

Claudia Derico:  Thank you very much, Dr. Eastham.  So, when it really comes to bladder control after surgery, time is going to be the most important factor for our patient -- for our patients and patients having it is also very key.   

So, pelvic floor muscle exercises will help patient strengthen the pelvic floor muscle.  These muscles will help support the bladder.   

So, most men do experience incontinence after surgery.  Most being the high 90 percent range.  But the expectation is that these patients will recover and become fully confident within one year.   

So, that is our expectation for our surgical prostatectomy surgical patient.  If their continence is slower to recover, sometimes there are formal physical therapy that can help.  And at MSK, we're very fortunate to offer pelvic floor physical therapy for our patients as a rehab session after the surgery.  So, we offer those as well.  So, I would say time is key and also the exercises.   

James Eastham:  Right.  So, again, it's met -- much of this is managing expectations.  If a man after treatment expects to be unaffected by that treatment meaning unchanged urinary function, unchanged bowel function, normal sexual function, that man's going to be disappointed because, unfortunately, all of the treatments we deliver do impact quality of life, mostly in a negative way, but ultimately men will recover.   

And while their new quality of life will be different, it certainly doesn't have to be a bad quality of life.  So, changes are expected.  Some of the changes are better than before, some are not as good.  But ultimately, with experts such as Dr. Mulhall and in our physical therapy, we also have voiding function experts, et cetera, we tried to optimize quality of life for these patient.   

One of the areas that we have done a lot of research at Memorial is in looking at ways to still cure prostate cancer but try to have less of an impact on quality of life and that’s what's called focal therapy.  It's very -- it's essentially the same as doing a lumpectomy or just to just removing a portion of the breast in breast cancer rather than removing the entire breast.   

So, the concept is delivering an energy source to the prostate in the area where the cancer is located.  The energy source can be a variety of different things.  It can be radiation therapy like a seed implant, it can be cold or freezing the prostate which is cryotherapy, it can be heating the prostate which is done with either laser or a focused ultrasound, high-intensity focused ultrasound.   

So, there are a number of different energy sources that can be used which destroyed prostate tissue.  And if we destroy less tissue, the likelihood of impacting continence or sexual function should be left as well.   

The difficulty is in knowing exactly where the cancer is located and ablating or destroying the cancer.  And that's the research aspect of delivering these energy sources.   

We know we can kill prostate tissue quite effectively.  It's just how much do we kill or how little do we kill and that's where clinical trials are still being done.  So, you will find centers around the country including our own that deliver HIFU or some other energy source to do partial treatment of the prostate to destroy the prostate cancer.   

But it truly is investigational.  It is not considered to be a standard of care and it should be given as under the guise of a clinical trial so that we can get the information that's required to know if it is appropriate and if it is appropriate, who are the best patients?   

So, we do have physicians in our urology department that deliver focal therapy but it is in a very select group of men that qualify for our clinical trial.  So, focal therapy is certainly something that will be used increasingly in prostate cancer, it's just not ready for every man at this particular time.   

So, I want to go back to Dr. Rathkopf for a moment because, unfortunately, surgery and radiation therapy don't always cure the patient.  And the way we determine that in almost all instances, it's with monitoring PSA.   

So, I know it's two separate issues for a surgery patient versus a radiation patient, but let's assume the patient has demonstrated by his PSA test that he has recurrence.  What is you recommendation for evaluation and then how are most of these men managed if their PSA is deemed worrisome enough to warrant treatment?   

Dana Rathkopf:  Thank you, James.  So, unfortunately despite all our best practices and we've heard about all these different surgical and radiation-based techniques, there will be some proportion of patients that will have a recurrence in their prostate cancer as measured by PSA.   

And that’s a difficult situation to be in because PSA is pathognomonic for prostate cancer.  Meaning that it's made only by the prostate and if you have the prostate irradiated or the prostate removed, you should not have detectable amounts of PSA that are rising dramatically in the body.   

And so, if that -- if that starts to happen the way we typically assess a patient is we look at not just the absolute value which is the actual number but how fast the PSA is going up.  We look at the initial the initial -- the initial factors of the prostate cancer meaning what was the Gleason Score which I had referred to earlier, was it high risk?  Which might suggest that the cancer cells have spread beyond the area of the prostate.   

Was it intermediate risk?  At the time of surgery, were there lymph nodes involved?  Is the margin positive or negative?  And maybe James, you can talk to that a little bit more in a moment.   

But all the things give us some clues as to whether the cancer driving, the PSA, is still in the area where the prostate was which we would call the prostate bed, pelvic area, or if the cancer cells may have -- might have spread beyond that area and have metastasized in a way that we won't be able to cure it.   

And so, oftentimes, the evaluation of a patient who has a rising PSA felt to be related prostate cancer after surgery or radiation is that we'll do imaging of some type.  That could be a cat scan, a bone scan, an MRI.  There's some investigational research tests, PET scans that we’ll sometimes use.   

And all of this is looking for residual cancer.  But more often than not, we won't see cancer and these imaging studies because it's very, very early detected by PSA or blood test only.  And in that setting, we need to use all these different factors to decide whether we are still able to cure the cancer which would mean that the cancer is still in the area where the prostate was and might consider hormones and radiation for a period of time to that area are directly or if the cancer is more likely to have spread beyond the prostate area, in which case, we would consider it metastatic and we would have a different -- we wouldn't be able to cure the cancer necessarily in that setting but we would certainly be able to treat it and treat it for many years to come.   

And so, I think I'll stop there before I take up the whole time.   

James Eastham:  No.  It's a -- it's an important but as most topics with prostate cancer, it's quite complicated and on an individual basis, there may be different scenarios.  So, it's certainly not your PSA is going up a little bit after surgery or it's going up a little bit after radiation therapy, you have to immediately do something.   

I know everyone worries about their PSA and certainly PSA after treatment that is increasing typically does signify persistence or recurrence of cancer but not all rising PSAs carry the same threat and not all of them require the same management.  Now, one of the treatments that is often used either in combination with radiation therapy for high-risk patients or certainly in patients who have more advanced prostate cancer that has spread beyond the prostate to other parts of the body is hormonal therapy.   

And hormonal therapy is the most important and the initial treatment for metastatic prostate cancer.  So, I'll ask Dana what about hormonal therapy?  What is the expectation of response, and again, PSA will be utilized and how do you counsel patients about the potential side effects from hormonal therapy?   

Dana Rathkopf:  So, hormone therapy refers to using treatments that lower the sex hormone testosterone.  And testosterone is a male hormone that's analogous to estrogen in women; women make estrogen from their ovaries.  And overtime, the ovaries convolute or stop making estrogen and that induces a menopause type of state.   

All women who get to certain age will experience that situation.  But for me, the testicles which make testosterone continue to function well into old age.  And what we do in the setting of prostate cancer is we artificially shut off the production of testosterone from the testicles because we've learned overtime that testosterone binds to a receptor on the cancer cells called the androgen receptor and actually causes the cancer cells to grow.   

So, testosterone is like the food for prostate cancer.  And that's why when we have a patient with recurrent metastatic prostate cancer, that we feel needs to be treated, we will very, very frequently use this type of hormonal therapy to shut off testosterone.  And in doing so, we starve the cancer cells, we stop them from growing.   

Now, when we remove testosterone from the body, we're starving the cancer cells and they may shrink and they will stop growing.  And as a result, they become less active and the PSA will come down.  But the prostate cancer cells are not killed typically by removing testosterone.   

There may be some that -- a few that may die early from that initial shock but most of the prostate cancer cells will still be in the body, they're just not functioning, they're not growing because they don't have -- they don’t have this food testosterone.   

Some of the side effects of removing testosterone from the body can be very similar as I sort of alluded to earlier to menopausal-type symptoms and there's really a continuum of toxicities.  So, some men experience very significant and severe side effects from removing testosterone and it can be fatigue, mood changes, certainly change in sexual function, not just the inability to maintain an erection that loss of libido.   

Hot flashes that can keep them awake at night overtime.  Loss of bone density, muscle mass.  But the majority of these side effects or toxicities from removing hormone can be managed.  They might not be completely reversed, but there are a lot of ways that we can think about controlling these toxicities and some of the ways we can do that is through lifestyle and exercise.   

And certainly, here at Memorial Sloan Kettering, we have many centers there, we have nutrition program to help with diet.  We have rehabilitation and physical therapy medicine to help with muscle loss, we have an excellent endocrinology service so we can think about bone health and bone protection.   

We have counseling to deal with mood changes, specifically targeted for men with prostate cancer.  Of course, John Mulhall, I'd be remiss if I didn’t mention our erectile dysfunction clinic which is harder to see him than it is to see me, the waitlist is so long.   

And I can go on and on about this.  But I think the important thing to know about -- the take home message about removing testosterone from the body is that it starves the cancer cells but doesn’t kill the cancer cells.  And that most of the toxicities, although they may be, of course, irritating, the majority of the toxicities can be managed.   

It's typically not dangerous to a patient to receive hormone therapy.  Although again, it often requires lifestyle management and close interaction with your physician to discuss these side effects as they start to occur.   

James Eastham:  Thanks, Dana.   

Maybe a slightly off topic but something I think that is coming up more frequently in clinics is the role of testosterone replacement.  So, men have lower testosterone level as they grow older and replacing testosterone has become an industry onto itself.  And some men have prostate cancer but also have low testosterone levels.   

So, I know that’s an area where Dr. Mulhall has some experience.  So, John, what do you tell a man who has prostate cancer?  He may be on just active surveillance or he may have been treated for prostate cancer, what is your conversation with that gentleman about testosterone replacement.  Is it safe?  Is it wise?  Should he not do it?  Why don’t you go through some of those aspects?   

John Mulhall:  So, that’s a course -- a topic that’s worthy of an entire hour lecture.  So, let me give you just high points.  First of all, the label for testosterone product say do not give testosterone therapy to men with prostate or breast cancer.  OK?  So, that’s in the label.   

So, the use of testosterone therapy in the patient with prostate cancer, whether it'd be active surveillance, prostatectomy, radiation, double or triple therapy for prostate cancer is an off-label indication.  OK?   

And while we have among the world's largest experience in all three of those groups in testosterone therapy, the patient needs to be aware of the absence of long-term safety data for testosterone therapy and these groups.  It would require many thousands of men followed for 10-15 years to really define its absolute safety and we just don't have that.   

We have been getting testosterones for prostatectomy patients for 16 years.  We have to giving testosterone to active surveillance patients for 10 years and likewise, radiation.   

If you don't have prostate cancer, giving you testosterone therapy does not increase your risk of prostate cancer.  That’s a very, very important thing that you need to understand.  The indications for testosterone therapy or men who have what's called testosterone deficiency and that is defined as the presence of low testosterone, that's too early morning total testosterone levels that are abnormal and we use less than 300.  That is the guidelines.  Combined with the presence of symptoms and/or signs of low testosterone.  So, you need both of those two things to become a candidate for the rational approach to testosterone therapy.   

Now, the symptoms are very straightforward.  Low energy, afternoon fatigue, decreased strength, decreases endurance, losing muscle, putting on fat, particularly around the middle, irritability, depression, decreased productivity at work, decreased response to exercise, and low sex life.   

They are also the symptoms of chronic stress, chronic fatigue, and depression.  So, they are not specific to low testosterone.  There are two very specific signs that are worthy of consideration.  One is an elevated hemoglobin A1c, men who have new onset prediabetes may be put into that situation because the testosterone level is low, and then bone density lost.   

I'm sure you're from the term osteoporosis in menopausal women, that can occur in men also and one of the more common causes of that is low testosterone.  So, when a man comes in to us, he meets the definition of testosterone deficiency, then it's those discussion about the pros and cons of risks and benefits of testosterone therapy.   

It's very important to understand that in a well-structured established program like we have at Memorial, we don't give demand to help them build muscle and to help them feel 18 years of age again and to look good at the gym.   

We give testosterone therapy to men because very low levels of testosterones, certainly levels below 200 are associated with three major medical problems, prediabetes and diabetes, osteopenia or osteoporosis, and premature cardiovascular death, heart attacks and strokes.  That is irrefutably established in the medical literature.   

So, much of what we do is to prevent those things happening.  The conversation in the active surveillance and the prostatectomy patient and radiation patient, it is complicated.  We have clinical care pathways, the algorithms for treating these men, and I think perhaps James beyond the scope of this discussion unless you wanted me to get into it to have a kind of a granular discussion about that.   

James Eastham:  Right.  So, yes, it's not -- as Dr. Mulhall appropriately mentioned, it's not someone who's trying to build muscle up, who doesn't have the low testosterone and/or -- or and symptoms related to low testosterone, it's a very specific clinical situation in which testosterone would be replaced and has to be closely monitored in every man including a man with prostate cancer.   

I wanted to bring Claudia back in to the conversation because many men will ask, well, what are the symptoms I'm going to experience with prostate cancer, should I be looking for something?  Men on active surveillance frequently say, well, what are the signs and symptoms that will be worrisome to me?  So, Claudia, can you address what -- what will a man who have prostate cancer, will they experience any symptoms and what might they be?   

Claudia Derico:  Sure.  So, initially, there really are essentially no physical symptoms of early prostate cancer in the very early stages.  That’s why as you said in the beginning of discussion, it's really so crucial that routine PSA monitoring is performed and physical exams are done so that there is early detection of disease.   

Later as the disease does progress, some patients do experience impacts to their urinary function and also some issues when it comes to bone density.  But again, really early in the early stages of prostate cancer, we do not see or have patients look at for specific physical symptoms simply because they just won't exhibit them.   

James Eastham:  All right.  Thank you, Claudia, for that.   

I wanted to -- and I'll take the stage for a couple of minutes.  A couple of things came up during some of the responses.  One from Dr. Rathkopf mentioned about positive margins and the pathology that we are able to achieve with a prostate removal.  A positive margin is a risk factor for recurrence.  So, let me take a step back and tell you what a positive margin is.   

So, when a prostate is removed, the first thing the pathologist will is paint the outside of the entire prostate with ink.  The prostate is then cut just like a loaf of bread into many slices and those slices the looked at under the microscope.   

If the pathologist sees a cancer cell near the ink or at the ink, that is what a positive margin is.  So, a positive margin is a finding under the microscope that is basically a cancer cell adjacent to the ink edge.  That is not the same as there are cancer cells left in the patient that are alive.  And that’s why we do not recommend that a patient be treated simply because their margin was positive at the time of surgery.   

Now, it may mean there are some cancer cells behind but that is determined by what the PSA does.  So, a positive margin does increase the chance that a PSA becomes detectable after surgery but it's not everyone with a positive margin recurs.  In some situations, there may have been a few cells left behind but they are now disconnected from their blood supply and they die.   

So, while the margin was positive, there are no viable cells left within the patient.  Margin can also be what are called artificial, meaning that during the processing, the tissue of the prostate may have cracked a little bit and that will allow ink to run deeper into the prostate that was truly the edge.  So, a positive margin is just the finding, it does not mean that there will be definite recurrence of cancer which is where PSA comes into consideration.   

The other area and this was a -- just trying to get the other questions, but I think we have a little bit of time to address this is with active surveillance which means a patient with a low risk prostate cancer who is being monitored, one of the questions was how do you monitor?  And there is set definition of how every center monitors patient on active surveillance.   

What we typically do is we check PSA test about every six months, we obtain MRIs sequentially about every 18-24 months, and we do biopsies no more frequently unless something changes which I'll define in a moment, no more frequently than about every three years.   

So, we have cut down on the number of biopsies that we do because we have not found that doing more frequent biopsies is beneficial and certainly that is the assessment that carries the most discomfort and the most risk.   

So, if a patient's PSA is stable and their MRI doesn't change, biopsies are still performed and that's because the biopsy is the only true way to know what's going on within the prostate even if the PSA and the MRI are unchanged, you can still have changes under the microscope.  So, that's why we need to do biopsy.   

So, it is truly active surveillance.  We actively monitor the patient to be sure that the risk of the cancer has not changed.  The final set of questions which I'll address initially to Sean and then to Dana relate to the genetics of prostate cancer.   

So, Sean, from a radiation standpoint, are there genetic aspects that you used either in the initial treatment of a -- of a patient or if someone has gone through surgery and it failed and they are a candidate for local radiation to the prostate, can genetics help guide how you would recommend treatment in those two different situations?   

Sean McBride:  I think that’s a -- that’s a great question, James.  And right now, we're not at the point where genetic information about a man's prostate cancer impacts the radiation treatment either at diagnosis or if a man's recurred after surgery.  There are studies that are looking at combinations, the certain types of medication -- and Dana could probably expound on this a little more -- certain types of medications with radiation in men who have certain types of mutation namely a BRCA2, BRCA1, the BRCA gene mutations.  But those are being done on clinical trials and are not part of our standard care at this point in time.   

Now, that said, we'll still oftentimes, the men with high-risk localized prostate cancer will obtain genetic information about a man's tumor and about whether a man has an inherited predisposition towards cancer.  But that's not really modifying the treatment we're delivering at this point although it may, in the future.   

James Eastham:  OK.  And, Dana, in the -- in the metastatic setting, how are -- how is genetic evaluation used to perhaps select the man for one form of treatment versus another?  Is that ready for primetime or is it still investigational?   

Dana Rathkopf:  So, it's very much ready for primetime which is exciting.  So, as Sean alluded to, we'll often ask patient permission to look at their tumor to see if there are any alterations in the genes in that humor that we might be able to target with specific therapies or if they might, just in case they might predict for how a patient is going to respond to different therapies overtime.   

There's also -- we'll ask permission sometimes not just to look at the genes in the tumor which we suspect have some alterations, just by nature of the fact that these normal cells have turned into cancer cells but also there are sometimes familial or inheritable mutations that are in the patient own germline, their own DNA that can be passed on between family's most commonly in 2020, the ones that we talk about as Sean has mentioned are the DNA damage repair genes, BRCA1 and BRCA2 although there are others as well.   

And so, for cases that have DDR mutations, whether it's in the tumor or in their germline, we have, just recently, gotten permission from the FDA to use a class of drugs called PARP inhibitors which have been used in other cancers with this type of mutation for many years.   

And finally, we've been able to show that they're also useful in prostate cancer and that’s very exciting, this class of drugs called PARP inhibitors and there are a number of different ones that appear to work.   

We'll also use genetics and genomic profiling to think about other types of intervention.  So, I think one of the most commonly asked questions for me and the clinic is about immunotherapy and it turns out that prostate cancer, in general, tends to be what we call a cold tumor.  It doesn’t have a lot of immunogenicity.   

So, it doesn’t really attract your own immune system to attack it.  But we have found that for patients that have something called microsatellite instability high, that they are able to attract the immune system better than prostate cancer patients who don't have that.  And so, in that setting, we will sometimes use immunotherapy in prostate cancer patients, but still that's a probably less than 5 percent of prostate cancer patients at the moment who have that type of presentation.   

There a large number of clinical trials that we're looking at, asking questions about other alterations that we find in the genome.  For example, PTEN is one that you might hear about.  It can be a poor prognosticator, meaning that men who have lost the PTEN gene may have worse outcomes.   

And so, we've been looking at drugs that target that pathway.  And recently, there was a large Phase 3 clinical trial called it IPATential 150 that showed that a drug called ipatasertib that targets AKT had some increased activity in patients with PTEN loss and that’s, of course, exciting but not quite ready to be used in the clinic.   

James Eastham:  So, yes, thank you.  So, genetics are certainly already being used in prostate cancer.  It's not every single man that has what we call an actionable finding meaning they have a genetic change that we can actually target with a specific drug.  But certainly, in the laboratory and within our -- our center in our research effort progress is being made quite rapidly in this arena.   

Looking at the time, unfortunately, we're coming to an end of this session.  First of all, I would like to thank everyone on the call for sticking with us.  I'm sure we didn’t address every single topic that was on everyone's mind.  For that, I apologize.  But there are limitations to what we can do on a phone conference, but I do hope this was beneficial to you in one way or another.   

I also want to thank, of course, the panel members.  I think, at least from my standpoint, I learned a little bit listening to the folks talk about the various aspects of care and so, I want to thank all of the panel members for participating, and hopefully, providing the information that was beneficial to the folks on the call.   

We certainly plan to have more calls like this, not necessarily for prostate cancer, but if you periodically check the website mskcc.org, you will have the latest updates available to you when informational discussions like this are planned.   

The final two things, certainly don't ignore your healthcare.  I know that COVID is very scary.  Certainly, I'm nervous about it and I know there are precautions, we all can and should take in terms of social distancing, masks, washing hands, et cetera.  But certainly, we do have to be aware of our other healthcare needs including cancer screening such as prostate cancer.   

So, I would like to, again, thank everyone for participating on the call.  Do be safe and take care of yourself and your loved ones and I hope this was -- provided the information that you were looking for.  And thank you very much.  I don't know if anyone wants to add anything to that, but if you do, I will be quiet.   

Operator:  This concludes today's call.  Thank you for joining Memorial Sloan Kettering's Information Session for Patients and Caregivers.  Have a good evening.