D. Mitteldorf              Hello.  Welcome, everyone.  I see over 140 of you already on the call, and I imagine a few more are going to be popping on, because I can see the numbers growing every second.  My name is Darryl Mitteldorf, and welcome to the first of a six-part series, Conversations About Treating Advanced Stage Prostate Cancer.


This series is being brought to you by Malecare.  Briefly, Malecare was founded in 1998; it’s our country’s largest all volunteer men’s cancer support and advocacy non-profit, and in fact we’re actually on three continents now, we have groups in Australia, Europe, and here in the States.  A couple of things you probably know, if not, we’re unique in our focus on gay men and prostate cancer and on our program for prostate cancer diagnosed under the age of 50.  Our online support groups and quite large and dynamic, and everyone here is invited to join them.  You could start off by visiting malecare.org and follow various links to our various Websites.


Tonight the program is brought to you by our Advanced Stage Prostate Cancer Program, which has been in effect for about three years now.  We’re going to have a conversation with Dr. James McKiernan and Mr. Joel Nowak.


Dr. McKiernan is Vice Chairman of the Department of Urological Oncology at New York Presbyterian Hospital, Columbia University Medical Center.  We’re pleased to have him here, because he treats many patients with high-risk cancer diagnoses, in particular around prostate cancer.  Dr. McKiernan is actively involved with ongoing research programs focused on improving patient outcomes.  He’s authored and co-authored more than 80 articles, book chapter, and abstracts in the field of urologic oncology.  His research and discoveries have been published in journals such as Urology, Journal of Urology, Journal of Clinical Oncology, Cancer, and Cancer Research.  In short, he knows what he’s talking about.


If any of you want to connect with him after this, and I would imagine sometime during the week for a private consult or just to follow-up, his phone number is 212-305-5526, and that will be repeated at the end of the broadcast.


The other conversant is Mr. Joel Nowak, who is Director of Advanced Disease and Advocacy at Malecare, and he himself is a four-cancer survivor; he’s diagnosed with melanoma, thyroid, kidney, and advanced stage prostate cancer.


This teleconference is being recorded, so if you miss your notes or want to hear it again you can hear it on our Website; it will probably be up in a week or two.  It will last approximately 60 minutes.  A large number of you sent in e-mailed questions.  There’s a slight chance we might have time for live questions from our live audience, which means you, the listener, but with all the questions that we have and the conversations that Joel and Dr. McKiernan are probably going to have I think we’re in for a stimulating hour.


So I turn it over to both of you gentlemen.


J. Nowak                     Thank you.  This is Joel Nowak, and first I’d like to welcome everybody to the teleconference, and especially I’d like to welcome and thank Dr. McKiernan for his participation.  In the interest of full disclosure, I want to also let everyone know that I am a very fortunate individual, because Dr. McKiernan is one of my own personal physicians.  He is the surgeon who, when I was diagnosed with renal cancer, that removed my kidney, and he continues to follow-up and head my care in the area of renal cancer.  I also have the added benefit of his expertise when it comes to figuring out and planning my next moves and what I should and shouldn’t do with the treatment of my advanced prostate cancer.  I am very appreciative of him, and I am thrilled that he’s able to join us.


Good evening, Dr. McKiernan.  How are you this evening?


Dr. McKiernan            Good evening.  I’m great, Joel.  Thank you.  Thanks for having me.  It’s my pleasure to have this opportunity to participate in the call and hopefully share some of my thoughts on what’s happening right now in advanced prostate cancer and to field any questions anybody may have.


J. Nowak                     Terrific.  First, I’m actually going to start off with some very basic issues, and that’s the PSA.  PSA is the most used, or one of the most used, biomarkers for diagnosing prostate cancer, but PSA also has a role in understanding advanced prostate cancer and understanding the significance in when a reoccurrence happens.  I would really appreciate, just to get started, if you could talk a little bit about how you use PSA for someone who has had primary treatment and what decisions are made using those numbers.


Dr. McKiernan            Sure.  So PSA I think no one today in the United States can wake up any given morning and not either hear something about PSA on the radio or read an article about PSA in the newspaper; it always seems to be in the focus of controversy and debate.  Most of the controversy surrounds use of PSA as a screening tool, which means testing patients who are asymptomatic in the general population to try to find someone who has prostate cancer, and that’s a very hotly debated topic.


But your question really was about post-diagnosis use of PSA where it actually functions a little bit more accurately, a little bit better.  In particular, the classic example would be post-surgically.  So if a patient has a radical prostatectomy, removal of the entire prostate gland, PSA becomes a fantastic biomarker to determine whether or not the patient is indeed in complete remission or has relapsed.  And it’s very simple, it’s very binary; it’s either undetectable or less than 0.1 or it’s detectable at some level, and if it’s detectable it means the cancer is back.


After primary radiation therapy it’s a little bit more difficult to interpret.  It’s still a very good test there, but in general patients will drop their PSA to a low level, less than 1, and hopefully stay in that range forever, but three consecutive rising PSAs are usually what we use to determine the potential for a biochemical or PSA based relapse.


J. Nowak                     Terrific.  Now I know, as you mentioned, that it’s harder to use the PSA number post-radiation.  I know that it takes a while, that PSA will bounce around.  How long does one have to normally wait before one starts panicking and saying, “Oh my gosh, I have a reoccurrence.”


Dr. McKiernan            Yes.  After radiation is probably the most anxiety provoking, because, first of all, in the first year following radiation you usually actually don’t see the PSA stop falling until about nine months, twelve months, sometimes even as long as eighteen months after external beam radiation, and that’s what we call the PSA nadir, or the low point of the PSA, but then after that it can bounce around.  There’s even a medical term for PSA bouncing around, it’s called a PSA bounce phenomenon, and that’s seen most commonly after brachytherapy or seed implantation, and usually it’s seen in younger men under the age of 60 who have a PSA that suddenly jumps up at about twelve months to eighteen months following the seed implantation and actually does not indicate a problem.  It’s hard to interpret that sometimes, it does prompt patients to go for biopsies of their prostate, but usually that kind of PSA will decline suddenly again and get back down to a low level.


So we really look for three consecutive rising PSAs over the baseline nadir, or the low point.  If you achieve that, if that happens, you really should be evaluated with either a prostate biopsy or some type of imaging or both.


J. Nowak                     Right.  I have to say that the last year and a half or so has been really exciting when it comes to the area of new drug development, and specifically FDA approval.  I actually think that the last year and a half has been fairly unprecedented.  We just had three different drug approvals, Jevtana, Degarelix, and Provenge.  Could you tell us a little bit about these drugs?


Dr. McKiernan            Sure.  Yes, you’re absolutely right.  If you take a few steps back, if you’re new to the prostate cancer world, there have been decades in which we haven’t seen a new FDA approval, literally decades, and so to see three new drugs approved, all for advanced prostate cancer, all within the same really almost six-month period, is totally unprecedented.  I hope it’s a sign of things to come and a combination of more progressive research and development, both in the pharma world, as well as in the private sector, and I hope it’s also potentially a sign of the FDA paying more attention to prostate cancer and trying to expedite some of the drugs that, of course, work and are effective.  We don’t want things approved that don’t work.


But those three drugs, Degarelix is actually new form or hormonal deprivation therapy, and it functions as what’s called a LHRH antagonist.  It’s in the same class of drugs as LHRH Agonists that manipulate the hypothalamus and pituitary glands in the brain, and these are the drugs that are more commonly recognized as Leuprolide or Lupron and Zolodex or Goserelin Acetate, Eligard is another brand name.  So a lot of patients may have heard of these drugs or have been on these drugs at one time or another.


Degarelix is designed, actually, to work as an inhibitor of this access.  So it’s a slightly complicated difference, but most of the commonly approved drugs in that category are actually stimulators of a receptor and work by over stimulating a receptor that then causes production of testosterone to decline.  So it’s actually coming from a reverse mechanism and is not associated with the commonly described PSA or testosterone flare phenomenon.  When you first start a patient on Lupron or Zoladex there’s actually a sudden rise in testosterone, which can sometimes result in a rise in PSA—transiently, but some people think that that could be significant.  So Degarelix does not do that.  It’s an antagonist, and therefore it could potentially lead to faster drops in testosterone for people starting hormone therapy.


The other two drugs that you mentioned, one Provenge, I think most people on the call have probably heard of in some way or another.  It was in the news quite a bit a few years back when the FDA decided not to approve its use after a smaller clinical trial was positive.  But the company now, Dendreon, went back and did a much larger clinical trial that actually was powered appropriately and did prove to be positive for a survival advantage.


It’s a drug that works as a vaccine of sorts against prostate cancer.  It uses a patient’s own immune system, or white blood cells, and the cells are taken out of a patient, stimulated in a laboratory environment with an antigen or protein from prostate cancer, and then retransfused back into the patient to fight their cancer.  And actually it marks the first ever prostate cancer, or, in fact, first ever cancer immunotherapy, which has ever been approved by the FDA, which is a milestone amongst milestones.  It’s really a major event that happened in the very end of April.  That was tested in patients who had hormone refractory metastatic prostate cancer and proved to be more beneficial than the standard of care in those patients.


Then the final one was the most recent one to be approved, I want to say that was in mid-June, that was a drug called Jevtana, which the generic name which is cabazitaxel, which is in the family of docetaxel and paclitaxel, those are both chemotherapies that have been previously used in prostate cancer.  This is a new generation taxane that was tested in patients who had been treated with chemotherapy in the past and the chemotherapy didn’t work anymore, and it actually showed a significant benefit in that population of patients.  So that was approved just recently.


J. Nowak                     Terrific.  So it gives us an approved alternative once chemotherapy has stopped working.


There have been some questions raised on the advanced prostate cancer list serve about the possibility of Degarelix being used as a second line hormone therapy.  Have you any thoughts about that possibility, those using Lupron first and then when it fails to move on to Degarelix?


Dr. McKiernan            I’m sure it will be done.  Physiologically it does make some sense, although it was not studied or approved for that use.  In other words, there’s never been a study to show, at least to my knowledge, that it has a greater efficacy in that setting than any of the other drugs, but since it works by a different mechanism of action and potentially lowers testosterone without that surge phenomenon it could make sense.  I would liken that to switching a patient from an oral antiandrogen like Flutamide to an oral antiandrogen like Casodex; they both attempt to do the same thing, which is block the androgen receptor, but they do it in a slightly different manner.  So I’m sure it will be done.


J. Nowak                     Right.  Do you think that if when used Degarelix, obviously as a first line treatment, is there a need to combine it with a Casodex or an antiandrogen?


Dr. McKiernan            Well, that’s a great question.  There certainly won’t be a need for that in terms of blocking the flare phenomenon, because that does not occur.  But the age old question in hormone depravation therapy, which still remains quite controversial today, is in fact does combined androgen blockade, which means the use of an LHRH agonist and an antiandrogen, is that better than, equal to, or inferior to the simple use of monotherapy with an LHRH agonist.  This is a question that’s been studied extensively over the course of the past 20 years, and the vast majority of the evidence would suggest that combined androgen blockade is slightly more effective than the use of an LHRH agonist alone, and slightly being defined as a difference of very, very small measured amount of time over a very long period of time.


So there are believers that combined androgen blockade is the standard of care, and I think they probably will use Degarelix with an antiandrogen.  Then there are other people who feel that it’s powerful enough treatment on its own, and there’s no reason to expose a patient to the side effects and/or the cost of an oral antiandrogen.


J. Nowak                     I see.  Now, of course, one of the things that we hear so much about is the fact that the drugs that have been approved recently really have not in their clinical trials demonstrated a huge survival benefit.  We’re measuring survival in a matter of months.  I think for Provenge it was either 4.2 months or 4.5 months, and Provenge comes with a whopping price tag of $93,000.  So the question comes is it worth it?  How do we deal with that, how do we weigh the value of a drug for limited survival, and are those survival figures real figures?


Dr. McKiernan            Yes.  That’s a great question.  Very hot topic amongst people in both politics and medicine these days.  I’m not a politician, so thankfully I don’t necessarily have to be the one who decides how to spend our limited healthcare dollars right now.


But as a physician I always find it interesting when we turn the spotlight onto the issue of cost and what is worth X or Y number of dollars.  I think we need to do it across the board and start looking at the entire field of medicine, because when we zoom in on one small treatment for one very serious type of cancer, let’s say Provenge for advanced prostate cancer, and say, look, four months for $93,000, that’s a very stark example, but there are examples in prostate cancer in which patients undergo radiation therapy, which is approximately a $55,000 treatment, and gain no benefit, in fact gain side effects only.


So we could probably save more money by making better decisions in primary treatment in prostate cancer, who should be on surveillance, who should not have surgery, who should not have hormone therapy, than we could in trying to sort of pinch pennies, if you will, in patients who are clearly in need of help.  Patients with metastatic androgen independent prostate cancer there is no debate need help.  Patients with localized prostate cancer that are in their late 70s, early 80s with low risk disease probably don’t need our help, and yet we spend a lot more money there and probably don’t help anyone.  So I always have to caution people when they start focusing on the cost only of things like that.


But, having said that, the four month median survival in that trial, the 2.5 median survival in the docetaxel trial, all these numbers are summarized statistics over a very large population of patients, sometimes up to 600 patients, 800 patients in some of these clinical trials, and it’s a way to summarize what happened to all these people.  But there are people in the trial who got quite a bit more benefit than that and there are some people in the studies that got no benefit and, in fact, were harmed by the drug or by the treatment.  So you have to individualize that type of decision and try to identify the patient who is most likely to get a durable or excellent response out of the treatment, and realize that four months or five months over a span of twenty months of life expectancy is a potentially substantial improvement in the patient’s quantity and, by the way, quality of life.  In most of these studies pain scores were improved, quality of life is improved.


So it’s a lightening rod subject and very difficult to even have a non-emotional conversation about, I think, for most people, but it’s going to be a huge issue going forward, there’s no question.


J. Nowak                     Yes.  Absolutely.  Maybe it wasn’t fair to ask you as a physician such a philosophical and political question.  I apologize.


Dr. McKiernan            No, no, it’s a perfectly appropriate question.  I probably won’t get elected to office with any of my answers, though.


J. Nowak                     I would vote for you anyway.


I know that some men question how long ADT can be expected to last and when they try to decide should they go on ADT even though they’re asymptomatic, they don’t have symptoms.  I know that one person had sent in a question actually saying that their doctor had said although they had a reoccurrence, their PSA was actually up over 5, and the doctor had said that he would not put him on ADT because he was asymptomatic, that he should just anticipate 18 months from ADT, but I know a lot of us don’t buy that.  So I was wondering what your experience has been.


Dr. McKiernan            Yes.  So you’re striking on, yet again, one of probably the core controversies in our field, which is in a patient who’s relapsing, after almost anything, including prior surgery, radiation, or even prior hormone manipulations, you’ve identified the relapse by an unequivocal rising PSA, you have a patient who is asymptomatic, has normal scans, normal CAT scan, let’s say normal bone scan, doesn’t even know that their cancer is back, but yet you have a blood test, very powerful, accurate blood test, that says yes it’s back.  What to do?  And now you have a tool, the main tool in the toolbox there being hormone deprivation therapy, ADT, and when do you deploy it.


So, of course, we love to look to the clinical trial world to say okay, well there must be a study that would help answer that question, and in fact there aren’t.  The closest thing we have to a study that could answer those questions are actually fairly old studies, which look at starting hormone deprivation early versus very late, and very late in those studies was defined by when a patient became symptomatic, and there’s no question that there’s clear cut evidence to support the use of early versus very late hormone therapy, but there is no definition of in between.  So none of those studies actually use PSA as a cut point or a trigger point to begin Androgen Deprivation Therapy.


So we’re left with a gray zone between let’s say a PSA that’s 3 to 5 and symptoms, and of course symptoms we know to be too late.  If a patient complains of back pain, bone pain, weight loss, those types of things, those are ominous signs, and usually their PSA will be in a 30 to 40 range by that point.  But is 6 better than 7 or 9 better than 10?  We really don’t know.  Oftentimes I will look towards something called a PSA doubling time, which is actually looking at the rate of rise of the PSA and not so much focusing on the absolute value, and I oftentimes find that to be a better predictor of who should or should not begin Androgen Deprivation Therapy.


J. Nowak                     Terrific.  Once I start ADT how long will it last?


Dr. McKiernan            Yes.  So traditionally ADT was a lifelong commitment.  In other words, a doctor would start a patient on ADT, and, prior to 1990, the most common way to do that was an irreversible form of ADT, surgical castration.  Nowadays we do have the capacity to give medical ADT or medical castration, and that can be reversed, obviously, it can be started, it can be stopped, it can be turned on and turned off.  So what’s out there right now is either continue it for life or continue it for a certain period of time until you achieve a nadir PSA, less than 1, less than 0.1 possibly, and then stop, and we call it intermittent Androgen Deprivation Therapy.  It’s commonly talked about.  Most patients are interested in it, because it does give the opportunity for a patient to be off the drug or off the side effect profile.


But we still don’t know for sure whether that intermittent Androgen Deprivation is better than, equal to, or inferior to non-stop, continuous Androgen Deprivation Therapy.  My gut feeling is it probably is at least equal to, if not possibly even a little bit better than, continuous Androgen Deprivation Therapy in terms of the probability of surviving longer and, of course, the side effects being minimized.


J. Nowak                     Right.  Of course, some of those side effects include issues of heart and vascular disease, which by themselves can kill you.


Dr. McKiernan            That’s correct.  Yes, that is correct.  The more we study and learn about men on testosterone suppressing therapies the more we realize that the side effects are pervasive, and they’re not just the hot flashes that everyone potentially experiences or the weight gain or the decreased muscle mass or the potential change in cognition and mental function, which are all debilitating enough, but there’s even more pervasive ones, like, as you mentioned, alternations in the cardiovascular system that may involve cholesterol, may involve things like C-reactive protein or some other more difficult to monitor factors that could increase a risk for heart attack, stroke, cardiovascular problems.  And that’s come out of some clinical trials in which men have been randomized to receive either placebo or hormone deprivation therapy.


So it’s a big decision to start on Androgen Deprivation Therapy, and I think throughout the 1990s and early part of 2000s we took that decision a little bit lightly.  We thought well, it’s relatively non-toxic compared to chemo, it’s just an injection, you only have to come in once every three months, why not just start it on everybody, and I think it was overused quite a bit.


J. Nowak                     Now I’m facing a time, fortunately I don’t think I am yet, but facing a time where I’m becoming hormone refractory.  What are you going to tell me to do, what’s my next best step?


Dr. McKiernan            Yes.  Well, the first thing is look at the calendar and see what year it is, and hope the calendar says 2015, because I really think that in the future we’re going to have even a lot more options than we have now.  Right now we have more options than we had six months ago.  So this is the kind of thing sometimes patients will come in and say, “Well it doesn’t look good for me, doc, right, but you could keep me going for a while?”


“Yes, definitely.”


“Are there new things on the horizon, so if I can get through this year maybe next year you’ll have something else for me?”


That’s a very powerful, hope-filled message, but oftentimes in cancer it’s just not true, because things don’t happen that fast.  But right now in prostate cancer there’s no question that’s true, and if you can keep things in a stalled situation long enough and keep your eyes on the news you will actually see newer things coming out.


So at the moment an asymptomatic hormone refractory patient who is non-metastatic it would be a clinical trial or observation with a secondary hormone manipulation.  Those would be the most common recommendations.  If they’re asymptomatic and show a metastasis Provenge would probably be the right thing to do right now; it’s FDA approved, it shows a big survival benefit in terms of relative survival advantage, and it’s relatively non-toxic.  So that’s where I’d be looking right now.


J. Nowak                     Do you see any role for drugs similar to estrogen, you know with DES, as a second line hormone manipulation, or ketoconazole?


Dr. McKiernan            No so much DES; I don’t have much experience with DES.  I know some people still do use it.


I think ketoconazole is a mainstay of secondary hormone manipulations, but I think what’s exciting there, and is what’s coming I hope very soon in the future, is a drug called Abiraterone.  Now just give a caveat to everybody on the line, this is not FDA approved, but it is a drug that’s in fairly advanced phase III clinical trials, which we’re hoping to hear some results on mid-fall, November ish maybe of this year.


It’s a testosterone-lowering agent, so technically it’s not a chemotherapy.  It is a hormonal therapy, but it functions by inhibiting an enzyme that’s critical in the synthesis pathway of testosterone directly in cells that are making testosterone wherever they are in the body, including the testicles, which are the mainstay, the adrenal gland, and even in the cancer cells.  Because there’s more and more evidence now that suggests that some of the most advanced prostate cancer cells have figured out how to make their own testosterone and perhaps feed themselves with the fuel despite us, the doctors, knocking out the production of testosterone in all the other organs.  So this drug could actually target synthesis of testosterone wherever it occurs.


As I said, it’s being tested in two large phase III trials now.  I’m not sure if I’d call that a secondary hormone manipulation, but that’s what I’m most excited about going forward in the hormone manipulation category.


J. Nowak                     Right.  And do you think that the second line androgen deprivation can extend life, or is that kind of an unknown yet?


Dr. McKiernan            It’s an unknown.  It’s an unknown.  There’s never been a clinical trial that has proven beyond a shadow of a doubt that the secondary hormone manipulations do extend life.  What we do know that they do is about 25% to 30% of the time they will cause a PSA response, which will usually be transient, will usually last six months to seven months, and then the PSA will go back up again.  But the fact that it’s never been proven to extend life doesn’t mean that it doesn’t, but it means that we haven’t done the right kind of study yet to prove that it does.  So it may or it may not, we’re not sure.  We’re pretty sure that something that’s non-toxic and lowers your PSA is not bad for you, so it’s at worst neutral and potentially beneficial.  So I think it’s commonly done.


J. Nowak                     Yes.  Right.  And one of the other big controversies within the survivor community is the use of Avodart or Proscar as part of the ADT regimen.  Can you tell us a little bit about the issue, and perhaps how you feel about it and why?


Dr. McKiernan            Yes.  I know about the issue, and basically what it stems from is the fact that Avodart and Proscar are enzyme inhibitors.  They’re obviously both not approved for cancer treatment, they’re approved for benign prostate hyperplasia, and what they do is they inhibit the conversion of testosterone to its metabolite, which is called dihydrotestosterone, which in a lot of cells is actually the more active form of the chemical or of the hormone, and it’s actually the form of the hormone that’s responsible for both male prostate enlargement, as well as for male pattern baldness or hair loss.  So these drugs are actually marketed to prevent hair loss as well, which is a nice side effect for some patients.


But the idea that blocking that metabolite could be helpful in prostate cancer is a little bit nebulous.  In other words, it’s not completely borne out or proven.  But I would put it in the category of things that are extremely unlikely to be harmful, because the side effect profile for 5-alpha-reductase inhibitors, like Avodart and Proscar, are extremely mild compared to most anti-cancer treatments and might be helpful.  We know, of course–not everyone on the call may know–but both of those drugs have been studied in very large clinical trials to determine if they can prevent the formation of prostate cancer in otherwise asymptomatic healthy men, and they both can, and very powerfully so.  So they are active in prostate cancer.


J. Nowak                     Right.  Bisphosphonates are often part of the mainstay of our treatment, and I was wondering if you could share with us how they work, why they work, why do we use them?


Dr. McKiernan            Sure.  Yes.  So, bisphosphonates are a category of drug that actually were originally derived from a chemical soap, almost like a detergent, like phosphate you might think of when you hear about old laundry detergents, and someone somewhere realized that that chemical can actually inhibit a type of cell called an osteoclast.  An osteoclast is a cell that normally exists in everyone and lives in your bones, and is responsible for essentially chewing up your bones and helping get them ready for remodeling or laying down of new bone, which occurs every day in everybody.


The problem is that in prostate cancer patients, or any cancer patient for that matter, if cancer spreads to your bones the osteoclast activity is stimulated by the presence of cancer, and so you get into a vicious cycle of increased bone turnover and destruction with abnormal reprocessing of the bone.  So the bone gets broken down and rebuilt very rapidly, but in a very disorganized fashion, and that’s what leads to inflammation and swelling in the bones, pain in the bones, as well as the potential for a fracture, like a hip fractural or vertebral column facture.


So bisphosphonates are potent inhibitors of osteoclasts, and oral bisphosphonates are used uniformly all over the world for osteoporosis prevention, and drugs like alendronate, or Fosamax, are used everyday by post-menopausal women.  But in prostate cancer patients the most powerful from of bisphosphonates has been an intravenous bisphosphonate, which is known as zoledronic acid, or Zometa, which is the brand name, and that was approved by the FDA in 2002 for the use in prostate cancer patients to prevent what are called skeletal related events, which means basically bad things happening to your bones, and they work.


J. Nowak                     When in the treatment process should one actually consider starting to take them?


Dr. McKiernan            Well right now the FDA has approved them for use in patients who have androgen independent prostate cancer, also known as hormone refractory prostate cancer, which has metastasized to the bones.  But, interestingly, they are being used a fair amount earlier than that in the setting of patients who have osteoporotic bone loss from Androgen Deprivation Therapy.  Now that is not currently an FDA approved use of the drug, but in many areas of the country that I’ve traveled to patients are actually being treated, and there is a fair amount of clinical evidence to suggest that it’s beneficial, to prevent osteoporosis, which is a completely different objective than preventing a fracture from metastases.  So in the asymptomatic non-metastatic patient you will frequently see Zometa or zoledronic acid used to prevent osteoporosis.


J. Nowak                     Right.  Now it’s common for breast cancer survivors to be told that they should have genetic counseling, but I don’t think I have ever met a man with advanced prostate cancer who’s been given the same advice.  Should they be getting genetic screening, and if so what would be the value of it?


Dr. McKiernan            Yes.  Well, in general, prostate cancer patients don’t get a lot of things that breast cancer patients get, which I think is a problem.  I think breast cancer, both the doctors and the patients, have done a better job at unwinding or figuring out what causes it.  So, of course, in breast cancer there’s a gene called BRCA1, which is Breast Cancer Gene 1, that’s actually been very well identified, sequenced, and can be tested for, and it will determine a woman’s risk for breast cancer.  So that’s one of the main reasons that genetic counseling is offered to most women.


Unfortunately in prostate cancer we don’t have quite that magic bullet in terms of genetic screening; that’s one problem.  The other problem is that one in six men get prostate cancer, so almost everyone is at what we would consider high risk for getting prostate cancer.  So it’s a little bit difficult to come up with a good test that figures out who’s at higher risk, because the background sort of level of prostate cancer in the country is so high.


I usually basically tell patients that if you have a primary family member with prostate cancer you’re at increased risk, and you should be screened more carefully, checked more frequently, just clinically checked with PSA and digital rectal exam, and I don’t go much beyond that.  But if you do come across a family where multiple primary relatives, brothers or father, son, have prostate cancer then there are familial screening programs at some centers, I know John Hopkins runs one in Baltimore, where they will do a pretty detailed genetic analysis for their own research purposes, but also to counsel you and keep a closer eye on you.  But the familial form of prostate cancer, where it’s really inherited, is actually fairly rare.


J. Nowak                     I see.  Now you must get tons of questions from your patients, including me, and I imagine that many of these questions are repeats you must hear over and over and over.  Now I’m going to take the opportunity and reverse that on you.  What do you wish they would ask you and what do you wish they knew when they first came to see you?


Dr. McKiernan            Yes.  That’s a great question.  Because I’m a urologist and I take care of a lot of patients with primary prostate cancer and operate on patients most of the new consultations of patients I meet are actually people who are newly diagnosed.  So one thing I wish is that we had about six hours every time we met.  I always find myself, particularly with patients that are well read and well educated, I feel like time is always short, because it’s an extremely complicated topic.


I try to get people to realize that they should be educating themselves about this process before jumping into a decision.  I try to tell people that you should be asking all your doctors a series of questions, taking notes, sitting back down at home, going over them, and then almost going back around again and wrapping it up with another visit to a radiation oncologist, to a surgeon.  Because I think it’s an extremely difficult decision for patients to make about primary treatment in a first interview, one-on-one, “Okay, I’m going to have my prostate removed,” or “I’m going to go ahead and have radiation.”  You can’t undo these treatments; I mean these are permanent things.


There’s a doctor at our hospital named Mehmet Oz who says you spend more time when you go out to purchase a refrigerator than sometimes when you make a big medical decision, because you just say, “Well the doctor said have radiation, so we’re going to start on Monday.”  But the reality is this is a far more gray area field, and a patient, unfortunately, has to get very involved in making this kind of decision before they go ahead and do something.


J. Nowak                     Right.  Being a surgeon you must have the opportunity to have that terrible experience of opening somebody up and seeing that there’s not a lot you can do.  I imagine that happens.  What does that feel like for you when that happens?


Dr. McKiernan            Well it’s very frustrating, it’s very disappointing.  Thankfully with modern medicine we usually get a lot of warning signs before that happens.  In the old days that would happen when things looked good going in, and you’d have to come out of the operating room with that kind of dire news that you found something very unexpected and very bad.  So what I try to do is prepare for those worst-case scenarios whenever I see signs that they might happen.  So if someone, for instance, in prostate cancer has a very high Gleason Score and let’s say a PSA of 15 or 20 or 25 and they want to consider surgery, well we know that all those signs indicate that it may have spread to the lymph nodes or it may be outside the prostate gland.  So I like to spend a lot of time ahead of time going over that with the patient and saying.  “Look, we could very well run into some seriously bad news when we get in there, and this is what I would do if that happened, this is what I would do in option scenario B or C.”


So we don’t like surprises or bad news in the operating room, and when we find it, it is, it’s personally very frustrating and disappointing.  I don’t like not being able to help somebody.  I went into this field so that I could help other people, and when I feel like cancer’s beaten me it gets me angry, honestly.  I don’t like it.


J. Nowak                     I can imagine.  Now, of course you’re seeing a lot of older patients, so I’m curious if when you see a particularly older man, and they pose their own set of problems, how do you deal with their particular areas of concern or issues they face because of their age?


Dr. McKiernan            Yes.  I recently reviewed the last 50 years or 60 years of U.S. Census data and just looked back at the average age of the American population, the American man, and just to try to get a handle on what’s happening around the country.  It seemed like I was seeing more and more people making tough cancer decisions in their mid 80s or early 80s, and when I was in medical school just 15 years, 20 years ago that didn’t seem to be happening that often.  It turns out that, of course, people are living longer, and that started happening the early part of the last century and it hasn’t stopped.


Right now in American there’s estimated, this Census last year, 2010 is not over yet, but there’s going to be probably about 100,000 people in America that are over 100.  Think about that, 100,000 people over the age of 100 currently.  So when you start talking about as a physician not necessarily being sensitive to or recognizing what do you do with a prostate cancer patient who’s 101 years old.  Well in the old days you used to say wow, just forget about it, because he’s going to die of something else soon, he’s 101.  But what if he lives to 110 or 105, never mind the 82-year old or 83-year old.


So I think that’s when you have to get really good at figuring out all the other health related issues in a patient; are they very, very fit, healthy, active, running, playing tennis, jogging at 81, and their parents both lived until 90, and they have an excellent cardiologist and internist, they take all their medicines.  Okay, well this kind of patient here we have to take a prostate cancer issue very seriously, because this could end up really hurting him in his lifetime, and then see what kind of treatment he can tolerate.


J. Nowak                     So it takes a lot of skill and some guess work, I imagine.


Dr. McKiernan            It does.  It does.  It’s a little bit–  I usually tell patients in those situations if I had a crystal ball and it told me you were going to live another six months I would know exactly what to do for your prostate cancer, nothing, because there are very few scenarios in which it will become life threatening in six months.  But if I had another crystal ball that told me you’re going to live to 105 and you’re currently 75, well then we ought to put together a very aggressive treatment strategy, because unless we do everything right this prostate cancer could potentially become very serious in your lifetime.


J. Nowak                     Right.  I am guessing that you probably have some patients who come to you and somewhere along they identify themselves as being gay.  I was wondering if, in your experience, that those patients who have identified themselves being gay do they have different issues that you have to deal with from the medical standpoint, and how do you cope with that?


Dr. McKiernan            Yes.  Well, practicing in New York City it’s a common scenario.  I think the first thing is recognition, making sure that if they’re in a stable relationship their partner is involved in the decision making, making sure that they feel comfortable with that, and then going over the side effect profile that has to do with prostate cancer when it comes to both urinary and sexual and erectile function and incorporating it into any other medical conditions they may have.  There’s obviously, was and still is, a fair amount of controversy about the incidence of prostate cancer in HIV positive patients and whether or not that’s different or whether it’s increased, whether the morbidity of prostate cancer is higher or lower in that population.  We have an excellent infectious disease department in our hospital that talks a lot about that.


So we have to put all the issues out on the table.  They are sometimes very different issues.  Make sure that the patient’s aware of them and is comfortable in the environment asking questions about it, and if they’re not then trying to get them into a situation with someone where they are.


J. Nowak                     I see.  What about for your patients who may be people of color or Asian versus Caucasian, are there needs different or the concerns that they bring to the table different?


Dr. McKiernan            Yes, I think so.  I think culturally, racially, ethnically when people are diverse, again being able to be in New York City it’s a rare day when I don’t sit down with new patients of various backgrounds, religious, cultural, ethnic backgrounds.  I have to be very sensitive to any kind of gap in culture or understanding of what’s happening and not run through that.  In other words, if a patient is uncomfortable asking questions or is being explained a situation in a language that they physically don’t speak, first of all, or in kind of a medicalese, if you will, where we’re using extremely technical terms, because the previous patient was someone with a PhD in physics and they wanted to know about all the statistics and the next patient maybe not that well educated, we have to be able to shift gears back and forth and, more importantly, just recognize when there’s that gap.  Because the biggest problem is when you have someone across from you who you think is on the same wavelength with you, whether that’s an age wavelength or a racial wavelength or an ethnic wavelength, and it turns out they’re not.  But you’re their only counselor and now they’re going to make a decision, but they didn’t quite get what you were talking about.


So whether that physically involves a translator, which is common in our hospital having multi-language translators available, or just having let them go home for a minute, meet with their family, and come back with a new set of concerns and find out wow, I didn’t realize that the patient was a Jehovah’s Witness, for instance.  Big issue, but it didn’t come up, because we were talking all about prostate cancer.  So, yes, that’s what makes it interesting.  That’s why they call it practicing medicine.


J. Nowak                     Well, I’m glad you’re sensitive to it.


And now I want to actually move into that big elephant that’s sitting in the room and I’ve avoided.  You talk briefly about hormone therapy failure, but now we’ve moved beyond hormone therapy, we’ve moved beyond second line therapies and we’re going into chemotherapy, and we all know at some point that’s going to fail also.  What’s a man to do?


Dr. McKiernan            Yes.  Well, pre-chemotherapy, in other words after hormone therapy fails, the timing of chemotherapy, I think, is just as important as the timing of hormone therapy.  If you’re going to do chemotherapy you don’t want to start it at such a late phase that you can’t physically tolerate it.  That’s important.  A lot of patients in the clinical trials that don’t do well it’s because they actually started the treatment when their cancer was so advanced they were so weakened that they physically couldn’t receive much treatment.  So there is a window of opportunity, not too early, but not too late, and usually it’s when the patient is very, very minimally symptomatic or maybe even not symptomatic at all that they’re going to get the best response out of it.


J. Nowak                     Right.


Dr. McKiernan            If chemotherapy stops working, let’s say it’s the currently FDA approved first line chemotherapy, which is Taxotere, docetaxel, their options really are to switch over to a different drug, like mitoxantrone, which actually is rarely beneficial, but occasionally some patients will respond to that, or go into this second line chemotherapy that we mentioned earlier, which is cabazitaxel, or enter into a clinical trial, and if they’re in a setting where there’s an academic institution or a research center nearby that’s probably one of the best options.


J. Nowak                     Right.  And if one asks one’s doctor if they can recommend what trials are around, and sometimes doctors aren’t always as aware as we’d like to know, what options do they have?


Dr. McKiernan            Well, probably the best one is the National Institute of Health, which runs an excellent Website that’s called clinicaltrials.gov, I believe, www.clinicaltrials.gov, and that takes you into the National Institute of Health, National Cancer Institute Website.  There’s a fairly interactive page there where they’ll ask you to put in a little bit of information about yourself, where are you located, what type of cancer do you have, and then it will do a search of all the currently registered clinical trials for prostate cancer, let’s say, around the country, and then give you the primary contact information for the research coordinators at each hospital.  You can just call up and say, “Well, this is my situation.  Do you think I might benefit from some of the research you’re doing,” and they’ll tell you, even on the phone usually, if you’d be eligible or not.


J. Nowak                     Right.  Well thank you.  We actually received a number of questions from people prior to the call, and I just wanted to get to a few of them if I could since you’ve been so kind to answer all of mine.


Dr. McKiernan            Sure.


J. Nowak                     I have a question from Rich from New York, and he asks, “Do you think there may be times when hormone therapy is not needed in the treatment of advanced prostate cancer and might a strict, low calorie, all vegetable diet, coupled with vigorous exercise program, work by itself?”


Dr. McKiernan            It might.  It very well might.  Patients with advanced prostate cancer who have either a stable or undetectable PSA, high risk localized prostate cancer, there’s been a fair amount of research, and still is a lot of research, on what we call complementary and alternative medical approaches.  He’s mentioned a few of them there, exercise, dietary modification, taking supplements.  One of my partners, his name is Dr. Aaron Katz, does a lot of work in that field at Columbia.  I would say that a lot of it shows promise.


One specific trial that was run through UCLA looked at a simple juice, called pomegranate juice, which I’m sure everyone’s heard of, and that seemed to actually stabilize a fair number of men’s PSAs that were rising after failed surgery or radiation.  So there’s definitely something to it there, but I would stop short of saying that any of that approach has been proven to be more effective than hormone deprivation therapy, which is still the mainstay of treatment.  But pre the use of Androgen Deprivation Therapy I think it’s excellent to get a patient engaged in their own healthcare, and it’s probably helpful for their heart and their overall life expectancy to have them eating better, exercising.  There’s no way that that could be harmful, so I’m all for it.


J. Nowak                     Right, but he’s asking as an alternative.


Dr. McKiernan            Well, I would say a pre-alternative, meaning prior to starting hormone therapy.  But if that doesn’t work and your PSA continues rising, I would start to caution against sort of solely utilizing that approach.  I like to explain to patients the reason why the term complementary medicine has become more popular amongst sort of traditional physicians is that it implies that you’re going to do some things that are not “directly out of the FDA approved handbook”, if you will, but you’re going to do it in order to complement the more traditional things, as opposed to replace.  The other term is integrative medicine, which implies the same thing.  In other words, I’m going to take a major dietary change and a series of supplements that I think are the best ones, but I’m also going to get my PSA checked every three months, go for a rectal exam, get a scan when the doctor tells me to.  As opposed to I’m going to abandon traditional medicine and switch to this other form of medicine, which I have a lot of faith in.  That gets me a little scared.


J. Nowak                     And Rick has asked, “Can prostate cancer continue to metastasize even when you have an undetectable PSA and you’re on hormone deprivation?”


Dr. McKiernan            As far as we know the answer to that is no; it’s actually very rare to see prostate cancer move around, grow, or metastasize with an undetectable PSA.  Now, what can happen is the PSA can be very low and rising, and something can be happening.  So oftentimes, not often, but infrequently, we will see patients who have been on hormone deprivation therapy for a very long time and then will have a slowly rising PSA, from .5 to 1 to 1.5, and we’ll do a scan and we’ll find several nodules, which seem out of proportion to the PSA level, and this is something you don’t see in prostate cancer patients who are not treated with hormone deprivation therapy.  It’s very specific, because we think that the PSA machinery, or genetics, if you will, of the cells is turned off and the cells that are growing actually are not making much PSA, and that can happen.


J. Nowak                     Right.  Matt from New York has progressed, he’s now on chemotherapy, he’s having a particularly hard time with it, but he is still staying with it.  He is looking around for possible clinical trials, which I think is one of your recommendations for when chemotherapy stops working.  He actually wanted to know if you had any particular trials in mind, you may not, that you think are promising and that somebody in his case should perhaps look towards?


Dr. McKiernan            Yes.  Well, I’ll tell you right now what’s probably the most promising there is the cabazitaxel, or Jevtana, which is no longer in clinical trials, it’s actually FDA approved.  My associate at our cancer center, Daniel Petrylak, and that’s P-E-T-R-Y-L-A-K, is the director of our chemotherapy clinical trials, so if there was a different trial that was available he would have it, and I’d be happy to leave his number if anybody wants it.


Getting Jevtana right now is a little bit of a challenge, I would imagine, because it was only FDA approved I want to say two weeks to three weeks ago, maybe five weeks ago, so it might just be kind of hitting the shelf, if you will.  But if anybody has it, he would.


J. Nowak                     Right.  I actually did see a news release from the pharmaceutical company saying that they were now going to, I think as of August the 15th, be able to start stocking or getting it out to the doctors’ offices.  So hopefully that will really happen.


And I have a young man whose wife has asked a question, and I don’t think you can have a specific answer, but she’s really expressing a lot of frustration.  She has a husband who is 54-years old and has young children.  He’s has a prostatectomy and he’s on hormone therapy and has had an IMRT, and his life is just, as she refers to it, “falling apart” and he feels like they’re banging their heads against a brick wall.  Do you have any great insight for them?  It’s tough enough for older people, but young people it really hurts.


Dr. McKiernan            Yes.  Sure.  No, I understand that.  I would say it depends a little bit on what’s causing them the frustration and the anguish right now.  If it’s the side effect profile, which sort of sounds from the question that he’s been pretty beaten up by the treatments themselves and just feels like he has a lot of side effects from that, I would really seriously talk to the doctors and find out if he still needs to continue on the hormone deprivation therapy, is he in remission, what is his PSA.  I’ve met some patients who have had surgery, radiation, and hormone therapy all in a short order of time, and things are actually going fairly well but someone is telling them they should stay on the hormone therapy forever, which was the kind of standard recommendation throughout the 1990s and early 2000s for patients with high risk localized prostate cancer.


But if he has no known metastases and his PSA has gone down to 0 and stayed there for a while then I would seriously consider giving him a break if he’s that debilitated by it, particularly if he’s a young man, because his testosterone level will probably bounce back pretty quickly and he’ll feel a lot better.


J. Nowak                     Right.  Well, unfortunately, we’re coming up to the hour.  I truly want to thank you so much for taking the time to share your knowledge with us this evening.  I appreciate your willingness to field my questions.  Some of them I think were a tad unusual for a call like this, so I appreciate your candor.


Again, I would like to repeat that if anyone would be interested in seeing Dr. McKiernan, and again, take it from me, from my own personal experience, he’s an extraordinary physician, you can call his office to set up an appointment, and his phone number is 212-305-5526.  I’ll repeat that one more time, 212-305-5526.


Before we sign off, Dr. McKiernan, is there anything you’d like to add, anything that I missed you think is important?


Dr. McKiernan            Well, no.  I want to thank you, Joel, for having me, and for everybody for staying on the call and listening; it’s my pleasure.  I hope, without having met anybody out there on the call, I hope I’ve helped some people and I hope I’ve been able to shed some light on some of these things.  I want to thank you again for the questions, because I think you hit on the top 10 list of controversial and hot topics in prostate cancer today.


I would just say keep engaged with the system, keep your ears open, and keep following what’s happening in the world.  Ask a lot of questions of your doctor.  If you don’t like that answers get another doctor.  That’s my advice.


J. Nowak                     Can I ask you to repeat that?  I think that’s such an important statement.


Dr. McKiernan            Yes.  What I said was it’s critical for patients to stay engaged; stay in a support group, stay online, stay knowledgeable about your condition.  Because you’re your own best advocate, and really the empowered patient that asks a lot of questions and comes to their doctor not in a confrontational way, but just in a friendly way, and says, “Hey, look, I’m wondering why am I on this; do I have to have that, is there anything else out there for me,” that’s the kind of patient that we want in our practice if we’re really comfortable with what we’re doing, we’re fairly up to speed on what’s going on, and ask a lot of questions.  If you get the wrong kind of answer or if you’re told just stop asking questions then get another doctor, because that’s what’s great about the American healthcare system, you can still do that.


J. Nowak                     Perfect.  Thank you, again.  I truly appreciate it.


Dr. McKiernan            My pleasure.


J. Nowak                     Have a good evening.  Good evening, everybody.