Personalizing Therapy for Advanced Prostate Cancer - Episode 4
Transcript:Raoul S. Concepcion, MD, FACS: Historically, using traditional ultrasound-guided 12-core biopsy, we understage and we undersample. Where we sample just with our little 12 cores, we sample less than 1% of the prostate. We have a range anywhere from 8% to 25%, upgrading and upstaging—and this is the Johns Hopkins’s data. Again, this is speaking to the heterogeneity of the disease, and speaking to the lack of a good imaging technique and biopsy technique. We understand that, again, there has never been any head-to-head trials with these tests, but the most recent joint guidelines from AUA (American Urological Association), SUO (Society of Urologic Oncology, and ASTRO (American Society for Radiation Oncology), despite this undergrading and understaging, basically said that they didn’t see a need for molecular testing in the low-risk patient. Glen, what are your thoughts on that?
Glen Gejerman, MD, DABR: I think the NCCN guidelines, talking about the low- to very low-risk, that’s perhaps where it has the greatest utility. Those are really the patients who struggle. Do they need to have a definitive treatment with all the attendant side effects? Whether it’s radiation or surgery, these patients do have significant quality of life issues.
If you have a low PSA, and are either very low- or low-risk based on your Gleason score, everyone’s looking for one additional piece of information. A genomic test can eventually prove this, but we’re not there yet. I agree that the company has done a very good job putting datasets together, but we need to validate it in a much larger group of patients in the real world. If we could do that, that would make patients and the physicians much more comfortable with the decision. “You can wait. You don’t need treatment now. We’ll put you on active surveillance and follow that protocol.”
Raoul S. Concepcion, MD, FACS: Mike and Evan, as medical oncologists, obviously, you guys generally, historically, are not involved in the decision making for the localized people with low-grade disease. In your experience and in your practice, do you get a lot of patients who will come to you, walk in and say, “Hey doctor, I got diagnosed with prostate cancer. What do you think about this?” What is your view from a medical oncology standpoint?
Evan Y. Yu, MD: Occasionally, we’ll be the tiebreaker, right? There is the urologist who says, “You should do surgery.” You see the radiation oncologist and they say, “You should do radiation.” The patient says, “I want to see a cancer doctor.” OK, we’re supposed to break the tie.
I make most of my decisions on which treatment to move forward with based on side effects, quality of life, and patient desires—the issue about whether you should be treated or not. Low-risk prostate cancer should be observed. And I think the real question is, “How much benefit are in these tests?” I think you pointed out nicely that for somebody who’s low-risk, you can find out whether they’re really low-risk or whether they’re a little bit higher low-risk. And what ends up happening is people that are a little bit higher low-risk probably get some sort of treatment, rightfully or wrongfully so. I think that’s the real point. In some ways, it helps alleviate anxiety. So, we have to ask ourselves whether that’s a good reason to do a test or not.
Michael A. Carducci, MD, FACP: I have a question for Neal, though. The younger man with prostate cancer versus the older guy doesn’t want incontinence. They might want active surveillance, but they have a long life left to potentially live. Do these tests help, in that situation, make that decision or make you feel more comfortable?
Neal D. Shore, MD, FACS: Absolutely. Actually, there was a very nice paper that came out in the New England Journal of Medicine. I don’t want to misquote the hospital. It was just presented at the American Urological Association’s Annual Meeting. Active surveillance is absolutely a reasonable approach for men diagnosed under age 55. Historically, we had this notion that, “Oh, you’re younger. You’ve got to get something because you have a longer time to live with the disease.” The key thing, as Raoul said earlier, is this is not watchful waiting. This is active surveillance. And with the surveillance protocols, there’s not unanimity about how to best do it.
But, the way I look at it is, I don’t want to inflict the comorbidity or the consequences of surgery, or radiation in somebody who might have worsening voiding symptoms or sexual dysfunction. I don’t want somebody to progress outside the prostate. You’re going to survey them regularly with follow-up biopsies, etc. And the data are mostly single institution. It’s not super long. It’s 3 to 7 years in most institutions. It’s low, single digits—the percentages, the number of patients—if you’re reasonably surveying them. You would lose an opportunity to ultimately treat them.
And the other thing that I think about is, over the course of time, we keep getting better and better with newer therapies that hopefully would be less morbid and put patients at less risk. And then, of course, there’s the issue that something can happen to you along that time that you’re being surveyed that makes it all moot anyway.
I really think that the markers are very, very helpful. We could talk and debate about the economic utility, but I think the clinical utility is there. Too many of our colleagues have a hard time with the dialogue just based upon DRE, PSA, the Gleason score, and percentage and number of cores. Getting a fourth independent variable to help further that education is important to make the right decision, which could be to do active treatment. It’s not always just to do surveillance.
Raoul S. Concepcion, MD, FACS: Plus, Neal, the endpoints of some of these tests are very different. The endpoint of 1 test is basically the likelihood of dying in metastatic disease at 10 years, and the likelihood of progression. The endpoint of another test is the likelihood, at a set point in time—vs-à-vis the time at biopsy—the presence or absence of unfavorable or favorable histopathology. So, again, that even adds more to the confusion in terms of some of our partners and our colleagues.
And I think the other thing that goes along with that is, even though you’re on or we may recommend active surveillance, it doesn’t necessarily mean you’ll never need to be treated. It just means that, at this point in time, at the time of the biopsy, there’s nothing to indicate that you should go ahead and move on to treatment. But, that could change in a year. And I think what’s interesting, and we don’t really have that data, is if you ordered the molecular test—I don’t think anybody would ever advocate that—molecularly, could it change? I think there are absolutely no data on that.
Again, it’s another area where we want the viewing audience to understand that this is not simple. Like our discussion earlier on genetic testing, it’s not simple. There’s a lot of dialogue. There’s a lot of confusion. And again, I think for a lot of our colleagues, they really do have to take the time to understand the nuances of all these tests.
Transcript Edited for Clarity