Molecular Testing in Prostate Cancer

Transcript:Raoul S. Concepcion, MD, FACS: In this next segment, we’re going to be discussing some of the various tissue assays currently available to guide therapy. We know, now, that prostate cancer is a heterogenous disease, and not all prostate cancer actually needs to be treated. The concept now is, number 1, which patients—based upon histopathology and based upon clinical characteristics—are candidates for active surveillance, what we used to call watchful waiting? And which candidates, or which patients, based upon, again, histopathology or other criteria, are candidates that need to move on to active therapy? We know that there are some significant side effects and morbidities associated with active therapy.

The challenge for urologists is 2-fold. Especially early on, the challenge is, who to biopsy. Which patients truly need biopsies? Again, we know that about 50% of newly diagnosed prostate cancer patients really do have low-risk disease. We also know that there is a significant complication of bleeding and infection associated with multiple biopsies. And then, once we do have a diagnosis, the question is, if you have low-risk disease, is there anything else besides histopathology that can help guide us to determine who is a candidate for active surveillance or who really needs to move on to active treatment?

Glen, in your particular practice, because you have a big radiation oncology practice, you obviously see a lot of prostate cancer. How are you using molecular tests? What are some of the differences out there? How are you incorporating that into your practice in terms of utilizing them to determine treatment versus surveillance?

Glen Gejerman, MD, DABR: Clinicians who manage patients with prostate cancer, particularly early on in their journey, are in a very unique position in that we have to counsel patients whether they should be treated or not. And that’s in contradistinction to all other oncology models. Once you have a positive biopsy, you’re off to the races. You’re discussing treatment, treatment options, and relative efficacies. That’s not true in prostate cancer. Much of our time is spent counseling patients about whether they need treatment.

The key question the patients and their physicians have to ask is, “Is this a potentially lethal prostate cancer, or a potentially indolent one?” And while we use clinicopathologic features to try to sort that out, we know that’s insufficient. So, we now use genomic tools that help us add information to the discussion.

For example, the patient presents with a biopsy. He’s got low-to-intermediate risk cancer, perhaps a 3 + 4 Gleason score. We discuss the PSA and the Gleason score, but that patient probably should have an Oncotype DX study that will give them a sense of, what are the odds that they’re going to have progressive disease? Now, it’s always important to discuss this with patients. This is not a binary test that proves that based on 1 score you’re going to treat and in another score, you won’t. But, it does add to the information.

Similarly, in patients that decide to have a radical prostatectomy and don’t have organ confined disease—in other words, there’s extracapsular extension, seminal vesicle invasion, or positive margins—we know those patients are at risk for recurrence. The question is, how high is that risk? One can use the Prolaris test or Decipher examination. These are tools that will give them, again, a percentage of what their risk for progression is. And that adds to the discussion, but I always counsel patients. We need a more robust dataset to validate these studies, but it does help the patient and the physician to have a better understanding of what they’re facing so they can make the right decisions.

Raoul S. Concepcion, MD, FACS: Neal, you’ve done a fair amount of work, research, and publications on the various biomarkers, especially in early use in prostate cancer—whether it be diagnosis or potentially, often, therapy. Can you tell us how you view phosphate biomarkers relative to determining who to biopsy, who to proceed with active surveillance, who needs radiation, and those types of things?

Neal D. Shore, MD, FACS: It’s a field that has just been exceptionally fertile. Almost every other month there’s a new test coming out—a new acronym. It can be tissue-based, serum-based, or urine-based. And I think that, in and of itself, this creates a certain level of confusion. A busy clinician just throws his or her hands up and says, “I can’t make any heads or tails of this.” And that’s why we need to do high quality evidence-based trials.

I do think that companies such as Myriad Genetics, Genomic Health, and GenomeDx Biosciences—Decipher, Prolaris, and Oncotype DX—have really tried extremely hard and have a body of literature to support their claims of helping with better decision making. There are multivaried analyses on top of the clinical pathologic findings, for example, in newly diagnosed settings. Whether it’s a DRE (digital rectal exam), PSA, or Gleason score, you have a fourth test, a score—such as Oncotype DX or Prolaris—to help you better understand how aggressive this disease is. And to your point, “Am I good a candidate for surveillance?” Or, “Am I good candidate for an active treatment?”

Historically, we’ve underutilized active surveillance. The government sees that. We all know this. It’s not controversial. If you look at SEER-Medicare data, most recently in a contemporaneous lookback—which we’re doing at LUGPA because we’re working on an advanced alternative payment model—about 22% or 23% of patients are getting surveyed. I think most of us would agree that that number could be 45% to 55%.

I like the genomic assays because I think it will give both patients and physicians, in this shared decision-making concept that we really have now embraced that has been initially forced upon us, what is really important to become better educators. And if you get a fourth variable, as Glen said, that’s an independent variable that can help better predict aggressiveness—that’s really a value.

But getting back to the whole biomarker issue of acronyms, we have urine- and serum-based tests for who to biopsy on top of PSA, who to rebiopsy in the setting of a negative biopsy, and of course, then, there’s also MR (magnetic resonance) that plays into that. And then, the third bucket is, what do I do with newly diagnosed? The GPS (genomic prostate score) or the Prolaris test. Then, the fourth is post-prostatectomy. What’s the likelihood, post-prostatectomy, with the Decipher or Prolaris test? How can that help me better decide the intensity of, if any, adjuvant therapy? So, I think of those 4 buckets, and there’s a list of tests that are diagnostic biomarkers that are out there. It keeps growing. Every week, every month we see more. I think you’ve got to just stay on top of it and follow the data.

Transcript Edited for Clarity