Patient Scenario 1: A 55-Year-Old Man With Metastatic Hormone-Sensitive Prostate Cancer


Key opinion leaders in the field of prostate cancer management consider optimal molecular testing practices in a patient with metastatic hormone-sensitive disease.

Alan H. Bryce, MD
: Welcome everyone to this CancerNetwork® program titled, “Optimizing Treatment for Metastatic Castration-Sensitive Prostate Cancer: Expert Perspectives.” I’m your host, Dr Alan Bryce. I’m a medical oncologist at the Mayo Clinic here in Arizona, with the background, of course, being Bryce Canyon because that’s where my family likes to hang out. I have a great panel here tonight consisting of health care professionals for this virtual discussion on prostate cancer. I’d like to have my fellow panelists introduce themselves. Let’s start with Dr Zhang.

Tian Zhang, MD, MHS: Hi everyone, I’m Tian Zhang. I’m a GU [genitourinary] medical oncologist at University of Texas Southwestern [Medical Center] in Dallas, Texas.

Alan H. Bryce, MD: All right, and Dr Lowentritt?

Benjamin H. Lowentritt, MD, FACS: Hi, my name is Ben Lowentritt. I’m a urologist practicing at Chesapeake Urology in Maryland.

Alan H. Bryce, MD: All right, and Dr Petrylak?

Daniel P. Petrylak, MD: Hi, I’m Dan Petrylak, GU division chief and medical oncologist at Yale University.

Alan H. Bryce, MD: Excellent. Thank you all for joining me. Today we’re going to discuss genetic testing, treatment options, patient education, and communication strategies for metastatic castration-sensitive prostate cancer. Let’s go ahead and get started.

What we have is a series of cases based on real patients, but modified to try to highlight certain discussion points. The first case is a gentleman who comes in, with an initial presentation to the ED [emergency department]. The 55-year-old man comes in with some back and hip pain. Initial imaging shows this: lytic spinal lesions as well as a destructive mass in the right iliac bone with some soft tissue extension. This is obviously a concern for cancer. He gets admitted to the hospital for initial work-up, and a biopsy shows a high-grade adenocarcinoma consistent with a prostate primary. It stains positive for PSA [prostate-specific antigen], but negative for synaptophysin and chromogranin. PSA is found to be 590 ng/mL. There’s no family history of cancer for this gentleman; he has 2 siblings, 2 adult children. Starting there, Dr Lowentritt, what further testing would you order for this gentleman? Let’s say he’s out of the hospital now and comes to your clinic.

Benjamin H. Lowentritt, MD, FACS: Certainly I’m interested in learning as much as I can from the tissue we have. I would send the biopsy specimen for further somatic testing to get any information we can out of the genetics from the fresh metastatic tissue we have. I would plan for the patient and set him up to get germline testing as well.

Alan H. Bryce, MD: Yes, absolutely. When you’re discussing somatic testing in this setting, how do you think about the pros and cons and talk that through with the patient? Because with germline testing, we have a clear recommendation from the NCCN [National Comprehensive Cancer Network], from ASCO [American Society of Clinical Oncology], from AUA [American Urological Association]. With somatic testing there’s a bit more equipoise in the hormone-sensitive setting, right?

Benjamin H. Lowentritt, MD, FACS: I think that’s just right now. I don’t think any of us believe that the somatic information is not going to be relevant as soon as we get more information about treating patients earlier if we know they have a specific profile. I’m preparing somewhat for the future both academically, but also for this patient, if they have one of those especially certain markers like BRCA2 or something, you might suspect that they’re going to fail more quickly on whatever treatment we’re putting them on. Even if we’re not talking about a pure, predictive outcome for a specific treatment, there are certainly prognostic elements there to some extent. To get the complete picture, we do know that only about half of the patients who have some sort of genetic alteration that’s relevant, especially in the HRR [homologous recombination repair] pathway, only about half of them are going to be in the germline setting, and at least half of them are going to be in the somatic. I think it’s a critical thing to get the information when you have good viable tissue. I know personally, the longer the tissue has been around, it’s harder to get a reliable result. If you can, I think it’s valuable to get it up front even if you may not use it immediately.

Alan H. Bryce, MD: Fair enough. All right, I appreciate that. Dr Petrylak, how about in your practice? How do you approach somatic testing, and is there anything you look for specifically for the hormone-sensitive patients? What markers are most meaningful to you?

Daniel P. Petrylak, MD: I think the somatic testing could be useful in clinical trial entry. The TALAPRO-3 trial recently closed. That was a trial that was looking at talazoparib in those patients with DNA repair mutations. So, that’s one situation the somatic testing can be useful in. There are other target agents that potentially could be used in clinical trials. We don’t have standard treatment that these would be useful in, but certainly the AR [androgen receptor] degraders may work better in those patients who have AR mutations. But again, those are for clinical trials. I think it would help the clinical trial entry. It certainly would also give the patient a road map. If this patient did progress after hormones, if he’s BRCA positive, that’s one thing I would put a patient on quickly. You would have that information at your fingertips and not have to know what to do at that particular point. Those are the advantages of having a somatic mutation panel.

Alan H. Bryce, MD: Yes, absolutely. We have a lot of urologists who will watch this program. What is the role of Prolaris or Decipher testing in these settings? Do you feel like they add to your decision-making or do you find a use for them?

Daniel P. Petrylak, MD: No, here, I don’t think they’re going affect my decision-making. For localized disease they might help, but here it’s not really useful. What I’m going to decide to do is [based partly on] the patient’s volume of disease. Whether this patient has de novo or progressive prostate cancer after local therapy, that’s important. Also there are other risk factors and the general medical condition. Those are the things that are going to be coming into play in terms of what I do.

Alan H. Bryce, MD: Absolutely.

Transcript edited for clarity.

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