Case 1: 64-Year-Old African American Man With nmCRPC

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Alicia Morgans, MD:Thank you for joining us for thisTargeted Oncology™ Virtual Tumor Board®, which is focused on prostate cancer. In today’s presentation, my colleagues and I will review 3 clinical cases. We will discuss an individualized approach to treatment for each patient, and review key trial data that impact our decisions.

My name is Alicia Morgans, and I’m an associate professor and medical oncologist at Northwestern University’s Feinberg School of Medicine, in Chicago, Illinois.

Today, I’m joined by Dr Neal Shore, the medical director of the Carolina Urologic Research Center, and a urologist at Atlantic Urology Clinics in Myrtle Beach, South Carolina; Dr Ken Kernen, a partner in the Michigan Institute of Urology, and the director of research for the Michigan Institute of Urology in West Bloomfield, Michigan; and Dr Jorge Garcia, an associate professor of medicine and genitourinary medical oncologist at the Cleveland Clinic Lerner College of Medicine, and the Kerscher Family Chair for Clinical Prostate Cancer Research at the Cleveland Clinic, in Cleveland, Ohio.

Thank you for joining us. Let’s get started with our first case. Dr Shore?

Neal Shore, MD, FACS:Thanks, Alicia, Jorge, and Ken. Great to go over this case with you. Let me get into it. It’s an interesting case, because I think this is really getting to where we are now in newly approved indications and new therapies. So, October 2016. A 64-year-old African American man gets referred to the urology clinic. His PSA [prostate-specific antigen] is 6.8 [ng/mL]. Interestingly, his past medical history is notable for having had seizures. He’s on anti-epileptic medication. He has a family history that’s notable for a mother and sister with breast cancer, and a brother with pancreatic cancer.

His rectal examination reveals, essentially, normal—there are no nodules or induration—and the urologist here chose, before doing the biopsy, to get a multiparametric MRI [magnetic resonance imaging]. It shows he has an enlarged gland, about 58 cc. There appears to be a very concerning lesion in the left peripheral zone. It’s a PI-RADS [Prostate Imaging Reporting and Data System] 4/5, and it’s about 1.8 cm. There’s even a suggestion that there’s seminal vesicle infiltration on 1 side.

He then undergoes, the following month, a fusion biopsy. The results reveal 4 of 12 cores that are positive; and the index lesion, interestingly, has 3 out of 3 cores positive. And the highest Gleason interpretation is a Gleason group 4, or a 4 + 4—the other cores have 3 + 4—so he’s now ISUP [International Society of Urological Pathologists] Grade Group 4.

A bone scan and a CT [computed tomography] scan are obtained, presumably because of the ISUP 4, and they’re negative for metastases. His performance status is very good. It’s a 0. He then chooses to undergo a robotically assisted prostatectomy with an extended lymph node dissection. The final pathology shows T3b, nodes are negative, and at further pathological assessment, he’s still Grade Group 4. There is a positive surgical margin at the apex. The patient otherwise does well. Six weeks later, his PSA is 0.15 [ng/mL], and it’s obviously concerning that it hasn’t gone to undetectable. His urologist recommends adjuvant radiation therapy to the prostate bed. One could potentially argue for pelvic radiation as well for the pT3 disease, but the patient declines to undergo radiation. I don’t know all of the reasons. Maybe it’s because of a desire for sexual function? Maybe it’s fear of the toxicity of radiation? We can certainly talk about that.

What’s interesting about this case is now the patient is basically saying, “I’m going to monitor my PSA. Let’s see what happens here.” And so, several months later, it’s July, and the patient has got a PSA of 0.18 [ng/mL]. Eventually, the PSA, in the fall, October, is now up to 0.58 [ng/mL]. By January of 2018, it’s 2.8 [ng/mL]. And then in May of the following year, 2018, it’s 4.2 [ng/mL].

Again, a discussion ensues regarding salvage radiation. Restaging scans are done—bone scan, CT scan, presumed full body—and are negative for metastases. No other novel next-generation imaging is done at this time. A decision is made to start the androgen deprivation therapy [ADT], and he gets a 6-month depot formulation of leuprolide.

The PSA now goes, a couple months later, down to 1.2 [ng/mL]. And then from August to October, it’s 1.6 [ng/mL]. And in January of 2019, so we’re getting contemporaneous now, it’s 1.9 [ng/mL]. It’s interesting. You’ll see there’s no real pattern to the regularity of the PSAs—monthly, to 3 months, to 4 months—which probably is explained by sometimes getting PSAs from primary care physicians. Or maybe we’ll talk about what’s the strategy? What’s the tempo for getting follow-up PSAs? But by April, it’s now 2.35 [ng/mL]. In July, it’s 3.12 [ng/mL]. And then we come to October 2019, today, as we’re presenting this tumor board now, and his PSA is 3.81 [ng/mL]. For all practical purposes, he is asymptomatic. Obviously, he doesn’t have any tumor burden. His imaging is negative. He may have some fatigue related to his ADT therapy. He may have some hot flashes, and may have some loss of libido. And a doubling time is calculated. His PSA doubling time is 8.6 months.

So here we are. He gets restaged, again, with a full-body CT and technetium bone scan. It’s negative. So the patient now has an opportunity, given where we are, in October 2019. We now have 3 FDA-approved therapies for nonmetastatic castration-resistant prostate cancer [nmCRPC] patients. Indeed, this gentleman falls into that category, or what the AUA [American Urological Association] CRPC guidelines callIndex Case 1. Prior to 2018, January, we had no level 1 evidence. Now we sort of have an embarrassment of riches. We now have 3 therapies to choose from. And so, this particular patient was started on a darolutamide in an BID [twice a day] oral formulation.

It’s kind of a cool case, in that we really couldn’t be having this conversation literally a year-and-a-half ago. Now we can have this conversation.

Transcript edited for clarity.