Patient Profile 7: Gleason 7 Prostate Cancer


A look at the patient profile of a 62-year-old man presenting with reduced urinary flow and hematuria.

Neal Shore, MD, FACS: Great discussion. Let’s go to our last case, and it’s interesting because it’s into this area of the nmCRPC [nonmetastatic castration-resistant prostate cancer], or what we used to call index case 1 AUA [American Urological Association] M0. Larry, would you like to review this?

Lawrence Saperstein, MD: A 62-year-old man presents with reduced urinary flow and hematuria. Past medical history is significant for hypertension controlled with medication. Family history, father had lung cancer in his early 70s. Clinical work-up, PSA [prostate-specific antigen] is 7.9 ng/mL. Prostate biopsy shows Gleason score of 7 (4+3). Treatment and follow-up, the patient undergoes robotic-assisted laparoscopic prostatectomy and pelvic node dissection. Results show pT3b, focal extracapsular extension and seminal vesicle invasion, margins negative, N1, M0. Postoperative PSA is 0.53 ng/mL. The patient undergoes adjuvant radiation therapy and is started on leuprolide. PSA is undetectable. Follow-up, 2 years later the patient presents with rising PSA of 0.5 ng/mL, 4 months later PSA is 0.8 ng/mL.

Neal Shore, MD, FACS: This is a classic patient with nonmetastatic castration-resistant prostate cancer. The next question, if we are going to a tumor board now compared to just a few years ago when we were doing the phase 3 trials, the SPARTAN, PROSPER, and ARAMIS that led to the approval of those 3 androgen receptor [AR] drugs, respectively apalutamide, enzalutamide, and darolutamide. Those were all done on conventional imaging using CT scan and technetium bone scan, and they had to be negative, had to have a doubling of less than 10 months to get into those trials comparing the AR inhibitor vs placebo. Now, I guess the question is what’s the role for PSMA [prostate-specific membrane antigen] PET [positron emission tomography] in nmCRPC? This is summarizing the points I was making. Perhaps Larry you want to comment on this nice work that was done by [Wolfgang] Fendler, [MD,] and colleagues and looked at the use of PSMA PET in these patients who would have qualified for SPARTAN, PROSPER, or ARAMIS. What are your thoughts about the results of the PSMA PET in these patients?

Lawrence Saperstein, MD: It’s an interesting retrospective study. Probably to do it justice, I am going to respectively defer to my clinical colleagues.

Neal Shore, MD, FACS: I’ll go on with it because I know this well. Of 200 patients who would have been in enrolled in SPARTAN, PROSPER, and ARAMIS, 98% had positive findings. About 55% had findings within the pelvis and 45% above the pelvis based upon PSMA PET. But it gets back to our prior conversation, how would that change what you would do? Today, those 3 trials have led to the level 1 evidence in virtually all of our international guidelines, including NCCN [National Comprehensive Cancer Network], that says if the doubling time is less than 10 months, go with an AR inhibitor, apalutamide, enzalutamide, or darolutamide. It’s interesting, the label for those drugs doesn’t talk about the doubling time. But it is still fascinating in this paper that 198 of the 200 patients who would have had no findings, were found to have clear findings, and half had disease findings above the pelvis. What are your thoughts about that? Maybe I will ask Mike first and then Steven.

Michael Gorin, MD: Because many of these drugs are approved in every line of therapy now, whether it’s newly diagnosed metastatic prostate cancer, nonmetastatic castration-resistant, or metastatic castration-resistant, in some ways it’s neither here nor there because they are going to see all these different lines of therapy anyway. But imagine a scenario where the patient has seen androgen deprivation, they have received an androgen receptor blocker, and they haven’t received docetaxel yet. And docetaxel wouldn't be indicated in nonmetastatic castration-resistant, but we know it would be in metastatic castration-resistant. Here, almost half of the patients have metastatic disease, can we start pulling the trigger and moving docetaxel into an earlier line of therapy for these patients who did not see it in their first or second course of treatment? There are no data to support doing that of course, but it really begs the question of whether these patients could potentially be candidates for that in the future.

Neal Shore, MD, FACS: Steven, your thoughts?

Steven Finkelstein, MD, DABR, FACRO: I think we are going to find a situation where the imaging gets so good that we are going to be able to find sites of disease in every patient we look at, where the PSA is rising. However, what we are defining is its own unique subset. It’s not that we couldn’t find it anymore, it’s just low volume disease. It’s disease where you need next-generation imaging to be able to find it, and we know those drugs worked when we couldn’t point to where the individual spots were. We know these drugs will work when we say it’s low volume disease, it’s only detectable by fancy next-generation imaging. I don’t want us as specialists to throw the baby out with the bath water. We should embrace the history of what we have done. The imaging is going to drive, “Oh my goodness, there is a whole bunch of disease we see on this picture, or hey, there is only a little bit of disease on this picture.” We are going to be able to temper our enthusiasm for pulling the right treatment at the right time in the right patient.

Now, a lot of this is undiscovered country. We have to do those trials to use the imaging with some of the agents that we have classically used to find out if there are better agents to potentially use in certain scenarios. But like Mike alluded to, a lot of drugs that we use are indicated across the spectrum of the prostate cancer continuum. I think we are going to find that a lot of these drugs are just going to be moved up as we are able to find the disease and point to it sooner.

Transcript edited for clarity.

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