Clinical Scenario 2: A 64-Year-Old Man With nmCRPC


Shared insight on a clinical scenario of a patient with nonmetastatic castration-resistant prostate cancer who was treated with prostatectomy and adjuvant therapy.


Evan Y. Yu, MD: Let's move on to module 2 which is focused on advances in non-metastatic or M0 castration resistant prostate cancer so let's discuss the case. This is a 64 year old gentleman who presents with nocturia has a past medical history that's significant for hypertension controlled with medications. Family history: his father had lung cancer in his mid-60s. PSA [prostate specific antigen] is 6.8 ng/mL and undergoes a prostate needle biopsy that reveals 4 plus 3 equals 7, adenocarcinoma of the prostrate. Patient undergoes a radical prostatectomy and pelvic lymph node dissection and is found to have seminal vesicle involvement so PT3B, focal extra capture extension as well and negative surgical margins. Patient does have positive lymph node as well, so this is N1 disease and no distant metastases on imaging. Postoperatively the patient's PSA drops to 0.4 ng/mL and at that point they decide to give the patient adjuvant radiation and start the patient on androgen deprivation therapy. The patient's PSA goes undetectable and 2 years the later the patient is still on androgen deprivation therapy a couple years later. They were planning for 2 years and then stop but just then the PSA had been slowly starting to rise for the last few months and had gotten up to 7.2. Four months after that while the patient is still on androgen deprivation therapy the PSA has now risen to 16.8 ng/mL. Conventional re-staging imaging with CT and bone scan still do not reveal any detectable metastases at all so this patient essentially has the M0 non-metastatic castration resistant prostate cancer disease state. Before we attack that because that's a big discussion here, I want to know what you all think about how this patient was treated and the fact that this patient had radical prostatectomy and then underwent multiple adjuvant therapies with both radiation and adjuvant androgen deprivation therapy for a couple of years. Now granted the PSA started to rise but is that how you all would have treated this patient or any other considerations, anyone want to jump in?

Andrew J. Armstrong, MD, MSc: Yes I can start. Certainly, there's been multiple randomized trials now testing early salvage radiation versus adjuvant and it's fairly well closed the door on adjuvant radiation for most patients. This patient with seminal vesicle invasion, node positive disease is going to be much higher risk than the average patient in those trials and that analysis. Could you say that as a young patient, an aggressive approach- he certainly had the kitchen sink thrown at him and he still relapsed so in his case more would be more and he’s still failing with non-metastatic CRPC. It's hard to look back and regret that but you might have considered a more potent AR inhibitor in the hormone sensitive space as per the STAMPEDE trial in an earlier setting instead of radical prostatectomy, but he didn't know that he had node positive disease. If he had been staged appropriately with a PSMA PET maybe it would have picked it up.

Evan Y. Yu, MD: Nice plug there all right Mary-Ellen?

Mary-Ellen Taplin, MD: Evan, NRG has a trial I believe that's going on now for patients who have positive lymph nodes prostatectomy which is evaluating these second-generation androgens signaling inhibitors.

Evan Y. Yu, MD: So that'll be useful information for us. Would any of you have treated this patient differently or to the best of the data and knowledge that you have at this point in time, something similar?

Dr. Pedro C. Barata: I think what's challenging here is actually the case is presented as having intermediate risk; PSA below 10, Gleason seven, I'm assuming clinically T1 let's say and so that's the tricky part because if you have characteristics that would make us think of high risk I think the future- our friends from Europe and Australia and other places in the world are already doing standard of care PET scanning. We know that will upstage over 20 percent of the times and to me if I would go retrospective which is always easier to do, you go back and say well I could have done something different. This is one of the patients that he probably had metastatic disease you just cannot see it with the conventional scanning available at the time so that perhaps would be the difference. My comment would be of course it's alarming that with the PSA post-surgery let's assume this is 16 weeks post-surgery confirmed 0.4, the patient is not cured so it's actually persistent disease which is a great point that Andrew made regarding early salvage versus adjuvant.

Evan Y. Yu, MD: Is this even adjuvant or is it salvage?

Pedro C. Barata, MD, MSc: Exactly my point, for persistent disease we're trying to cure him a second time and the fact that it didn't work is an educated guess, right? What we're thinking is let's say the recurrent disease or persistent disease is seen in the pelvic area because that's how we're going to address local therapy and we bring ADT on top of it based on data like A2 that will show that improves outcomes but the reality of it is we're guessing. That's another setting where PET scanning allows us to be smarter because if you see disease outside that area- you're not going to cure that patient but we can adjust expectations a little bit better. We can think about treatment intensification as Andrew alluded to and again more is more in some cases and it seems like this would be a good patient for that.

Andrew J. Armstrong, MD, MSc: Or pelvic radiation, the SPORT trial was just published showing pelvic radiation might extend relapse free survival.

Transcript edited for clarity.

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