Recent Advances in the Treatment of Metastatic Castration-Sensitive Prostate Cancer (mCSPC) - Episode 7
Shared insight on optimal patient monitoring strategies while administering therapy for metastatic castration-sensitive prostate cancer.
Neeraj Agarwal, MD: I’d like to touch base on the last question in this case before going on to the next case. How do you monitor your patients when you’ve started them on ADT [androgen deprivation therapy] plus apalutamide? Simon or Bobby, say you started somebody on ADT plus enzalutamide, how do you monitor these patients in the real world? These aren’t clinical trial patients. Many are frail with suboptimal kidney function, maybe a GFR [glomerular filtration rate] of 80 mL/m or 70 mL/min, who may not be the best candidate to handle IV [intravenous] contrast for more than 1 or 2 years? How do you monitor? I’ll start with Simon and then go to Bobby.
Simon Chowdhury, MD: It’s a learning process for ourselves and for the clinical nurses who support us. PSA [prostate-specific antigen] is a good marker. You and I have talked about it a lot with the TITAN steering committee, and other studies are looking at this as well. Patients who achieve an undetectable PSA do very well. We see this in terms of quality of life as you’ve demonstrated. We also see this in terms of radiographic progression-free survival, PFS2 [time to second objective disease progression], and overall survival. I used to scan more often because you get into those habits, but I do it less often now. COVID-19 has been good for that because, in the United Kingdom, there’s been less availability. The patient population in the real world is older and frailer and more vulnerable to COVID-19, so bringing them in for a scan when their PSA is undetectable and they’re well at home doesn’t make much sense.
Occasionally PSA lets you down, but it’s very rare that it lets you down outside clinical symptoms like pain, appetite, energy, hemoglobin, LDH [lactate dehydrogenase], liver function tests, albumin, which are relatively simple tests. You were teaching me this with a patient that you had, and you said the first thing we saw was the LDH. What’s the LDH? What’s alpine phosphatase? That’s more sensitive. For me, PSA is probably good enough.
With the scanning frequency, I vary a little. It depends on what’s happened initially and the prognosis of the disease. If you’ve got someone with oligometastatic disease with a good prognosis and undetectable PSA, I don’t scan them that frequently, to be honest. Sometimes it’s driven by patients, and sometimes I want to get them off therapy or think about de-escalation. It’s an evolving piece, but some of the simple tests and the simple blood tests in addition to PSA are useful. There’s a field element with it, like any therapy, and we’re all still learning. I imagine we’ll talk about novel imaging as well, which may have a role that’s evolving going forward, particularly with metastasis-directed therapy, which was very honestly and eloquently [described earlier by Dr Liaw].
Neeraj Agarwal, MD: Thank you. Bobby, regarding ADT plus enzalutamide, we saw the data from the ARCHES trial presented by Dr [Andrew] Armstrong regarding the discordance with radiographic progression-free survival, which was the primary end point. He reported intriguing data at ASCO [American Society of Clinical Oncology Annual Meeting] 2022: 67% of patients receiving ADT plus enzalutamide on the ARCHES trial did not have PCWG2 [Prostate Cancer Working Group 2]–defined PSA progression when they experienced radiographic progression. Not only that, but 42% of patients receiving ADT plus placebo, not enzalutamide, did not have PCWG2-defined PSA progression while experiencing radiographic progression. I was surprised and intrigued with these data. Are these data going to change your practice as far as getting scans more often is concerned, or you would like these data to be validated? That’s the No. 1 question. No. 2, do you think these data could be related to enzalutamide and not as much to abiraterone or apalutamide? What’s your take, Bobby?
Bobby Liaw, MD: Maybe I can answer the second part of that question first because there’s a specific mechanistic reasoning behind enzalutamide and its compatriots. My suspicion is that it’s not an enzalutamide-specific issue. Coming back to how we survey and how some of these data informing my own decision-making process, I’ll admit that for some time we’ve mostly been focusing on symptoms and PSA. If we feel the PSA is a reliable biomarker, a good metric of their disease, then we’ve been primarily using PSA as 1 thing that helps us inform whether we need to do imaging. This type of data has started to come out over the last couple of years, and this is probably also informed by my own experience, in which 1 or 2 patients with some aggressive recurrence did not show up on PSA at all. We were caught a little surprised. But I’ve come around to thinking that way for a lot of my patients who’ve been on combination ADT-abiraterone, ADT-enzalutamide, or ADT-apalutamide. I started to think about doing scans at least every 1 to 2 years as a way to keep tabs on it. Unfortunately, this is not well supported by level 1 evidence. But we know that PSA isn’t the perfect marker, especially for a lot of patients on long-term use. Some people on abiraterone or enzalutamide, and they’re on it for 3.5 to 4 years. It’s not always a bad idea to get another restaging look to see how things go, but we’re far from the days of doing it every 3 months just to keep tabs on things.
Neeraj Agarwal, MD: Thank you very much. Just to summarize for our listeners, how to monitor patients on treatment who have metastatic castration-sensitive prostate cancer, PSMA [prostate-specific membrane antigen] is a test that’s widely used by all of us, but we’re trying to do scans at least once or twice a year to make sure we don’t allow disease to progress without PSA progression being appreciated and to make sure our patients are safe. But it doesn’t look as if we’re going to be offering scans to the patients at the level we offered them on the clinical trials, which was every 3 months or sometimes every 2 months, because that’s simply impractical—but not possible—for many of our patients. Most of our patients don’t wish to do so. Thank you very much.
Transcript edited for clarity.