Recent Advances in the Treatment of Metastatic Castration-Sensitive Prostate Cancer (mCSPC) - Episode 6

Selecting Therapy for Low-Volume mCSPC

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Panelists provide comprehensive insight on treatment strategies specific to the setting of low-volume metastatic prostate cancer.

Neeraj Agarwal, MD:
I’ll come to Ben. As a urologist, you are a lot more likely to see low volume metastatic prostate cancer that occurs in the backdrop of a localized prostate cancer. Is there any unique strategy you employ in your clinic then as a surgeon when you see these patients who have, instead of, say 6 bone metastases, have [a few bone metastasis, otherwise completely asymptomatic, had radical prostatectomy 3 years prior to onset of these 2 bone mets [metastases]? How do you approach these patients?

Benjamin Lowentritt, MD: It’s a great question. I think on top of all of this, although it’s not the focus of our discussion, is the increased availability of PSMA [prostate-specific membrane antigen] PET [positron emission tomography] scanning and the increased ability to detect metastases earlier in the timeframe, potentially in the recurrent stage or even in the staging stage. We’re finding these patients and trying to determine do they equal the patients we’re seeing in some of these trials where it was more by conventional imaging. There’s still that effort to try to say, OK, can we consider any targeted therapy that is going to be in any way curative? If it’s a small number of metastases can we consider metastasis-directed therapy when appropriate? Typically, I am using, because the TITAN trial and others have shown that both in large volume and lower volume disease, there is a survival benefit. There is a rPFS [radiographic progression-free survival] benefit. I do tend to intensify their treatment rather than just do ADT [androgen deprivation therapy] alone. There, frankly, aren’t very many circumstances at all where I’m considering doing ADT alone at this point for patients, saving maybe the adjuvant radiation short-term setting. I am still treating patients with what you described, ADT plus a novel hormonal agent.

Neeraj Agarwal, MD: I will give you a case for the sake of recollection for our viewers and listeners today. This is a 63-year-old man, Gleason score 5 + 4, and a history of radical prostatectomy 3 years ago. He came with PSA [prostate-specific antigen] recurrence, a PSA close to 15 ng/mL. The bone scan shows 2 bone metastases, no other evidence of metastasis, and the patient wants to have the best treatment possible for his prostate cancer and wants to live as long as possible, like all our healthy young patients. What would be your strategy in this patient based on level 1 evidence?

Bobby Liaw, MD: I do agree with a lot of the things that Ben talked about before. There are great data from apalutamide and enzalutamide in the patients with low volume burden. Similarly, this is a 63-year-old man, I’m certainly looking to help protect as many years as possible, so I will be still moving toward combination therapy as part of the systemic management. To the end that it’s oligometastatic disease, we’ve certainly gone the route of still delivering prostate-directed radiation if they still have a prostate that’s intact. In his case, he doesn’t have one. I wouldn’t say there’s quite the same level 1 evidence, but metastasis-directed radiation therapy I think has been shown to at least have some potential progression-free survival and better long-term disease control. If the spots of disease are in areas that would not lend to significant toxicities from radiation, I am trying to refer my patients to see my radiation oncology colleagues.

Neeraj Agarwal, MD:If you decide to give metastasis-directed radiation therapy to these 2 sites of bone metastases, would you still use ADT plus say enzalutamide or apalutamide, or will you not pursue any androgen deprivation therapy in this patient?

Bobby Liaw, MD: That’s a question I struggle with myself. Whenever I refer anyone for metastasis-directed radiation therapy, I take great care to tell them that I do not consider it to be curative-intent radiation. To that end, I think there is a need for continued use of systemic therapy. Now, whether that necessarily must be combination hormone plus AR [androgen receptor]-directed therapy, that’s where I don’t have a lot of great data to draw from. I do have some patients I will refer to metastasis-directed radiation therapy just because they’re having a difficult time with hormone therapy plus AR-directed therapy. We are trying to use this to justify buying them a break from hormone therapy and use it in more of an intermittent fashion, but that is primarily dependent on their tolerability of the systemic therapy. Generally, if they’re tolerating it well, if this guy’s still on apalutamide and ADT, if they’re tolerating it well even after radiation, I’m generally still recommending that we continue with the combination treatment.

Neeraj Agarwal, MD: Thank you very much. I’d like to add a piece of data to this discussion. We have consistently seen that there is a 50% attrition rate from first line to subsequent line of therapy in patients with metastatic prostate cancer in the United States based on Flatiron [Health] data, published by Dan George, [MD,] and team, and other publications by my colleague, Umang Swami, [MD], again, from the Flatiron database. I tell my patients that there is a 50% chance that you will not receive a subsequent line of therapy. My goal is to optimize and go ahead with the best therapy possible for you at this given point. If or unless I can completely avoid androgen deprivation therapy, I have a low level of enthusiasm to go for metastasis-directed therapy until the patient has complete reluctance to start ADT. Like your experience, Bobby, I agree with you. I do offer these patients systemic therapy unless they say they cannot get any testosterone-suppression therapy, which is a very small number of patients. My practice, until we have level 1 evidence from metastasis-directed therapy, I would continue to use ADT plus a novel hormonal therapy for our patients with a low volume non de novo metastasis. Just as a conclusion, I wanted to make that point.

Transcript edited for clarity.