The American Society of Clinical Oncology (ASCO) issued the first guidance, a provisional clinical opinion (PCO), on second-line hormonal therapy for chemotherapy-naive castration-resistant prostate cancer (CRPC). Today we are speaking about the guideline with one of its authors, Eric Singer, MD, a urologic oncologist at Rutgers Cancer Institute of New Jersey.
—Interviewed by Anna Azvolinsky
Cancer Network: Can you talk about why this guideline is particularly timely?
Dr. Singer: We have the good fortune in the management of prostate cancer to have new agents available, and in hearing from practitioners, patients, and patient advocates, I think there was a need to put more of a framework in place in terms of when these agents should be used and which men are the ideal candidates. ASCO has a very robust clinical practice guidelines committee and puts out guidelines regularly across the entire spectrum of cancer treatments, and so this seemed like a great opportunity for us to do one on second-line hormonal therapy for advanced CRPC, because there are now these options available.
Cancer Network: How was the PCO developed? What goes into deciding what is actually in the guideline?
Dr. Singer: ASCO has both guidelines and PCOs, and the goal for both is to provide the best evidence available. It’s a very robust, detailed process. There is an incredibly talented ASCO guideline staff, expert oncologists who form the clinical guideline committee membership, and individual guideline authorship teams. We do a detailed literature review, pulling published studies and presentations at national meetings, and go through all of the different levels of evidence to try to put together the most impactful and strongest evidence in support of doing something or sometimes not doing something.
The goal is to make it clear who we should be thinking about using an intervention in, when it should be used, how it should be used, and what the tradeoffs are in terms of toxicity vs increases or improvements in survival. We might perhaps address preventing complications or side effects, disease progression, metastasis, while also keeping in mind palliation and being thoughtful about financial toxicity—what impact would this treatment have on the patient in terms of out-of-pocket costs.
So we try to take all of those divergent pieces and interests and synthesize it down for our end users to something very readable, usable, and evidence-based.
Cancer Network: What is the weight of this PCO, how important is this for clinical care? Can you help put that into context?
Dr. Singer: The PCO—not quite the full weight of a formal guideline—was developed to try to be more nimble and more responsive to emerging evidence as the field continues to develop and mature. So in situations like CRPC where there are many studies, new agents coming out, new major reports being issued very regularly, the PCO allows us to still be able to get some guidance out there in a thoughtful and thorough manner—even though we know that the rate and pace of the field will change so that we will need to update this fairly regularly.
Cancer Network: Can you talk about the major recommendations within the PCO?
Dr. Singer: Some of the major recommendations from this PCO talk about when we should think about implementing second-line hormonal therapy in men with CRPC. Essentially, in men who do not have evidence of metastatic disease, who are M0, the thought is that we would typically not suggest treatment—unless they are at very high risk of developing metastasis because of a very rapidly progressing prostate-specific antigen (PSA) velocity.
Even in men who do have rapid PSA doubling time, if they don't have evidence of metastatic disease, we really want to counsel them carefully and make sure they fully understand the limitations of the evidence in terms of what benefit they might get from starting second-line hormonal therapy vs the side effects and costs that go along with it. And of course these are men who, very often, are eligible for clinical trials, and we certainly want to support men enrolling in clinical trials to try to answer these questions in a more robust fashion.
In terms of men who do have metastatic disease, so M1a or M1s, we would think about offering them second-line hormonal therapy—that would typically be abiraterone acetate (with prednisone) or enzalutamide, as both of these drugs have been shown to meet all of the endpoints that were specified in the clinical trials that looked at them. So they both increase the time to radiographic progression-free survival and improve survival. Those are the two agents that are currently being used in men with M1a and M1s CRPC.
Cancer Network: Anything else you would like to add, maybe the best way for clinicians to utilize the PCO?
Dr. Singer: I think one of the most important goals of the PCO is to help inform shared decision-making between our doctors and our patients. The PCO is intended to help synthesize all of the information out there so patients understand the potential benefits as well as the known risks that go along with starting a new line of therapy, and to remind all of our providers that palliation, attention to symptoms, and symptom management should be brought in very early on in the disease.
To reiterate, it is important to support clinical trials so that as we go forward and regularly update PCOs, like this one for second-line hormonal therapy, we’ll have the best data available to make the best recommendations possible.
Cancer Network: Thank you so much for joining us today, Dr. Singer.
Dr. Singer: Thank you, my pleasure.