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Metastatic Castration-Resistant Prostate Cancer: Treatment Selection and Sequencing With Tanya Dorff, MD

Tanya Dorff, MD

Prostate cancer is the most common tumor type among men in the United States. Typically, androgen deprivation therapy is administered for progressive disease. However, castration resistance or unresponsiveness to androgen deprivation therapy or to antiandrogens frequently develops over time. The transition from castration-sensitive to castration-resistant disease has yet to be understood and represents a significant unmet need. Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate-related mortality, accounting for an estimated 26,730 deaths annually. Median overall survival remains less than 2 years. In this interview, Tanya Dorff, MD, associate clinical professor at City of Hope, discusses challenges, recent advances, and the importance of clinical trials in the management of advanced CRPC.

What are some of the most challenging aspects of managing advanced CRPC?

Tanya Dorff, MD: The challenge that comes with so many new effective treatments approved for metastatic CRPC is that we're left with a lot of questions about how to best select the correct agent for each patient and how to optimally sequence the treatments. I think the other big challenge for metastatic CRPC is figuring out how to implement immunotherapy more effectively.

What practices would you recommend to community oncologists in managing advanced CRPC?

Dr. Dorff: That's a big question. I think oncologists have to pay attention to bone health. Anyone who's on prolonged androgen deprivation, and that includes our CRPC patients, need to be monitoring their bone marrow density. We also need to support them with vitamin D and an antiresorptive agent if indicated. We should also be paying attention to cardiovascular health because of the adverse effect of low testosterone on lipid metabolism and insulin resistance. In terms of treatment with approved therapies, I encourage practicing oncologists to think about clinical trials in addition to using drugs that are available. Clinical trials give some guidance as to what the future may hold and what the next generation of treatment will be.

Monitoring is the other big area where there's room for more rigorous guidelines to be followed. For instance, not taking a patient off of a therapy like enzalutamide or abiraterone simply due to rising PSA may be a poor treatment choice. We know that patients can have a slowly rising PSA and still be benefiting from the medication for an extended period. Clinicians should use imaging, as well as the patient's clinical characteristics, to help guide the decision to change therapy.

What questions do you commonly encounter from patients or caregivers about their treatment, and how do you counsel them?

Dr. Dorff: A very common question from patients is whether our treatments only slow the cancer down or if they actually kill cancer cells. We tell them that these treatments do kill cancer cells, but unfortunately, we haven't found a treatment yet that can kill every last cancer cell. This is why we get resistance, and sometimes need to sequence one treatment after the other.

Patients also ask about individualized treatment and whether there are blood tests that can be used to select a treatment, and unfortunately, we're not quite there yet, but those types of tests are on the horizon.

What are some other promising advances in CRPC treatment that you expect to see in the near future?

Dr. Dorff: There are currently multiple phase 3 trials, and I anticipate that at least one of the PARP agents should become available for metastatic CRPC with DNA repair deficiency in the near future. There are a couple of big advances pending that involve the PD-L-1 antibody in the context of enzalutamide progression.

What is the importance of getting patients with metastatic CPRC involved in clinical trials?

Dr. Dorff: That's such a soapbox of mine. What we've learned over the last three years is that when we take effective therapies and implement them earlier, we get more out of them. Clinical trials have shifted away from only being an option after you've exhausted all standard therapies, to requiring that you have not gone through all standard therapies. That's exciting because these clinical trials can have an even greater impact. But it means that if we don't think about clinical trials early in a patient's course, they're going to miss out on some of the most promising new drugs that are being considered for treatment of prostate cancer.

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