Nonmetastatic CRPC: Other Therapies and Coordinating Care

Charles Ryan, MD:Nonmetastatic CRPC is being evaluated with a number of different therapies right now. There’s apalutamide, an orally available AR antagonist. Darolutamide is another orally available AR antagonist. Abiraterone had been studied in this setting in phase II studies, and enzalutamide has been studied in this setting as well. So, those are the androgen receptor hormonal therapies that are being evaluated. There are a number of other smaller studies looking at different concepts, immunotherapies and things like that, in this setting, but none of them are quite to mainstream clinic yet.

The monitoring of patients with castration-resistant prostate cancer is undergoing a bit of an evolution because we’re seeing new generation imaging modalities come to the clinic. So, more specifically, we are very excited about things like the Gallium-68 PSMA-targeted peptides, which help us to lead to targeted imaging of prostate cancer. There are other approaches, fluciclovine and others like that, that are available in many clinics around the country. And so, this is part of the process of evaluating nonmetastatic castration-resistant prostate cancer.

Nonmetastatic castration-resistant prostate cancer exists to some degree because of the failing of our old imaging modalities. And so, the bone scans that we’ve used for decades are relatively weak and such, but they’re still used. CAT scans are still used. And I would actually add that one of the things I’ve noticed is that patients in a variety of clinic settings may have pelvic imaging done, may have bone imaging done, but actually many patients harbor lung metastases. And so, the imaging of a patient who’s felt to have nonmetastatic disease should also include a lung CT, at least one, at least at baseline.

I’m not sure it’s important exactly to know what the training discipline is of the physician treating the patient as long as they understand what they’re doing and they have experience doing it. In my clinical practice, I give all the hormonal therapy. I don’t really have any competition from urologists in terms of treating CRPC because in my community, that’s not what they do. The urologists are well educated on the side effects of therapy and how to monitor them, and on what’s available as a therapy for patients. In other words, anybody who’s treating a patient needs to know what the alternate treatments that are available and what they’re going to do if this patient’s treatment fails.

I think that any clinician who is treating castration-resistant prostate cancer now needs to understand the genomic revolution that we’re undergoing. They need to know what the genomic findings, if they obtain them from a patient, mean or the fact that they need to think about obtaining genomic findings from their patients because it will alter therapy in the future. And so, whether that patient has an oncologist or a urologist, I don’t really care. What’s important is the level of experience and the level of knowledge, and I’d also say the level of curiosity about the disease. Because this is a fascinating, nuanced and complex disease. And we are going to discover even new personal ways to treat it or new ways to research it, if we’re not asking questions and integrating new therapies and modalities into our clinical practice.

Patients with castration-resistant prostate cancer are enjoying the best survival they ever have. They have a number of treatment options available to them. And in addition to seeing new therapies enter the clinic, we’re seeing the established therapies demonstrate benefits earlier and earlier in the clinical course, which is going to allow us to give therapies in the context of patients who aren’t quite as ill and don’t have quite a high degree of tumor morbidity. And so, I think what this will translate into, over time, is a prolongation of the time in which patients are experiencing a preserved quality of life. They’re preventing complications and they’re going to live longer, and it’s very gratifying to be part of that movement.

Transcript edited for clarity.

January 2014

• A 66-year old retired African American male presents with reduced urinary flow and hematuria.
• PMH: High blood pressure. Currently taking enalapril 10 mg.
• FHx: Father lung cancer — age 74.
• Patient walks 3 miles a day.
• PSA 9.8 ng/ml
• Prostate biopsy shows Gleason 7 (4+3) prostate cancer
• Undergoes robotic-assisted laparoscopic prostatectomy (RALP) and pelvic lymph node dissection (PLND)
• Results show:
  • pT3b (focal extracapsular extension and seminal vesicle invasion) — margins negative
  • N1
  • M0
• Post-operative PSA=0.64 ng/ml
• Patient undergoes adjuvant radiation therapy and is started on leuprolide acetate.
• PSA drops to undetectable levels

January 2016

• PSA starts to rise to 0.3 ng/ml
  • Repeated 3 months later — 0.7 ng/ml
  • Bone scan and prostate-specific membrane antigen (PSMA) scan both negative
  • Diagnosis nonmetastatic castration-resistant prostate cancer (CRPC)
  • Patient declines additional therapy at this time

November 2017

• PSA continues to rise over the next 18 months going up to 9.8 ng/ml
• Bone scan shows lesion in the left superior pubic ramus
• Patient is asymptomatic