This month, Prostatepedia is talking about neuroendocrine prostate cancer, an aggressive form of the disease.
Dr. Neeraj Agarwal,e Director of the Genitourinary Oncology Program in the Oncology Division, the Co-Leader of the Urologic Oncology Multidisciplinary Program, and the Associate Director of Clinical Trials at the Huntsman Cancer Institute at the University of Utah, offers his insights into this month’s discussions.
Until 2010, the only drug treatment we had for advanced prostate cancer was chemotherapy with Taxotere (docetaxel). Since then, we have seen the advent of many new drugs, including the drugs to target androgen signaling. Androgen signaling is a critical player in prostate cancer progression. Testosterone is needed for prostate cancer as a fuel; testosterone interacts with the androgen receptor, which is necessary for transcription within the prostate cancer cells.
These drugs induce a deeper blockage of androgen signaling. They include Zytiga (abiraterone) with prednisone, which diminishes the production of testosterone within the prostate cancer cells and adrenal glands, and Xtandi (enzalutamide), which is a next-generation androgen receptor blocker. We also have several new drugs that target androgen signaling in similar fashions such as apalutamide (ARN-509), and darolutamide (ODM-201).
However, over the past five years, we have observed that literally every patient experiences disease progression on these newer androgen signaling targeting drugs. When they progress, some unique features are seen. In approximately 25% of these patients, their PSA values do not necessarily go up in proportion to their disease burden, while their scans show disease progression. This phenomenon is what we now call androgen indifferent prostate cancer, or neuroendocrine prostate cancer.
Neuroendocrine or androgen indifferent prostate cancer existed in the past. A small number of patients—maybe 5%—have neuroendocrine disease from the day they come in for their first biopsy. But now, as these patients are living longer, courtesy of the new androgen signaling inhibitors, the prevalence of neuroendocrine prostate cancer has been increasing steadily. These patients do not really respond well to further manipulation of androgen signaling.
We don’t have standard guidelines in place to diagnose neuroendocrine or androgen-indifferent prostate cancer, so physicians are not always sure what to do when they see this unusual presentation of prostate cancer. Many renowned experts, such as Dr. Ana Aparicio or Dr. Himisha Beltran who are featured this month in Prostatepedia, are working on diagnosis, treatment, and establishing biomarkers for these patients.
From a clinician’s perspective, I can tell a patient has neuroendocrine or androgen-indifferent prostate cancer when I notice disease progression on the scans with disproportionally low PSA levels, and an increase in other tumor markers, such as LDH (lactate dehydrogenase) and alkaline phosphatase.
If you notice these features I recommend consulting with an expert who specializes in neuroendocrine type prostate cancer. Seek out an NCI-designated comprehensive cancer center where oncologists are specializing in prostate cancer, and are likely going to be more familiar with this form of prostate cancer.
I think it’s worth spending extra time, money, and effort up front for the correct diagnosis and a more appropriate treatment plan.