Editor's Note: Neuroendocrine prostate cancer (NEPC) is a hormone-refractory late manifestation of prostate cancer and represents about 25% of late-stage disease. NEPC has a poor prognosis, with most patients surviving for less than 1 year after diagnosis. New research on the biology of NEPC has inspired novel approaches to treating this disease. Prostate cancer expert Himisha Beltran, MD, who is leading an ongoing phase 2 study of an aurora kinase inhibitor in NEPC, discussed with Medscape the molecular and genomic advances in NEPC and the challenges that remain for clinicians. Dr. Beltran is Assistant Professor of Medicine at Weill Cornell Medical College and Assistant Attending Physician at New York-Presbyterian Hospital.
Medscape: What are the major challenges for clinicians in diagnosing NEPC?
Dr. Beltran: NEPC is often not recognized because we have not been focused on it. Clinically, NEPC should be suspected in patients who develop rapidly progressive disease or visceral disease such as liver metastases or brain metastases in the setting of low prostate- (PSA). In those cases, biopsies should be considered to confirm or rule out NEPC. An important reason to be aware of the possibility of NEPC and to actively look for it is that drugs that target signaling are less likely to be effective in NEPC. That is an important implication for being able to select patients for individualized treatment.
Medscape: Why do some prostate cancers progress or transition to NEPC?
Dr. Beltran: Most are driven by hormonal signaling through the androgen receptor, which is why the mainstays of cancer patients are drugs that target the androgen signaling pathway. Neuroendocrine prostate tumors often demonstrate low or absent androgen receptor expression and may arise as a mechanism of resistance. NEPC rarely arises de novo, in the absence of prior treatment. Preclinical studies support the concept that if you strongly pressure the androgen receptor you can transform an adenocarcinoma cell into an androgen receptor-negative state.