San Antonio, Texas USA (UroToday.com) Castrate resistant small cell/neuroendocrine prostate cancer (NEPC) is a clinically aggressive variant of prostate cancer. It usually has low or stable PSA and usually metastasizes to visceral organs.
It was shown that this type of prostate cancer has lower androgen receptor expression. Smaller cells, lower androgen receptor and EMT changes are common when looking at circulating tumor cells of NEPC. NEPC circulating tumor cells can be found in 10% of CRPC patients. These patients demonstrate poor prognosis. It is not clear whether NEPC represents EMT, de-differentiation, 2 primary tumors or transformation into a new cancer. The implications of the answer to this question involve opportunities for early diagnosis, co-targeting and reversal of the neoplastic process. From data obtained by serially biopsying patients with CRPC (some of which developed NEPC) it was shown that NEPC stems from divergent clonal evolution rather than independent clonal expression. Whole exome sequencing of circulating tumor DNA (ctDNA) demonstrated similar whole exome profile of initially diagnosed CRPC and NEPC at 4 years from diagnosis. This suggests that NEPC alterations may be detectable in ctDNA potentially earlier than clinical and pathologic diagnosis of NEPC. Another similarity of CRPC and NEPC is the loss of androgen receptor signaling dependence. On the other hand, NEPC acquires distinct molecular features (e.g. loss of RB1, TP53) all of which may serve as therapeutic targets in the near future. In conclusion, NEPC is an aggressive subtype of CRPC. Intensive research is ongoing in this field.
Presented By: Himisha Beltran
Written By: Miki Haifler, MD, M.Sc., Society of Urologic Oncology Fellow, Fox Chase Cancer Center
17th Annual Meeting of the Society of Urologic Oncology - November 30 -December 2, 2016 – San Antonio, Texas USA