Neuroendocrine and Aggressive-Variant Prostate Cancer

Abstract

In prostate cancer, neuroendocrine (NE) differentiation may rarely present de novo or more frequently arises following hormonal therapy in patients with castration-resistant prostate cancer (CRPC). Its distinct phenotype is characterized by an aggressive clinical course, lack of responsiveness to hormonal therapies and poor prognosis. Importantly, a subset of CRPC patients exhibits an aggressive-variant disease with very similar clinical and molecular characteristics to small-cell prostate cancer (SCPC) even though tumors do not have NE differentiation. This aggressive-variant prostate cancer (AVPC) also shares the sensitivity of SCPC to platinum-based chemotherapy albeit with short-lived clinical benefit. As optimal treatment strategies for AVPC remain elusive, currently ongoing research efforts aim to enhance our understanding of the biology of this disease entity and improve treatment outcomes for our patients. This review is an overview of our current knowledge on prostate cancer with NE differentiation and AVPC, with a focus on their clinical characteristics and management, including available as well as experimental therapeutic strategies.

Neuroendocrine Differentiation of Prostate Cancer Is Not Systematically Associated with Increased 18F-FDG Uptake

“…While the former PET/CT showed very mild to moderate tracer uptake in a few pelvic and vertebral bone lesions (maximum Standardized Uptake Value (SUVmax): 2.5 vs. 4 at baseline), the latter showed a widespread, intensely Dotatoc-avid skeletal, pleural, and lymph nodal disease burden (SUVmax: 64 vs. 5 at baseline) (Panels ( C , D )). This result was interpreted as a progression of the NED part of the disease, not tracked by PSA kinetics in agreement with the acknowledged low-PSA secretion tendency of this kind of tumor [ 8 , 9 , 10 ]. On the one hand, the present case challenges FDG PET/CT’s acknowledged prognostic value in mCRPC patients.…”

Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer

“…Although the trial did not meet its primary endpoint of improved PFS, the tumors suggestive of N-myc and Aurora-A overactivity showed exceptional responses, including the complete resolution of liver metastases and prolonged stable disease. Many trials are currently ongoing in patients with AVPC and NEPC to test the activity of immunotherapy, PARP inhibitors, and EZH2 inhibitors in these patients [ 148 ].…”

Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment

“…Other regimens include cisplatin/irinotecan, carboplatin//irinotecan, gemcitabine/docetaxel/carboplatin, doxorubicin/cisplatin/etoposide, amrubicin, and everolimus [ 120 , 121 , 122 , 123 , 124 ]. Summarizing the data, the survival time is generally reported to be 7–16 months, indicating that the NEPC prognosis and aggressive/anaplastic mCRPC are very poor [ 11 , 125 , 126 ]. Although a few scattered reports were noted showing the efficacy of these treatments, none have been proven by clinical trials with a high level of evidence.…”