[Neuroendocrine prostate cancer]

Area of Science:

• Urology
• Oncology
• Cancer Biology

Background:

• Neuroendocrine prostate cancer (NEPC) often emerges as a treatment-adaptive response to androgen deprivation therapy (ADT) in metastatic castration-resistant prostate cancer (mCRPC).
• Approximately 30-40% of mCRPC cases exhibit neuroendocrine differentiation, while primary small cell prostate cancer is rare (<1%).
• High Gleason score is an independent risk factor for developing treatment-emergent NEPC (t-NEPC).

Purpose of the Study:

• To outline the clinical suspicion, diagnostic indicators, and treatment strategies for neuroendocrine prostate cancer.
• To differentiate t-NEPC from primary small cell prostate cancer.
• To guide therapeutic decisions based on prostate-specific antigen (PSA) levels in NEPC patients.

Main Methods:

• Clinical suspicion criteria for t-NEPC include aggressive mCRPC with disproportionately low PSA and elevated neuroendocrine markers (chromogranin A, neuron-specific enolase).
• Correlation analysis of initial Gleason score with t-NEPC development risk.
• Review of treatment protocols, including chemotherapy regimens for NEPC based on PSA levels.

Main Results:

• Chemotherapy with cisplatin and etoposide yields 30-60% response rates and <1 year median survival in PSA-negative NEPC.
• Carboplatin plus docetaxel is considered for NEPC patients with significantly elevated serum PSA levels.
• Initial Gleason score is a significant predictor for t-NEPC development.

Conclusions:

• NEPC requires high clinical suspicion in mCRPC patients presenting with aggressive disease, low PSA, and elevated neuroendocrine markers.
• Treatment approaches for NEPC are adapted from small cell lung cancer protocols, with specific chemotherapy choices dependent on PSA levels.
• Early identification and appropriate treatment selection are crucial for managing NEPC, given its aggressive nature and distinct therapeutic requirements.