Clinical features of neuroendocrine prostate cancer

Eur J Cancer. 2019 Nov:121:7-18. doi: 10.1016/j.ejca.2019.08.011. Epub 2019 Sep 13.


Background: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may arise de novo or in patients previously treated with hormonal therapies for prostate adenocarcinoma as a mechanism of resistance. Despite being important to recognise, the clinical features of NEPC are poorly defined and could help guide when to perform a biopsy to look for NEPC histologic transformation.

Methods: We reviewed baseline, treatment and outcome data of 87 patients with metastatic prostate cancer and tumour biopsy confirming NEPC histology. Forty-seven (54.0%) NEPC cases presented de novo, and 40 (46.0%) were therapy-related (t-NEPC). Thirty-six (41.4%) were classified as pure small-cell carcinoma, and 51 (58.6%) demonstrated mixed features with both small-cell carcinoma and adenocarcinoma present. Genomic data were available for 47 patients.

Results: The median age at time of NEPC was 68.1 years, median prostate-specific antigen (PSA) was 1.20 ng/ml (0.14 ng/mL small-cell carcinoma, 1.55 ng/mL mixed carcinoma) and sites of metastases included bone (72.6%), lymph node (47.0%), and viscera (65.5%). Median time from adenocarcinoma to t-NEPC diagnosis was 39.7 months (range, 24.5-93.8) with a median of two lines of prior systemic therapy. Platinum chemotherapy was used to treat 57.5% of patients, with a median progression-free survival of 3.9 months. Small-cell carcinoma was associated with worse overall survival (OS) than mixed histology (8.9 months from NEPC diagnosis versus 26.1 months, P < 0.001). Median OS of de novo NEPC was shorter than that of t-NEPC (16.8 months from prostate cancer diagnosis versus 53.5 months, P = 0.043). An average PSA rise per month of ≤0.7 ng/ml before t-NEPC; elevated lactate dehydrogenase levels, RB1 and TP53 loss and liver metastases were poor prognostic features.

Conclusions: We describe the clinical features of a cohort of patients with NEPC. These characteristics may inform future diagnostic strategies.

Keywords: Aggressive variant; Neuroendocrine prostate cancer; Small-cell carcinoma; Treatment resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Biopsy
  • Carcinoma, Neuroendocrine* / diagnosis
  • Carcinoma, Neuroendocrine* / mortality
  • Carcinoma, Neuroendocrine* / pathology
  • Carcinoma, Neuroendocrine* / therapy
  • Carcinoma, Small Cell / mortality
  • Carcinoma, Small Cell / pathology
  • Cohort Studies
  • Disease Progression
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Prostatic Neoplasms* / diagnosis
  • Prostatic Neoplasms* / mortality
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / therapy
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome