Clinical features of neuroendocrine prostate cancer

Abstract

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.

WITHDRAWN: Early Detection of Neuroendocrine Prostate Cancer as Lineage Plasticity in Recurrent Prostate Cancer After Radiation and Androgen Deprivation Therapy: A Case Report

“…NEPC is one of most aggressive prostate cancers, with a median prognosis of only 7 months [3,4]. NEPC arises after salvage ADT as a result of (i) lineage plasticity, (ii) differentiation from adenocarcinoma to a neuroendocrine tumor, and (iii) escape from androgen receptor (AR) pathway inhibitation [5][6][7][8]. Therefore, early NEPC detection is necessary.…”

Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer

“…Metastatic biopsies demonstrate morphologic features of small cell carcinoma, often with low or absent expression of the AR, downregulation of downstream AR-regulated markers such as prostatespecific antigen (PSA), and expression of classical neuroendocrine markers (e.g., chromogranin, synaptophysin) (6,7). The prognosis of CRPC-NE is poor due in part to late diagnosis and a lack of effective therapies (5,8). Similar to other poorly differentiated neuroendocrine carcinomas (9, 10), CRPC-NE frequently harbors genomic loss of RB1 and TP53 (4,6,11,12).…”

Immune molecular profiling of a multiresistant primary prostate cancer with a neuroendocrine-like phenotype: a case report

“…Rb loss, AURKA gain etc. ), however it did not exhibit many of the key clinical features such as low PSA rise and metastasis [ 36 ]. Conversely, we identified many novel molecules that are specifically expressed in the recurrent tissue which have strong links to more conventional PC pathologies and progression (e.g.…”