Low‐serum prostate‐specific antigen level predicts poor outcomes in patients with primary neuroendocrine prostate cancer

Abstract

Background The rarities of primary neuroendocrine prostate cancer (NEPC) and primary adenocarcinoma with neuroendocrine differentiation (NE differentiation) mean that their clinical characteristics have not been fully elucidated. Materials and Methods A total of 449 patients with NEPC, including 352 cases of pure NEPC and 97 cases of NE differentiation, together with 408 629 cases of prostate adenocarcinoma at diagnosis were retrieved from the Surveillance, Epidemiology, and End Results program (2010‐2015). Clinical parameters and prognoses were compared between patients with different histological types of NEPC using the χ2 test and Kaplan‐Meier analysis, respectively. The prognostic value of prostate‐specific antigen (PSA) in NEPC and adenocarcinoma was evaluated using Cox regression and the Kaplan‐Meier method. Results Pure NEPC had higher rates of visceral metastases (brain, lung, and liver: 4.58%, 26.72%, and 36.64%, respectively) but a lower rate of bone metastasis (65.65%) compared with NE differentiation and prostate adenocarcinoma. Moreover, patients diagnosed with pure NEPC had a poorer outcome (median survival time: 10 months) compared with patients with NE differentiation (26 months) and prostate adenocarcinoma (median survival time not reached). Using PSA 4.1 to 10 ng/mL as the reference, the adjusted hazard ratios (HRs) for PSA lower than or equal to 4.0 ng/mL were 2.24 (95% confidence interval [CI]: 1.11‐4.55, P = .025) in the NE differentiation group and 1.57 (95% CI: 1.11‐2.23, P = .011) in the pure NEPC group. Conclusions Patients with NE differentiation had different clinical characteristics and a better prognosis than patients with pure NEPC. In addition, low‐serum PSA levels were associated with a poorer prognosis in patients with either NEPC or NE differentiation.

Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological and Immunohistochemical Analysis of 94 Cases

“…Recent studies on T-NEPC had shown that AR often positively expressed in tumor cells, but despite the AR protein expression in the nucleus, the transcriptional activity of AR was very low, which indicated that epigenetic mechanisms may inhibit AR function ( 16 ). Our study found that the negative PSA expression was an independent prognostic factor, these results were consistent with previous reports ( 17 , 18 ). As T-NEPC and primary neuroendocrine prostate cancer showed similar molecular pathological characteristics ( 1 ), we validated our results using the SEER NEPC database.…”

Neuroendocrine Carcinoma as an Independent Prognostic Factor for Patients With Prostate Cancer: A Population-Based Study

“…In the present study, NEC patients with PSA levels higher than 4.0 ng/mL accounted for 43.7%, compared with 72.9% of adenocarcinoma patients. This result suggested that except for loss of AR, NEPC patients are typically manifested by the downregulation of PSA ( 28 ). Our investigation was consistent with previous studies, which demonstrated that the PSA marker was usually expressed in adenocarcinoma while SCC, large cell carcinoma, or mixed adenocarcinoma neuroendocrine histology were scarcely expressed PSA ( 29 ).…”

Incidental detection of localized prostate cancer with low PSA by computed tomography scan: A report of two cases

“…Low serum PSA levels are an independent negative prognostic factor in PCa. 16 , 17 , 19 PSA‐negative PCa potentially responds poorly to androgen deprivation therapy (ADT). 19 A study using cell lines has demonstrated that cells that express low PSA levels or no PSA preferentially express stem cell genes.…”