Risk factors associated with neuroendocrine differentiation of primary prostate carcinoma after neoadjuvant therapy: a whole-mount specimen based pilot study

Objective To explore the factors associated with neuroendocrine differentiation in primary prostate cancer (PCa) after neoadjuvant therapy. Patients and methods: A total of 371 patients with high-risk/locally advanced PCa who underwent robot-assisted radical prostatectomy (RP) after neoadjuvant therapy were included. According to the final pathology, patients were divided into two groups: with or without neuroendocrine differentiation. The baseline and prognostic information were collected and analyzed. Univariate and multivariate analysis were used to explore the independent factors which were found to be significantly associated with neuroendocrine differentiation. Results Neuroendocrine differentiation was observed only in 13 cases after neoadjuvant therapy. T stage, treatment regimen, and treatment duration were found to be associated with neuroendocrine differentiation in the univariate analysis. T stage and treatment duration were selected by multivariate analysis. Chemotherapy was more likely to drive neuroendocrine differentiation than abiraterone (P = 0.033) in the subgroup analysis. Furthermore, we found that the patients with neuroendocrine differentiation after neoadjuvant therapy had worse pathologic complete response (pCR ) (P < 0.001) and higher biochemical recurrence (BCR) (P = 0.006) rate compared to those without neuroendocrine differentiation. Conclusion T stage and neoadjuvant treatment duration could be independent factors of neuroendocrine differentiation in PCa patients after neoadjuvant therapy. Compared to abiraterone, chemotherapy was more likely to drive neuroendocrine differentiation, leading to poorer pCR and BCR.