title: Neuroendocrine Prostate Cancer (NEPC) progressing from conventional prostatic adenocarcinoma: factors associated with time to development of NEPC and survival from NEPC diagnosis-a systematic review and pooled analysis.
abstract: OBJECTIVE
  An often under-recognized late manifestation of prostate adenocarcinoma (PCa) is the development of treatment-related neuroendocrine prostate cancer (NEPC). The aim of this study is to identify the risk factors related to survival after NEPC diagnosis (NEPCS) and time from initial diagnosis of PCa to development of NEPC (TTNEPC).
  
  
  METHODS
  A literature search on NEPC was performed using databases such as MEDLINE and EMBASE. Studies were eligible if outcomes data (NEPCS and/or TTNEPC) were reported in patients with a prior history of PCa and histopathologically confirmed NEPC. NEPCS and TTNEPC were evaluated using the Cox regression model with the robust sandwich estimates of the covariance matrix.
  
  
  RESULTS
  There were 54 eligible publications, contributing 123 patients. The median TTNEPC was 20 months. In multivariable analyses, the Gleason score was significantly associated with shorter TTNEPC (hazard ratio [HR], 1.66; P = .032). The median NEPCS was 7 months. In multivariable analyses, the number of organs with metastatic disease at NEPC was significantly associated with shorter NEPCS (HR, 3.31; P = .001). Type of treatment after NEPC was significantly associated with longer NEPCS, with HRs of 0.66 (radiotherapy v palliative therapy; P = .034), 0.38 (chemotherapy v palliative therapy; P = .018), and 0.29 (chemoradiotherapy v palliative therapy; P = .012), respectively.
  
  
  CONCLUSIONS
  Treatment-related NEPC is an often under-recognized late manifestation of PCa with poor prognosis. Our study found that Gleason score was the only independent factor contributing to TTNEPC. Once NEPC is diagnosed, type of treatment and the number of organs with metastatic disease were the most important factors related to survival.
authors.affiliation: Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Hai Tao Wang, Bao Guo Li, Yong Tang, Research Group of Evidence-based Clinical Oncology; Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Key Laboratory of Cancer Prevention and Therapy; Ji Wu Chang, Tianjin Institute of Urologic Surgery, Tianjin, China. peterrock2000@126.com.
authors.forename: Hai Tao
authors.initials: HT
authors.lastname: Wang
authors.affiliation: Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Hai Tao Wang, Bao Guo Li, Yong Tang, Research Group of Evidence-based Clinical Oncology; Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Key Laboratory of Cancer Prevention and Therapy; Ji Wu Chang, Tianjin Institute of Urologic Surgery, Tianjin, China.
authors.forename: Yan Hong
authors.initials: YH
authors.lastname: Yao
authors.affiliation: Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Hai Tao Wang, Bao Guo Li, Yong Tang, Research Group of Evidence-based Clinical Oncology; Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Key Laboratory of Cancer Prevention and Therapy; Ji Wu Chang, Tianjin Institute of Urologic Surgery, Tianjin, China.
authors.forename: Bao Guo
authors.initials: BG
authors.lastname: Li
authors.affiliation: Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Hai Tao Wang, Bao Guo Li, Yong Tang, Research Group of Evidence-based Clinical Oncology; Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Key Laboratory of Cancer Prevention and Therapy; Ji Wu Chang, Tianjin Institute of Urologic Surgery, Tianjin, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Hai Tao Wang, Bao Guo Li, Yong Tang, Research Group of Evidence-based Clinical Oncology; Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Key Laboratory of Cancer Prevention and Therapy; Ji Wu Chang, Tianjin Institute of Urologic Surgery, Tianjin, China.
authors.forename: Ji Wu
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Hai Tao Wang, Bao Guo Li, Yong Tang, Research Group of Evidence-based Clinical Oncology; Hai Tao Wang, Yan Hong Yao, Bao Guo Li, Yong Tang, Jiao Zhang, Tianjin Key Laboratory of Cancer Prevention and Therapy; Ji Wu Chang, Tianjin Institute of Urologic Surgery, Tianjin, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000401:mortality / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000473:pathology