title: Initial biopsy Gleason score as a predictive marker for survival benefit in patients with castration-resistant prostate cancer treated with docetaxel: data from the TAX327 study.
abstract: BACKGROUND
  Since 2004, docetaxel has been the standard first-line systemic therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). With abiraterone recently becoming available in the predocetaxel setting, it is warranted to identify subgroups of patients who may obtain the greatest benefit from docetaxel and particularly qualify for receiving docetaxel as first-line treatment for mCRPC.
  
  
  OBJECTIVE
  We aimed to identify factors that could characterize subgroups of patients who obtain the greatest benefit from the use of docetaxel.
  
  
  METHODS
  TAX327 was multinational, randomized, phase 3 study that was conducted from 2000 to 2002 in 1006 men with mCRPC.
  
  
  METHODS
  Patients were randomized to receive docetaxel every 3 wk (D3), weekly docetaxel (D1), or mitoxantrone every 3 wk (M3), each with prednisone.
  
  
  METHODS
  We investigated whether patients with poorly differentiated tumors (Gleason score ≥7) at diagnosis had greater benefit from D3 compared with M3 than patients with better differentiated tumors (Gleason score ≤6). Using a Cox model, we compared overall survival (OS) between the treatment groups within each subgroup of Gleason score.
  
  
  CONCLUSIONS
  The TAX 327 data showed that the OS benefit of D3 versus M3 was greater in patients with high-grade tumors (median OS: 18.9 vs 14.5 mo; p=0.009) than in patients with low-grade tumors (median OS: 21.6 vs 20.7 mo; p=0.674). Limitations of a retrospective analysis apply.
  
  
  CONCLUSIONS
  The survival benefit obtained with docetaxel is most pronounced in patients with high-Gleason-score tumors (Gleason ≥7). In a time of shifting paradigms in mCRPC, with abiraterone becoming available prior to docetaxel chemotherapy, Gleason score may help in selecting patients who obtain the greatest benefit from docetaxel as first-line treatment for mCRPC. Prospective validation of these findings is warranted.
authors: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: r.vansoest@erasmusmc.nl.
authors: Robert J
authors: RJ
authors: van Soest
authors: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Ellen S
authors: ES
authors: de Morrée
authors: Sanofi, Malvern, PA, USA.
authors: Liji
authors: L
authors: Shen
authors: Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada.
authors: Ian F
authors: IF
authors: Tannock
authors: Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors: Mario A
authors: MA
authors: Eisenberger
authors: Department of Medical Oncology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Ronald
authors: R
authors: de Wit
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001706:Biopsy; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008942:Mitoxantrone / Q000627:therapeutic use; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology*; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen
keywords: Castration-resistant prostate cancer; Gleason score; Taxanes