title: Long-term oncological outcomes of a phase II trial of neoadjuvant chemohormonal therapy followed by radical prostatectomy for patients with clinically localised, high-risk prostate cancer.
abstract: OBJECTIVE
  To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer.
  
  
  METHODS
  In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only.
  
  
  RESULTS
  In all, 34 patients were enrolled and followed for a median of 13.1 years. Within 10 years most patients had biochemical recurrence (BCR-free probability 22%; 95% confidence interval [CI] 10-37%). However, the probability of disease-specific survival at 10 years was 84% (95% CI 66-93%) and overall survival was 78% (95% CI 60-89%). The CHT group had higher-risk features than the comparison group (123 patients), with an almost doubled risk of calculated preoperative 5-year BCR (69% vs 36%, P < 0.01). After adjusting for these imbalances the CHT group had trends toward improvement in BCR (hazard ratio [HR] 0.76, 95% CI 0.43-1.34; P = 0.3) and metastasis-free survival (HR 0.55, 95% CI 0.24-1.29; P = 0.2) although these were not statistically significant.
  
  
  CONCLUSIONS
  Neoadjuvant CHT followed by RP was associated with lower rates of BCR and metastasis compared with the RP-only group; however, these results were not statistically significant. Because this treatment strategy has known harms and unproven benefit, this strategy should only be instituted in the setting of a clinical trial.
authors.affiliation: Department of Urology, Tulane University Medical School, New Orleans, LA, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Silberstein
authors.affiliation: Department of Urology, Southern California Permanente Medical Group- Fontana Medical Center, Fontana, CA, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Poon
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Sjoberg
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Maschino
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Vickers
authors.affiliation: Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Bernie
authors.affiliation: Department of Urology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Badrinath R
authors.initials: BR
authors.lastname: Konety
authors.affiliation: Departments of Urology and Medical Oncology, Thomas Jefferson University and Hospitals, Philadelphia, PA, USA.
authors.forename: W Kevin
authors.initials: WK
authors.lastname: Kelly
authors.affiliation: Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Eastham
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D017239:Paclitaxel / Q000008:administration & dosage; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004961:Estramustine; D016190:Carboplatin; D017239:Paclitaxel
keywords: chemotherapy; hormone therapy; neoadjuvant; prostate neoplasms; radical prostatectomy; survival