title: Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.
abstract: BACKGROUND
  To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC).
  
  
  METHODS
  A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48).
  
  
  RESULTS
  Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005).
  
  
  CONCLUSIONS
  In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.
authors.affiliation: Department of Urology, University of Tuebingen, Tuebingen, Germany georgios.gakis@googlemail.com.
authors.forename: G
authors.initials: G
authors.lastname: Gakis
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Morgan
authors.affiliation: Institute of Urology, USC/Norris Comprehensive Cancer Center, Los Angeles.
authors.forename: S
authors.initials: S
authors.lastname: Daneshmand
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Keegan
authors.affiliation: Department of Urology, University of Tuebingen, Tuebingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Todenhöfer
authors.affiliation: Department of Urology, University of Tuebingen, Tuebingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Mischinger
authors.affiliation: Department of Urology, University of Tuebingen, Tuebingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schubert
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Zaid
authors.affiliation: 2nd Medical School, Department of Urology, Charles University, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Hrbacek
authors.affiliation: Urology and Nephrology Center, Mansoura Clinic, Mansoura, Egypt.
authors.forename: B
authors.initials: B
authors.lastname: Ali-El-Dein
authors.affiliation: Department of Radiooncology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Clayman
authors.affiliation: Department of Radiooncology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Galland
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, USA.
authors.forename: K
authors.initials: K
authors.lastname: Olugbade
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg.
authors.forename: M
authors.initials: M
authors.lastname: Rink
authors.affiliation: Department of Urology, University Hospital Regensburg, Regensburg, Germany.
authors.forename: H-M
authors.initials: HM
authors.lastname: Fritsche
authors.affiliation: Department of Urology, University Hospital Regensburg, Regensburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Burger
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Chang
authors.affiliation: 2nd Medical School, Department of Urology, Charles University, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Babjuk
authors.affiliation: Department of Urology, University Hospital Bern, Bern, Switzerland.
authors.forename: G N
authors.initials: GN
authors.lastname: Thalmann
authors.affiliation: Department of Urology, University of Tuebingen, Tuebingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Department of Radiooncology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Efstathiou
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000368:Aged; D000068196:Albumin-Bound Paclitaxel / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000628:therapy*; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D015653:Cystectomy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D020360:Neoadjuvant Therapy / Q000379:methods*; D017239:Paclitaxel / Q000008:administration & dosage; D019990:Perioperative Care; D012189:Retrospective Studies; D014521:Urethra / Q000601:surgery*; D014523:Urethral Neoplasms / Q000401:mortality / Q000628:therapy*; D014547:Urinary Diversion; D000093542:Gemcitabine
chemical_list: D000068196:Albumin-Bound Paclitaxel; D003841:Deoxycytidine; D016685:Mitomycin; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D007069:Ifosfamide; D000093542:Gemcitabine
keywords: adjuvant; chemoradiotherapy; chemotherapy; neoadjuvant; primary urethral carcinoma