title: Sensitivity to chemoradiation predicts development of metastasis in muscle-invasive bladder cancer patients.
abstract: OBJECTIVE
  In bladder-sparing approaches for muscle-invasive bladder cancer (MIBC) involving transurethral resection of the bladder tumor (TURBT) and chemoradiation, survival outcomes are excellent for patients who achieve tumor-free state after TURBT and chemoradiation but poor for those with persistent disease. Since metastatic disease accounts for most bladder cancer deaths, we hypothesized that tumor sensitivity to chemoradiation may reflect metastatic potential in MIBC.
  
  
  METHODS
  From 1997 to 2010, 179 cT2-4aN0M0 bladder cancer patients underwent TURBT and induction chemoradiation (40 Gy with cisplatin 20 mg/d for 5 days × 2). Study subjects were 73 patients who had had macroscopic disease after TURBT and were evaluated for tumor sensitivity to the induction chemoradiation; of the 73 patients, chemoradiation response was evaluated pathologically in partial and radical cystectomy specimens for 8 and 44 patients, respectively, and clinically for the remaining 21 who did not undergo cystectomy. Tumors were defined as chemoradiation-sensitive when they regressed to T0 pathologically for the 52 patients undergoing cystectomy or clinically for the 21 undergoing no cystectomy; otherwise, they were defined as chemoradiation-resistant. Primary and secondary endpoints were metastasis-free and cancer-specific survival, respectively. The association between chemoradiation sensitivity and development of metastasis was investigated in MIBC patients.
  
  
  RESULTS
  Of the 73 patients, 21 (29%: 13 pathologic and 8 clinical T0) had chemoradiation-sensitive tumors while 52 (71%) had chemoradiation-resistant tumors. Median follow-up was 53 months. Multivariate analysis identified chemoradiation resistance as the strongest independent predictor for the development of metastasis (hazard ratio (HR) 18.9, P < 0.0001). When stratified by chemoradiation sensitivity, 5-year metastasis-free and cancer-specific survival rates were 94.7% and 100%, respectively, for patients with chemoradiation-sensitive tumors, and 45.7% (P = 0.0005) and 41.0% (P < 0.0001), respectively, for patients with chemoradiation-resistant tumors.
  
  
  CONCLUSIONS
  Chemoradiation sensitivity predicts the development of metastasis in bladder cancer. Clinical and translational research results indicate that chemoradiation sensitivity is likely to reflect metastatic potential.
authors.affiliation: Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. Electronic address: f-koga.uro@tmd.ac.jp.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Koga
authors.forename: Noboru
authors.initials: N
authors.lastname: Numao
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Saito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Masuda
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujii
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kihara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000379:methods; D002945:Cisplatin / Q000627:therapeutic use; D015653:Cystectomy / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin