title: Pathology-based risk stratification of muscle-invasive bladder cancer patients undergoing cystectomy for persistent disease after induction chemoradiotherapy in bladder-sparing approaches.
abstract: What's known on the subject? and What does the study add? In bladder-sparing approach incorporating TURBT and chemoradiotherapy (CRT) to MIBC, patients who clinically achieve complete response to induction CRT enjoy favourable prognosis and quality of life with preserved functioning bladder, whereas those with persisting disease have poor prognosis despite salvage radical cystectomy. Risk factors for cancer death among the non-responders remain fully unknown. The current study showed that survival of the non-responders is clearly stratified into low- and high-risk groups based on pathology of cystectomy specimens; 5-yr CSS rates for low- (pTO-2pNO) and high-risk (pT3-4a or pN+) patients were 85% and 20%, respectively.
  
  
  OBJECTIVE
  To stratify patients with a clinical non-complete response (CR) after induction chemoradiotherapy (CRT) according to their risk of death from cancer, based on pathology of cystectomy specimens.
  
  
  METHODS
  From 1997 to 2009, 170 patients with cT2-4aN0M0 bladder cancer underwent transurethral resection followed by induction CRT (40 Gy with cisplatin). Clinical response was evaluated 4-6 weeks after completion of CRT. Patients who met partial cystectomy (PC) criteria underwent PC plus pelvic lymph node dissection for bladder preservation. Otherwise, radical cystectomy (RC) was recommended. PC criteria were unifocal tumours, intact bladder neck and trigone, and CR (defined as no evidence of residual disease) or minimal amounts of residual non-muscle-invasive bladder cancer after induction CRT. Pathological variables associated with cancer death were analysed in patients who underwent PC or RC using a multivariate Cox proportional hazard model.
  
  
  RESULTS
  Of 170 patients, 81 (48%) achieved a CR and 62 (36%) met the PC criteria. After CRT, 122 patients (72%) ultimately underwent PC (n = 44, 26%) or RC (n = 78, 46%). The 5-year cancer-specific survival (CSS) rate was 96% for the patients with a CR and 50% for patients with non-CR (P < 0.001, median follow-up for survivors: 48 months). In the 122 patients who underwent cystectomy, pT3-4a (hazard ratio [HR] 8.3 versus pTO-2, P < 0.001) and pN+ (HR 3.0 versus pNO, P = 0.037) were identified as significant and independent risk factors among variables including pT stage, lymph node yield at cystectomy, pN stage, and Iymphovascular invasion. A similar result was obtained through analysis of a sub-cohort of 69 patients with non-CR. Patients with non-CR were stratified according to their risk factors into low- (pT0-2pN0, 5-year CSS rate 85%) and high-risk (pT3-4a or pN+, 5-year CSS rate 20%) groups.
  
  
  CONCLUSIONS
  In CRT-based bladder-sparing approaches, patients with a clinical non-CR after induction CRT can be stratified into low- and high-risk groups for death from cancer based on pathology of cystectomy specimens. Patients at high risk are potential candidates for intensive adjuvant therapy including clinical trials.
authors.affiliation: Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. f-koga.uro@tmd.ac.jp
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Koga
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujii
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Masuda
authors.forename: Noboru
authors.initials: N
authors.lastname: Numao
authors.forename: Minato
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Ishioka
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Saito
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kihara
mesh_terms: D000368:Aged; D059248:Chemoradiotherapy; D015653:Cystectomy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012074:Remission Induction; D018570:Risk Assessment; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000628:therapy*