title: Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience.
abstract: BACKGROUND
  Whether organ-conserving treatment by combined-modality therapy (CMT) achieves comparable long-term survival to radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) is largely unknown.
  
  
  OBJECTIVE
  Report long-term outcomes of patients with muscle-invasive BCa treated by CMT.
  
  
  METHODS
  We conducted an analysis of successive prospective protocols at the Massachusetts General Hospital (MGH) treating 348 patients with cT2-4a disease between 1986 and 2006. Median follow-up for surviving patients was 7.7 yr.
  
  
  METHODS
  Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy (RT) after maximal transurethral resection of bladder tumor (TURBT) plus neoadjuvant or adjuvant chemotherapy. Repeat biopsy was performed after 40 Gy, with initial tumor response guiding subsequent therapy. Those patients showing complete response (CR) received boost chemotherapy and RT. One hundred two patients (29%) underwent RC-60 for less than CR and 42 for recurrent invasive tumors.
  
  
  METHODS
  Disease-specific survival (DSS) and overall survival (OS) were evaluated using the Kaplan-Meier method.
  
  
  CONCLUSIONS
  Seventy-two percent of patients (78% with stage T2) had CR to induction therapy. Five-, 10-, and 15-yr DSS rates were 64%, 59%, and 57% (T2=74%, 67%, and 63%; T3-4=53%, 49%, and 49%), respectively. Five-, 10-, and 15-yr OS rates were 52%, 35%, and 22% (T2: 61%, 43%, and 28%; T3-4=41%, 27%, and 16%), respectively. Among patients showing CR, 10-yr rates of noninvasive, invasive, pelvic, and distant recurrences were 29%, 16%, 11%, and 32%, respectively. Among patients undergoing visibly complete TURBT, only 22% required cystectomy (vs 42% with incomplete TURBT; log-rank p<0.001). In multivariate analyses, clinical T-stage and CR were significantly associated with improved DSS and OS. Use of neoadjuvant chemotherapy did not improve outcomes. No patient required cystectomy for treatment-related toxicity.
  
  
  CONCLUSIONS
  CMT achieves a CR and preserves the native bladder in >70% of patients while offering long-term survival rates comparable to contemporary cystectomy series. These results support modern bladder-sparing therapy as a proven alternative for selected patients.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA. jefstathiou@partners.org
authors.forename: Jason A
authors.initials: JA
authors.lastname: Efstathiou
authors.forename: Daphna Y
authors.initials: DY
authors.lastname: Spiegel
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.forename: Niall M
authors.initials: NM
authors.lastname: Heney
authors.forename: Donald S
authors.initials: DS
authors.lastname: Kaufman
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niemierko
authors.forename: John J
authors.initials: JJ
authors.lastname: Coen
authors.forename: Rafi Y
authors.initials: RY
authors.lastname: Skowronski
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Paly
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McGovern
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Zietman
mesh_terms: D000368:Aged; D001900:Boston; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy / Q000009:adverse effects / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006769:Hospitals, General; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D059351:Organ Sparing Treatments / Q000009:adverse effects / Q000401:mortality; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D013520:Urologic Surgical Procedures / Q000009:adverse effects / Q000401:mortality