title: Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233.
abstract: OBJECTIVE
  Multiple prospective Radiation Therapy Oncology Group (RTOG) protocols have evaluated bladder-preserving combined-modality therapy (CMT) for muscle-invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment. We performed a pooled analysis of long-term outcomes in patients with MIBC enrolled across multiple studies.
  
  
  METHODS
  Four hundred sixty-eight patients with MIBC were enrolled onto six RTOG bladder-preservation studies, including five phase II studies (RTOG 8802, 9506, 9706, 9906, and 0233) and one phase III study (RTOG 8903). Overall survival (OS) was estimated using the Kaplan-Meier method, and disease-specific survival (DSS), muscle-invasive and non-muscle-invasive local failure (LF), and distant metastasis (DM) were estimated by the cumulative incidence method.
  
  
  RESULTS
  The median age of patients was 66 years (range, 34 to 93 years), and clinical T stage was T2 in 61%, T3 in 35%, and T4a in 4% of patients. Complete response to CMT was documented in 69% of patients. With a median follow-up of 4.3 years among all patients and 7.8 years among survivors (n = 205), the 5- and 10-year OS rates were 57% and 36%, respectively, and the 5- and 10-year DSS rates were 71% and 65%, respectively. The 5- and 10-year estimates of muscle-invasive LF, non-muscle-invasive LF, and DM were 13% and 14%, 31% and 36%, and 31% and 35%, respectively.
  
  
  CONCLUSIONS
  This pooled analysis of multicenter, prospective RTOG bladder-preserving CMT protocols demonstrates long-term DSS comparable to modern immediate cystectomy studies, for patients with similarly staged MIBC. Given the low incidence of late recurrences with long-term follow-up, CMT can be considered as an alternative to radical cystectomy, especially in elderly patients not well suited for surgery.
authors.affiliation: Raymond H. Mak, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School; William U. Shipley, Jason A. Efstathiou, Donald S. Kaufman, Niall M. Heney, and Anthony L. Zietman, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Daniel Hunt, Radiation Therapy Oncology Group Statistical Center; William J. Tester, Albert Einstein Medical Center, Philadelphia, PA; and Michael P. Hagan, Veterans Health Administration, Richmond, VA. rmak@lroc.harvard.edu.
authors.forename: Raymond H
authors.initials: RH
authors.lastname: Mak
authors.affiliation: Raymond H. Mak, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School; William U. Shipley, Jason A. Efstathiou, Donald S. Kaufman, Niall M. Heney, and Anthony L. Zietman, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Daniel Hunt, Radiation Therapy Oncology Group Statistical Center; William J. Tester, Albert Einstein Medical Center, Philadelphia, PA; and Michael P. Hagan, Veterans Health Administration, Richmond, VA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hunt
authors.affiliation: Raymond H. Mak, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School; William U. Shipley, Jason A. Efstathiou, Donald S. Kaufman, Niall M. Heney, and Anthony L. Zietman, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Daniel Hunt, Radiation Therapy Oncology Group Statistical Center; William J. Tester, Albert Einstein Medical Center, Philadelphia, PA; and Michael P. Hagan, Veterans Health Administration, Richmond, VA.
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.affiliation: Raymond H. Mak, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School; William U. Shipley, Jason A. Efstathiou, Donald S. Kaufman, Niall M. Heney, and Anthony L. Zietman, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Daniel Hunt, Radiation Therapy Oncology Group Statistical Center; William J. Tester, Albert Einstein Medical Center, Philadelphia, PA; and Michael P. Hagan, Veterans Health Administration, Richmond, VA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Efstathiou
authors.affiliation: Raymond H. Mak, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School; William U. Shipley, Jason A. Efstathiou, Donald S. Kaufman, Niall M. Heney, and Anthony L. Zietman, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Daniel Hunt, Radiation Therapy Oncology Group Statistical Center; William J. Tester, Albert Einstein Medical Center, Philadelphia, PA; and Michael P. Hagan, Veterans Health Administration, Richmond, VA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Tester
authors.affiliation: Raymond H. Mak, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School; William U. Shipley, Jason A. Efstathiou, Donald S. Kaufman, Niall M. Heney, and Anthony L. Zietman, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Daniel Hunt, Radiation Therapy Oncology Group Statistical Center; William J. Tester, Albert Einstein Medical Center, Philadelphia, PA; and Michael P. Hagan, Veterans Health Administration, Richmond, VA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hagan
authors.affiliation: Raymond H. Mak, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School; William U. Shipley, Jason A. Efstathiou, Donald S. Kaufman, Niall M. Heney, and Anthony L. Zietman, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Daniel Hunt, Radiation Therapy Oncology Group Statistical Center; William J. Tester, Albert Einstein Medical Center, Philadelphia, PA; and Michael P. Hagan, Veterans Health Administration, Richmond, VA.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Kaufman
authors.affiliation: Raymond H. Mak, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School; William U. Shipley, Jason A. Efstathiou, Donald S. Kaufman, Niall M. Heney, and Anthony L. Zietman, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Daniel Hunt, Radiation Therapy Oncology Group Statistical Center; William J. Tester, Albert Einstein Medical Center, Philadelphia, PA; and Michael P. Hagan, Veterans Health Administration, Richmond, VA.
authors.forename: Niall M
authors.initials: NM
authors.lastname: Heney
authors.affiliation: Raymond H. Mak, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School; William U. Shipley, Jason A. Efstathiou, Donald S. Kaufman, Niall M. Heney, and Anthony L. Zietman, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Daniel Hunt, Radiation Therapy Oncology Group Statistical Center; William J. Tester, Albert Einstein Medical Center, Philadelphia, PA; and Michael P. Hagan, Veterans Health Administration, Richmond, VA.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Zietman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015653:Cystectomy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D009130:Muscle, Smooth / Q000473:pathology / Q000601:surgery*; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016017:Odds Ratio; D059351:Organ Sparing Treatments; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D016879:Salvage Therapy; D013997:Time Factors; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology / Q000601:surgery*; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*