title: Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years.
abstract: OBJECTIVE
  Preoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months.
  
  
  METHODS
  A total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival.
  
  
  RESULTS
  Of 799 eligible patients, 404 were randomly assigned to preoperative and 395 to postoperative CRT. According to intention-to-treat analysis, overall survival at 10 years was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P = .85). The 10-year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and postoperative arms, respectively (P = .048). No significant differences were detected for 10-year cumulative incidence of distant metastases (29.8% and 29.6%; P = .9) and disease-free survival.
  
  
  CONCLUSIONS
  There is a persisting significant improvement of pre- versus postoperative CRT on local control; however, there was no effect on overall survival. Integrating more effective systemic treatment into the multimodal therapy has been adopted in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival.
authors.affiliation: University of Erlangen, Erlangen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sauer
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
authors.forename: Susanne
authors.initials: S
authors.lastname: Merkel
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
authors.forename: Clemens
authors.initials: C
authors.lastname: Hess
authors.forename: Heinz
authors.initials: H
authors.lastname: Becker
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Raab
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Villanueva
authors.forename: Helmut
authors.initials: H
authors.lastname: Witzigmann
authors.forename: Christian
authors.initials: C
authors.lastname: Wittekind
authors.forename: Tim
authors.initials: T
authors.lastname: Beissbarth
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011184:Postoperative Period; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil