title: Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03.
abstract: OBJECTIVE
  Although chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma.
  
  
  METHODS
  Patients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  From August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P = .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence.
  
  
  CONCLUSIONS
  Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project (NSABP) Operations Cente, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA, USA. mark.roh@orlandohealth.com
authors.forename: Mark S
authors.initials: MS
authors.lastname: Roh
authors.forename: Linda H
authors.initials: LH
authors.lastname: Colangelo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: Greg
authors.initials: G
authors.lastname: Yothers
authors.forename: Melvin
authors.initials: M
authors.lastname: Deutsch
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Allegra
authors.forename: Morton S
authors.initials: MS
authors.lastname: Kahlenberg
authors.forename: Luis
authors.initials: L
authors.lastname: Baez-Diaz
authors.forename: Carol S
authors.initials: CS
authors.lastname: Ursiny
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Petrelli
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011300:Preoperative Care / Q000379:methods*; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*
chemical_list: D002955:Leucovorin; D005472:Fluorouracil