Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03.
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.
Roh
Mark S
MS
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
Colangelo
Linda H
LH
O'Connell
Michael J
MJ
Yothers
Greg
G
Deutsch
Melvin
M
Allegra
Carmen J
CJ
Kahlenberg
Morton S
MS
Baez-Diaz
Luis
L
Ursiny
Carol S
CS
Petrelli
Nicholas J
NJ
Wolmark
Norman
N
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*
D002955:Leucovorin; D005472:Fluorouracil