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Randomized Controlled Trial
. 2009 Nov 1;27(31):5124-30.
doi: 10.1200/JCO.2009.22.0467. Epub 2009 Sep 21.

Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03

Mark S Roh  1 , Linda H Colangelo, Michael J O'Connell, Greg Yothers, Melvin Deutsch, Carmen J Allegra, Morton S Kahlenberg, Luis Baez-Diaz, Carol S Ursiny, Nicholas J Petrelli, Norman Wolmark
Affiliations
Randomized Controlled Trial

Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03

Mark S Roh et al. J Clin Oncol. .

Abstract

Purpose: 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.

Patients and 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.

Conclusion: Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
(A) CONSORT diagram showing the flow of participants through each stage of National Surgical Adjuvant Breast and Bowel Project R-03 trial. (B) Diagram of chemotherapy and radiotherapy treatment regimens. (*) Forty-five Gy in 25 fractions with a 5.4 Gy boost within the original margins of treatment. FU, fluorouracil; LV, leucovorin; APR, anterior-posterior resection; RTX, radiation therapy.
Fig 2.
Fig 2.
(A) Disease-free survival of 254 patients randomly assigned to preoperative or postoperative chemoradiotherapy, National Surgical Adjuvant Breast and Bowel Project R-03 (NSABP R-03) trial. (B) Overall survival of 254 patients randomly assigned to preoperative or postoperative chemoradiotherapy, NSABP R-03.
Fig 3.
Fig 3.
(A) Cumulative incidence of recurrence in 254 patients who underwent complete resection of rectal cancer and chemoradiotherapy, according to treatment group, National Surgical Adjuvant Breast and Bowel Project R-03 (NSABP R-03) trial. (B) Cumulative incidence of local recurrence in 254 patients who underwent complete resection of rectal cancer and chemoradiotherapy, according to treatment group, NSABP R-03.
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References

    1. Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: A systematic overview of 8,507 patients from 22 randomized trials. Lancet. 2001;358:1291–1304. - PubMed
    1. Cammà C, Giunta M, Fiorica F, et al. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA. 2000;284:1008–1015. - PubMed
    1. Krook JE, Moertel CG, Gunderson LL, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991;324:709–715. - PubMed
    1. Wolmark N, Wieand HS, Hyams DM, et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000;92:388–396. - PubMed
    1. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–646. - PubMed

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