Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03
Mark S Roh, 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, Mark S Roh, 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
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.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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References
- 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.
- Cammà C, Giunta M, Fiorica F, et al. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA. 2000;284:1008–1015.
- 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.
- 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.
- 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.
- Bosset JF, Calais G, Mineur L, et al. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: Preliminary results–EORTC 22921. J Clin Oncol. 2005;23:5620–5627.
- Bosset JF, Calais G, Mineur L, et al. Preoperative radiation in rectal cancer: Effect and timing of additional chemotherapy, 5-year results of the EORTC 22921 trial. J Clin Oncol. 2005;23(suppl):247s. abstr 3505.
- Gérard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: Results of FFCD 9203. J Clin Oncol. 2006;24:4620–4625.
- Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–1740.
- White SJ, Freedman LS. Allocation of patients to treatment groups in a controlled clinical study. Br J Cancer. 1978;37:849–857.
- Gaynor JJ, Feuer EJ, Tan CC, et al. On the use of cause-specific failure and conditional failure probabilities: Examples from clinical oncology data. J Am Stat Assoc. 1993;88:400–409.
- Kaminsky-Forrett MC, Conroy T, Luporsi E, et al. Prognostic implications of downstaging following preoperative radiation therapy for operable T3–T4 rectal cancer. Int J Radiat Oncol Biol Phys. 1998;42:935–941.
- Rödel C, Martus P, Papadoupolos T, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23:8688–8696.
- Vecchio FM, Valentini V, Minsky BD, et al. The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys. 2005;62:752–760.
- Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12:19–23.
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