Chemotherapy with Preoperative Radiotherapy in Rectal Cancer
Open accessAbstract
BACKGROUND: Preoperative radiotherapy is recommended for selected patients with rectal cancer. We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer. METHODS: We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy, preoperative chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day, both given for 5 days. Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy. The primary end point was overall survival. RESULTS: We enrolled 1011 patients in the trial. There was no significant difference in overall survival between the groups that received chemotherapy preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The combined 5-year overall survival rate for all four groups was 65.2%. The 5-year cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the groups that received chemotherapy preoperatively, postoperatively, or both, respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002). The rate of adherence to preoperative chemotherapy was 82.0%, and to postoperative chemotherapy was 42.9%. CONCLUSIONS: In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control. (ClinicalTrials.gov number, NCT00002523 [ClinicalTrials.gov].).
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In two trials, the local recurrence rate was significantly lower in the preoperative chemoradiotherapy group than in the preoperative radiotherapy alone group.
“In two trials, the exception being the short-course radiotherapy trial, the local recurrence rate was significantly lower in the preoperative chemoradiotherapy group”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [116]
The Discussion (page unavailable) reports a 5-year local recurrence rate of 8.7% with preoperative chemoradiotherapy versus 17.1% with preoperative radiotherapy alone; its Figure 4 gives P=0.002. This supports the finding for this trial, but the paper reports results from one trial, not the claimed finding in two trials. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn Europe, four randomized controlled trials were performed to investigate the usefulness of adding chemotherapy to preoperative radiotherapy.
“In Europe, four randomized controlled trials, including the EORTC trial, were performed to investigate the usefulness of adding chemotherapy to preoperative radiotherapy.”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [116]
The introduction (p. 1115) identifies EORTC 22921 as a trial investigating preoperative chemoradiotherapy, and the Randomization and treatment section describes its four treatment groups. The paper does not establish that four separate randomized trials in Europe investigated this question; its four groups belong to one trial. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPathologic complete response rates were significantly higher in the preoperative chemoradiotherapy groups than in the preoperative radiotherapy alone groups.
“but the pathologic complete response rates (pCR) were significantly higher than in the preoperative radiotherapy alone groups.”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [116]
The Pathology section (page unavailable) reports significantly smaller tumors and less advanced pathological tumor stages after preoperative chemoradiotherapy than after radiotherapy alone. It does not report pathologic complete response rates or a significance test for their difference, so the specific pCR claim is not established by our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe incidence of acute-phase adverse events was significantly higher in the preoperative chemoradiotherapy groups than in the preoperative radiotherapy alone groups.
“The incidence of acute-phase adverse events was significantly higher in the preoperative chemoradiotherapy groups”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [116]
There was no significant difference between preoperative chemoradiotherapy and preoperative radiotherapy alone in sphincter preservation or survival rate.
“and there was no significant difference between the two groups in terms of sphincter preservation or survival rate [111–118].”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [116]
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- Authors
- Bosset, J.-F., Collette, L., Calais, G., Mineur, L., Maingon, P., Radosevic-Jelic, L., Daban, A., Bardet, E., Beny, A., & Ollier, J.-C.
- Affiliations
- Université de Franche-Comté (FR)
- European Organisation for Research and Treatment of Cancer (BE)
- Université de Tours (FR)
- Institut Sainte Catherine (FR)
- Université de Poitiers (FR)
- Rambam Health Care Campus (IL)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-09-14
- Volume
- 355
- Issue
- 11
- Pages
- 1114-1123
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2124886112
- Cited by
- 2,688
- References
- 31
- Citations by year
- 2026: 43 · 2025: 76 · 2024: 97 · 2023: 136 · 2022: 122 · 2021: 148 · 2020: 158 · 2019: 144 · 2018: 141 · 2017: 147 · 2016: 148 · 2015: 191 · 2014: 172 · 2013: 169 · 2012: 173
- FWCI
- 52.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Funders
- National Cancer Institute (2U10CA11488-24, 2U10-CA11488-33, 2U10CA11488-34, 2U10 CA11488-27, 2U10 CA11488-23, 2U10CA11488-28, 2U10CA11488-21, U10CA011488, 2U10-CA11488-25, 2U10 CA11488-32, 2U10 CA11488-22, 2U10CA11488-29, 2U10-CA11488-26, 2U10 CA11488-35, 2U10CA11488-30, 2 U10 CA11488-31)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Surgery › Colorectal and Anal Carcinomas
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Keywords
- rectal cancer, neoadjuvant chemoradiotherapy, preoperative radiotherapy, postoperative chemotherapy, 5-fluorouracil, leucovorin, overall survival, local recurrence, local control, medication adherence
- MeSH terms
- Adenocarcinoma, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Combined Modality Therapy, Female, Fluorouracil, Follow-Up Studies, Humans, Male, Middle Aged, Postoperative Care, Postoperative Complications, Preoperative Care, Rectal Neoplasms, Recurrence, Survival Analysis
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