Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer

Ceelen WP, Van Nieuwenhove Y, Fierens K

Published Online:

January 21, 2009

In rectal cancer patients, local control is improved by administering radiotherapy (RT) before surgery. Recently, studies have combined preoperative RT with chemotherapy aiming to further improve local control. This review compared preoperative RT with preoperative chemoradiation (CRT) in patients with stage II and III rectal cancer.

Based on the combined analysis of four randomized studies, we found that compared to preoperative RT alone, preoperative CRT enhances pathological response and improves local control in resectable stage II and III rectal cancer, but does not benefit disease free or overall survival. Combined CRT enhances treatment related acute toxicity, but does not affect postoperative complication rate. The effects of preoperative CRT on functional outcome and quality of life are incompletely understood and should be addressed in future trials.

Abstract (click to read)

Background:

Preoperative radiotherapy (RT) decreases local recurrence rate and improves survival in stage II and III rectal cancer patients. The combination of chemotherapy with RT has a sound radiobiological rationale, and phase II trials of combined chemoradiation (CRT) have shown promising activity in rectal cancer.

Objectives:

To compare preoperative RT with preoperative CRT in patients with resectable stage II and III rectal cancer.

Search strategy:

We searched the Cochrane Central Register of Controlled Trials, Web of Science, Embase.com, and Pubmed from 1975 until june 2007. A manual search was performed of Ann Surg, Arch Surg, Cancer, J Clin Oncol, Int J Radiat Oncol Biol Phys and the proceedings of ASTRO, ECCO and ASCO from 1990 until june 2007.

Selection criteria:

Relevant studies randomized resectable stage II or III rectal cancer patients to at least one arm of preoperative RT alone or at least one arm of preoperative CRT.

Data collection and analysis:

Primary outcome parameters included overall survival (OS) at 5 years and local recurrence (LR) rate at 5 years. Secondary outcome parameters included disease free survival (DFS) at 5 years, metastasis rate, pathological complete response rate, clinical response rate, sphincter preservation rate, acute toxicity, postoperative mortality and morbidity, and anastomotic leak rate. Outcome parameters were summarized using the Odds Ratio (OR) and associated 95% confidence interval (CI) using the fixed effects model.

Main results:

Four trials were identified and included in the meta-analysis. The addition of chemotherapy to preoperative RT significantly increased grade III and IV acute toxicity (OR 1.68-10, P = 0.002) while no differences were observed in postoperative morbidity or mortality. Compared to preoperative RT alone, preoperative CRT significantly increased the rate of complete pathological response (OR 2.52-5.27, P < 0.001) although this did not translate into a higher sphincter preservation rate (OR 0.92-1.31, P = 0.29). The indidence of local recurrence at five years was significantly lower in the CRT group compared to RT alone (OR 0.39-0.72, P < 0.001). No statistically significant differences were observed in DFS (OR 0.92-1.34, P = 0.27) or OS (OR 0.79-1.14, P = 0.58) at five years.

Authors' conclusions:

Compared to preoperative RT alone, preoperative CRT enhances pathological response and improves local control in resectable stage II and III rectal cancer, but does not benefit disease free or overall survival. The effects of preoperative CRT on functional outcome and quality of life are incompletely understood and should be addressed in future trials.

This record should be cited as:

Ceelen WP, Van Nieuwenhove Y, Fierens K. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD006041. DOI: 10.1002/14651858.CD006041.pub2

Assessed as up to date:

September 2, 2008

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Primary Review Group:

Colorectal Cancer Group

Health topics:

Cancer > Colorectal > Medical & adjuvant therapy

Gastroenterology > Cancer: colorectal > Medical & adjuvant therapy

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Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer

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