Radiotherapy alone versus radiotherapy combined with chemotherapy before operation of rectal cancer

Patients with cancer of the rectum, the end part of the large bowel immediately above the anus, are treated with surgery. When the tumour is deemed to present a high risk of recurrence after surgery, a course of radiotherapy (RT) is administered before the operation. It has been proven in clinical studies that this 'preoperative' radiotherapy improves the outcome in rectal cancer patients. Recently, several studies have investigated the combination of radiotherapy with chemotherapy (CRT) before surgery. In theory, adding chemotherapy enhances the antitumour activity of radiotherapy. This meta-analysis has summarized the results of five studies that compared preoperative RT alone with preoperative CRT in rectal cancer patients. All of these studies were randomized, which means that the decision to administer either RT or CRT was determined by chance (ballot draw). The results of the meta-analysis may be summarized as follows. Compared to RT alone, preoperative CRT leads to increased side effects during treatment. Also, postoperative complications are somewhat increased, although the risk of dying from postoperative complications is similar. Preoperative CRT is more effective in causing tumour shrinkage (downstaging), and in preventing local recurrence of the disease. However, addition of chemotherapy did not result in more sphincter preserving surgeries, and did not affect the overall survival in rectal cancer patients.

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.

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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 Register of Controlled Trials, Web of Science, Embase.com, and Pubmed from 1975 until June 2012. 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 2012.

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: 

Five trials were identified and included in the meta-analysis. From one of the included trials only preliminary data are reported. The addition of chemotherapy to preoperative RT significantly increased grade III and IV acute toxicity (OR 1.68-10, P = 0.002) and marginally affected postoperative overall morbidity (OR 0.67-1.00, P = 0.05) while no differences were observed in postoperative mortality or anastomotic leak rate. Compared to preoperative RT alone, preoperative CRT significantly increased the rate of complete pathological response (OR 2.12-5.84, P < 0.00001) although this did not translate into a higher sphincter preservation rate (OR 0.92-1.30, P = 0.32). The incidence 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.

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