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Meta-Analysis
. 2013 Feb 28;2013(2):CD006041.
doi: 10.1002/14651858.CD006041.pub3.

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

Laura De Caluwé  1 , Yves Van Nieuwenhove, Wim P Ceelen
Affiliations
Meta-Analysis

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

Laura De Caluwé et al. Cochrane Database Syst Rev. .

Abstract

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 methods: 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.

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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Conflict of interest statement

None.

Figures

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1
Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.10 Local Recurrence at 5y.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.12 HR_LR.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.1 Overall Survival at 5y.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.2 HR_OS.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.3 Disease free survival at 5 y.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.11 HR_DFS.
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7
Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.6 Grade III ‐ IV toxicity.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.7 Sphincter preservation.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.4 Mortality 30 d.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.5 Postop morbidity.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.9 Anastomotic leak.
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Forest plot of comparison: 1 radiotherapy vs radiochemotherapy, outcome: 1.8 pCR.
1.1
1.1. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 1 Overall Survival at 5y.
1.2
1.2. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 2 HR_OS.
1.3
1.3. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 3 Disease free survival at 5 y.
1.4
1.4. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 4 Mortality 30 d.
1.5
1.5. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 5 Postop morbidity.
1.6
1.6. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 6 Grade III ‐ IV toxicity.
1.7
1.7. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 7 Sphincter preservation.
1.8
1.8. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 8 pCR.
1.9
1.9. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 9 Anastomotic leak.
1.10
1.10. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 10 Local Recurrence at 5y.
1.11
1.11. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 11 HR_DFS.
1.12
1.12. Analysis
Comparison 1 radiotherapy vs radiochemotherapy, Outcome 12 HR_LR.
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Update of

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