Twelve RCTs (8,276 patients, range 52 to 2,963) were included in the review. Jadad scores were reported to range from 2 to 5. Seven trials had adequate randomisation. Five trials had adequate allocation concealment. Blinding was not feasible in any trial. Ten trials reported loss to follow-up. Nine trials used intention-to-treat analysis. Median follow-up (eight trials) was more than 60 months. The authors concluded that seven trials were fair quality and five were poor quality.
Five-year overall survival: Significant improvements were reported in favour of the combined intervention for patients with stage II colon cancer (HR 0.81, 95% CI 0.71 to 0.91; nine RCTs; Ι²=2%; low risk of publication bias) and for patients with stage II rectal cancer (HR 0.72, 95% CI 0.61 to 0.86; three RCTs; Ι²=38%; evidence of publication bias).
Five-year disease-free survival: Significant improvements were reported in favour of the combined intervention for patients with stage II colon cancer (HR 0.86, 95% CI 0.75 to 0.98; seven RCTs; Ι²=7%; low risk of publication bias) and for patients with stage II rectal cancer (HR 0.34, 95% CI 0.22 to 0.51; two RCTs; evidence of publication bias).
Recurrence and mortality: The combined intervention was favoured for patients with stage II colon cancer in terms of recurrence (RR 0.82, 95% CI 0.71 to 0.95; four RCTs; Ι²=0%; evidence of publication bias) but there was no statistical difference between study groups for mortality (four RCTs; Ι²=0%). There was insufficient data for a pooled result in patients with stage II rectal cancer.