Thirty-two studies (33 comparative groups, n=10,811) were included in the review. Twenty two studies (23 arms) administered postoperative chemotherapy. Ten studies administered pre/perioperative chemotherapy. Sample sizes ranged from 26 to 1,867 participants. The overall mean quality score was 21 (range 15 to 24).
Hazard ratios for overall mortality were similar for postoperative chemotherapy (HR 0.80, 95% CI 0.74 to 0.87; 22 studies) and pre/perioperative chemotherapy (HR 0.81, 95% CI 0.68 to 0.97; 10 studies) when compared with a control. There was no evidence of statistical heterogeneity between the two groups (p=0.81) or for all included studies (p=0.12, I2=23%). Indirect evidence that compared the two chemotherapy regimens showed no statistically significant difference (HR 0.99, 95% CI 0.81 to 1.21).
Similar results were reported for disease-free survival. Postoperative chemotherapy studies reported a hazard ratio for death or recurrence of 0.76 (95% CI 0.68 to 0.85) and a hazard ratio of 0.80 (95% CI 0.66 to 0.92) for pre/perioperative chemotherapy compared with a control. There was evidence of statistical heterogeneity for postoperative studies (p=0.014, I2=50%), but not for preoperative studies (p=0.154, I2=36%). Indirect comparison supported this and showed no statistically significant difference in chemotherapy timing (HR 0.96, 95% CI 0.77 to 1.20).
Meta-regression analysis did not find any significant associations between indirect comparison of overall survival and any of the variables investigated.
There was evidence of publication bias using Begg's test (p=0.047).