IPD from four RCTs were included (n=875). One other RCT was also identified, but was not included in the meta-analysis because IPD were not available on account of the age of the trial.
Adjuvant chemoradiation (3 trials, 478 patients).
There was no statistically significant difference in the risk of death with chemoradiation compared with no chemoradiation (HR 1.09, 95% CI: 0.89, 1.32, P=0.43). There was borderline statistically significant heterogeneity (P=0.05). Median survival was 15.8 months with chemoradiation and 15.2 months without. The 2- and 5-year survival rates were 30% and 12%, respectively, with chemoradiation and 34% and 17% without. The subgroup analysis showed no significant heterogeneity, except for a significant difference in the effect of chemoradiation on resection margin status (P=0.04), where chemoradiation was estimated to be effective in patients with positive resection margins. This treatment effect was not significant.
Adjuvant chemotherapy (4 RCTs, 686 patients).
The meta-analysis of all 4 RCTs showed that chemotherapy significantly reduced the risk of death compared with no chemotherapy (HR 0.75, 95% CI: 0.64, 0.90, P=0.001), but statistically significant heterogeneity was found (P=0.009). After removing one RCT with an unusually high proportion of patients with positive resection margins, significant heterogeneity was no longer present (P=0.29) and the reduction in risk of death with chemotherapy was still statistically significant (HR 0.65, 95% CI: 0.54, 0.80, P<0.001).
Median survival was 19 months with chemotherapy and 13.5 months without. The 2- and 5-year survival rates were 38% and 19%, respectively, with chemotherapy and 28% and 12% without.
The subgroup analysis showed no significant heterogeneity, except for a significant difference in the effect of chemotherapy on resection margin status (P=0.007), where chemotherapy was estimated to be less effective in patients with positive resection margins. This treatment effect was not significant.
The results for all subgroup analyses were reported.