Eight RCTs (1,058 evaluable patients; 533 undergoing surgery, 525 undergoing surgery with perioperative chemotherapy) were included in the review. Sample sizes ranged from 11 to 364 patients. Where reported, 59.3 to 97.5% of patients received their assigned treatment, 494 underwent surgery, and 391 completed chemotherapy. Where reported, 848 patients underwent resection. Most trials reported methods of randomisation and withdrawal, but none were reported as double-blind. Three trials were considered high quality. Follow-up ranged from 18 to 144 months (where reported).
Overall survival: The addition of perioperative chemotherapy to surgery did not significantly reduce overall mortality (I2=26%). Subgroup analyses did not significantly alter the results, although heterogeneity was no longer evident for trials using systemic chemotherapy (two RCTs).
Recurrence-free survival: Patients receiving perioperative chemotherapy in addition to surgery showed statistically significant improvements compared with surgery alone (HR 0.77, 95% CI 0.67 to 0.88; I2=25%). Subgroup analyses by type of therapy and analyses including only high quality trials did not significantly alter the findings. However, there was evidence of substantial heterogeneity in the subgroup analysis using intra-arterial chemotherapy (I2=54%); when a random-effects model was used for this data set, the results were no longer statistically significant (HR 0.72, 95% CI 0.51 to 1.02, five RCTs).
Toxicity: The most frequent grade 3 and 4 toxicities were generally mild and acceptable (as listed in the review). There were 10 treatment-related deaths (12%) in two trials.
There was evidence of publication bias, but this was no longer evident when one small trial was excluded.