Twelve RCTs (1,310 participants) were included in the review. Seven RCTs (988 participants) were included in the meta-analysis. The other 5 studies did not have sufficient survival data available for abstraction and so were excluded.
Quality indicators (randomisation procedure, allocation concealment, patient exclusions, calculation of end points) were insufficiently described in most of the studies. Only one study reported using intention-to-treat analysis.
There was no evidence of publication bias, as assessed by Begg's test (p=0.29) or Egger's test (p=0.94), and Begg's funnel plot was fairly symmetrical.
There was good evidence that chemotherapy plus surgery had a more beneficial effect on survival than surgery alone (HR 0.82, 95% confidence interval, CI: 0.69, 0.97, p=0.02). There was no evidence of statistical heterogeneity (p=0.98).
The absolute improvement in 5-year survival associated with chemotherapy plus surgery versus surgery alone was 6% (increasing from 14 to 20%). The absolute benefit differed by disease stage: 4% for stage Ia, 6% for stage Ib, 7% for stage IIa and IIb, 6 to 7% for stage IIIa and 3 to 5% for stage IIIb.
When excluding the 2 largest studies, chemotherapy plus surgery was still found to have a more beneficial effect on survival than surgery alone, but the effect did not reach statistical significance (HR 0.79, 95% CI: 0.59, 1.08, p=0.14). There was no evidence of statistical heterogeneity (p=0.90).
Sensitivity analyses found no evidence of a difference in effectiveness when trials were grouped according to type of chemotherapy used (platinum plus vinca alkaloid/etoposide; platinum plus taxane; other platinum regimen; p=0.99) or additional therapy (post-operative radiotherapy or chemotherapy; p=0.58).
Disease-free survival was analysed in 3 studies (457 participants). Chemotherapy plus surgery had a more beneficial effect on survival than surgery alone (HR 0.78, 95% CI: 0.52, 0.99, p=0.04); there was some evidence of statistical heterogeneity (p=0.07).