The role of secondary cytoreductive surgery in patients with recurrent epithelial ovarian, tubal, and peritoneal cancers: a comparative effectiveness analysis

Background. All published reports concerning secondary cytoreductive surgery for relapsed ovarian cancer have essentially been observational studies. However, the validity of observational studies is usually threatened from confounding by indication. We sought to address this issue by using comparative effectiveness methods to adjust for confounding. Methods. Using a prospectively collected administrative health care database in a single institution, we identified 1,124 patients diagnosed with recurrent epithelial, tubal, and peritoneal cancers between 1990 and 2009. Effectiveness of secondary cytoreductive surgery using the conventional Cox proportional hazard model, propensity score, and instrumental variable were compared. Sensitivity analyses for residual confounding were explored using an array approach. Results. Secondary cytoreductive surgery prolonged overall survival with a hazard ratio (95% confidence interval) of 0.76 (range 0.66-0.87), using the Cox proportional hazard model. Propensity score methods produced comparable results: 0.75 (range 0.64-0.86) by nearest matching, 0.73 (0.65-0.82) by quintile stratification, 0.71 (0.65-0.77) by weighting, and 0.72 (0.63-0.83) by covariate adjustment. The instrumental variable method also produced a comparable estimate: 0.75 (range 0.65-0.86). Sensitivity analyses revealed that the true treatment effects may approach the null hypothesis if the association between unmeasured confounders and disease outcome is high. Conclusions. This comparative effectiveness study provides supportive evidence for previous reports that secondary cytoreductive surgery may increase overall survival for patients with recurrent epithelial, tubal, and peritoneal cancers.