Front-line intraperitoneal versus intravenous chemotherapy in stage III-IV epithelial ovarian, tubal, and peritoneal cancer with minimal residual disease: a competing risk analysis

Yen-Hou Chang, Wai-Hou Li, Yi Chang, Chia-Wen Peng, Ching-Hsuan Cheng, Wei-Pin Chang, Chi-Mu Chuang

In the analysis of survival data for cancer patients, the problem of competing risks is often ignored. Competing risks have been recognized as a special case of time-to-event analysis. The conventional techniques for time-to-event analysis applied in the presence of competing risks often give biased or uninterpretable results. Using a prospectively collected administrative health care database in a single institution, we identified patients diagnosed with stage III or IV primary epithelial ovarian, tubal, and peritoneal cancers with minimal residual disease after primary cytoreductive surgery between 1995 and 2012. Here, we sought to evaluate whether intraperitoneal chemotherapy outperforms intravenous chemotherapy in the presence of competing risks. Unadjusted and multivariable subdistribution hazards models were applied to this database with two types of competing risks (cancer-specific mortality and other-cause mortality) coded to measure the relative effects of intraperitoneal chemotherapy. A total of 1263 patients were recruited as the initial cohort. After propensity score matching, 381 patients in each arm entered into final competing risk analysis. Cumulative incidence estimates for cancer-specific mortality were statistically significantly lower (p = 0.017, Gray test) in patients receiving intraperitoneal chemotherapy (5-year estimates, 34.5 %; 95 % confidence interval [CI], 29.5-39.6 %, and 10-year estimates, 60.7 %; 95 % CI, 52.2-68.0 %) versus intravenous chemotherapy (5-year estimates, 41.3 %; 95 % CI, 36.2-46.3 %, and 10-year estimates, 67.5 %, 95 % CI, 61.6-72.7 %). In subdistribution hazards analysis, for cancer-specific mortality, intraperitoneal chemotherapy outperforms intravenous chemotherapy (Subdistribution hazard ratio, 0.82; 95 % CI, 0.70-0.96) after correcting other covariates. In conclusion, results from this comparative effectiveness study provide supportive evidence for previous published randomized trials that intraperitoneal chemotherapy outperforms intravenous chemotherapy even eliminating the confounding of competing risks. We suggest that implementation of competing risk analysis should be highly considered for the investigation of cancer patients who have medium to long-term follow-up period.