Does Time-to-Chemotherapy Impact the Outcomes of Resected Ovarian Cancer? Meta-analysis of Randomized and Observational Data

Objectives: This study is a meta-analysis of prior publications evaluating the impact of time-to- chemotherapy (TTC) on disease recurrence and survival 3 years after the original surgery. Methods: We performed a meta-analysis of studies published in PubMed (1950-2016) as of April 2016. Inclusion criteria were as follows: randomized controlled trials and prospective or retrospective cohorts that included patients with ovarian cancer who had undergone surgery with curative intent and use of adjuvant chemotherapy. We compared rates of disease recurrence and death according to the TTC (early'' vs delayed'') using a random-effects model and performed a metaregression to evaluate the impact of covariates on these outcomes. Results: Of 239 abstracts in the original search, 12 were considered eligible. The cutoffs used for TTC were between 20 and 40 days. All studies used a platinum-based chemotherapy, and the rates of patients with suboptimal resection varied from 33% to 70%. A longer TTC was not associated with higher rates of disease recurrence (odds ratio, 0.89; 95% confidence interval, 0.63-1.24) or death at 3 years (odds ratio, 1.06; 95% confidence interval, 0.9-1.24). There was no evidence of significant publication bias (Egger test P = 0.472), but data were heterogeneous (I-2 = 64.3%). Metaregression showed that the percentage of patients with suboptimal surgery and values used as cutoff to define delayed'' chemotherapy combined were a significant source of bias (residual I-2 = 0%). Conclusions: In our analysis, TTC after surgery for ovarian cancer with curative intent was not associated with higher risk of disease recurrence or death. However, this association was influenced by the rate of optimal debulking and definition of late'' initiation of chemotherapy, so we must be careful when applying these data to patients with complete resection.