Investigating the effect of optimal cytoreduction in the context of platinum sensitivity in high-grade serous ovarian cancer

Abstract

Introduction: The survival benefits of surgical cytoreduction in ovarian cancer are well-established. However, the surgical outcome has never been assessed while controlling for the efficacy of chemotherapy. This leaves the possibility that cytoreduction may not be beneficial for patients whose cancer does not respond well to adjuvant treatment. We sought to answer whether surgical cytoreduction independently improves overall survival when controlling for chemotherapy outcome.

Material and methods: We performed a retrospective case-control study using our institution's ovarian cancer database to evaluate the effect of optimal cytoreduction on advanced stage, high-grade serous ovarian cancer. Patients' characteristics were compared using both univariate and multivariate regression modeling to assess for independent predictors of overall survival.

Results: A total of 470 patients were assessed for inclusion; 234 responders to chemotherapy and 98 nonresponders. Significant survival characteristics were identified and included in the multivariate analysis. Independent predictors of survival in the multivariate analysis were age, responder status, optimal cytoreduction, neoadjuvant chemotherapy, and number of chemotherapy cycles. Kaplan-Meier survival curves showed improved survival for both patients who responded to chemotherapy and for those undergoing optimal cytoreduction (p < 0.001). We also demonstrated improved survival for patients receiving optimal cytoreduction among both nonresponders and responders (p < 0.001).

Conclusions: Our analysis shows that patients who undergo optimal cytoreduction have an overall survival benefit regardless of their response to chemotherapy. Therefore, cytoreduction should be considered in all patients, even in those with advanced disease, if an optimal result can be achieved. This study was underpowered to assess patients who received neoadjuvant chemotherapy as a separate subgroup, but the order of treatment was controlled for in the overall analysis.

Keywords: cytoreduction; ovarian cancer; overall survival; platinum-resistant; platinum-sensitive.

FIGURE 1

Flow of included patients. Of 470 patients within our database, 332 met our inclusion criteria. Of these, 234 (70.5%) were considered responders and 98 were nonresponders, which is consistent with historical percentages for platinum sensitivity. F/U, follow‐up.

FIGURE 2

Multivariate cox proportional hazard model survival analysis. Significant variables in the survival univariate analysis (p < 0.05) were introduced in the multivariate analysis. The complexity index score was used to synthesize all surgical procedures in a single score. Figures in parentheses are reference values for the variables, eg the older the patient, the less survival. Patients who had suboptimal surgery and did not respond to chemotherapy had shorteer survival. Patients with more cycles of chemotherapy (up to six) had longer survival. CI, confidence interval; HR, hazard ratio.

FIGURE 3

Survival curves for response to chemotherapy and optimal cytoreduction. Kaplan–Meier survival curves representing overall survival in responders vs nonresponders (A), optimal CRS vs suboptimal CRS (B), and the two groups combined (C). Overall survival was significantly improved by both response to chemotherapy and optimal CRS. In (C), the p‐value demonstrating the overall effect of optimal CRS on survival was significant, with p < 0.001. However, with only 18 events in the subgroup analysis of nonresponders, we were unable to perform an adequate assessment of whether or not the benefit holds in this subgroup. CI, confidence interval; CRS, cytoreductive surgery.