Pathologic response to neoadjuvant chemotherapy in ovarian cancer and its association with outcome: A surrogate marker of survival

Abstract

Objective: We aimed to validate whether pathologic response (pR) to neoadjuvant chemotherapy (NACT) using a three-tier chemotherapy response score (CRS) is associated with clinical outcome in ovarian cancer (OC) and could be used as surrogate marker for survival. Methods: We conducted a retrospective study of OC patients with FIGO stage III/IV disease who received NACT and graded response as no or minimal (CRS 1), partial (CRS 2), or complete/near-complete (CRS 3) pR using tissue specimens obtained from omentum. Uni- and multivariate survival analyses were performed accounting for age, FIGO stage, debulking and BRCA status as well as neoadjuvant use of bevacizumab. Results: CRSs 1, 2 and 3 were found in 41(31%), 62 (47%) and 30 (22%) of the 133 examined cases. Response to NACT was associated with significantly improved progression-free (PFS, p < 0.001) and overall survival (OS, p = 0.011). Complete/ near-complete pathologic response (CRS3) was associated with improved PFS (median 24.8 vs. 12.5 months, unadjusted HR 0.28 [95%CI 0.15–0.54], p < 0.001; adjusted hazard ration (aHR) 0.31 [95% CI 0.14–0.72], p = 0.007) and OS (median 63.3 vs. 32.1 months, unadjusted HR 0.27 [95%CI 0.10–0.68], p = 0.006; aHR 0.32 [95% CI 0.09–1.11], p = 0.072) when compared to no or minimal response (CRS1). Conclusions: We validate a three-tier CRS for assessment of pathologic response to NACT in OC and demonstrate its prognostic independence of BRCA status or neoadjuvant bevacizumab use. Improving pR rates may be a useful goal of NACT in OC with the expectation of improved survival. The CRS may be a useful endpoint in clinical trials in OC.