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

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. 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. 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). 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.

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Copyright © 2023. Published by Elsevier Inc.

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Declaration of Competing Interest Dr. Salani reports consulting fees with Merck, Seagen, GSK, Eisai, Regeneron and Immunogen. She has received payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from UpToDate and Elsevier. Additionally, she serves as IGCS treasurer elect. Dr. Chase is a consultant and speaker for Astra Zeneca, GSK, Immunogen, Seagen/Genmab and Eisai. She also participates in the Data Safety Monitoring Board for NRG. Dr. Konecny reports the following: Speaker Bureau: GSK, Immunogen, Merck and AZ; research support to the institution: Lilly and Merck; Advisory boards: Mersana, Immunogen, GSK.