A Modified 2 Tier Chemotherapy Response Score (CRS) and Other Histopathologic Features for Predicting Outcomes of Patients with Advanced Extrauterine High-Grade Serous Carcinoma after Neoadjuvant Chemotherapy

SIMPLE SUMMARY: Reliable predictive indicators of response to neoadjuvant chemotherapy of advanced-stage extrauterine high-grade serous carcinoma are still lacking. Moreover, changes evident in tumor samples from interval surgery are not well understood. Our retrospective study aimed to address the prognostic value of chemotherapy response score (CRS) and identify additional predictive features for the risk of progression and death. In a cohort of 245 patients, we demonstrate that the modified two-tier CRS was prognostic for survival, and this significance was independent of scoring site; our data support expansion of CRS use to the adnexal samples. In addition to the CRS, oncocytic change, inflammation, and desmoplasia were additional histopathologic parameters related to survival. We recommend using the two-tier CRS, together with the additional histological features serving as secondary criteria for scoring, to identify patients at high risk for recurrence, allow tailored adjuvant therapy strategies, or consider clinical trials. ABSTRACT: Background: The impact of chemotherapy response score (CRS) on prognosis has varied among studies. We addressed the prognostic significance of CRS and the prognostic value of previously undescribed histologic features using a cohort of 245 patients. Methods: Retrospective study in patients with advanced extrauterine high-grade serous carcinomas treated with neoadjuvant chemotherapy followed by interval tumor reductive surgery from 1990 to 2018 in our hospital. Gynecologic pathologists assessed tumor CRS and other histologic features. Clinical information was collected, and multivariate analyses were conducted. Results: A modified 2 tier CRS (CRS 1/2 versus CRS 3) was significantly associated, independent of scoring site (omental versus adnexal), with overall survival (OS) (omentum, p = 0.018; adnexa, p = 0.042; entire cohort, p = 0.002) and progression-free survival (PFS) (p = 0.021, p = 0.035, and p = 0.001, respectively). On multivariate survival analysis, 2 tier CRS, oncocytic change, inflammation, and desmoplasia were significant for OS (p = 0.034, p = 0.020, p = 0.007, and p = 0.010, respectively). Likewise, 2 tier CRS, inflammation, and desmoplasia were significant for PFS (p = 0.012, p = 0.003, p = 0.011, respectively). Conclusions: The modified 2 tier CRS was significantly associated with survival, independent of scoring site. Additional histologic features including oncocytic change, inflammation, and desmoplasia can also predict patient outcomes.