Six Cycles of Neoadjuvant Chemotherapy Followed by Cytoreduction in High-Grade Serous Ovarian Cancer: Prognostic Implications of the Chemotherapy Response Score, CA-125, and Tumor-Infiltrating Lymphocytes

To evaluate the prognostic value of the chemotherapy response score, a histopathologic grading system for tumor regression following neoadjuvant chemotherapy, along with post-treatment serum CA-125 levels and tumor-infiltrating lymphocyte density, in patients with high-grade serous ovarian carcinoma treated with 6 cycles of neoadjuvant chemotherapy followed by surgery. This retrospective cohort study included patients with histologically confirmed high-grade serous ovarian carcinoma treated at a single institution between 2008 and 2021. All patients completed 6 cycles of carboplatin- and paclitaxel-based neoadjuvant chemotherapy. The chemotherapy response score was assessed in omental and adnexal specimens and categorized as 1, 2, or 3. Tumor-infiltrating lymphocyte density in pre- and post-treatment samples was classified as low (<10%) or high (≥10%). Associations among the chemotherapy response score, CA-125 levels, tumor-infiltrating lymphocytes, and survival outcomes-including overall survival and disease-free survival-were analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Of 294 patients screened, 110 met the inclusion criteria. In the omentum, 35.6% had a Chemotherapy Response Score of 3, with a median overall survival of 56.7 months (HR 0.34, 95% CI 0.19 to 0.61). In the adnexa, 43.8% had a score of 2, 41.7% had a score of 1, and 14.6% had a score of 3. Median overall survival for adnexal score 2 was 50.6 months, compared to 33.8 months for score 1. Post-treatment CA-125 levels ≤35 U/mL were associated with higher chemotherapy response score categories and improved survival (HR 0.45, 95% CI 0.28 to 0.73). Tumor-infiltrating lymphocyte density ≥10% was more frequent in adnexal score 2 cases (88.5%, p = .006), but tumor-infiltrating lymphocyte levels-both pre- and post-treatment-were not independently associated with overall survival or disease-free survival. The chemotherapy response score and post-treatment CA-125 levels are independent prognostic indicators following 6 cycles of neoadjuvant chemotherapy. Tumor-infiltrating lymphocyte density showed site-specific patterns but lacked independent prognostic significance for survival outcomes.