KELIM and post-chemotherapy CA-125 for assessing chemosensitivity in high-grade serous carcinoma

Abstract Background Accurate assessment of platinum chemosensitivity is important for treatment planning and translational research in ovarian high-grade serous carcinoma. CA-125 kinetics has been proposed as a surrogate marker of chemosensitivity, but different CA-125-based scoring strategies have rarely been compared within the same patient cohort. We performed an exploratory comparison of seven CA-125-based measures representing model-based, multi-timepoint, and single-timepoint approaches in patients treated with neoadjuvant chemotherapy or primary debulking surgery in the prospective DECIDER cohort. Measures were analyzed separately in patients treated with neoadjuvant chemotherapy and primary debulking surgery. Results Longitudinal CA-125 values from 96 patients were analyzed, including 55 treated with neoadjuvant chemotherapy and 41 treated with primary debulking surgery. In the neoadjuvant chemotherapy group, KELIM and Percentage Reduction were significantly associated with platinum-free interval and progression-free survival. Reduction-based measures also showed the highest accuracy for predicting complete cytoreduction after interval debulking surgery, with area under the curve values up to approximately 0.75. In the primary debulking surgery group, reduction-based measures showed weaker associations, consistent with reduced dynamic range after removal of bulk tumor before chemotherapy. Post-Chemotherapy Level showed the most consistent association with overall survival among the evaluated measures. Homologous recombination deficiency-associated trends were observed but were not statistically significant after correction for multiple testing. Conclusions CA-125-based measures showed treatment-context-specific associations with clinically relevant indicators of chemosensitivity in high-grade serous carcinoma. KELIM was most informative in patients receiving neoadjuvant chemotherapy, whereas Post-Chemotherapy Level emerged as a simple and broadly applicable marker, particularly after primary debulking surgery. These findings show that CA-125-based measures capture different aspects of treatment-associated CA-125 dynamics, with associations that depend on treatment strategy. However, discrimination was insufficient to support clinical decision-making in this cohort, and the results should be interpreted as exploratory. Trial registration ClinicalTrials.gov, NCT04846933. Registered 2021-04-12. The present manuscript reports an observational secondary analysis of patients enrolled in the DECIDER cohort. Retrospectively registered.