Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study

SIMPLE SUMMARY: Ovarian clear-cell carcinoma is a unique subtype of epithelial ovarian cancer. This collaborative study aimed to provide important information regarding patient demographics and treatment-associated prognostic factors in ovarian clear-cell carcinoma in Asia. Given the difference in prognoses between early- and advanced-stage cohorts, varying predictors between these two cohorts were clarified in separate analyses. Efforts should be made to promote early diagnosis and the inclusion of advanced-stage patients in clinical trials. Additionally, early recognition of poor responders to platinum-based chemotherapy and those with cancer progression occurring within seven months after completing primary chemotherapy should be emphasized in research and clinical settings. Our findings suggest that treatment selection for patients with platinum-resistant/refractory features (e.g., novel biomarkers) or relapsed disease should be based on the results of ongoing clinical trials for ovarian clear-cell carcinoma. Our results (if confirmed) will guide and inform treatment recommendations for patients at risk for poor prognosis. ABSTRACT: This large-scale study aimed to determine the long-term influences of potential prognostic predictors and progression-free interval (PFI) criteria for grading platinum-sensitivity in ovarian clear cell carcinoma (OCCC). We retrospectively reviewed the medical records of OCCC patients presenting at nine tertiary centres (1995–2015), and evaluated patient characteristics, therapeutic factors, clinical outcomes, and hazard ratios for disease progression and death. We enrolled 536 patients (median follow-up, 36.6 months) and developed newly defined distributions of PFIs (seven and 14 months) for grading platinum sensitivity. In the multivariate model, preoperative CA125 levels and chemo-response independently predicted early-stage progression-free survival (PFS) risk. Post-progression cytoreduction correlated with reduced mortality risk. No unfavourable outcomes were observed with respect to coexisting endometriosis, fertility-sparing strategies, or platinum-based regimens. A PFI of <7 months, the strongest predictor of both post-progression mortality and second relapse risks, correlated with chemo-resistance, advanced tumour stage, and shortened post-progression survival. Chemotherapy regimens commonly used in front-line or relapse settings were limited in improving prognoses, especially in the advanced-stage cohort. Clinical trials of novel targeted agents and/or innovative biomarkers for chemoresistance should be comprehensively investigated and offered early to advanced-stage patients or those with OCCC progression occurring within seven months after receiving chemotherapy.