Platinum refractory advanced stage ovarian clear cell carcinoma: time to reconsider primary therapy?

Abstract

Objectives: Clear Cell Ovarian Carcinoma (CCOC) is known for its chemoresistance, high rates of relapse, and poor overall survival. Despite this, upfront treatment has remained relatively unchanged for decades. The objective of this study was to compare demographic and pathologic characteristics of patients with rapidly progressive versus chemo-sensitive advanced stage (III or IV) CCOC in order to better identify a cohort of patients who may benefit from innovative upfront treatment strategies. Methods: After IRB approval, patients diagnosed with CCOC between 2008 and 2020 at our University were identified and reviewed. Demographic information including age, parity, and menopausal status at time of diagnosis was collected in addition to tumor data such as percent clear cell and the presence or absence of coexisting endometriosis. Those diagnosed with stage I or II disease and those who have not yet completed adjuvant therapy were excluded. Progression-free survival (time from chemotherapy completion to progression or death) was estimated with a Kaplan-Meier curve. Patients were divided into one of two cohorts: chemo-sensitive (lack of progression or death at one year from chemotherapy completion) or rapidly progressive (evidence of progression or death within one year) and cohorts were compared using Wilcoxon rank-sum tests and Fisher's exact tests. Results: Thirty-four patients met inclusion criteria. All subjects underwent surgical staging or debulking and adjuvant platinum/taxane chemotherapy. Median progression-free survival was 6.1 months (95% confidence interval: 3.3-24.3 months). Thirteen patients (43.3%) were identified as chemo-sensitive, and seventeen (56.7%) as rapid progressors. Four patients did not have enough follow-up to be classified. All rapid progressors recurred or progressed within seven months of primary chemotherapy completion. The cohort of patients with rapidly progressive disease were younger (median age 53 vs 64, p=0.048) and more likely to be premenopausal (41% vs 7.7%, p=0.11). Rates of endometriosis, pure clear cell histology and residual disease after surgery were also higher in this group (53% vs 31%, p=0.34, 65% vs 46%, p=0.5 and 65% vs 46%, p=0.5 respectively), although these differences did not reach statistical significance. Download : Download high-res image (53KB) Download : Download full-size image Conclusions: Over half of patients with advanced clear cell ovarian carcinoma demonstrated rapid progression following or during platinum based chemotherapy. Further characterization of this cohort is indicated and molecular studies are underway to better identify patients that will experience no benefit from the current standard of care. Targeting this cohort of women with innovative, upfront clinical trials is warranted.