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Review
. 2025 Jan 17;30(1):oyae325.
doi: 10.1093/oncolo/oyae325.

Ovarian clear cell carcinoma: open questions on the management and treatment algorithm

Roberta Rosso  1 , Margherita Turinetto  2 , Fulvio Borella  3 , Nicolas Chopin  4 , Pierre Meeus  4 , Alexandra Lainè  4 , Isabelle Ray-Coquard  4 , Olivia Le Saux  4 , Domenico Ferraioli  4
Affiliations
Review

Ovarian clear cell carcinoma: open questions on the management and treatment algorithm

Roberta Rosso et al. Oncologist. .

Abstract

Ovarian clear cell carcinoma (OCCC) accounts for ~10% of all epithelial ovarian cancers and is considered a different entity from the more common high-grade serous ovarian carcinoma (HGSC), with distinct clinical presentations, different risk, and prognostic factors, and specific molecular features. Most OCCCs are diagnosed at an early stage and show favorable outcomes, in contrast to those diagnosed at advanced stages, which exhibit intrinsic resistance to platinum-based chemotherapy regimens and a very poor prognosis. The standard treatment of advanced OCCC is currently based on primary debulking surgery followed by platinum-based chemotherapy according to recent international guidelines. However, these recommendations are extrapolated from several trials mainly featuring a large cohort of HGSC, with only a small minority of OCCC. Because of its rarity, many questions remain unanswered regarding the surgical and medical treatment. Lymph node staging, fertility-sparing treatment, the use of targeted therapies and radiotherapy as well as the adjuvant treatment for early-stage disease and second or further lines of chemotherapy are still under debate. This review aims to address these unresolved issues, by providing a comprehensive overview of the current data on this disease, and to suggest possible directions for future research.

Keywords: clear cell; clear cell ovarian carcinoma; management; ovarian cancer; prognosis; target therapy; treatment.

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Conflict of interest statement

O.L.S. reports honoraria from MSD and Clovis, and travel/accommodation/expenses from Eisai. The other authors declare the absence of any commercial or financial relationships that could be construed as a potential conflict of interest for this review.

Figures

Figure 1.
Figure 1.
Main molecular alterations and possible therapeutic targets for OCCC. ARID1A mutation activates the PI3K/ATK/mTOR pathway that interacts with the homologous recombination repair (HRR) system and leads to an increased production of IL-6. ARID1A mutation is also involved in the inhibition of PTEN and the loss of expression of the BAF250a protein. PARPi and Temsirolimus can target, respectively, HRR system and mTOR, while bevacizumab and ICIs interact with VEGF and tumors that present microsatellite instability.
Figure 2.
Figure 2.
Proposal of a management algorithm for a newly diagnosed OCCC. FSS: fertility-sparing surgery, MTB: multidisciplinary tumor board, NACT: neoadjuvant chemotherapy, OCCC: ovarian clear cell carcinoma, PDS: primary debulking surgery.
Figure 3.
Figure 3.
Proposal of a management algorithm for adjuvant treatment. CT: chemotherapy.
See this image and copyright information in PMC

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