Molecular and pathologic data to guide selection of patients with endometrioid endometrial cancer for ovarian preservation.

Objectives: To investigate the association of molecular and pathologic factors with concurrent or recurrent ovarian disease to guide ovarian preservation in endometrioid endometrial cancer.
Methods: Patients with endometrial cancer ≤50 years of age at diagnosis were grouped by elective oophorectomy versus ovarian preservation at staging (January 2010 to June 2021). Tumors were stratified by molecular sub-type and CTNNB1 mutational status with next generation sequencing and immunohistochemistry. Germline data identified patients with Lynch syndrome. Associations between molecular/pathologic features and concurrent ovarian disease in patients electing oophorectomy were compared with the Wilcoxon rank-sum and Fisher's exact tests. Associations with isolated ovarian recurrences in patients who chose ovarian preservation were examined using survival analyses.
Results: Among 317 patients with endometrial cancer who underwent bilateral oophorectomy, 27 (9%) had malignant ovarian tumors, of whom 11 (41%) had no gross ovarian involvement on intra-operative survey. For patients with sequencing, concurrent malignant ovarian tumors were diagnosed in 0/14 (0%) POLE , 2/48 (4%) copy number-low/no specific molecular profile, 10/22 (45%) microsatellite instability-high, and 3/6 (50%) copy number-high/ TP53 abnormal patients (p<0.001). Concurrent malignant ovarian tumors were present in 1/30 (3%) hotspot CTNNB1 -mutated versus 10/60 (17%) wildtype/ CTNNB1 non-hotspot mutated endometrial cancer patients (p=0.11) and 7/28 (25%) Lynch versus 7/74 (9%) non-Lynch syndrome patients (p=0.06). Concurrent malignant ovarian tumors were present in patients with higher grade endometrial cancer (5% grade 1 vs 20% grade 2 and 24% grade 3; p<0.001), present versus absent lymphovascular space invasion (20% vs 6%; p=0.004), positive versus negative pelvic washings (28% vs 7%; p=0.016), and ≥50% versus <50% myoinvasion (24% vs 7%; p=0.004). Of 103 patients who chose ovarian preservation, four had isolated ovarian recurrences (two had high-risk pathologic features and two had high-risk molecular features).
Conclusions: The integration of molecular and pathologic data may improve risk stratification of pre-menopausal patients with endometrial cancer and enhance candidate selection for ovarian preservation.
Competing Interests: Competing interests: Outside the submitted work, NRA-R reports research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. ML reports personal fees from Medtronic, Intuitive Surgical, J&J/Ethicon, and Immunogen. BW reports research funding from Repare Therapeutics, outside of the current work. The other authors have no potential conflicts of interest to disclose.
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