Co-existent endometrial and ovarian carcinoma: molecular and pathological features define low risk entity.

Objective: Most co-existent endometrial and ovarian carcinomas are clonally related and exhibit an indolent disease course. Pathologic assignment and clinical management of this entity vary greatly. The International Federation of Gynecology and Obstetrics (FIGO) 2023 endometrial carcinoma staging/risk stratification system introduced a new substage for co-existent endometrial and ovarian carcinomas that meet strict pathologic criteria (stage IA3, distinct from IIIA1). Our aim was to validate if FIGO IA3 identifies a subset of co-existent endometrial and ovarian carcinomas at very low risk of recurrence and determine whether further refinement, through molecular features and expanded ovarian pathologic criteria, could improve prognostic discernment and direct more patients for consideration of de-escalation.

Methods: Clinicopathologic, molecular, and outcome data were collected on patients with co-existent endometrial and ovarian carcinoma, extracted from pathology archives and molecularly classified endometrial carcinoma cohorts.

Results: Among the 154 co-existent endometrial and ovarian carcinoma patients, higher recurrence rates were observed with the p53abn (2/6, 33%), mismatch repair deficiency (MMRd) (7/34, 21%) or no specific molecular profile (NSMP) estrogen receptor (ER) negative-low (2/15, 13%) molecular sub-types, compared with patients with POLEmut or NSMP ER strong positive tumors. Thirty-two patients met FIGO IA3 criteria, with one recurrence and death event (MMRd). Eliminating patients with adverse molecular features (p53abn or MMRd endometrium or ovary, or NSMP ER negative-low endometrium) and expanding criteria to include any POLEmut or cases with bilateral ovarian involvement, intra- or pre-operative ovarian rupture, or ovarian surface involvement significantly improved risk stratification (p = .008) and added 48 co-existent endometrial and ovarian carcinoma patients (>2-fold increase) with no recurrence events (mean follow-up: 6 years). There was 91% concordance of molecular sub-type assignment between endometrial and ovarian tumors.

Conclusions: FIGO IA3 criteria identify a subset of co-existent endometrial and ovarian carcinomas with excellent outcomes. However, incorporating molecular features into the definition enables greater prognostic discernment and supports the inclusion of patients with a broader range of pathologic features with indolent disease (increased from 20% to 49% of the cohort, 0 recurrences) who may be candidates for treatment de-escalation.