Co-existent endometrial and ovarian carcinoma: molecular and pathological features define low risk entity
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".