Eric J Yang

Prognostic performance of FIGO 2023 endometrial carcinoma staging: a comparison to FIGO 2009 staging in the setting of known and unknown molecular classification

AimsThe 2023 FIGO staging criteria for endometrial cancer (EC) introduced marked changes from the 2009 version. The full implication of these changes for patient diagnosis and treatment is unknown. We evaluate the differences in staging and prognostication between the two systems, with and without inclusion of molecular classification.Methods and resultsWe assigned (1) FIGO 2009, (2) 2023 molecular‐agnostic and (3) 2023 molecular‐informed stages to 404 fully staged and molecularly classified patients with EC. Disease‐specific and progression/relapse‐free survival were analysed via the Kaplan–Meier method and compared with log‐rank testing; 118 of 252 (47%) FIGO 2009 stage I patients were upstaged based on histopathological findings alone. Stage I/II subgroup survival distribution analysis showed a worse prognosis in FIGO 2023 IIB and IIC patients. In the molecular‐informed FIGO 2023 system, three of 15 (20%) POLE‐mutated stage I/II cases were downstaged from FIGO 2009 and eight (53%) were downstaged from molecular‐agnostic FIGO 2023. Fifty‐one of 60 (85%) p53‐abnormal tumours were upstaged from the FIGO 2009, whereas 13 of 60 (22%) were upstaged from the 2023 molecular‐agnostic stage. Molecular classification improved prognostic stratification for both 2009 and 2023 FIGO systems.ConclusionsDownstaging based on POLE mutation more accurately represents patient outcomes. However, in the absence of known POLE status, applying molecular‐agnostic FIGO 2023 criteria for stage I/II disease should be conducted with caution. For aggressive histotypes, additionally reporting FIGO 2009 stage should be considered. Upstaging based on substantial lymphovascular space invasion, aggressive histotype with any myometrial invasion and abnormal p53 improves prognostic discernment. Further subdivisions within stage I/II provide minimal additional prognostic information.

Molecular classification of metastatic and recurrent endometrial endometrioid carcinoma: prognostic relevance among low‐ and high‐stage tumours

AimsMolecular classification according to The Cancer Genome Atlas (TCGA) improves endometrial endometrioid carcinoma (EEC) prognostication and has specific treatment implications; however, original data were skewed towards low‐grade and low‐stage tumours. Herein, we molecularly classify EECs metastatic at the time of diagnosis or with subsequently documented recurrent/metastatic disease to examine correlation with clinical outcomes.MethodsTCGA categories include POLE‐mutated, microsatellite instability (MSI), p53 abnormal (p53 abnl) and no specific molecular profile (NSMP). POLE targeted sequencing at exons 9, 11, 13 and 14 and immunohistochemistry (IHC) for PMS2, MSH6 and p53 were performed to establish molecular classification.ResultsThe distribution in our cohort of 141 EECs was similar to that generally reported in EEC, with nine POLE‐mutated (6%), 45 MSI (32%), 16 p53 abnl (11%) and 71 NSMP (50%), with similar distributions between low‐ and high‐stage cohorts. We demonstrate that when stratified by molecular subtype, disease‐specific survival from the time of high‐stage (stages III–IV) presentation or time of recurrence in low‐stage (stages I–II) disease among metastatic and/or recurrent EEC is strongly associated with TCGA classification (high‐stage P = 0.02, low‐stage P = 0.017). Discordant molecular classification between primary and metastatic/recurrent tumours occurred in four of 105 (3.8%) patients, two related to PMS2/MSH6 IHC and two related to p53 IHC.ConclusionsWe demonstrate that molecular classification is prognostically relevant not only at the time of diagnosis, but also at the time of recurrence and in the metastatic setting. Rare subclonal alterations occur and suggest a role for confirming TCGA classification in recurrent/metastatic tumours.