No Prognostic Role for FIGO grading in Mismatch Repair Deficient Endometrial Carcinoma

Introduction The prognostic value of FIGO grading in endometrial cancer (EC) varies across molecular subgroups: it is no longer considered relevant in POLE mut and p53abn tumours, but remains prognostic in NSMP tumours. Its relevance is unclear in mismatch repair deficient (MMRd) EC. Using a large collection of molecularly classified EC, this study evaluated the prognostic role of FIGO grading in MMRd EC. Methods Data from three randomised trials (PORTEC-1 (n=714); PORTEC-2 (n=427); PORTEC-3 (n=660)) and five clinical cohorts (n=1357) were pooled, yielding patients with stage I-III endometrioid and non-endometrioid EC. Tumours were molecularly classified according to the 2020 WHO diagnostic algorithm, with central pathology review by an expert gynaecopathologist. Cause-specific cumulative incidence was estimated using the Aalen-Johansen method and compared using Gray's test. The independent prognostic value of FIGO grading was assessed using multivariable cause-specific Cox regression models. Results In total, 2621 (83.0%) of the 3158 EC cases were molecularly classified, including 730 (27.9%) MMRd tumours: 405 (55.5%) were low-grade and 325 (44.5%) were high-grade. Median follow-up was 7.2 years. Five-year cumulative incidence of overall recurrence (18.0% vs. 18.8%, p=0.67) and cancer-specific death (12.3% vs. 14.2%; p=0.44) did not differ between low- and high-grade MMRd EC. In multivariable analyses, corrected for age, stage, histotype, LVSI and adjuvant treatment, FIGO grading was not independently associated with overall recurrence (HR 0.83 [95%CI 0.56-1.24]; p=0.37) or cancer-specific death (HR 0.97 [0.62-1.51]; p=0.89). Conclusion In conclusion, FIGO grading has no prognostic role in MMRd EC and may be omitted in risk stratification and adjuvant treatment decisions.