Prognostic value of "aggressive" histology in surgically staged clinically uterine-confined endometrial carcinoma.

Objective: We compared oncologic outcomes across "aggressive" histopathological subtypes of apparent early-stage, high-grade endometrial carcinoma.

Methods: Patients who underwent surgical staging at our institution for newly diagnosed high-grade endometrial adenocarcinoma between January 1, 2009, and June 30, 2021, were retrospectively identified. We defined "aggressive" histology as International Federation of Obstetrics and Gynecology grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, and undifferentiated/dedifferentiated subtypes. Clinicopathologic details were extracted from medical records. Continuous variables were analyzed using the Kruskal-Wallis test, categorical variables using Fisher's exact test or the χ² test, and survival outcomes using the Kaplan-Meier method and Cox proportional hazards models.

Results: Of 1087 patients, 308 (28.3%) had grade 3 endometrioid adenocarcinoma, 357 (32.8%) serous adenocarcinoma, 64 (5.9%) clear cell carcinoma, 194 (17.8%) carcinosarcoma, 101 (9.3%) mixed adenocarcinoma, and 63 (5.8%) undifferentiated/dedifferentiated adenocarcinoma. Overall, 719 patients (66.1%) had International Federation of Obstetrics and Gynecology 2009 stage I, 51 (4.7%) stage II, 232 (21.3%) stage III, and 85 (7.8%) stage IV disease. Median age at surgery was 65.1 years (range; 24.8-92.1) and varied among histologies (p < .001). Overall, 462 patients (42.5%) had lymphovascular invasion, 333 (30.6%) had deep myometrial invasion (≥50%), and 160 (15.0%) had positive peritoneal cytology; all varied across histologies (p < .001). Rates of 5-year progression-free and overall survivals were 79% (standard error [SE] ± 3%) and 83% (SE ± 2%) for grade 3 endometrioid, 63% (SE ± 3%) and 66% (SE ± 3%) for serous, 73% (SE ± 6%) and 77% (SE ± 6%) for clear cell, 51% (SE ± 4%) and 54% (SE ± 4%) for carcinosarcoma, 59% (SE ± 5%) and 65% (SE ± 5%) for mixed, and 71% (SE ± 6%) and 76% (SE ± 6%) for undifferentiated/dedifferentiated (P<.001 for both). Peritoneal cytology, lymphovascular invasion, and age at surgery were independent predictors of worse progression-free and overall survivals on multivariable analysis.

Conclusions: High-grade "aggressive" histologies in endometrial cancer are diverse tumors with distinct oncologic outcomes; therefore, they should not be treated as a single entity or used as a staging criterion.