Molecular Subtyping Predicts Recurrence and Survival Benefits in Endometrial Cancer

Patients with certain molecular subtypes of stage III endometrial cancer, including those with disease that was microsatellite instability–high (MSI-H), p53 abnormal, and of no specific molecular pattern (NSMP), benefitted from chemotherapy and sequential radiation therapy following surgical resection, according to findings from a retrospective study presented during the 2025 SGO Winter Meeting.1 Additionally, MSI-H and p53 abnormal status were associated with worsened survival outcomes compared with NSMP due to higher rates of relapse, according to the investigators.

Data from the study demonstrated that patients with MIS-H disease who received 4 to 6 cycles of chemotherapy (n = 15), 1 to 3 cycles (n = 7), 0 cycles (n = 9), and more than 6 cycles (n = 1) experienced median overall survivals (OS) of not yet reached (NR; 95% CI, NR-NR), 61.5 months (95% CI, 10.3-NR), NR (95% CI, 24.0-NR), and 27.0 months (95% CI, NR-NR). The respective median disease-free survival (DFS) values were NR (95% CI, NR-NR), 55.6 months (95% CI, 32.0-NR), 61.0 months (95% CI, 36.6-NR), and 12.5 months (95% CI, NR-NR).

Patients with NSMP disease (n = 41) experienced a 5-year OS rate of 80.8% compared with 68.6% among patients who had MSI-H disease (n = 32) and 56.2% in those who had p53 abnormalities (n = 42). The 5-year DFS rates were 86.6%, 63.4%, and 45.7%, respectively.

“Endometrial carcinoma is a heterogeneous group of cancers arising from the endometrium of the uterine cavity [and] is the most common gynecologic cancer among Canadian women,” the study authors wrote in a poster presentation of their results. “The shift from histomorphological classifications to molecular of endometrial carcinomas have [been] shown to improve prognostic relevance and should be incorporated in diagnostics, treatment protocols, and future studies.”

The study included all patients in British Columbia, Canada, who were diagnosed with FIGO stage III endometrial cancer between 2017 and 2021. Patients were stratified into 5 groups: POLE-mutated (n = 1), MSI-H, p53 abnormal, NSMP, and molecular subtypes unknown (n = 2).

The POLE-mutated group included patients who also had p53 wild-type and MSI-H disease, those who also had a p53 abnormality, and those who were also MSI-H. The MSI-H group included patients who also had p53 wild-type and POLE wild-type disease, those with POLE not tested, patients only MSI tested, and those with abnormal p53 and MSI-H. The p53 abnormal group encompassed patients who were MSI-low and POLE wild-type, as well as those with POLE not tested and abnormal p53. The NSMP group included patients who had p53 wild-type, MSI-low, and POLE wild-type; POLE not tested, p53 wild-type, and MSI-low; only MSI tested and MSI-low; and only p53 tested and p53 wild-type diseases.

The study objective was to evaluate the survival outcomes of patients with stage III endometrial cancer stratified by molecular subtypes, with and without postoperative therapy receipt. DFS and OS outcomes were calculated via Kaplan-Meier estimates.

Additional findings showed a trend towards worsened DFS for patients with a p53 abnormality who did not receive chemotherapy compared with those who did (P = .084). The median DFS in this group for patients who received 4 to 6 cycles of chemotherapy (n = 29), 1 to 3 cycles (n = 4), 0 cycles (n = 7), and more than 6 cycles (n = 2) was 59.1 months (95% CI, 23.9-NR), 61.2 months (95% CI, NR-NR), 33.8 months (95% CI, 32.2-NR), and 14.1 months (95% CI, 10.5-NR), respectively. The median OS values for these respective subgroups all matched the median DFS values.

In all subgroups examined, patients who received sequential postoperative radiotherapy experienced prolonged OS and DFS compared with those who did not, regardless of if they also received chemotherapy (P < .0001). The median OS among patients who received adjuvant radiation (n = 89) was NR (95% CI, NR-NR) vs 38.7 months (95% CI, 21.3-NR) for those who did not (n = 31). The median DFS was NR (95% CI, NR-NR) compared with 60.7 months (95% CI, 35.8-NR), respectively.

Patients who received no chemotherapy and no radiotherapy (n = 17) experienced a median DFS of 41.5 months (95% CI, 26.3-NR), compared with NR (95% CI, 31.6-NR) for those who received radiotherapy only (n = 18), NR (95% CI, NR-NR) for those who received chemotherapy and radiation (n = 71), and 25.3 months (95% CI, 13.8-NR) among those who received chemotherapy alone (n = 14). The 5-year DFS rate for the overall cohort (n = 120) was 67.2% (95% CI, 57.1%-79.0%).

Findings from a multivariable analysis which correlated median OS with several factors demonstrated that a more advanced stage of disease, FIGO stage 3C compared with stage 3A (HR, 3.416; 95% CI, 1.076-10.848) and FIGO grade 3 compared with grade 1 (HR, 2.779; 95% CI, 0.712-10.847), was independently predictive or trended towards predictive of worse survival.

Reference

1. Chi J, Rajkumar G, Huang L, Sun SZ, Ko JJ. The addition of chemotherapy (CT) and radiation therapy (RT) for patients with stage III endometrial cancer treated with curative intent surgery and their impact on recurrence and survival for molecular subtypes. Presented at: SGO 2025 Winter Meeting. January 30-February 1, 2025; Whistler, British Columbia, Canada.