Molecular Classification and Association With Survival Outcomes in High-Intermediate and High-Risk Early-Stage Endometrial Cancers: Ancillary Analysis of GOG-0249

Authors

• Lindsay Kuroki
• Danielle Enserro
• Heather Lankes
• Kyle Strickland
• Rebecca Previs
• Aine Clements
• Matthew Powell
• Ann Klopp
• Elena Ratner
• Paul DiSilvestro
• Casey Cosgrove
• Guilherme Henrique Cantuaria
• Nicola Spirtos
• Michael Carney
• Mitchell Edelson, Abington Jefferson HealthFollow
• Gottfried Konecny
• Penny Anderson
• Christopher Tarney
• Britt Erickson
• Meredith Newton
• Krishnansu Tewari
• Premal Thaker
• David Warshal
• Amy Armstrong
• Xun Clare Zhou
• Angeles Alvarez Secord

Document Type

Article

Publication Date

5-26-2026

Comments

This article is the author’s final published version in Gynecologic Oncology, Volume 210, 2026, Pages 63-71.

The published version is available at https://doi.org/10.1016/j.ygyno.2026.05.013. Copyright © 2026 The Authors.

Abstract

OBJECTIVE: Determine whether mismatch repair (MMR) and p53 expression predict recurrence-free survival (RFS) and overall survival (OS) in early-stage endometrial cancer (EC) patients treated with vaginal cuff brachytherapy plus chemotherapy (VCB/C) versus pelvic radiation therapy (RT).

METHODS: In the GOG-0249 trial, 601 patients with high-intermediate risk (HIR) early-stage EC were randomized to VCB/C (carboplatin/paclitaxel for 3 cycles) or pelvic RT. Molecular subgroups, deficient MMR (dMMR), p53 wildtype (p53wt), p53 abnormal (p53abn), were determined by immunohistochemistry. Five-year RFS and OS were analyzed using Kaplan-Meier curves and Cox proportional hazards models, adjusting for lymphadenectomy, planned VCB, and treatment group.

RESULTS: Among 315 patients, 23.5% had EC exhibiting p53abn expression, 32.1% had dMMR, and 44.4% had p53wt. p53abn EC was associated with older age (p = 0.004), serous histology (p <  0.001), lymphadenectomy (p = 0.02), and planned VCB (p <  0.001). Five-year RFS and OS were worse in patients with p53abn cancers, 58.7% [Hazard Ratio (HR) = 4.0 (95% Confidence Interval (CI): 2.1-7.5)] and 70.7% [HR = 9.4 (95%CI: 3.8-23.6)] and dMMR cancers 74.4% [HR = 1.8 (95%CI: 0.9-3.3)] and 84.3% [HR = 3.0 (95%CI: 1.2-7.8)] compared to those with p53wt (referent) (83.4% and 95.3%) (p <  0.001). The RFS (p = 0.7) and OS (p = 0.8) rates did not differ by treatment within molecular subgroups.

CONCLUSION: Molecular classification is prognostic for survival outcomes in patients with stage I-II HIR/high-risk EC. Patients with p53abn cancers seem to have the highest risk of relapse and death. Molecular subgroups do not appear to predict benefit from VCB/C as compared to pelvic RT. Novel therapeutic approaches are needed, especially for those with dMMR and p53abn expressing cancers.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Recommended Citation

Kuroki, Lindsay; Enserro, Danielle; Lankes, Heather; Strickland, Kyle; Previs, Rebecca; Clements, Aine; Powell, Matthew; Klopp, Ann; Ratner, Elena; DiSilvestro, Paul; Cosgrove, Casey; Cantuaria, Guilherme Henrique; Spirtos, Nicola; Carney, Michael; Edelson, Mitchell; Konecny, Gottfried; Anderson, Penny; Tarney, Christopher; Erickson, Britt; Newton, Meredith; Tewari, Krishnansu; Thaker, Premal; Warshal, David; Armstrong, Amy; Zhou, Xun Clare; and Alvarez Secord, Angeles, "Molecular Classification and Association With Survival Outcomes in High-Intermediate and High-Risk Early-Stage Endometrial Cancers: Ancillary Analysis of GOG-0249" (2026). Abington Jefferson Health Papers. Paper 143.
https://jdc.jefferson.edu/abingtonfp/143

PubMed ID

42190623

Language

English