Molecular classification and association with survival outcomes in high-intermediate and high-risk early-stage endometrial cancers: Ancillary analysis of GOG-0249
Year: 2025
Type: article
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.
Source: Gynecologic Oncology
Authors: Lindsay M. Kuroki, Danielle M. Enserro, Heather A. Lankes, Kyle C. Strickland, Rebecca Previs, Aine Clements, Matthew A. Powell, Ann Klopp, Elena Ratner, Paul DiSilvestro, Casey Cosgrove, Guilherme Henrique Cantuaria, Nicola M. Spirtos, Michael Carney, Mitchell Edelson, Gottfried Konecny, Penny Anderson, Christopher Tarney, Britt K. Erickson, Meredith Newton, Krishnansu S. Tewari, Premal H. Thaker, David Warshal, Amy Armstrong, Xun Clare Zhou, Angeles Alvarez Secord
Institutions: Washington University in St. Louis, Roswell Park Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, NRG Oncology, Duke Medical Center, Duke Cancer Institute, OhioHealth, The University of Texas MD Anderson Cancer Center, Yale Cancer Center, Yale University, Smilow Cancer Hospital, Women & Infants Hospital of Rhode Island, Northside Hospital, Women's Cancer Center of Nevada, University of Hawaii Cancer Center, Thomas Jefferson University, Sidney Kimmel Cancer Center, University of California, Los Angeles, UCLA Jonsson Comprehensive Cancer Center, Fox Chase Cancer Center, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, University of Minnesota, University of North Carolina at Chapel Hill, University of California, Irvine, Cooper University Hospital, University Hospitals of Cleveland, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center, Hartford Hospital
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,380
Funders: U.S. Department of Health and Human Services, Mayo Clinic, Roswell Park Cancer Institute, V Foundation for Cancer Research, Yale University, Duke University, Wayne State University, Indiana University, University of Pennsylvania, Ohio State University, Memorial Sloan-Kettering Cancer Center, Wake Forest University, University of New Mexico, University of Chicago, University of Minnesota, Cleveland Clinic, Cleveland Clinic Foundation, Division of Cancer Prevention, National Cancer Institute, University of Kentucky, University of Texas Southwestern Medical Center, University of Pittsburgh, University of Oklahoma, University of Cincinnati, Case Western Reserve University, Pennsylvania State University, Rush University, Medical College of Wisconsin, Moffitt Cancer Center, St. John Hospital and Medical Center, NorthShore University HealthSystem, Greenville Health System, Barbara Ann Karmanos Cancer Institute, NRG Oncology, Kay Yow Cancer Fund, Seoul National University, Seoul National University Hospital, Stony Brook University, National Institutes of Health, University of North Carolina at Chapel Hill, University of Oklahoma Health Sciences Center, University of California, San Francisco, Cancer Institute, University of Pittsburgh, SUNY Downstate Medical Center, Washington University School of Medicine in St. Louis, Walter Reed National Military Medical Center, Cancer Center, University of Colorado, National Cancer Institute, Comprehensive Cancer Center, University of Chicago Medical Center
OpenAlex ID: W4414650672