Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258

Aine Clements; Danielle Enserro; Kyle C. Strickland; Rebecca Previs; Daniela Matei; David Mutch; Matthew Powell; Ann Klopp; David Scott Miller; William Small; Paul DiSilvestro; Nick Spirtos; Casey Cosgrove; Greg Sfakianos; J. Rebecca Liu; Roberto Vargas; Mark Shahin; Bradley Corr; Kimberly Dessources; Frederick Ueland; David Warshal; Jessica Gillen; Angeles Alvarez Secord

doi:10.1016/j.ygyno.2025.01.006

Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258

Aine Clements^*, Danielle Enserro, Kyle C. Strickland, Rebecca Previs, Daniela Matei, David Mutch, Matthew Powell, Ann Klopp, David Scott Miller, William Small, Paul DiSilvestro, Nick Spirtos, Casey Cosgrove, Greg Sfakianos, J. Rebecca Liu, Roberto Vargas, Mark Shahin, Bradley Corr, Kimberly Dessources, Frederick UelandDavid Warshal, Jessica Gillen, Angeles Alvarez Secord

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT). Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype. Results: ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had serous histology (p < 0.001). Median follow up was 113 months. Five-year RFS and OS were worse with p53abn (29 % [Hazard Ratio (HR) = 3.39 (95 % Confidence Interval (CI): 2.34–4.91)] and 39 % [HR = 4.64 (95 % CI: 3.16–6.79)] compared to those with p53wt (referent) (p < 0.001). The five-year RFS and OS for dMMR cancers were (58 % [HR = 1.30 (95 % CI: 0.85–1.97)] and 77 % [HR = 1.53 (95 % CI: 0.99–2.36)] compared to those with p53wt (69 % and 85 %). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77 % vs 60 %; HR = 0.54 (95 % CI: 0.32–0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups. Conclusion: Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS.

Original language	English (US)
Pages (from-to)	119-129
Number of pages	11
Journal	Gynecologic oncology
Volume	193
DOIs	https://doi.org/10.1016/j.ygyno.2025.01.006
State	Published - Feb 2025

Funding

This study was funded by the National Cancer Institute awards to the Oncology SDMC (1 U10 CA180822), NRG Operations (U10CA180868) and NCORP (UG1CA189867), the Kay Yow Cancer Fund/ The V Foundation for Cancer Research, the American Association of Obstetrics and Gynecology Foundation, and the OhioHealth Research Institute. The following NRG Oncology member institutions participated in the primary treatment studies: Women and Infants Hospital, Women's Cancer Center of Nevada, Ohio State University, Georgia Center for Oncology Research and Education (CORE), Cancer Trials Support Unit, Cancer Research Consortium of West Michigan NCORP, Case Western Reserve University, Abington Memorial Hospital, University of Colorado Cancer Center-Anschutz Cancer Pavilion, University of North Carolina at Chapel Hill, University of Kentucky, Cooper Hospital University Medical Center, Cancer Research for the Ozarks NCORP, University of California Medical Center at Irvine-Orange Campus, Metro-Minnesota CCOP, Washington University School of Medicine, University of Oklahoma Health Sciences Center, Yale University, University of Iowa Hospitals and Clinics, MD Anderson Cancer Center, Wake Forest University Health Sciences, The Hospital of Central Connecticut, Rush University Medical Center, Stony Brook University Medical Center, Memorial Sloan Kettering Cancer Center, Kaiser Permanente-Vallejo, Indiana University Hospital/Melvin and Bren Simon Cancer Center, University of New Mexico, Fox Chase Cancer Center, Mayo Clinic, University of Wisconsin Hospitals and Clinics, Froedtert and the Medical College of Wisconsin, Lewis Cancer and Research Pavilion at St. Joseph's/Candler, Walter Reed National Military Medical Center, Wayne State University/Karmanos Cancer Institute, University of California at Los Angeles Health System, Cleveland Clinic Foundation, University of Chicago, Carolinas Medical Center/Levine Cancer Institute, University of Hawaii, Wichita CCOP, Iowa-Wide Oncology Research Coalition NCORP, Sanford NCI Community Oncology Research Program of the North Central Plains, Columbus NCI Community Oncology Research Program, Southeast Cancer Control Consortium CCOP, University of Alabama at Birmingham, University of Mississippi Medical Center, Fred Hutchinson Cancer Research Center, Abramson Cancer Center of The University of Pennsylvania, University of Virginia, University of Texas - Galveston, Gynecologic Oncology of West Michigan PLLC, Aurora Women's Pavilion of Aurora West Allis Medical Center, Baystate Medical Center, Kalamazoo CCOP, Saint Vincent Hospital, Duke University Medical Center, University of Minnesota Medical Center - Fairview, Penn State Milton S Hershey Medical Center, State University of New York Downstate Medical Center, Seoul National University Hospital, Rutgers Cancer Institute of New Jersey, Allegheny General Hospital, Wisconsin NCI Community Oncology Research Program, Central Illinois CCOP, Northern Indiana Cancer Research Consortium, Geisinger Medical Center, Nevada Cancer Research Foundation CCOP, Greenville Health System Cancer Institute/Greenville CCOP, Florida Hospital Cancer Institute CCOP, Sanford Roger Maris Cancer Center, Montana Cancer Consortium-CCOP, and John H. Stroger Jr. Hospital of Cook County. This study was funded by the National Cancer Institute awards to the Oncology SDMC (1\u202FU10 CA180822), NRG Operations (U10CA180868) and NCORP (UG1CA189867), the Kay Yow Cancer Fund/ The V Foundation for Cancer Research, the American Association of Obstetrics and Gynecology Foundation, and the Ohio Health Research Institute.

ASJC Scopus subject areas

Oncology
Obstetrics and Gynecology

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10.1016/j.ygyno.2025.01.006

Cite this

Clements, A., Enserro, D., Strickland, K. C., Previs, R., Matei, D., Mutch, D., Powell, M., Klopp, A., Miller, D. S., Small, W., DiSilvestro, P., Spirtos, N., Cosgrove, C., Sfakianos, G., Liu, J. R., Vargas, R., Shahin, M., Corr, B., Dessources, K., ... Secord, A. A. (2025). Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258. Gynecologic oncology, 193, 119-129. https://doi.org/10.1016/j.ygyno.2025.01.006

@article{fc5e0fccae3d4f46b670b61b6db0cc00,

title = "Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258",

abstract = "Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT). Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype. Results: ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had serous histology (p < 0.001). Median follow up was 113 months. Five-year RFS and OS were worse with p53abn (29 % [Hazard Ratio (HR) = 3.39 (95 % Confidence Interval (CI): 2.34–4.91)] and 39 % [HR = 4.64 (95 % CI: 3.16–6.79)] compared to those with p53wt (referent) (p < 0.001). The five-year RFS and OS for dMMR cancers were (58 % [HR = 1.30 (95 % CI: 0.85–1.97)] and 77 % [HR = 1.53 (95 % CI: 0.99–2.36)] compared to those with p53wt (69 % and 85 %). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77 % vs 60 %; HR = 0.54 (95 % CI: 0.32–0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups. Conclusion: Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS.",

author = "Aine Clements and Danielle Enserro and Strickland, {Kyle C.} and Rebecca Previs and Daniela Matei and David Mutch and Matthew Powell and Ann Klopp and Miller, {David Scott} and William Small and Paul DiSilvestro and Nick Spirtos and Casey Cosgrove and Greg Sfakianos and Liu, {J. Rebecca} and Roberto Vargas and Mark Shahin and Bradley Corr and Kimberly Dessources and Frederick Ueland and David Warshal and Jessica Gillen and Secord, {Angeles Alvarez}",

note = "Publisher Copyright: {\textcopyright} 2025",

year = "2025",

month = feb,

doi = "10.1016/j.ygyno.2025.01.006",

language = "English (US)",

volume = "193",

pages = "119--129",

journal = "Gynecologic oncology",

issn = "0090-8258",

publisher = "Academic Press Inc.",

}

Clements, A, Enserro, D, Strickland, KC, Previs, R, Matei, D, Mutch, D, Powell, M, Klopp, A, Miller, DS, Small, W, DiSilvestro, P, Spirtos, N, Cosgrove, C, Sfakianos, G, Liu, JR, Vargas, R, Shahin, M, Corr, B, Dessources, K, Ueland, F, Warshal, D, Gillen, J & Secord, AA 2025, 'Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258', Gynecologic oncology, vol. 193, pp. 119-129. https://doi.org/10.1016/j.ygyno.2025.01.006

TY - JOUR

T1 - Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes

T2 - Ancillary analysis of GOG-0258

AU - Clements, Aine

AU - Enserro, Danielle

AU - Strickland, Kyle C.

AU - Previs, Rebecca

AU - Matei, Daniela

AU - Mutch, David

AU - Powell, Matthew

AU - Klopp, Ann

AU - Miller, David Scott

AU - Small, William

AU - DiSilvestro, Paul

AU - Spirtos, Nick

AU - Cosgrove, Casey

AU - Sfakianos, Greg

AU - Liu, J. Rebecca

AU - Vargas, Roberto

AU - Shahin, Mark

AU - Corr, Bradley

AU - Dessources, Kimberly

AU - Ueland, Frederick

AU - Warshal, David

AU - Gillen, Jessica

AU - Secord, Angeles Alvarez

PY - 2025/2

Y1 - 2025/2

N2 - Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT). Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype. Results: ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had serous histology (p < 0.001). Median follow up was 113 months. Five-year RFS and OS were worse with p53abn (29 % [Hazard Ratio (HR) = 3.39 (95 % Confidence Interval (CI): 2.34–4.91)] and 39 % [HR = 4.64 (95 % CI: 3.16–6.79)] compared to those with p53wt (referent) (p < 0.001). The five-year RFS and OS for dMMR cancers were (58 % [HR = 1.30 (95 % CI: 0.85–1.97)] and 77 % [HR = 1.53 (95 % CI: 0.99–2.36)] compared to those with p53wt (69 % and 85 %). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77 % vs 60 %; HR = 0.54 (95 % CI: 0.32–0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups. Conclusion: Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS.

AB - Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT). Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype. Results: ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had serous histology (p < 0.001). Median follow up was 113 months. Five-year RFS and OS were worse with p53abn (29 % [Hazard Ratio (HR) = 3.39 (95 % Confidence Interval (CI): 2.34–4.91)] and 39 % [HR = 4.64 (95 % CI: 3.16–6.79)] compared to those with p53wt (referent) (p < 0.001). The five-year RFS and OS for dMMR cancers were (58 % [HR = 1.30 (95 % CI: 0.85–1.97)] and 77 % [HR = 1.53 (95 % CI: 0.99–2.36)] compared to those with p53wt (69 % and 85 %). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77 % vs 60 %; HR = 0.54 (95 % CI: 0.32–0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups. Conclusion: Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS.

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UR - http://www.scopus.com/inward/citedby.url?scp=85215582609&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2025.01.006

DO - 10.1016/j.ygyno.2025.01.006

M3 - Article

C2 - 39854806

AN - SCOPUS:85215582609

SN - 0090-8258

VL - 193

SP - 119

EP - 129

JO - Gynecologic oncology

JF - Gynecologic oncology

ER -

Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258

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