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Original research
Impact of molecular classification on recurrence risk in endometrial cancer patients with lymph node metastasis: multicenter retrospective study
  1. Gabriella Schivardi1,2,
  2. Giuseppe Caruso1,2,
  3. Luigi A De Vitis1,2,
  4. Giuseppe Cucinella1,
  5. Francesco Multinu1,2,
  6. Vanna Zanagnolo2,
  7. Glauco Baiocchi3,
  8. Louise De Brot3,
  9. Tommaso Occhiali1,4,
  10. Giuseppe Vizzielli4,
  11. Robert Giuntoli5,
  12. Angela J Fought6,
  13. Michaela E McGree6,
  14. Maryam Shahi7,
  15. Andrea Mariani1 and
  16. Gretchen E Glaser1
    1. 1Department of Obstetrics and Gynecology, Division of Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota, USA
    2. 2Department of Gynecology, IEO, European Institute of Oncology IRCCS, Milan, Italy
    3. 3Gynecologic Oncology, A.C. Camargo Cancer Center, Sao Paulo, Brazil
    4. 4Department of Medicine, Clinic of Obstetrics and Gynecology, University of Udine, Udine, Italy
    5. 5Division of Gynecologic Oncology, Penn Medicine, Philadelphia, Pennsylvania, USA
    6. 6Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
    7. 7Department of Pathology, Mayo Clinic, Rochester, Minnesota, USA
    1. Correspondence to Dr Gretchen E Glaser, Department of Obstetrics and Gynecology, Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; glaser.gretchen{at}mayo.edu

    Abstract

    Objective To assess the distribution of molecular classes and their impact on the risk of recurrence in endometrial cancer patients with lymph node metastasis at the time of primary surgery.

    Methods Endometrial cancer patients with lymph node micrometastasis or macrometastasis (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIC) after surgical staging at five referral centers worldwide from October 2013 to September 2022 who underwent molecular classification were identified. Endometrial cancers were categorized into four molecular classes: POLE mutated, mismatch repair deficient, p53 abnormal, and no specific molecular profile. Survival analyses using Kaplan–Meier and Cox models (univariate and multivariate) were conducted to evaluate the relationship between molecular class and 5-year recurrence free survival.

    Results 131 patients were included: 55 (42.0%) no specific molecular profile, 46 (35.1%) mismatch repair deficient, 1 (0.8%) POLE mutated, and 29 (22.1%) p53 abnormal. During a 5 year follow-up period, 50 (38.2%) patients experienced a recurrence with a median time of 1.2 years (interquartile range (IQR) 0.5–1.8). Median follow-up for the remaining 81 patients was 3.1 years (IQR 1.3–4.5). Survival analysis revealed a significant difference in recurrence-free survival between no specific molecular profile, mismatch repair deficient, and p53 abnormal classes (log rank p<0.01). In a model adjusted for type of lymph node metastasis and tumor grade, the molecular class did not retain significance (p=0.13), while in a model adjusted for type of lymph node metastasis and adjuvant therapy, the molecular class retained significance (p<0.01).

    Conclusion Among patients with stage IIIC endometrial cancer, POLE mutated tumors exhibited an extremely low prevalence, with no specific molecular profile emerging as the largest molecular subgroup. Despite the significant difference in recurrence-free survival between molecular classes, conventional histopathologic parameters retained crucial prognostic value. Our findings highlight the necessity of integrating molecular classes with pathological characteristics, rather than considering them in isolation as crucial prognostic factors in stage IIIC endometrial cancer.

    • Endometrial Neoplasms
    • Lymphatic Metastasis
    • Endometrium

    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

    https://doi.org/10.1136/ijgc-2024-005672

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      Data availability statement

      All data relevant to the study are included in the article or uploaded as supplementary information.

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      Footnotes

      • X @gcarusomd, @Cucinella_G, @Fmultinu, @glaucobaiocchi

      • Presented at The results were presented as a poster presentation at European Society of Gynaecological Oncology (ESGO) Conference 2023.

      • Contributors All named authors have contributed significantly to the work, have read the manuscript, and have agreed to its submission. Authors who have contributed in planning the work: GS, GG, AM, and GCu. Authors who have contributed in conducting the work: GS, GG, AM, GCu, FM, VZ, GB, LDB, TO, GV, RG, AJF, MM, and MS. Authors who have contributed in reporting the work: GS, GG, AM, GCa, AJF, and MM. GG is acting as guarantor of the work.

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

      • Competing interests None declared.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.