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Original research
Molecular profile is a strong predictor of the pattern of recurrence in patients with endometrial cancer
  1. Ana Luzarraga Aznar1,
  2. Vicente Bebia1,
  3. Carlos López-Gil2,
  4. Beatriz Villafranca-Magdalena2,
  5. Lourdes Salazar-Huayna3,
  6. Josep Castellvi3,
  7. Eva Colàs2,4,
  8. Antonio Gil-Moreno1,2,5 and
  9. Silvia Cabrera1,4
    1. 1Department of Gynecologic Oncology, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital, Barcelona, Catalunya, Spain
    2. 2Group of Biomedical Research in Gynecology, Vall Hebron Institute of Research Hospital, Vall d’Hebron Barcelona Hospital Campus. Universitat Autònoma de Barcelona (UAB). CIBERONC, Barcelona, Catalunya, Spain
    3. 3Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Catalunya, Spain
    4. 4Universitat Autònoma de Barcelona, Barcelona, Spain
    5. 5Department of Gynecology, Vall d'Hebron University Hospital, Barcelona, Catalunya, Spain
    1. Correspondence to Vicente Bebia, Department of Gynecologic Oncology, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital, Barcelona, Catalunya 08035, Spain; vicente.bebia{at}vallhebron.cat

    Abstract

    Objectives To investigate the pattern of first recurrence of disease in patients with endometrial cancer according to molecular classification, and to assess the independent role of molecular profiling in each type of failure.

    Methods Retrospective single-center study including patients diagnosed with endometrial cancer stage I–IVB (International Federation of Gynecology and Obstetrics 2009) between December 1994 and May 2022, who underwent primary surgical treatment and had a complete molecular profile. First recurrence was classified as isolated or multiple, and as vaginal, pelvic, peritoneal, nodal, and distant according to its location. The log-rank test and univariate and multivariate adjusted Cox regression models were used for comparison between groups.

    Results A total of 658 patients were included. Recurrence was observed in 122 patients (18.5%) with a recurrence rate of 12.4% among mismatch-repair deficient tumors, 14.5% among non-specific molecular profile, 2.1% among POLE-mutated, and 53.7% among p53-abnormal tumors. Recurrences were found to be isolated in 80 (65.6%) and multiple in 42 (34.4%) patients, with no differences in molecular subtype (p=0.92). Patients with p53-abnormal tumors had a recurrence mainly as distant (28.4%) and peritoneal (21.1%) disease, while patients with non-specific molecular profile tumors presented predominantly with distant failures (10.3%), and mismatch-repair deficient tumors with locoregional recurrences (9.4%).

    On multivariate analysis, p53-abnormal molecular profile was the only independent risk factor for peritoneal failure (OR=8.54, 95% CI 2.0 to 36.3). Vaginal recurrence was independently associated with p53-abnormal molecular profile (OR=6.51, 95% CI 1.1 to 37.4) and lymphovascular space invasion. p53-abnormal and non-specific molecular profiles were independent predictors for distant recurrence (OR=3.13, 95% CI 1.1 to 8.7 and OR=2.35, 95% CI 1.1 to 5.0, respectively), along with lymphovascular space invasion and high-grade tumors. Molecular profile was not independently associated with pelvic and nodal recurrences.

    Conclusions Endometrial cancer featured different patterns of recurrence depending on the molecular profile. p53-abnormal molecular profiling was the only independent risk factor for peritoneal relapse, while non-specific molecular profile showed a strong association with distant failures.

    • Endometrial Neoplasms
    • Pathology
    • Surgical Oncology

    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-2023-005165

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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

      • EC, AG-M and SC contributed equally.

      • Contributors ALA, VB, and SC conceived and planned the study. VB performed the statistical analysis. ALA carried out the manuscript preparation. SC, AG-M and EC are the senior members of the project and supervised the whole study. All authors (ALA, VB, CL-G, LS, JC, BV-M, EC, AG-M, SC) gave final approval of the version to be published. ALA is responsible for the overall content of the study as the guarantor.

      • Funding ISCIII grants (PI20/00664, PI20/01566), Miguel Servet grant (CP22_00147), RETOS Colaboración (CPP2021-008440), Fundación Científica AECC (GCTRA1804MATI), Biomedical Research Center Network CIBERONC (CB16/12/00328) and Generalitat de Catalunya (2021SGR11757). As well, this project was supported by AECC and ISCIII (PERME212443COLA and AC21_2/00030), under the frame of ERA PerMed.

      • Competing interests None declared.

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

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