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Prognostic value of molecular classification in stage IV endometrial cancer
  1. Margot H Uijterwaal1,
  2. Dione van Dijk2,
  3. Christianne A R Lok3,
  4. Cor D De Kroon4,
  5. Jenneke C Kasius5,
  6. Ronald Zweemer6,
  7. Cornelis G Gerestein6,
  8. Nanda Horeweg7,
  9. Tjalling Bosse2,
  10. Jacolien van der Marel8 and
  11. Linda S Nooij4
    1. 1Department of Gynecology, Rijnstate Hospital, Arnhem, The Netherlands
    2. 2Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
    3. 3Department of Gynecologic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
    4. 4Department of Gynecologic Oncology, Leiden University Medical Center, Leiden, The Netherlands
    5. 5Department of Gynecologic Oncology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
    6. 6Department of Gynecologic Oncology, UMC Utrecht, Utrecht, The Netherlands
    7. 7Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands
    8. 8Department of Gynecology, Roosevelt Clinics, Leiden, The Netherlands
    1. Correspondence to Dr Linda S Nooij, Department of Gynecological Oncology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands; l.s.nooij{at}lumc.nl

    Abstract

    Objectives Multiple studies have proven the prognostic value of molecular classification for stage I–III endometrial cancer patients. However, studies on the relevance of molecular classification for stage IV endometrial cancer patients are lacking. Hypothetically, poor prognostic molecular subtypes are more common in higher stages of endometrial cancer. Considering the poor prognosis of stage IV endometrial cancer patients, it is questionable whether molecular classification has additional prognostic value. Therefore, we determined which molecular subclasses are found in stage IV endometrial cancer and if there is a correlation with progression-free and overall survival.

    Methods A retrospective multicenter cohort study was conducted using data from five Dutch hospitals. Patients with stage IV endometrial cancer at diagnosis who were treated with primary cytoreductive surgery or cytoreductive surgery after induction chemotherapy between January 2000 and December 2018 were included. Exclusion criteria were age <18 years or recurrent disease. The molecular classification was performed centrally on all tumor samples according to the World Health Organization 2020 classification (including POLE and estrogen receptor status). The Kaplan–Meier method was used to calculate progression free and overall survival in the molecular subclasses, for the different histological subtypes and for estrogen receptor positive versus estrogen receptor negative tumors. Groups were compared using the log-rank test.

    Results 164 stage IV endometrial cancer patients were molecularly classified. Median age of the patients was 67 years (range 33–86). Most patients presented with a non-endometrioid histological subtype (58%). Intra-abdominal complete cytoreductive surgery was achieved in 60.4% of the patients. 101 tumors (61.6%) were classified as p53 abnormal, 35 (21.3%) as no specific molecular profile, 21 (12.8%) as mismatch repair deficient, and 6 (3%) as POLE mutated. Molecular classification had no significant impact on progression free (p=0.056) or overall survival (p=0.12) after cytoreductive surgery. Overall survival was affected by histologic subtype (p<0.0001) and estrogen receptor status (p=0.013).

    Conclusion The distribution of the molecular subclasses in stage IV endometrial cancer patients differed substantially from the distribution in stage I–III endometrial cancer patients, with the unfavorable subclasses being more frequently present. Although the molecular classification was not prognostic in stage IV endometrial cancer, it could guide adjuvant treatment decisions.

    • Uterine Cancer
    • Cytoreduction surgical procedures
    • Pathology

    Data availability statement

    Data are available in a public, open access repository.

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    Data availability statement

    Data are available in a public, open access repository.

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    Footnotes

    • X @NandaHoreweg

    • MHU, JvdM and LSN contributed equally.

    • Correction notice This article has been corrected since it was first published. The spelling of author name

      Dione van Dijk has been corrected.

    • Contributors MU: investigation and writing. DvD: writing–original draft. CARL: conceptualization, resources, and writing–review and editing. CDK: resources, and writing–review and editing. JCK: resources and writing–review and editing. RZ: resources. CGG: resources. NH: methodology, formal analysis, data curation, and writing–review and editing. TB: conceptualization, investigation, resources, and writing–review and editing. JvdM: conceptualization, methodology, investigation, writing and guarantor. LN: conceptualization, methodology, investigation, writing and guarantor.

    • 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 NH is the co-inventor, not owner, of a patent in preparation on an artificial intelligence model on endometrial cancer, unrelated to the current work; member of the DSMB of the Apollo study (EudraCT No 2022-002500-21); and member of the steering committee of the RAINBO Research Consortium.

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