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How deep is too deep? Assessing myometrial invasion as a predictor of distant recurrence in stage I endometrioid endometrial cancer
  1. Giorgia Dinoi1,
  2. Simone Garzon2,
  3. Amy Weaver3,
  4. Michaela McGree3,
  5. Gretchen Glaser4,
  6. Carrie Langstraat4,
  7. Amanika Kumar4,
  8. John Weroha5,
  9. Allison E Garda6,
  10. Maryam Shahi7,
  11. Emilia Palmieri4,8,
  12. Giovanni SCAMBIA1,8,
  13. Francesco Fanfani1,8 and
  14. Andrea Mariani4
    1. 1UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
    2. 2Department of Obstetrics and Gynaecology, University of Verona, Verona, Italy
    3. 3Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
    4. 4Division of Gynecologic Surgery, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA
    5. 5Division of Medical Oncology, Mayo Clinic Rochester, Rochester, Minnesota, USA
    6. 6Department of Radiation Oncology, Mayo Clinic in Rochester, Rochester, Minnesota, USA
    7. 7Department of Pathology, Mayo Clinic, Rochester, Minnesota, USA
    8. 8Università Cattolica del Sacro Cuore, Rome, Italy
    1. Correspondence to Dr Giorgia Dinoi, Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy; giorgiadinoi{at}


    Objectives The goal of this study was to evaluate the depth of myometrial invasion as a predictor of distant recurrence in patients with node-negative stage IB endometrioid endometrial cancer.

    Methods A retrospective multicenter study, including surgically staged endometrial cancer patients at Mayo Clinic, Rochester (MN, USA) between January 1999 and December 2017, and Fondazione Policlinico Universitario A. Gemelli (Rome, Italy) between March 2002 and March 2017, was conducted. Patients without lymph node assessment were excluded. The follow-up was restricted to the first 5 years following surgery. Recurrence-free survival was estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to evaluate the association of clinical and pathologic characteristics with the risk of recurrence.

    Results Of 386 patients, the mean (SD) depth of myometrial invasion was 70.4 (13.2)%. We identified 51 recurrences (14 isolated vaginal, 37 non-vaginal); the median follow-up of the remaining patients was 4.5 (IQR 2.3–7.0) years. At univariate analysis, the risk of non-vaginal recurrence increased by 64% (95% CI 1.28 to 2.12) for every 10-unit increase in the depth of myometrial invasion. International Federation of Gynecology and Obstetrics (FIGO) grade and myometrial invasion were independent predictors of non-vaginal recurrence. The 5-year non-vaginal recurrence-free survival was 95.2% (95% CI 92.0% to 98.6%), 84.0% (95% CI 76.6% to 92.1%), and 67.1% (95% CI 54.2% to 83.0%) for subsets of patients with myometrial invasion <71% (n=207), myometrial invasion ≥71% and grade 1–2 (n=132), and myometrial invasion ≥71% and grade 3 (n=47), respectively. A total of 256 (66.3%) patients received either vaginal brachytherapy only or no adjuvant therapy. Patients who received adjuvant chemotherapy, regardless of receipt of external beam radiotherapy or vaginal brachytherapy, had an approximately 70% lower risk of any recurrence (HR adjusted for age, grade, myometrial invasion 0.31, 95% CI 0.12 to 0.85) and of non-vaginal recurrence (adjusted HR 0.32, 95% CI 0.10 to 0.99).

    Conclusion The invasion of the outer third of the myometrium and histologic grade were found to be independent predictors of distant recurrence among patients with endometrioid, node-negative stage IB endometrial cancer. Future studies should investigate if systemic adjuvant therapy for patients with myometrial invasion of the outer third would improve outcomes.

    • Endometrial Neoplasms
    • Uterine Cancer
    • Gynecology

    Data availability statement

    Data are available upon reasonable request.

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    Data availability statement

    Data are available upon reasonable request.

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    • Contributors GD: data curation; methodology; conceptualization; writing - original draft. SG: conceptualization; writing review and editing. AW: methodology; data curation; formal analysis. MMcG: data curation; formal analysis. GG: writing review and editing. CL: writing review and editing; data curation. AK: writing review and editing; data curation. SJW: writing review and editing. AEG: writing review and editing. MS: writing review and editing. EP: review and editing. GS: project administration. FF: project administration; writing review and editing. AM: conceptualization; methodology, writing review and editing; supervision. GD is the overall 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 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.