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Endometrial cancer in young women: prognostic factors and treatment outcomes in women aged ≤40 years
  1. Ji Son1,
  2. Caitlin Carr1,
  3. Meng Yao2,
  4. Milena Radeva2,
  5. Anju Priyadarshini1,
  6. Jessica Marquard3,
  7. Chad M Michener4 and
  8. Mariam AlHilli4
  1. 1Women's Health Institute, Department of OBGYN, Cleveland Clinic, Cleveland, Ohio, USA
  2. 2Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
  3. 3Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA
  4. 4Women's Health Institute, Department of Gynecologic Oncology, Cleveland Clinic, Cleveland, Ohio, United States
  1. Correspondence to Dr Mariam AlHilli, Women's Health Institute, Department of Gynecologic Oncology, Cleveland Clinic, Cleveland, Ohio, United States; mariam.alhilli{at}


Objective Endometrial cancer in pre-menopausal patients aged ≤40 years is rare and poses both diagnostic and management challenges. The goal of this study was to investigate the clinical and pathologic factors associated with endometrial cancer in this group and their impact on survival.

Methods Patients with endometrial cancer treated between January 2004 and August 2016 were retrospectively reviewed. Patients who underwent either primary surgical treatment or fertility-sparing therapy were included. Exclusion criteria were age >60 years and patients who received neoadjuvant chemotherapy or primary radiation. Age at diagnosis was used to classify patients into two groups: ≤40 and 41–60 years. Clinical and pathologic variables were compared between the groups. Progression-free survival and overall survival were estimated using Cox proportional hazards.

Results A total of 551 patients were evaluated, of which 103 (18.7%) patients were ≤40 years and 448 (81.3%) were 41–60 years. Age ≤40 years was associated with higher body mass index (38.8 vs 35.8 kg/m2, p=0.008), non-invasive cancers (54.2% vs 32.6%, p<0.001), lower uterine segment involvement (27.2% vs 22.5%, p<0.001), and less lymphovascular space invasion (16.8% vs 29.1%, p=0.015). The rate of synchronous ovarian cancer was 9.2% vs 0.7% in age 41–60 years (p<0.001), and 19% of women with endometrial cancer aged ≤40 years underwent fertility-sparing therapy. Grade, stage, myometrial invasion, lymphovascular space invasion, and lymph node status were associated with survival, and fertility-sparing therapy adversely affected the recurrence rate of the age ≤40 years cohort. Among all patients aged ≤60 years, mismatch repair deficiency due to MLH1 methylation was associated with worse progression-free survival, 48.6% vs 83.3% (HR 1.98, 95% CI 1.06 to 3.17, p=0.032), and overall survival, 56.5% vs 90.0% (HR 2.58, 95% CI 1.13 to 5.90, p=0.025).

Conclusions Patients aged ≤40 years with endometrial cancer have more favorable prognostic factors and higher rates of synchronous tumors. Fertility-sparing therapy was associated with higher recurrence rates. The prognostic value of MLH1 methylation in this population warrants further investigation.

  • endometrial neoplasms
  • endometrium
  • ovarian neoplasms
  • pathology
  • lynch syndrome II

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  • Contributors JS: study design, data collection abstraction, and manuscript writing. JM, CC, AP: data collection abstraction. MY, MR: statistical analysis. CMM: manuscript review and editing. MA: study design, data analysis, manuscript writing and editing.

  • 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.

  • Patient consent for publication Not required.

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

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