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#Grand Rounds

ENOCA Study Results: Is There a Link Between Endometriosis and Risk for Ovarian Cancer?

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BACKGROUND AND PURPOSE:

  • Previous literature has suggested a link between endometriosis and increased risk of ovarian cancer, especially clear-cell and endometrioid subtypes
    • However, these studies have been underpowered
  • Hermens et al. (AJOG, 2020) assessed the association between endometriosis and ovarian cancer in a large population-based cohort study

METHODS:

  • Population-based cohort study
    • Endometriosis and Ovarian Cancer (ENOCA) Study
  • Data source
    • The Dutch nationwide registry of histopathology and cytopathology
  • Participants
    • Histologically confirmed diagnosis of endometriosis
    • Control cohort included women with a benign dermal nevus
  • Study design
    • Women in the endometriosis and control cohorts were matched on age and inclusion year
    • Histological diagnoses of ovarian, fallopian tubes, and peritoneal cancers between January 1990 and July 2017 were retrieved
    • Incidence rate ratios were estimated for ovarian cancer and its subtypes for
      • Entire follow-up period
      • Women with >1 person-year at risk | Women with <1 person-year at risk were excluded to limit detection bias (endometriosis was found as a secondary finding at the time of ovarian cancer diagnosis)  
  • Primary outcome
    • Incidence of ovarian cancer

RESULTS:

  • 131,450 women in endometriosis cohort | 2043 cases of ovarian cancer
  • 132,654 women in control cohort | 471 cases of ovarian cancer
  • In endometriosis cohort
    • 12,940 women had <1 person-year at risk
      • 1630 women had ovarian cancer
  • Follow-up (median)
    • Endometriosis cohort: 14 years (range 0–27 years) | 1,836,582 person-years
    • Nevus cohort: 16 years (range 0–27 years) | 2,029,538 person-years
  • Overall incidence of ovarian cancer
    • Age-adjusted incidence rate ratio (endometriosis/nevus)
      • 7.18 (95% CI, 6.17 to 8.36)
  • Endometrioid and clear-cell ovarian cancers had the highest incidence rate ratios
    • Endometrioid age-adjusted incidence rate ratio
      • 29.06 (95% CI, 20.66 to 40.87)
    • Clear-cell age-adjusted incidence rate ratio
      • 21.34 (95% CI, 14.01 to 32.51)
  • Women in the endometriosis cohort were younger at ovarian cancer diagnosis (P<0.05)
    • Endometriosis cohort: 56 years (IQR 49 to 63)
    • Control cohort: 60 years (IQR 53 to 67)

Following removal of women with <1 person-year at risk following an endometriosis diagnosis from the analysis

  • Age-adjusted incidence rate ratio was no longer significant for overall ovarian cancer
    • 1.08 (95% CI, 0.87 to 1.35)
  • However, age-adjusted incidence rate ratios for clear-cell and endometrioid ovarian cancers were still statistically significant
    • Clear-cell age-adjusted incidence rate ratios
      • 2.29 (95% CI, 1.24 to 4.20)
    • Endometrioid age-adjusted incidence rate ratios
      • 2.56 (95% CI, 1.47 to 4.47)

CONCLUSION:

  • Women with endometriosis had a significantly higher incidence of clear-cell and endometrioid ovarian cancer and were diagnosed 2 to 4 years younger compared to controls
  • In approximately 80% of patients, endometriosis and ovarian cancer were diagnosed concurrently after menopause
    • Risk of ovarian cancer in endometriosis patients persists even in absence of symptoms of endometriosis
  • The authors suggest that with further research, models could be created to identify which women with endometriosis are at higher risk for ovarian cancer and prevention strategies (e.g., OCP or risk-reducing salpingo-oophorectomy) could then be offered

Learn More – Primary Sources:

Incidence of endometrioid and clear-cell ovarian cancer in histological proven endometriosis: the ENOCA population-based cohort study

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