Role of pre-diagnostic reproductive factors on long-term (10 years or greater) survival of epithelial ovarian cancer: The Extreme study

OBJECTIVE: Several reproductive factors are associated with ovarian cancer risk but the association with survival is less clear. The main aim was to examine the impact of pre-diagnostic reproductive factors on long-term ovarian cancer survival (≥10 years). METHODS: We included all women with epithelial ovarian cancer in Denmark, 1990-2014. Information on reproductive factors and covariates were obtained from nationwide registers. Using pseudo-values, we estimated the absolute and relative 10-year survival probabilities and 95% CIs for each reproductive factor and ovarian cancer overall, restricted to serous tumors and stratified into localized and non-localized tumors. A relative survival probability >1 indicates better survival. Adjusted models considered age, diagnosis year, histology, stage, comorbidity, and income. In a sub-population sensitivity analysis, we also adjusted for residual disease. RESULTS: The cohort comprised 11,870 women. In the adjusted models, pre-diagnostic parity (relative survival probability 1.08, 95% CI 1.01 to 1.16) and endometriosis (relative survival probability 1.17, 95% CI 1.02 to 1.34) increased the likelihood of surviving ≥10 years in women with localized cancer. Previous infertility also improved the 10-year survival in women with localized ovarian cancer (relative survival probability 1.18, 95% CI 1.07 to 1.29) and in women with a non-localized tumor (relative survival probability 1.45, 95% CI 1.15 to 1.84). Pre-diagnostic pelvic inflammatory disease enhanced 10-year survival in women with localized serous (relative survival probability 1.24, 95% CI 1.03 to 1.49) and non-localized cancer (relative survival probability 1.35, 95% CI 1.04 to 1.76). Previous tubal ligation or hysterectomy were not significantly associated with 10-year survival. Adjustment for residual disease did not substantially change estimates, except for parity and pelvic inflammatory disease, where the associations disappeared. CONCLUSION: Pre-diagnostic reproductive factors, such as endometriosis or infertility, were associated with improved long-term survival. However, causality cannot be established in this observational study, and more research to confirm our findings and into potential mechanisms is warranted.