Introduction/Background Endometrial cancer (EC) is the most common gynaecological cancer in Norway, with rising incidence. There is a strong need for primary and secondary prevention strategies. While non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to improve survival in other cancers, data in patients with EC is conflicting.

Methodology This population-based, retrospective cohort study linked data from the Cancer Registry of Norway with The Norwegian Prescription database. These registries cover more than 99% of the Norwegian population including all patients in an unselected manner. Patients diagnosed with EC from 2004 – 2018 were included. Biometric data were available from four large health studies for a subgroup of patients. Post-diagnostic exposure to aspirin and non-aspirin NSAIDs was defined as at least three consecutive NSAID prescriptions at least 30 days after the diagnosis of EC. The main outcome measures were overall survival (OS) and endometrial cancer specific survival (CSS). Hazard ratios were calculated with multivariable Cox-regression model.

Results A total of 7751 patients diagnosed with EC were included, with 685 (9%) exposed to aspirin and 620 (8%) exposed to non-aspirin NSAIDS. The median follow-up time was 5.0 years, with 1518 (20%) deaths observed (728, 9%, EC-specific). In multivariable analysis, non-aspirin NSAID use was associated with poorer OS (HR 1.12, 95% CI 0.93–1.34) and CSS (HR 1.37, 95%CI 1.08–1.73) compared to non-users. This association was robust to additional adjustment for BMI. Associations between non-aspirin NSAID use and CSS were strongest among women with BMI <25 kg/m2. Aspirin use was not associated with OS or CSS.

Conclusion In line with a previous population-based study, we report a higher risk of death among patients that used non-aspirin NSAIDs after the diagnosis of EC. Use of aspirin was not associated with survival. The interaction between the immune system, chronic inflammation and EC should be further explored.