Impact of remission status in endogenous Cushing's syndrome on cancer incidence

Objective: Endogenous Cushing's syndrome (CS) has been linked with an increased risk of cancer. We aimed to evaluate the association between cancer risk and disease remission postsurgery in adrenal CS and Cushing's disease (CD). Design: A nationwide retrospective matched-cohort study of patients with CS diagnosed between 2000 and 2023 in Israel, using Clalit Health Services’ database. Methods: Patients with CS were matched 1:5 with controls by age, sex, socioeconomic status, and BMI. Remission status postsurgery was assessed within 2 years after the diagnosis of CS. The outcome measured was time to first diagnosis of malignancy, at least 3 years post-CS diagnosis, excluding those who died or developed cancer earlier. Malignancy risk, stratified by remission status, was evaluated using Cox proportional hazards with death as a competing event. Results: The cohort comprised 388 cases and 1862 controls [mean age at diagnosis, 47.4 ± 16.8 years; 1534 (68.2%) women]. Among patients with CD, those who did not achieve remission within 2 years postdiagnosis (n = 69) had a higher risk of malignancy compared to those who achieved remission (n = 99) (HR 3.89, 95% CI 1.41-10.75). Cancer risk in patients with CD who achieved remission was similar to that of the controls (HR 0.58, 95% CI .23-1.47). In patients with adrenal CS, the risk of cancer was comparable between those who did not achieve early remission (n = 39) and those who did (n = 113) (HR 1.68, 95% CI .83-3.40). Conclusion: Though cancer risk is higher in both CD and adrenal CS, we have shown that achieving surgical remission within 2 years may attenuate cancer risk in patients with CD, but not in those with adrenal CS.