Nicotinamide for Eyelid Skin Cancer Chemoprevention: A Comparative Study

Purpose: While oral nicotinamide use has been shown to decrease subsequent nonmelanoma skin cancer, the role of nicotinamide in eyelid cancer prevention has not been previously examined. Methods: This retrospective cohort study used a deidentified database of 150 million patients (January 2006–2026). Among 1,519,126 patients with prior nonmelanoma skin cancer, 12,944 had subsequent oral nicotinamide use within 5 years of diagnosis; after 1:1 propensity score matching, 23,004 patients were analyzed. The primary outcome was incident nonmelanoma eyelid cancer; secondary outcomes included nonmelanoma skin cancer at any body site and eyelid cancer among patients without prior eyelid involvement. Results: The nicotinamide group had significantly fewer eyelid cancers than the no-nicotinamide group (212 [1.84%] vs. 338 [2.94%]; relative risk (RR), 0.627; 95% confidence interval [CI]: 0.529–0.743; p < 0.001), representing a 37.3% RR reduction. This exceeded the risk reduction for nonmelanoma skin cancer anywhere else on the body (RR = 0.771; 95% CI: 0.750–0.792). The reduction in eyelid cancer was concentrated within the first year after nicotinamide initiation (first-year RR = 0.449; 95% CI: 0.358–0.561); no significant difference was observed beyond the first year (RR = 1.023; 95% CI: 0.806–1.298). Conclusions: Oral nicotinamide use was associated with reduced subsequent basal and squamous cell carcinoma in patients with prior skin cancer. The association was most significant in the first year after initiation, suggesting that benefit may be greatest with early and sustained use. Prospective studies are indicated to establish causality and optimal dosing for eyelid cancer chemoprevention.