Risk of Cancer in Patients With First-Time Seizure

Importance: Seizures are a known complication of cancer, but whether they may be the first sign of undiagnosed neurological and nonneurological cancer remains unclear. Objective: To examine neurological and nonneurological cancer risk in patients with first-time seizures vs the general population. Design, Setting, and Participants: This population-based cohort study was conducted using nationwide Danish medical registries from January 1996 through December 2022. Follow-up extended until cancer diagnosis (excluding nonmelanoma skin cancer), emigration, death, or December 31, 2022. Analyses were performed from January 2025 through December 2025. All persons aged 18 years or older with a first-time hospital diagnosis of seizure and no preceding cancer were included. Exposure: First-time seizure diagnosis. Main Outcomes and Measures: The primary outcomes were absolute risks (ARs) of cancer and standardized incidence ratios (SIRs) relative to the general Danish population with 95% confidence intervals, which were computed for all cancers, neurological and nonneurological cancers, and site-specific cancer within 1 year, from 1 to less than 5 years, and from 5 to 20 years after the first seizure. Results: Among 49 894 adults with first-time seizure (median [IQR] age at seizure diagnosis, 51.5 [35.6-67.8] years; 20 648 [41.4%] women), a total of 1172 neurological and 850 nonneurological cancers were observed within the first year of follow-up; 87 neurological and 1226 nonneurological cancers were observed during the period from 1 to less than 5 years; and 112 neurological and 2120 nonneurological cancers were observed during the period from 5 to 20 years. In these time periods, the ARs for any cancer were 4.1%, 3.5%, and 13.4%, with SIRs of 5.30 (95% CI, 5.07-5.54), 1.18 (95% CI, 1.12-1.25), and 1.34 (95% CI, 1.28-1.40). ARs for neurological cancers were 2.4%, 0.2%, and 0.7%, with SIRs of 76.1 (95% CI, 71.8-80.6), 1.85 (95% CI, 1.48-2.28), and 1.46 (95% CI, 1.20-1.75). ARs for nonneurological cancers were 1.7%, 3.3%, and 12.8%, with SIRs of 2.32 (95% CI, 2.17-2.48), 1.15 (95% CI, 1.09-1.22), and 1.33 (95% CI, 1.28-1.39). Conclusions and Relevance: Per the results of this cohort study, first-time seizures were associated with clearly elevated short-term relative risk of cancer and slightly elevated long-term risk, indicating they may be an early clinical sign of both neurological and nonneurological occult cancers. These findings highlight the importance of considering broader diagnostic assessments after first-time seizures in select patients.