Risk of second primary malignancies after bladder cancer diagnosed at a young age: a SEER population-based analysis

Bladder cancer diagnosed at a young age is uncommon, but survivors often have long life expectancy, making long-term risks such as second primary malignancies (SPMs) clinically relevant. However, the incidence and patterns of SPMs in young-onset bladder cancer survivors remain poorly characterized. We aimed to quantify the risk and distribution of SPMs in this population.

We conducted a retrospective cohort study using data from 17 registries in the Surveillance, Epidemiology, and End Results (SEER) program (2000-2022). Patients diagnosed with a first primary urothelial carcinoma of the bladder before age 50 were included. Follow-up for SPMs began two months after diagnosis. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated overall, by sex, and by cancer site. Age-related trends were assessed using Poisson regression, and sensitivity analyses were performed.

A total of 13,378 eligible patients contributed 140,014 person-years at risk to the SPM analysis. During follow-up, 1,272 SPMs were identified, excluding bladder and non-melanoma skin cancers, corresponding to a significantly elevated overall risk compared with the general U.S. population (SIR 1.67; 95% CI 1.58-1.76). Increased risk was observed in both men (SIR 1.81) and women (SIR 1.27). The largest elevations occurred for urinary tract malignancies outside the bladder, followed by colorectal, respiratory, renal cell carcinoma, and prostate cancers among men. No significant age-related trend was observed.

Young-onset bladder cancer survivors experience a sustained elevation in second primary malignancy risk, underscoring the importance of long-term survivorship awareness and informing counseling and follow-up strategies in this population.