Objectives: This study aimed to identify the sites and risks of developing second primary malignancies (SPMs) after urogenital cancers, as well as their associations with race, gender, and age.

Methods: This was a retrospective cohort study involving 140,620 subjects with primary urogenital cancer. The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, covering the duration from January 1975 to April 2025. This study included only those patients who were diagnosed with primary urogenital cancer. Descriptive statistics, absolute excess risk (AER), and observed-to-expected ratios (O/E) were calculated.

Results: Out of the 140,620 patients observed, 106,377 (75.64%) were male. Among the patients diagnosed with urogenital cancer, 33,680 (23.9%) developed an SPM. The mean age for the development of an SPM was 75.12 years. The risk of developing an SPM in patients with urogenital cancer was significantly higher compared to the general population (O/E = 1.31, confidence interval (CI) = 1.30-1.33, AER = 67.83). Male genital system cancers (O/E = 1.27, CI = 1.24-1.30, AER = 13.41), respiratory system cancers (O/E = 1.75, CI = 1.71-1.80, AER = 26.02), and urinary system cancers (O/E = 2.28, CI = 2.22-2.33, AER = 29.16) were among the most commonly identified SPMs. A total of 17,869 (53%) patients with an SPM belonged to the >75 years age group.

Conclusion: Compared to the general population, patients with urogenital cancer had a considerably higher risk of developing an SPM. Most SPM cases were observed in individuals aged 50-74 years and those over 75. A latency period of 12-59 months was commonly noted before the development of an SPM. The most frequently reported SPMs involved the male genital, respiratory, and urinary systems.

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