Cause-specific mortality beyond prostate cancer in young men: a population-based study of second malignancies and non-tumor causes.

[OBJECTIVES] To investigate the cause-specific mortality patterns in young people (<50 years) diagnosed with prostate cancer (PCa).

[METHODS] Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified young PCa patients diagnosed between 2000 and 2018. Causes of death were analyzed, and standardized mortality ratios (SMRs) were calculated. An independent clinical cohort (n=200) was used for external validation.

[RESULTS] Among 19,352 patients with localized PCa, 1,177 deaths were observed, of which 21.4% were due to pCAs, 22.9% to site-specific malignancies (SMTs), and 55.7% to other non-tumor causes. Colorectal cancer exhibited a significantly reduced mortality risk among SMTs (SMR: 0.67) compared to the general population. Heart disease (SMR: 0.67) was the leading non-cancer cause of death. In 4,445 individuals with regional PCa, 540 deaths were observed, with PCa-specific causes accounting for 54.6%. Lung cancer mortality was significantly reduced (SMR: 0.51). Among 1,070 patients with metastatic PCa, 769 deaths were recorded, with 87.6% attributed to PCa. This stage-specific mortality pattern was consistently validated in the independent clinical cohort.

[CONCLUSIONS] Cause-specific mortality among young PCa patients varies substantially by disease stage at diagnosis. Non-PCa causes predominate in patients with localized disease, whereas PCa remains the principal cause of death in metastatic cases.