Risk and survival of third primary cancers in a population-based cohort of prostate cancer survivors.

Objective: To estimate the long-term risk and survival of third primary cancers (TPCs) among prostate first primary cancer (FPC) survivors.

Methods: A population-based cohort of 13 222 males with a prostate FPC diagnosed between 2000 and 2009, registered by the North Region Cancer Registry of Portugal, was followed until 2021 for TPCs and vital status. We estimated the cumulative incidence of TPCs and the risk of death among TPCs. TPCs were compared to matched patients with a second primary cancer (SPC) only (1:1, by age group, the time between FPC and SPC, and SPC site) for risk and adjusted hazard of death.

Results: For a period of up to 22 years after a prostate cancer diagnosis, 169 TPCs were identified, predominantly, in digestive, intrathoracic, and urinary tract organs; this corresponds to 15- and 20-year cumulative incidences [95% confidence interval (CI)] of 1.2% (1.0-1.4%) and 1.5% (1.2-1.8%), respectively, among the FPCs, and 9.1% (7.6-10.5%) and 12.0% (8.2-15.9%), respectively, among the SPCs. The 15-year all-cause cumulative mortality was 88.2% (82.2-94.3%) among TPCs and 75.7% (69.6-81.7%) among SPC only patients; the corresponding age-adjusted hazard ratio (95% CI) was 1.79 (1.37-2.34).

Conclusions: Among males with a prostate FPC that are diagnosed with an SPC, just over 10% are expected to be diagnosed with a TPC within 20 years, and these have a nearly two-fold higher death hazard than those with an SPC only.