Family history of early onset or lethal prostate cancer and the risk of prostate cancer death in Sweden.

Background: A family history (FH) of prostate cancer (PCa) increases the risk of PCa, but its association with PCa mortality remains unclear.

Methods: FH was defined as having a first-degree relative who was diagnosed before age 60 or died from PCa. We used Cox regression to estimate associations between FH and PCa characteristics at diagnosis, radical treatment, and PCa death in men born after 1932 and diagnosed with PCa between 1998-2020 in Sweden.

Results: Among 125 272 men with PCa, 13 193 had a FH of early onset or lethal PCa. At diagnosis, men with FH had 1.4 years lower median age, 0.87 ng/ml lower serum PSA, lower proportion of Gleason score 8-10 cancer (14.8% vs. 17.6%), lower odds for metastatic disease (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.73-0.86), and higher odds for radical treatment (OR, 1.25; 95% CI, 1.18-1.32). With a median follow-up of 6.9 years and 12 773 PCa deaths, mortality was lower (crude hazard ratio (HR), 0.77; 95% CI, 0.73-0.82) in men with FH. Adjustment for PCa characteristics attenuated this association (adjusted HR, 0.94; 95% CI, 0.88-1.00).

Conclusions: Men with PCa and a FH of early onset or lethal PCa had more favorable cancer characteristics, higher likelihood of radical treatment, and similar PCa mortality compared with men without FH.

Impact: In men with PCa, the risk of PCa death appears unaffected by a FH of early onset or lethal PCa after controlling for clinical characteristics. More research is needed about the potential role of screening.