In univariable and multivariable Cox regression, age (hazard ratio [HR], 1.04; 95% CI, 1.02-1.07), PSA (HR, 1.06; 95% CI, 1.04-1.07), and PSA density (HR, 1.41; 95% CI, 1.30-1.52) remained consistently associated with prostate cancer risk, whereas other variables showed either no association or inconsistent results across models.<h4>Conclusions and relevance</h4>This cohort study found that a low baseline PSA level was associated with low long-term prostate cancer risk among men aged 45 to 70 years, supporting risk-adapted screening with extended intervals for men with low PSA levels. Here, KLK3 is linked to prostate carcinoma.