SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 8 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 313,780 new cases of prostate cancer will be diagnosed in 2025 and 35,770 men will die of the disease. Prostate cancer remains one of the most pressing global cancer burdens, with mortality rates projected to double by 2040 as populations age and life expectancy increases.
PSA is one of the most widely used prostate cancer biomarkers, and the widespread use of PSA testing in the recent years has resulted in a dramatic increase in the diagnosis and treatment of prostate cancer. PSA-based screening is widely debated due to false positives, overdiagnosis, and overtreatment.
The question of how and in whom to implement early detection strategies, continues to challenge clinicians and public health systems. The European Randomized Study of Screening for Prostate Cancer (ERSPC), initiated in 1993, represents the most comprehensive effort to evaluate whether population-based Prostate-Specific Antigen (PSA) screening reduces prostate cancer mortality. Now, with more than two decades of follow-up completed for over 160,000 men, the ERSPC provides its final unified analysis, offering critical insights into both the enduring benefits and ongoing challenges of PSA-based screening.
Study Overview and Screening Approach
The ERSPC spanned eight European countries and included a predefined core cohort of men aged 55–69 years at randomization. Participants were assigned to organized repeated PSA screening or to usual care without screening invitations. Screening protocols varied modestly by country, but all centers relied on standardized PSA assays and risk-based biopsy thresholds. Most participants received screening every four years, although the interval ranged from two to seven years. The Primary outcome was prostate cancer mortality.
- Population: 162,236 men (55–69 yrs)
- Screening group: 72,888
- Control group: 89,348
- Screening Protocol: Repeated PSA, 2–8 invitations, biopsies for elevated PSA
- Follow-Up: Median 23 years
- Outcomes:
- Relative reduction in prostate cancer death: 13%
- Absolute risk reduction: 0.22%
Key Points for Clinical Practice:
Three decades after its inception, the ERSPC provides unequivocal evidence that PSA-based screening reduces prostate cancer mortality. However, it also highlights that how screening is implemented may matter, as much as whether it is implemented at all.
- PSA-based screening reduces prostate cancer mortality by ~13% over 23 years; absolute benefit continues to rise with long-term follow-up.
- Overdiagnosis and overtreatment remain central harms. Risk-adapted strategies (MRI, biomarkers, active surveillance) mitigate these risks.
- Screening should ideally start at age 50 for maximal benefit and continue based on life expectancy rather than age alone.
- Modern guidelines support selective biopsy only in patients with high-risk features and conservative management/active surveillance for low-risk disease, to optimize the harm–benefit ratio.
- Individualized decision-making and cessation of screening is essential, particularly for older men or those with competing health risks.
Such strategies aim to preserve the mortality benefit demonstrated in ERSPC while minimizing harms associated with overdiagnosis and overtreatment.
Conclusion
The final unified analysis of the ERSPC confirms that PSA screening offers a sustained reduction in prostate cancer mortality that becomes more pronounced over long-term follow-up. While screening continues to carry risks, particularly through detection of indolent disease, its harm–benefit balance has improved with time and can be further optimized through modern, risk-adapted approaches. As prostate cancer incidence continues to rise worldwide, these data provide essential guidance for developing screening policies that maximize benefit, reduce harm, and ensure evidence-based care for patients at risk.
European Study of Prostate Cancer Screening-23-Year Follow-up. Roobol MJ, de Vos II, Månsson M, et al for the ERSPC Investigators. N Engl J Med 2025;393:1669-1680.
