By Mads Hvid Poulsen, PhD
Consultant, Head of Research, Associate Professor
Department for Urology, Esbjerg and Grindsted Hospital, University Hospital of Southern Denmark
Department of Regional Health Research, University of Southern Denmark

Prostate cancer remains the most frequently diagnosed malignancy in men across Europe, and early detection through screening has the potential to improve survival outcomes. However, the benefits of early detection must be balanced against the risks of over-diagnosis and costs. Recent evidence from European studies and expert consensus models support the evolution toward structured, risk‐based screening programs that optimize benefits while minimizing harms.

Large-scale studies have evaluated the impact of prostate-specific antigen (PSA) based screening on prostate cancer outcomes. For instance, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 21% reduction in prostate cancer mortality at 13 years, with benefits increasing (up to 25–49% reduction) in men who underwent repeated screening rounds. In contrast, the US-based PLCO trial did not demonstrate a significant mortality benefit at 17 years, a discrepancy partly explained by high rates of opportunistic screening. The Cluster randomized trial of PSA testing for prostate cancer (CAP) was designed to evaluate the impact of a single PSA screening test, did not demonstrate a significant mortality benefit at 10 years. Notably, PSA-only screening is associated with over-diagnosis rates of 27% to 41%.

To address the limitations of PSA-only screening, European studies have integrated additional diagnostic tools. Trials such as Göteborg2 have shown that coupling PSA testing with magnetic resonance imaging (MRI) of the prostate significantly reduces the detection of low-grade, clinically insignificant cancers. New biomarkers and risk calculators—like those outlined in the recent European risk-stratified model— may further refine patient selection for imaging and biopsy, ensuring that only men at meaningful risk receive invasive follow-up.
The European Union supports piloting and further research, to evaluate the feasibility and effectiveness of the implementation of organised programmes within screening for prostate cancer. This was outlined in the recent EU Council recommendations from 2022. Several major initiatives and trials are currently underway across Europe that aim to refine screening strategies and optimize outcomes:

Ongoing randomized clinical trials

Göteborg2 (Sweden): Evaluates standard versus MRI-targeted biopsy strategies among men with elevated PSA levels. This trial has demonstrated significant mortality reduction and a lower number needed to diagnose compared with opportunistic testing.

ProScreen (Finland): Employs a sequential screening strategy that begins with PSA testing, followed by a kallikrein panel and MRI. This approach is designed to optimize patient selection for prostate biopsies, balancing early detection with fewer unnecessary procedures.

PROBASE (Germany): Designed to evaluate risk-adapted prostate cancer screening strategies by comparing screening initiation at age 45 versus 50. PROBASE stratifies patients based on PSA levels into low, intermediate, and high-risk groups, with high-risk individuals (PSA ≥3 ng/mL) receiving additional MRI and biopsy follow-up.

PRAISE-U Initiative (EU-wide): A collaborative project across several European countries, including Ireland, Lithuania, Poland, and Spain, the PRAISE-U Initiative evaluates proposed screening algorithm by the EAU, using stratification based on PSA and age followed by MRI and target biopsy into an organized screening program.

Upcoming trials

TRANSFORM Trial (UK): Focuses on integrating rapid imaging protocols with PSA testing and genetic profiling to further refine risk stratification. This trial aims to personalize screening pathways and optimize early detection strategies in the UK setting.

PROMAP (Denmark): the trial it built upon a sequential screening process of age and PSA testing, followed by MRI evaluation and targeted only biopsies. PROMAP specifically targets men aged 50–69 with the goal of reducing prostate cancer-specific mortality by 30% while limiting over-diagnosis to below 10%.

National initiatives

OPT Trial (Sweden): Implements an organized screening protocol with systematic invitations and re-invitations every two years for men aged 50–75, using a PSA threshold of 3 μg/L to guide targeted biopsies. The pilot projects across all the Swedish regions aim to demonstrate the feasibility and effectiveness of a structured, large-scale screening approach.

Screening in Lithuania: Since 2006, Lithuania has conducted a national screening program for men aged 50–74 (and for men 45–49 with a family history) using a PSA threshold of 3 ng/mL followed by urologist evaluation. Initially performed annually (2006–2008), the screening has shifted to a biennial schedule, achieving coverage of up to 45.5% per screening round, with 70% of the target population having been screened at least once.

These trials and initiatives collectively aim to establish a more effective, organized, and risk-adapted approach to prostate cancer screening that minimizes unnecessary procedures while maximizing mortality reduction.
Shifting from opportunistic to organized prostate cancer screening requires a strong infrastructure for patient outreach, follow-up, and data management. Integrating risk calculators, biomarkers, and MRI into standard clinical protocols has demonstrated benefits in reducing over-diagnosis and improving diagnostic accuracy. However, the long-term feasibility and cost-effectiveness of these approaches require further validation through ongoing studies.

Organized screening programs have demonstrated superior outcomes—both in reducing mortality and curtailing over diagnosis—compared with opportunistic testing. Nevertheless, we still need to tailor this.

TRI-NOR-000103 03 2025