The Proposed Introduction of a Prostate Cancer Screening Program in Germany: Procedure, Necessary Studies before Implementation, Benefits, and Risks

Background: Both the new German (S3-level) Clinical Practice Guideline on Prostate Cancer (2025) and the European Union (2022) recommend risk-adapted early detection of prostate cancer by measurement of the prostate-specific antigen (PSA) level combined with magnetic resonance imaging (MRI).In this article, we describe the available screening instruments and the implications of various different methods that might be used for the introduction of a prostate cancer screening program in Germany.

Methods: This narrative review is based on pertinent publications that were retrieved by a literature search from November 2024 to November 2025.

Results: Compared to purely PSA-based screening, a PSA-based, risk-adapted screening program lowers the incidence of clinically indolent prostate cancer (ISUP gradation group 1) from approximately 50% to 24% if begun at age 45–50. The cumulative incidence of clinically relevant prostate cancer is 0.6% and thus comparable to the detection rate of breast cancer screening in patients of this age group. Prostate cancer screening starting at an older age increases the number of overdiagnoses leading to unnecessary treatment and is in all likelihood not cost-efficient.

Conclusion: Prostate cancer screening that starts at age 45–50 and proceeds on the basis of a risk-adapted concept has a better benefit-to-harm ratio than a screening program introduced all at once over a wide age range (e.g., 50–70) or opportunistic screening (i.e., no organized screening program). Implementation studies and model calculations on cost-efficiency are needed before organized screening can begin.

Cite this as: Albers P, Carlsson S, Krilaviciute A, Seibold P, Becker N: The proposed introduction of a prostate cancer screening program in Germany: Procedure, necessary studies before implementation, benefits, and risks. Dtsch Arztebl Int 2026; 123: 303–9.

DOI: 10.3238/arztebl.m2026.0040

Although screening for prostate cancer (PCa) based on prostate-specific antigen (PSA) testing has been shown to reduce cancer-specific mortality (1), current advice is against its introduction as a population-based program due to an unfavorable benefit-to-harm assessment.

Risk-adapted screening strategies have the potential to reduce harm and so provide the basis for a new approach to organized, population-based screening. In 2022, the European Union called for the evaluation of risk-adapted screening models. This initiative is currently being carried forward through the PRAISE-U projects (2) and the Joint Action EUCanScreen (www.eucanscreen.eu). The 2025 amendment to the German (S3-level) Clinical Practice Guideline also addresses this issue and recommends risk-adapted early screening (3). However, the need for action is now also acknowledged in Germany, if only because the new guideline advises against the previously recommended digital rectal examination, thereby necessitating revisions to the statutory prostate cancer screening program (4).

At the request of patient representatives, the German Joint Federal Committee initiated a consultation process in October 2025 on risk-adapted screening and authorized the Institute for Quality and Efficiency in Health Care (IQWiG) to assess the current state of knowledge (www.g-ba.de/presse/pressemitteilungen-meldungen/1290/).

The present review outlines the current evidence on available screening methods and compares the benefits and harms of different approaches for introducing a risk-adapted PCa screening program in Germany.

Methods

This narrative review article is based on an expert-guided literature search conducted in PubMed in 2024 and 2025 using the search terms “prostate cancer, screening, detection rate” (n = 295) and “prostate cancer, overdiagnosis, active surveillance” (n = 10). Articles relevant to the topic were selected and form the basis for the work.

Results

Prostate cancer screening: evidence

Evidence for the effectiveness of an organized population-based PCa screening program using PSA testing is based on the European ERSPC trial (1) which showed reduced PCa-specific mortality by 20% after 16 years and 13% after 23 years (absolute prostate cancer [PCa]-specific mortality after 23 years: 1.4% in the screening group; 1,.6% in the control group; absolute risk reduction: 0.22%). This corresponds to an improvement in the number needed to screen from 628 to 456 and in the number needed to diagnose from 18 to 12. Nevertheless, the introduction of PSA-based screening programs was rightly discouraged, most recently in Germany by the IQWiG in 2020 (5). The underlying reason is the large number of “overdiagnoses,” which makes the benefit-to-harm balance of a screening program appear unfavorable (5). “Overdiagnosis” is the potential detection through screening of cancers of no clinical significance that would never have manifested themselves clinically but for screening, would never have required treatment, and would not have resulted in death. As with other cancers (for example, colorectal cancer), the impact of screening on all-cause mortality is only marginal and would be detectable in a randomized trial only by including unrealistically large sample sizes (6).

Overdiagnosis is a particular problem in PCa, given that the prevalence of prostate lesions that fulfill the criteria for cancer increases non-linearly from around 5% in men aged below 30 to about 60% in those over 70. The prevalence of PCa, therefore, is particularly high in older-aged men, although a large proportion of those affected never develop clinically manifest disease during their lives, nor will they develop metastases or die as a result (7).

Prostate cancer—diagnostic investigations and treatment

The aggressiveness of PCa is classified into five ISUP (International Society of Urological Pathology) grade groups (GG). From a clinical view, there is general agreement that ISUP GG 1 lesions are considered “low-risk cancers” and can be managed with surveillance (8, 9, 10). The aim of active surveillance (AS) is to detect progression to “clinically significant” ISUP GG ≥2 disease promptly and initiate appropriate treatment. In the PRIAS study, metastasis-free survival after 15 years of surveillance was 97.3% among 8910 men with ISUP GG 1 PCa, and only eight patients died from PCa (11). Although the proportion of ISUP GG 1 cancers in the British ProtecT trial was only approximately 70%, metastasis-free survival after 15 years was 91% even under AS, and fewer than 3% of these patients died from PCa, with or without active treatment (12). These large AS trials have been interpreted as showing that not only patients with ISUP GG 1 disease but also those with favorable prognostic factors and ISUP GG 2 disease may be managed with AS (13). This is also consistent with the current recommendations of the German Clinical Practice Guideline.

With respect to preventing metastatic and potentially fatal disease progression, it is widely agreed that cases of PCa with an ISUP GG score ≥3 require immediate action. Recent screening studies show that the proportion of patients with ISUP GG ≥2 disease is at least 50% (14). In this regard, it is important to note that under the current opportunistic PSA screening approach in Germany, the proportion of PCa diagnosed at presentation with metastatic disease remains 17% (15), despite an unnecessarily high rate of PSA testing. Generally, the term “clinically significant” PCa is increasingly being questioned (16).

Screening methods

PSA testing

PSA is a protein whose blood levels vary continuously and depend, amongst other things, on prostate size, which increases with age (Figure 1). Benign prostatic enlargement in a 45– to 50-year-old does not generally result in elevated PSA levels. A retrospective cohort study showed that a PSA level measured at this age is, in fact, predictive of the subsequent development of metastatic PCa (17).

Figure 1

Figure 1

Magnetic resonance imaging (MRI)

Magnetic resonance imaging has been available for some years as a diagnostic tool for assessing abnormal screening results (18, 19, 20) and has been evaluated as a primary instrument for early detection of PCa (21).

Polygenic Risk Score (PRS)

PRS comprises a panel of several hundred genetic loci, at which PCa-associated single-nucleotide polymorphisms (SNPs) have been identified. This test is also currently being assessed as a primary screening instrument for PCa (22).

Other serum biomarkers

PSA protein derivatives, such as human kallikrein 2, intact PSA, free PSA, and combinations of these biomarkers with clinical parameters (particularly prostate volume) are utilized in various commercially available tests (such as the 4kscore test and the Stockholm-3 test) to improve the specificity of the PSA value. They are also currently included in the Finnish screening trial (ProScreen) for risk assessment before undergoing magnetic resonance imaging (MRI) (23).

Risk-adapted screening

In recent years, a risk-adapted approach has been adopted to reduce overdiagnosis and frequent false-positive screening results. The PSA test serves as the screening instrument, while MRI is used for further diagnostic assessment of abnormal results and to avoid unnecessary biopsies. The German PROBASE trial is currently the largest study of its kind worldwide. Using a randomized protocol, it assesses, amongst other things, starting screening at 45 versus 50 years of age and follows a baseline approach that takes advantage of the predictive value of early PSA testing (24, 25).

In PROBASE, PSA screening was initiated in men aged 45 and 50 years from a baseline PSA level, according to which they were classified into “PSA risk groups”: a “low-risk group” (PSA <1.5 ng/mL), an “intermediate-risk group” (1.5 ≤PSA <3.0 ng/mL), and a “high-risk group” (PSA ≥3.0 ng/mL). PROBASE participants in the low-risk group are invited for their next screening only once every five years. Since almost 90% of the 45-year-old and 80% of the 50-year-old screening participants fall into this group, risk stratification represents an enormous increase in efficiency compared with a fixed annual or biennial screening schedule in several ways: the costs incurred by more frequent screening are avoided, together with the inevitable false-positive screening results arising from unnecessary screening rounds, the associated anxiety among screening participants, and the subsequent diagnostic tests to clarify these results. Evidence that this approach is effective is provided by the fact that only 0.3% of the men with a low risk at age 45 were reclassified into the high-risk group five years later, and only a fraction of these indeed had PCa (25, 26).

Whereas the intermediate PSA risk group is screened biennially, a PSA level of 3.0 ng/mL is defined as the threshold for the “high-risk PSA group”, above which further diagnostic workup is generally initiated. More recent analyses from PROBASE have shown the extent which false-positive results can reach: up to 40% of PSA levels above the threshold proved to be false-positive and already fell out of the high-risk area merely by repeating the test within two to four weeks, thus avoiding the otherwise indicated diagnostic workup (25). These so-called confirmatory PSA tests are currently becoming established internationally (27).

In one to 3% of men aged 45 to 50 years, an MRI-based diagnostic workup is required for an elevated PSA ≥3 ng/mL. The proportion of these men needing further investigation increases with age, however, and has already reached approximately 7% by age 55 and approximately 12% by age 60 (Table 1). The criteria for interpreting MRI findings ultimately determine the extent to which PSA screening leads to biopsies. The restriction of biopsy to PIRADS 4 and 5 lesions in the German guideline recommendation reduces not only overdiagnosis but also sensitivity for aggressive PCa (28).

Table 1

Number of men with a PSA >3 ng/mL requiring further investigation in various screening trials

Apart from the psychological burden on the patient of having an increased risk of PCa above a PSA level of 3 ng/mL, the required MRI scans are also a significant cost factor. It is therefore crucial for any future screening program to specify the age at which the initial PSA level should be determined.

Risk-adapted screening not only reduces the cohort of those requiring an invasive diagnostic workup, but the positivity rate is also increased from approximately 25% for a biopsy merely for an increased PSA level to 68% if only men with a PSA ≥3 ng/mL, a confirmatory PSA measurement, and a pathological MRI result (PIRADS 4 or 5) are biopsied (28).

Discussion

Key issues of a PCa screening strategy include avoiding frequent false-positive screening results, unnecessary biopsies, and overdiagnosis, as well as achieving cost-effectiveness of the approach.

Avoiding false-positive results and unnecessary biopsies

Risk-adapted sequential screening with PSA followed by MRI and, where appropriate, the inclusion of additional serum biomarkers can reduce the number of MRI scans and, above all, the detection of low-risk cancers by over 50% in some cases (18, 19, 20, 28).

In risk-adapted screening trials that are currently still recruiting participants, clinically significant PCa (ISUP GG ≥2) was detected in 68% of cases in the PROBASE and OPT trials (27, 28) and in over 80% of cases in the STHLM3-MRI and ProScreen trials (19, 23).

In older age groups (over 60 years), the declining rate of ISUP GG 1 cancer diagnoses managed with active surveillance has already resulted in a reduction in the harms associated with screening (29).

Detecting clinically significant PCa and avoiding overdiagnosis

In the context of screening programs, as opposed to the clinical perspective, it remains uncertain whether the detection of ISUP grade 1 prostate cancer in men aged between 45 and 55 years should really be regarded as overdiagnosis.

The life expectancy of these men ranges from 30 to 40 years. In addition, the ERSPC trial treated low-risk cancers, and it remains uncertain whether treatment of these lesions in younger men ultimately produced the reduction in mortality observed in the study. From a clinical standpoint, it is the way screening findings are communicated that is crucial. Labeling ISUP GG 1 disease as “cancer” may lead to overtreatment. If ISUP GG 1 lesions were classified as event-free, metastasis-free dysplasia based on favorable outcome data, the resulting harm from active treatment, initiated prematurely at the patient’s own request, would be markedly reduced (8, 9, 10).

Potential screening strategies

An application for review of a prostate cancer screening program based on the combination of PSA testing and MRI , and supported by data from the PROBASE trial, has been submitted to the German Joint Federal Committee.

A rough estimate of the resources required was therefore made in the event that this approach were adopted as a screening strategy. A scientific cost-effectiveness analysis was not conducted.

If screening in Germany were recommended only for the cohort of men aged 50 years (for example, 503 000 eligible men born in 1978), with a PSA threshold of 3 ng/mL, the number of men requiring further diagnostic evaluation (confirmed PSA ≥3.0 ng/mL) would, depending on the participation rate, be 1258 (10% participation), 2515 (20% participation), 3773 (30% participation), and 6288 (50% participation) (Table 2). However, given that prostate volume, as the most important risk parameter, has a median value of 41 ml at age 50 (PROBASE data), routine measurement of prostate volume is unnecessary. Only one-third of the 2.5% of men requiring further diagnostic evaluation after screening at age 50 would be found to have PCa after guideline-indicated MRI and subsequent biopsy (Figure 2). In the first ten years of such a risk-adapted screening strategy, approximately 33% of participants would have to undergo MRI, corresponding to about 33 000 MRI examinations over 10 years, assuming a participation rate of 20%. (eFigures 1, 2).

Figure 2

Hypothetical invitation to all men at age 50

Table 2

Eligible male population and age-adjusted proportions with a positive screening test

eFigure 1

Hypothetical invitation of a 50-year-old male cohort (PROBASE data*1)—initial screening round

eFigure 2

Re-invitations over 10 years (men at age 50)

If older men are included from the outset, the need for further diagnostic evaluation, for example, increases approximately eightfold by the age of 60 (20.1% in the first screening round of the ERSPC trial) (1). This high need for MRI-based diagnostic workup, at approximately 18 to 20%, was confirmed in Scandinavian screening studies (18, 19). With a participation rate of 20% among men aged 50 to 70, approximately 160 000 to 200 000 MRI examinations would need to be performed immediately after the invitation, depending on the average age (Figure 3), and at least one third of these men would subsequently require biopsy (Figure 3) (19). The capacity for performing prostate MRI examinations in Germany is currently about 50 000 scans per year (30). Less than half of the radiology departments currently meet the Q1 and Q2 quality criteria set by the German Radiological Society, which are required by the guideline and define both the technical requirements and the radiologist’s expertise in interpreting prostate MRI examinations.

Figure 3

Hypothetical invitation to all men aged 50–70

An additional problem with risk-adapted screening is the active surveillance of the clinically non-significant PCa in about 22% of initially diagnosed cancers. If all 21 cohorts of men aged 50 to 70 years were invited simultaneously (approximately 11 million in all), and assuming a participation rate of 20%, it is expected that around 6000 men would require long-term surveillance with serial PSA measurements, MRI examinations, and repeat biopsies. The costs of active surveillance and the psychological burden on the patient of discontinuing surveillance and progressing to active treatment in over 50% of cases after five years of surveillance must be considered in any assessment of the screening program (29).

The available data from the PROBASE trial (as of 2025), with a cumulative PCa incidence of 0.6%, provide a good overview of the results of risk-adapted screening from ages 45 or 50 up to age 55 (31). If this screening strategy were continued for the next age cohort, however, the rate of false-positive findings would be similarly high to that observed without risk adaptation. An advantage of the age-cohort approach – baseline PSA testing at age 45 or 50 followed by risk-adapted continuation of screening until the age of 60 – would arise only if the screening data could be used to identify a low-risk group in whom screening could be discontinued early, for example, at the age of 60. However, an effective strategy for this purpose has yet to be developed and remains a focus of ongoing research. To accurately assess the consequences and cost-effectiveness of a screening program, modeling is required to compare the approach of simultaneously inviting 50- to 70-year-old men for 10 to 20 years of surveillance with the approach of successively inviting only the 50-year cohort each year.

Conclusions

Risk-adapted PSA screening, combining age cohort–based invitations for baseline PSA testing, PSA-dependent re-invitation intervals, confirmatory repeat PSA measurements, MRI assessment of abnormal PSA results, and biopsy where indicated, has the potential to reduce the proportion of overdiagnosed men compared with PSA-based screening alone while maintaining the detection rate of clinically significant PCa. It would therefore yield tumor detection and overdiagnosis rates comparable to those of the current mammography screening program (31). Risk-adapted screening prevents the misallocation of diagnostic and therapeutic resources and reduces harm to affected men caused by overly frequent re-invitations and unnecessary diagnostic workup. For older men, risk-adapted screening is likely to be cost-inefficient due to the large number of follow-up investigations required and, in the long term, will not prevent overdiagnosis and, in some cases, overtreatment.

Conflict of interest statement

The authors declare that no conflict of interest exists.

Manuscript received on November 18, 2025, revised version accepted on March 4, 2026

Translated from the original German by Dr. Grahame Larkin

Corresponding author:
Prof. Dr. med. Peter Albers

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