Prostate Cancer: Early Detection, Diagnostic Evaluation, and Individualized Treatment Decisions

Editorial to accompany the articles: “The Early Detection, Diagnostic Evaluation, and Local Treatment of Prostate Cancer: A Paradigm Shift” by Peter Albers et al. and “The Probability of Remaining Under Active Surveillance for Localized Prostate Cancer: An Analysis of Young Patients in the Framework of the Multicenter ProjuMa Registry Study” by PD Dr. med. Kevin Claaßen et al. in this issue of Deutsches Ärzteblatt International

PSA-based screening for prostate cancer and the resulting over-diagnosis and over-treatment have for many years been the subject of controversial and at times emotional debate. At the request of patient representatives, the German Joint Federal Committee (Gemeinsamer Bundesausschuss) last reviewed prostate-specific antigen (PSA) screening in December 2020. This review found that while prostate cancer screening reduces prostate cancer-specific mortality and metastasis, this “benefit” does not outweigh the “harm” caused by biopsies in men without the disease and over-treatment of indolent tumors that do not require treatment (1, 2).

The concept of active surveillance

The over-treatment of patients with localized prostate cancer becomes particularly apparent in the British ProtecT study: With a follow-up period of 15 years, the cancer-specific mortality rate was around 3%, regardless of whether patients underwent surgery or radiotherapy or were randomized to the study arm receiving active monitoring (3). However, active monitoring, and the “more careful” active surveillance in Germany, must primarily be seen as concepts that delay local treatment (and thus the possible side effects thereof such as incontinence and impotence) in low or intermediate risk patients without increasing the risk of mortality: 61% of patients ultimately underwent local treatment over the course of the ProtecT study and “only” (or rather, “as many as”?) 24% required no prostate cancer treatment whatsoever.

A 70-member interdisciplinary group involving 22 specialist societies and working groups led by the German Society of Urology (Deutsche Gesellschaft für Urologie) has evaluated this and other data in a structured manner and just published new recommendations on the screening, diagnosis, and local treatment of prostate cancer (4). In their CME article, Albers et al. summarize the main changes in the updated S3 guideline on prostate cancer (5). The new recommendations focus on reducing over-diagnosis and -treatment. They include a new PSA- and magnetic resonance imaging (MRI)-based algorithm for the early detection of significant cancers while reducing unnecessary biopsies and identifying “indolent” tumors. At the same time, the aim is to reduce over-treatment of cancers in the low-risk group—here, (initial) active surveillance is now the only option.

Contradiction to the screening directive

Shortly after the first consensus conference, however, the lay press was already focusing on a different recommendation: The digital-rectal examination (DRE) should no longer be performed for screening. In the opinion of the patient representatives, among others, it had deterred a number of men from prostate cancer screening. Newer findings from the PROBASE study led by Albers et al. demonstrate that DRE is not only inferior for PSA testing, but also unsuitable due to its high rate of false-negative and false-positive results (6). Thus, the new guideline now contradicts the screening directive, which specifies the DRE as the only screening measure to be covered by statutory health insurance (7).

The PSA test now as the basic test

The basic screening test is now PSA determination, which is recommended from the age of 45 years. The guideline group deliberately decided on a life expectancy of at least 10 years and against an upper age limit for individual screening, even though an upper age limit of, for example, 70 years would certainly be justifiable for a systematic screening program. Former President Biden is an unfortunate example of how missed screening can have negative consequences, even though metastatic prostate cancer is now associated with survival times of between 5 and 7 years thanks to modern hormone and other systemic treatment. Nevertheless, while the side effects of hormone therapy may appear moderate at first glance compared to other systemic therapies, they can cause considerable impairment to physical—and cognitive—performance, which may have significant implications particularly for older (frail) patients.

In the case of low PSA levels, the new guideline recommends follow-up at 5 (< 1.5 ng/mL) or 2 years (< 3 ng/mL). In contrast, a confirmed PSA level ≥ 3 ng/mL prompts further diagnostic evaluation by means of prostate MRI in those requiring it based on risk factors (for example, PSA density, genetic predisposition, etc.). However, contrary to the earlier approach, only patients with probable and highly probable malignant lesions on MRI (PI-RADS 4 + 5) or equivocal findings (PI-RADS 3) and high risk should undergo biopsy (4). This will drastically reduce the number of prostate biopsies: In the past, a PSA-based approach in the 4- to 10-ng/mL range detected cancer in one in four patients, whereas PI-RADS 4–5 findings on MRI now result in the detection of what is usually a clinically significant carcinoma in around three out of four men (8).

Strong recommendation for active surveillance in low-risk prostate cancer

Another major change relates to the treatment recommendation for patients with localized, low-risk prostate cancer: For this risk group, there is now only the strong recommendation for active surveillance, whereas for the higher risk categories, various alternative treatment options “shall be proposed.” The indication for active surveillance has already been expanded since the previous version of the guidelines to include men with tumors in the favorable intermediate risk profile. However, this requires a considerable rethink among treatment providers, as highlighted by the original article in this issue by Claaßen et al. on the ProjuMa study: Even in prostate cancer centers in Germany, the rate of active surveillance, at one third, is significantly below the rates of other countries such as the USA and Canada (60–69 %). The study also shows that a high proportion of patients aged under 60 discontinue active surveillance within 2 years, i.e., very early—without progression or patient wishes being documented as the reason (9).

In summary, these two recent articles, in the context of the updated S3 guideline on prostate cancer, set out an evidence-based path to reducing over-diagnosis and over-treatment as part of an individualized screening. It is now up to us as physicians, in particular urologists and radiotherapists, to leave long-established paths and pursue new, in many ways more conservatives paths for the good of our patients. Particularly with regard to active surveillance, it is essential that we convince our patients to be on board. We can only hope that policymakers and health care providers will support us in this endeavor.

Conflict of interest statement
The author declares that no conflict of interest exists.

Manuscript submitted on 19 June 2025, revised version accepted on
20 June 2025.

Corresponding author
Prof. Dr. med. Marc-Oliver Grimm

Cite this as
Grimm MO: Prostate cancer: Early detection, diagnostic evaluation, and individualized treatment decisions. Dtsch Arztebl Int 2025; 122: 399–400. DOI: 10.3238/arztebl.m2025.0112

References

1. Gemeinsamer Bundesausschuss (G-BA). Pressemitteilung – Prostatakrebs: G-BA hält an PSA-Wert-Bestimmung bei der Behandlung fest – kein Einsatz in der Früherkennung. 17.12.2020 (last accessed on 16 June 2025); www.g-ba.de/presse/pressemitteilungen-meldungen/918/.

2. Gemeinsamer Bundesausschuss (G-BA). Beschluss: Krebsfrüherkennungs-Richtlinie: Bewertung des Prostatakrebs-Screenings mittels Bestimmung des PSA. 17.12.2020 (last accessed on 16 June 2025); www.g-ba.de/beschluesse/4618/.

3. Hamdy FC, Donovan JL, Lane JA, et al.: Fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J Med 2023; 388: 1547–58

4. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, D.K., AWMF). S3-Leitlinie Prostatakarzinom, Langversion 8.01, 2025, AWMF-Registernummer: 043–022OL 2025 (last accessed on 19 June 2025) www.leitlinienprogramm-onkologie.de/leitlinien/prostatakarzinom/.

5. Albers P, Franiel T, Kötter T, Kristiansen G, Hermann K, Wiegel T: The early detection, diagnostic evaluation, and local treatment of prostate cancer: A paradigm shift. Dtsch Arztebl Int 2025; 122: 420–6. DOI: 10.3238/arztebl.m2025.009

6. Krilaviciute A, Becker N, Lakes J, et al.: Digital rectal examination is not a useful screening test for prostate cancer. Eur Urol Oncol 2023; 6: 566–73

7. Gemeinsamer Bundesausschuss (G-BA). Richtlinie des Gemeinsamen Bundesausschusses über die Früherkennung von Krebserkrankungen (Krebsfrüherkennungs-Richtlinie/KFE-RL; in der Fassung vom 18. Juni 2009, zuletzt geändert am 19. Dezember 2024, in Kraft getreten am 20. Februar 2025). 2025 (last accessed on 17 June 2025); www.g-ba.de/downloads/62-492-3735/KFE-RL_2024-12-19_iK-2025-02-20.pdf.

8. Fazekas T, Shim SR, Basileet G, et al.: Magnetic resonance imaging in prostate cancer screening: A systematic review and meta-analysis. JAMA Oncol 2024; 10: 745–54

9. Claassen K, Justenhoven C, Hermann S, et al.: The probability of remaining under active surveillance for localized prostate cancer: An analysis of young patients in the framework of the multicenter ProjuMa registry study. Dtsch Arztebl Int 2025; 122: 401–5. DOI: 10.3238/arztebl.m2025.008