No screening test in medicine generates more debate than the prostate-specific antigen (PSA) test. Advocates say it saves lives by detecting prostate cancer early. Critics say it leads to overdiagnosis and overtreatment of cancers that would never have caused harm. Both are right — and that's exactly the problem.

The evidence: a mixed picture

The two landmark PSA screening trials reached seemingly opposite conclusions. The European ERSPC trial (n≈182,000) showed a 20% reduction in prostate cancer mortality after 16 years of follow-up. The US PLCO trial (n=76,685) showed no benefit.

The difference? The PLCO trial was contaminated — a large proportion of men in the "control" group had already been screened with PSA before the trial began, or got screened during the trial outside the protocol. It wasn't really comparing screened vs. unscreened — it was comparing "screened" vs. "also screened." When statisticians accounted for how intensively each trial actually screened, both trials provided compatible evidence that screening reduces prostate cancer mortality.

So PSA screening works — in the sense that it detects prostate cancer earlier, and earlier detection reduces mortality. The problem is what else it detects.

The overdiagnosis problem

Prostate cancer is remarkably common. A systematic review of autopsy studies found prostate cancer in about 60% of men over 79 who had died of other causes — and most of these cancers are low-grade, slow-growing, and would never have caused symptoms or death. They are "cancers" only in the pathological sense.

PSA screening can't distinguish between aggressive cancers that will kill you and indolent ones that won't. An elevated PSA triggers a biopsy, a biopsy finds cancer, and the word "cancer" triggers treatment — often surgery or radiation — with significant side effects including incontinence and erectile dysfunction.

After 16 years of ERSPC, about 570 men had to be invited and 18 additional cancers diagnosed to prevent one prostate cancer death. The USPSTF estimates that 20–50% of screen-detected cancers may be overdiagnosed. That's a difficult trade-off, and it's why the USPSTF (2018; an update is in progress) rates PSA screening as Grade C for men 55–69 (individual decision) and Grade D for men 70 and older; for men under 55 it found the evidence insufficient to make a recommendation.

Shared decision-making — not a blanket recommendation

The correct approach to PSA screening is shared decision-making: a genuine conversation between physician and patient about the benefits (mortality reduction), harms (overdiagnosis, overtreatment), and the patient's individual risk profile. This conversation takes time and nuance — which is exactly what a 15-minute annual physical doesn't have.

Who benefits most from PSA screening

The risk-benefit calculation shifts significantly based on individual risk factors:

  • Men with family history of prostate cancer (especially first-degree relative diagnosed before 65): higher benefit; European guidelines suggest offering testing from 45
  • Men of African descent: higher risk; European guidelines likewise suggest offering testing from 45
  • BRCA2 carriers: significantly elevated prostate cancer risk; PSA testing offered from 40
  • Men over 70 with limited life expectancy: screening is unlikely to benefit and likely to cause harm

A reasonable approach

Evidence-based practice for PSA testing looks roughly like this. For well-informed men from about 50 — from 45 with a family history or African descent, from 40 for BRCA2 carriers — the physician should initiate the shared decision-making conversation — with enough time to actually have it properly. If you are in this group and nobody has raised the topic, it is reasonable to bring it up with your own doctor.

If PSA is elevated, the next step is not automatic biopsy. It's multiparametric MRI (mpMRI) — a non-invasive imaging study that can identify clinically significant cancers with high accuracy. A suspicious lesion (PI-RADS 4–5) calls for targeted biopsy; for an equivocal PI-RADS 3 lesion, PSA density also guides the decision. If MRI is normal and suspicion low, biopsy can often be replaced by repeat PSA monitoring.

This MRI-first approach dramatically reduces unnecessary biopsies — and it's increasingly recognized as the standard of care in European urology (EAU Guidelines 2024).

References

  1. Hugosson J, et al. A 16-yr follow-up of the European Randomized study of Screening for Prostate Cancer. Eur Urol. 2019;76(1):43-51. doi:10.1016/j.eururo.2019.02.009.
  2. Andriole GL, et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst. 2012;104(2):125-132.
  3. Tsodikov A, et al. Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials. Ann Intern Med. 2017;167(7):449-455.
  4. Bell KJL, et al. Prevalence of incidental prostate cancer: a systematic review of autopsy studies. Int J Cancer. 2015;137(7):1749-1757.
  5. US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319(18):1901-1913.
  6. EAU. Prostate Cancer Guidelines 2024.
  7. Kasivisvanathan V, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis (PRECISION). N Engl J Med. 2018;378(19):1767-1777.
Prof. Dr. med. Markus Guba

Head of Liver Surgery and Transplantation at LMU University Hospital Munich. Edits this independent journal in a private capacity; views are his own. About →

This article is general information and not individual medical advice. Decisions about tests and treatment belong in a conversation with your own physician.