Assessment of prostate‐specific antigen screening: an evidence‐based report by the German Institute for Quality and Efficiency in Health Care

Abstract

Context Prostate‐specific antigen (PSA) testing increases prostate cancer diagnoses and reduces long‐term disease‐specific mortality, but also results in overdiagnoses and treatment‐related harms. Objective To systematically assess the benefits and harms of population‐based PSA screening and the potential net benefit to inform health policy decision‐makers in Germany. Evidence Acquisition We performed a protocol‐guided comprehensive literature search according to the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) statement. All steps were performed by one or two investigators; any discrepancies were resolved by consensus. To allow subgroup analyses for identifying the optimal screening parameters, the eight national trials conducted under the umbrella of the European Randomised study of Screening for Prostate Cancer (ERSPC) were included as individual trials. Evidence Synthesis We included a total 11 randomised controlled trials (RCTs) with a total of 416 000 study participants. For all‐cause mortality, we found neither benefit nor harm. PSA screening was associated with a reduced risk of both prostate cancer mortality and the development of metastases. For the outcomes of health‐related quality of life, adverse effects and the consequences of false‐negative screening results there was no difference; however, this was due to the lack of eligible RCT data. Finally, PSA screening was associated with large numbers of overdiagnoses with adverse downstream consequences of unnecessary treatment (e.g. incontinence, erectile dysfunction) and large numbers of false‐positive PSA tests leading to biopsies associated with a small but not negligible risk of complications. Limitations of this assessment include the clinical heterogeneity and methodological limitations of the underlying studies. Conclusions The benefits of PSA‐based prostate cancer screening do not outweigh its harms. We failed to identify eligible screening studies of newer biomarkers, PSA derivatives or modern imaging modalities, which may alter the balance of benefit to harm. Patient Summary In the present study, we reviewed the evidence on the PSA blood test to screen men without symptoms for prostate cancer. We found that the small benefits experienced by some men do not outweigh the harms to many more men.

A Unified Transcriptional, Pharmacogenomic, and Gene Dependency Approach to Decipher the Biology, Diagnostic Markers, and Therapeutic Targets Associated with Prostate Cancer Metastasis

“…The PSA test's non-invasive and easily accessible nature is what made it a very popular early detection test for PrCa. However, its reliability is questionable because of the low specificity (high false-positive rate) resulting from the test [9][10][11]. This prompted the search for alternative ELISA-based tests to detect more reliable serum-or urine-based markers [62,63].…”

“…A widely used screening tool for undiagnosed PrCa is the ELISA-based PSA (prostatespecific antigen) assay. However, the diagnostic test is highly controversial given its high false-positive rate (due to high PSA levels among men with benign prostatic hyperplasia and prostatitis), the minimal benefit (~1 or fewer death per 1000 men screened, within ten years), and the adverse consequences of unnecessary treatment (such as impotence) [9][10][11].…”

Commentary: Kappen S, Jürgens V, Freitag MH, Winter A. Attitudes Toward and Use of Prostate-Specific Antigen Testing Among Urologists and General Practitioners in Germany: A Survey

“…Accordingly, it is now indisputable that PSA screening results in a decrease in CSM (by 35% after 18 years of follow-up in the Göteborg arm of the European Randomized study of Screening for Prostate Cancer) and a lower incidence rate of metastatic disease stages, but it is also associated with a substantial risk of overdiagnosis ( 1 , 4 ). False-positive findings and resulting eventual complications of prostate biopsy as well as subsequent overtreatment represent potential harm to patients invited for PSA-based screening ( 5 ).…”

“…In addition, the introduction of innovative strategies for PSA-based early PCa detection (risk-adapted approach, integration of multiparametric magnetic resonance imaging) poses new challenges for physicians involved ( 1 , 6 , 7 ). Meritoriously, the working group around Sanny Kappen analyzed the attitudes of dominant professional groups responsible for opportunistic PSA-based screening in Germany (namely general practitioners (GPs) and urologists) using a comprehensive survey ( 5 , 8 – 13 ). With great interest we noticed their recently published results which we would like to comment ( 11 ).…”

Usefulness of MRI targeted prostate biopsy for detecting clinically significant prostate cancer in men with low prostate-specific antigen levels

“…In Germany, Paschen, U et al reported there was no benefit nor harm in PSA screening 6 . Collectively, these challenges have led to a need for more selective modalities in the diagnosis of PCa.…”