Evidence Trace, complete trial record
In plain terms
In plain terms: PSA screening for prostate cancer has some human trial evidence supporting it, but the evidence is not yet strong enough for EBL to call it established. It is worth knowing about and worth discussing with your clinician.
PSA screening for prostate cancer
B
Supported: a good trial, backed by more
The endpoint this grade is based on: Hard clinical endpoint (mortality, major event)
The evidence as the record states it
ERSPC (Hugosson et al., Eur Urol, 2019; PMID 30824296): 162,389 men aged 55 to 69 in eight European countries; at 16 years prostate cancer deaths 20% lower (rate ratio 0.80, 0.72 to 0.89), 0.18 percentage points absolute; 570 men invited and 18 diagnosed to prevent one prostate cancer death. CAP (Martin et al., JAMA, 2024; PMID 38581198): 415,357 men aged 50 to 69 at 573 UK practices, one PSA test invitation; primary outcome at 10 years null; at 15 years, a prespecified secondary outcome, prostate cancer deaths 0.69% against 0.78% (0.92, 0.85 to 0.99), more low-grade and localized cancers found, death from any cause 0.97 (0.94 to 1.01). PLCO (Pinsky et al., Cancer, 2017; PMID 27911486): 76,683 US men, annual PSA for 6 years; prostate cancer deaths 255 against 244 (1.04, 0.87 to 1.24) at about 15 years; an estimated 86% of control men also had PSA tests; death from any cause 0.977 (0.950 to 1.004). Bretthauer et al. (JAMA Intern Med, 2023; PMID 37639247): lifetime gained 37 days (-37 to 73), not significant.
PMID 30824296 PMID 38581198 PMID 27911486 PMID 37639247
Evidence by specific use
Prostate cancer deaths, men aged 55 to 69
Grade B
ERSPC (Hugosson et al., Eur Urol, 2019; PMID 30824296): prostate cancer deaths 20% lower at 16 years; 570 men invited to prevent one death. CAP (Martin et al., JAMA, 2024; PMID 38581198): 0.69% against 0.78% at 15 years after a single test invitation, a secondary outcome after a null primary at 10 years. PLCO (Pinsky et al., Cancer, 2017; PMID 27911486): no difference, with an estimated 86% of control men also tested. One large positive trial supported by a second: B.
PMID 30824296 PMID 38581198 PMID 27911486
Death from any cause, men invited to PSA screening
Grade D
Death from any cause was not lower in CAP (0.97, 0.94 to 1.01; PMID 38581198) or PLCO (0.977, 0.950 to 1.004; PMID 27911486), and a pooled lifetime analysis estimated 37 days, not significant (Bretthauer et al., 2023; PMID 37639247). Tested, no benefit: D on Route 2.
PMID 38581198 PMID 27911486 PMID 37639247
Why Grade B and not Grade A
Grade B reflects moderate human evidence -- typically a single strong trial, multiple smaller trials, or surrogate endpoint data without hard clinical outcome replication. To reach Grade A, PSA screening for prostate cancer would require at least one additional independent randomized trial demonstrating a hard clinical endpoint or objectively measured functional outcome in a comparable population.
What this grade covers and what it does not
Grade B on prostate cancer deaths in men aged 55 to 69: ERSPC found them 20% lower at 16 years (PMID 30824296), and CAP found them 8% lower at 15 years after one test (PMID 38581198). WHY NOT A: CAP's primary 10-year outcome was null and its 15-year result is a secondary analysis, and PLCO found no difference (PMID 27911486), though most of its control group was also tested. Grade D, tested, on death from any cause: neither of the two trials that report it, CAP and PLCO, found it lower (PMIDs 38581198, 27911486), and a pooled lifetime analysis was not significant (PMID 37639247). WHAT THIS GRADE DOES NOT COVER: screening pathways that use MRI before biopsy, which the three trials did not test; men over 70; men with urinary symptoms, for whom PSA is a diagnostic test; and men at high inherited risk, such as BRCA2 carriers or men with several affected relatives.
What would move this grade
An independent randomized trial demonstrating a hard clinical endpoint -- mortality, major adverse event, or objectively confirmed functional improvement -- in an adequately powered sample, with results independently replicated, would support Grade A.
How to track whether this is working
Measured in the trials: deaths from prostate cancer and from any cause, and prostate cancer diagnoses by grade and stage.