Does Prostate-Specific Antigen (PSA) screening reduce all-cause mortality?

PSA Screening Does Not Reduce All-Cause Mortality

PSA screening does not reduce all-cause mortality, and you should not recommend it for this purpose. The most comprehensive and recent evidence consistently demonstrates no benefit for overall survival across all age groups and screening strategies 1, 2.

Primary Evidence on All-Cause Mortality

The highest quality evidence from multiple large randomized controlled trials definitively shows:

• Meta-analysis of five major RCTs (721,718 men) found no difference in all-cause mortality (IRR 0.99,95% CI 0.98 to 1.01) between screened and unscreened men 2

• The European ERSPC trial, despite showing a small reduction in prostate cancer-specific mortality, demonstrated identical all-cause mortality in screened versus control groups (RR 1.00,95% CI 0.98 to 1.02) after 11 years of follow-up 1

• The U.S. PLCO trial found no reduction in all-cause mortality through 13 years of follow-up 1

• The UK CAP trial, the most recent large-scale study (415,357 men, median 10-year follow-up), showed no difference in all-cause mortality (RR 0.99,95% CI 0.94 to 1.03; P = .49) 3

Why PSA Screening Fails to Reduce All-Cause Mortality

The biological reality explains this finding:

• Competing mortality dominates in the screening age group. Even in the ERSPC trial's "core" age group of 55-69 years, only 462 of 17,256 deaths (2.7%) were due to prostate cancer 1

• Most men with prostate cancer die of other causes. Long-term registry data show that 75% of men with well-differentiated prostate cancer die of causes other than prostate cancer, versus only 7% from prostate cancer itself 1

• Any potential prostate cancer mortality benefit is too small to impact overall survival. At best, screening prevents 1 prostate cancer death per 1000 men screened over 10 years—a benefit completely overwhelmed by deaths from cardiovascular disease, other cancers, and age-related conditions 1

The Harms That Offset Any Theoretical Benefit

The 2018 BMJ guideline and 2012 USPSTF recommendation emphasize that screening harms are substantial and occur early:

• PSA screening probably has little or no effect on all-cause mortality (about 4 fewer per 1000 men, 95% CI 10 to 0 fewer) even in higher-risk subgroups 1

• Treatment-related mortality exists: Up to 5 in 1000 men die within 1 month of prostate cancer surgery 1

• Overdiagnosis affects up to 50% of screen-detected cancers, subjecting men to treatment harms for cancers that would never have caused symptoms 1, 4

• Treatment complications are common and persistent: 200-300 per 1000 treated men experience urinary incontinence or erectile dysfunction 1

Clinical Algorithm for Counseling Patients

When patients ask about PSA screening for reducing their risk of death:

1. State clearly that PSA screening does not reduce all-cause mortality based on the highest quality evidence from multiple large trials 1, 2

2. Explain the competing mortality concept: Most men in the screening age range (55-69 years) will die of cardiovascular disease, other cancers, or age-related conditions—not prostate cancer 1

3. Acknowledge the small prostate cancer-specific mortality benefit: At best, 1 fewer prostate cancer death per 1000 men screened over 10 years, but this does not translate to living longer overall 1, 2

4. Emphasize the certainty of harms: For every 1000 men screened, approximately 25 will experience erectile dysfunction, 3 will require pads for incontinence, and 1 will be hospitalized for sepsis from biopsy complications 2

5. Recommend against routine screening unless the patient has exceptional circumstances and explicitly values the small prostate cancer mortality reduction despite understanding it won't help them live longer 1

Common Pitfalls to Avoid

• Do not conflate prostate cancer-specific mortality with all-cause mortality. Some studies show a small reduction in prostate cancer deaths, but this has never translated to overall survival benefit 1

• Do not assume younger, healthier men will benefit more. Subgroup analyses by age showed no effect of screening on all-cause mortality regardless of age at screening 4, 2

• Do not ignore the 10-15 year time horizon required for any benefit. Men with life expectancy less than 10-15 years cannot benefit from screening, as any mortality reduction takes at least 9-10 years to emerge 1, 4

• Do not offer screening without explicitly discussing that it does not reduce overall mortality. The 2012 USPSTF and 2018 BMJ guidelines emphasize that shared decision-making must include this critical fact 1

The Bottom Line for Practice

No screening strategy—including PSA testing at any interval, age, or threshold—has demonstrated a reduction in all-cause mortality. The 2012 USPSTF Grade D recommendation against PSA screening and the 2018 BMJ weak recommendation against routine screening are based on this fundamental finding 1, 2. While some organizations support individualized screening decisions, the evidence is unequivocal that PSA screening does not help men live longer overall.