What is the evidence for using Prostate-Specific Antigen (PSA) for prostate cancer screening?

PSA Screening for Prostate Cancer: Evidence Summary

The evidence shows that PSA screening provides at most a small reduction in prostate cancer-specific mortality (approximately 1.3 deaths prevented per 1000 men screened over 13 years) with no reduction in all-cause mortality, while causing substantial harms including overdiagnosis, unnecessary biopsies, and treatment complications—therefore, routine PSA screening should not be performed, but rather discussed selectively with men aged 55-69 years who express a clear preference for screening after understanding the limited benefits and significant harms. 1, 2

Current Guideline Recommendations

The most recent high-quality guidelines show evolving positions:

• The 2018 USPSTF guideline recommends individualized decision-making for men aged 55-69 years (Grade C), stating clinicians should not screen men who do not express a preference for screening, and recommends against screening men ≥70 years (Grade D). 2

• The 2018 BMJ guideline provides a weak recommendation against PSA screening, acknowledging that most informed men would decline screening, though some may choose it after understanding the trade-offs. 1

• The 2013 American College of Physicians emphasizes that physicians should not offer PSA screening unless prepared to engage in shared decision-making enabling informed choice with full understanding of benefits and harms. 1

Mortality Benefits: The Critical Evidence

Prostate Cancer-Specific Mortality

The European Randomized Study of Screening for Prostate Cancer (ERSPC) provides the strongest evidence for any mortality benefit:

• Absolute benefit: 1.3 fewer prostate cancer deaths per 1000 men screened over 13 years in men aged 55-69 years 2
• Relative risk reduction: 21% reduction in prostate cancer mortality (RR 0.79,95% CI 0.68-0.91) after 11 years 3
• Number needed to screen: 1,410 men need to be screened and 48 additional cancers detected to prevent 1 prostate cancer death 1

All-Cause Mortality

Critically, PSA screening shows no reduction in all-cause mortality—the outcome that matters most to patients. 1, 2, 4

• Over 10 years: 0 fewer deaths per 1000 men (95% CI: 3 fewer to 3 more) 1
• This means men live no longer with screening, they simply die with a different cause of death listed on their death certificate 4

Conflicting Trial Results

The Prostate, Lung, Colorectal and Ovarian (PLCO) trial found no mortality benefit (RR 1.09,95% CI 0.87-1.36), contrasting with ERSPC. 3 This discrepancy exists because:

• PLCO compared organized annual screening versus opportunistic screening (usual care in the US already included substantial PSA testing), making it underpowered to detect differences 1
• ERSPC compared screening versus minimal/no screening, providing the most relevant evidence for screening efficacy 1

Substantial Harms of Screening

Overdiagnosis and Overtreatment

The most significant harm is overdiagnosis—detecting cancers that would never cause symptoms or death:

• 29-44% of all PSA-detected cancers represent overdiagnosis 1
• For every 1 prostate cancer death prevented, 37 additional men receive a cancer diagnosis through screening 3
• These men experience no benefit but are exposed to all treatment harms 1

False-Positive Results

• 80% of positive PSA results are false-positives when using PSA cutoff of 2.5-4.0 μg/L 1
• False-positive results cause psychological adverse effects lasting up to 1 year 1
• Lead to unnecessary anxiety and additional testing 1

Biopsy Complications

Men with elevated PSA undergo prostate biopsy, which carries risks:

• Infection, bleeding, urinary retention 1
• Pain and anxiety from the procedure 1

Treatment-Related Harms

Treatment complications are severe and common, affecting quality of life substantially:

• Urinary incontinence: 1 in 5 men (20%) develop long-term incontinence after radical prostatectomy 2
• Erectile dysfunction: 2 in 3 men (67%) experience long-term erectile dysfunction after surgery 2
• Bowel symptoms: Common with radiation therapy 2

These harms occur in many men who would never have been harmed by their cancer. 4

Age-Specific Considerations

Men Aged 55-69 Years

This is the only age group where any potential benefit exists:

• Shared decision-making is essential before any screening occurs 1, 2
• Only men who express a definite preference for screening after understanding harms should undergo PSA testing 3, 2
• Life expectancy must be at least 10 years for any potential benefit 1

Men Aged 70+ Years

Do not screen men ≥70 years—harms clearly outweigh benefits:

• Greater risk of false-positives due to benign prostatic hyperplasia 1
• Increased biopsy complications 1
• Higher treatment-related morbidity 1
• Competing causes of death make any cancer-specific mortality benefit irrelevant 2

Men Under Age 55 Years

No evidence supports screening men <55 years except those at very high risk (strong family history, African American race). 1

• The AUA suggests baseline PSA at age 40 for risk stratification, but this is not based on mortality benefit data 1

Screening Test Characteristics

PSA Test Performance

The accuracy of PSA for detecting clinically important prostate cancer cannot be determined with precision:

• Sensitivity for aggressive cancer: 91% (PSA ≥4.0 μg/L) 1
• Specificity: 91% for any prostate cancer 1
• However, many detected cancers are not clinically significant 1

Factors Affecting PSA Levels

Common pitfalls that cause false elevations or reductions:

• Benign prostatic hyperplasia and prostatitis elevate PSA 1
• 5α-reductase inhibitors (finasteride, dutasteride) decrease PSA by ~50% 5
• Recent urinary catheterization falsely elevates PSA 5

Practical Clinical Approach

For Men Aged 55-69 Years Asking About Screening

Use this structured discussion framework:

1. Explain the small potential benefit: "Screening 1,000 men for 13 years prevents about 1 prostate cancer death, but doesn't help men live longer overall." 2

2. Describe the common harms: "For every cancer death prevented, 37 men get diagnosed and treated who didn't need to be. Of men treated, 1 in 5 become incontinent and 2 in 3 develop erectile dysfunction." 3, 2

3. Assess patient values: Does the patient prioritize avoiding any cancer diagnosis, or avoiding unnecessary treatment and its complications? 1

4. Only proceed if patient expresses clear preference for screening after this discussion 2

For Men Aged 70+ Years

Recommend against screening regardless of patient preference—the evidence shows net harm. 2

Screening Interval (If Screening Chosen)

• Biennial (every 2 years) screening reduces harms compared to annual screening while maintaining most benefits 3
• ERSPC used 2-4 year intervals 1

Critical Caveats

Common clinical errors to avoid:

• Never order PSA without prior discussion of harms and benefits—this violates informed consent principles 1
• Do not screen men with limited life expectancy (<10 years) from comorbidities—they cannot benefit 1
• Avoid screening men who would not accept treatment if cancer were found 1
• Do not assume screening saves lives—it does not reduce all-cause mortality 1, 2

The Value Proposition

PSA screening as currently practiced represents low-value care:

• Minimal mortality benefit at best 4
• Substantial harms affecting quality of life 4
• High healthcare costs for marginal benefit 4
• Better detection and treatment strategies are needed before widespread screening can be justified 4