What is the recommended frequency for checking Prostate-Specific Antigen (PSA) levels in adult males, particularly those over 40 or with a family history of prostate cancer?

PSA Screening Frequency Guidelines

For average-risk men starting at age 45-50, PSA screening should be repeated every 1-2 years if PSA is ≥1.0 ng/mL, and every 2-4 years if PSA is <1.0 ng/mL, with screening discontinued at age 70 in most men. 1

Risk-Stratified Screening Initiation

Baseline PSA testing should begin at age 45 for all men with at least 10 years life expectancy, according to the National Comprehensive Cancer Network. 2, 1 However, screening initiation varies by risk category:

• Average-risk men: Begin at age 45-50 years 2, 1
• African American men: Begin at age 45 years 1
• Men with one first-degree relative diagnosed before age 65: Begin at age 45 years 1
• Men with multiple first-degree relatives diagnosed before age 65: Begin at age 40 years 1

The American Urological Association recommends obtaining a baseline PSA at age 40 for all men to establish future risk stratification, as baseline PSA above the median is a stronger predictor of future prostate cancer risk than family history or race alone. 1

Screening Intervals Based on Initial PSA Results

The frequency of repeat testing should be risk-stratified based on PSA results rather than using fixed annual intervals for all men. 1

For PSA ≥1.0 ng/mL:

• Repeat testing every 1-2 years 2, 1
• Annual testing is appropriate for PSA 1-2.5 ng/mL 1

For PSA <1.0 ng/mL:

• Repeat testing every 2-4 years 1
• If baseline PSA obtained at age 40, repeat at age 45, then follow standard intervals 1

Evidence Supporting Interval-Based Screening:

Screening every 2 years reduces advanced prostate cancer diagnosis by 43% compared to every 4 years, though it increases low-risk cancer detection by 46%. 1 The strongest randomized trial evidence supports testing at age 55, showing approximately 1.3 fewer prostate cancer deaths per 1,000 men screened over 13 years. 1, 3

When to Increase Screening Frequency

Consider more frequent testing or immediate biopsy referral if:

• PSA increases by ≥1.0 ng/mL in any 12-month period, regardless of absolute PSA value 4
• PSA rises by 0.7-0.9 ng/mL in one year—repeat PSA in 3-6 months and perform biopsy if any further increase 4
• PSA velocity >0.35 ng/mL per year when PSA <4 ng/mL 4
• PSA velocity >0.75 ng/mL per year when PSA 4-10 ng/mL 4

PSA velocity should be calculated from at least 3 consecutive measurements over 18-24 months for reliability. 4, 5

When to Stop PSA Screening

Discontinue routine PSA screening at age 70 in most men. 1, 3 Continue beyond age 70 only in very healthy men with:

• Minimal comorbidity
• Prior elevated PSA values
• Life expectancy >10-15 years 1

The US Preventive Services Task Force recommends against PSA screening in men aged 70 years and older, as potential benefits do not outweigh expected harms. 1, 3 Randomized trials demonstrated benefits only in men up to age 70. 1

Men aged 60 with PSA <1 ng/mL have only 0.5% risk of metastases and 0.2% risk of prostate cancer death, suggesting screening can safely stop in this low-risk group. 1 Similarly, men aged 75 years or older with PSA <3.0 ng/mL are unlikely to die from prostate cancer and may safely discontinue screening. 1

Critical Considerations Before Testing

Factors That Affect PSA Accuracy:

• Avoid testing within 48 hours of ejaculation, as it causes false-positive elevations 5
• Avoid testing within 3-6 weeks of prostate manipulation, urinary tract infection, or ejaculation 5
• Use the same laboratory assay for serial measurements, as assays vary by 20-25% 5
• Confirm elevated PSA values after 3-6 weeks, as 40-44% of initially elevated values normalize on repeat testing 5

5-Alpha Reductase Inhibitor Considerations:

Failure to achieve a 50% PSA decrease on finasteride/dutasteride, or any PSA increase while on these medications, is associated with increased prostate cancer risk. 4, 5

Common Pitfalls to Avoid

• Starting screening too late may miss opportunities to identify aggressive cancers when still curable, particularly in men under 50 who present with symptoms and have significantly higher risk disease 6
• Not accounting for risk factors (race, family history) when determining screening initiation age leads to delayed diagnosis in high-risk populations 1
• Continuing screening beyond age 70 in men with limited life expectancy increases harms without clear benefit 1, 3
• Using fixed annual screening intervals for all men rather than risk-stratifying based on baseline PSA results leads to unnecessary testing and false-positives 1
• Acting on a single elevated PSA value without verification with a second measurement 5
• Failing to have informed discussions about the benefits and limitations of PSA screening violates guideline recommendations and may lead to unwanted downstream consequences 1