How often should Prostate-Specific Antigen (PSA) tests be performed for a patient with a history of results within normal limits (WNL)?

PSA Screening Frequency for Men with Normal Results

For men aged 45-75 years with normal PSA levels, screening frequency should be stratified by PSA value: recheck every 2-4 years if PSA is less than 1.0 ng/mL, and every 1-2 years if PSA is 1.0 ng/mL or higher. 1

Risk-Stratified Screening Intervals

Men with PSA <1.0 ng/mL

• Screen every 2-4 years based on age and clinical context 1
• Younger men (age 45-50) with PSA approaching 1.0 ng/mL should be screened at 2-year intervals 1
• Older men (age 65-75) with very low PSA (<0.5 ng/mL) can safely extend to 4-year intervals 1
• Men with PSA <1.0 ng/mL have only a 0.23% risk of cancer at 4 years and 0.49% at 8 years 1
• Men aged 60 years with PSA ≤1.0 ng/mL have only 0.5% risk of metastasis by age 85 and 0.2% risk of prostate cancer death 1

Men with PSA ≥1.0 ng/mL

• Screen every 1-2 years regardless of age within the screening window 1
• This more frequent interval is warranted due to higher baseline cancer risk 1
• Men with PSA 1.0-2.0 ng/mL have only 1.2% positive test rate at 1 year and 2.6% at 2 years, supporting biennial screening even in this range 1

Age-Specific Considerations

Starting Age

• Begin screening at age 45 years for average-risk men 1, 2
• Begin at age 40 years for high-risk men, including those with multiple first-degree relatives diagnosed before age 65 1, 2
• African American men should begin screening at age 45 years due to higher incidence and earlier onset 1, 2

Stopping Age

• Discontinue routine screening at age 70 years for most men 1
• Only continue screening beyond age 70 if life expectancy exceeds 10 years 1, 3
• The US Preventive Services Task Force recommends against screening in men ≥70 years due to harms outweighing benefits 3
• Stopping screening at age 69 versus 74 reduces overdiagnosis by 50% while decreasing life-years saved by only 27% 1

Evidence Supporting Biennial Screening

Mortality Benefits

• The European ERSPC trial, which demonstrated prostate cancer mortality reduction, used a 4-year screening interval 1
• Biennial screening retains 87-95% of life-years saved compared to annual screening 1, 2
• Screening every 2 years reduces advanced cancer diagnosis by 43% compared to 4-year intervals 1

Reduction in Harms

• Biennial screening reduces total PSA tests by 59% compared to annual screening 1, 2
• Overdiagnosis decreases by 13% with biennial versus annual screening 1, 2
• False-positive results are reduced by 50% with 2-year intervals 1
• The average delay in cancer diagnosis when moving from annual to biennial screening is only 5-6 months 1, 2

Critical Clinical Caveats

Shared Decision-Making

• Always engage in shared decision-making before initiating or continuing PSA screening 2, 3
• Discuss the modest mortality benefit (1.3 deaths prevented per 1000 men screened over 13 years) 3
• Explain overdiagnosis risk: approximately 3 cases of metastatic cancer prevented per 1000 men, but many more low-risk cancers detected 3
• Address treatment harms: 20% develop long-term urinary incontinence and 67% experience erectile dysfunction after radical prostatectomy 3

Common Pitfalls to Avoid

• Do not screen men over age 70 routinely, as harms exceed benefits in this population 1, 3
• Avoid annual screening in men with PSA <1.0 ng/mL, as this provides minimal additional benefit while increasing false-positives 1
• Do not use a one-size-fits-all approach—tailor intervals based on actual PSA value, not just age 1
• Men aged 45-49 with PSA ≤1.0 ng/mL can defer additional testing until age 50 2

Biopsy Threshold Considerations

• Consider using a PSA threshold of 3.0 ng/mL (rather than 2.5 ng/mL or 4.0 ng/mL) for biopsy decisions to balance cancer detection with overdiagnosis 2
• In men over 70 who are still being screened, raise the PSA threshold for biopsy to further reduce overdiagnosis 2