At what age should prostate-specific antigen (PSA) testing start for men with no family history of prostate cancer?

Age to Start PSA Screening for Men with No Family History of Prostate Cancer

For men with no family history of prostate cancer, PSA screening should begin at age 50 for average-risk men, while those at higher risk (African American men) should begin at age 45. 1

Risk-Based Screening Algorithm

Starting Age Based on Risk Factors:

• Age 50: Average-risk men with no family history 1
• Age 45: Higher-risk men (African American) with no family history 1
• Age 40: Very high-risk men (multiple first-degree relatives with prostate cancer diagnosed before age 65) 1

Evidence Supporting This Recommendation

The 2018 BMJ clinical practice guideline synthesizes recommendations from multiple major organizations 1. The US Preventive Services Task Force (USPSTF), American College of Physicians, and American Urological Association all support shared decision-making about PSA screening for men aged 55-69, with most guidelines recommending against routine screening for men under 50 who are at average risk 1.

The American Cancer Society recommends that average-risk men receive information about screening beginning at age 50, while higher-risk men (African Americans and those with family history) should receive this information at age 45 1.

The National Comprehensive Cancer Network (NCCN) guidelines recommend initiating PSA screening at age 45 for all men, with the strongest evidence supporting testing at age 55 1. However, they acknowledge that randomized clinical trials focused primarily on men aged 55-69 years 1.

Baseline PSA Testing Considerations

Some evidence suggests potential value in baseline PSA testing at younger ages (40-45) for future risk stratification:

• A single PSA test before age 50 may predict subsequent prostate cancer risk up to 30 years later 1
• Men with PSA values above the median (0.6-0.7 ng/mL) in their 40s may be at higher risk for prostate cancer 1
• However, the PROBASE trial found very low prevalence of aggressive prostate cancer in 45-year-old men (only 4 cases of ISUP ≥3 cancers among 23,301 participants) 2

Important Caveats and Considerations

1. Limited mortality benefit: PSA screening programs in men aged 55-69 may prevent approximately 1.3 deaths from prostate cancer per 1000 men screened over 13 years 3

2. Potential harms:

   • False-positive results requiring additional testing and possible biopsy
   • Overdiagnosis and overtreatment
   • Treatment complications (incontinence, erectile dysfunction)

3. Upper age limit: Most guidelines recommend against PSA screening in men over 70 years or those with life expectancy less than 10 years 1, 3

4. Shared decision-making: All major guidelines emphasize the importance of discussing potential benefits and harms of screening before testing 1, 3

5. Follow-up intervals: For men who choose screening, follow-up intervals can be risk-stratified:

   • PSA ≥1.0 ng/mL: Repeat testing at 1-2 year intervals
   • PSA <1.0 ng/mL: Repeat testing at 2-4 year intervals 1

In conclusion, while some evidence supports earlier baseline testing, the strongest evidence and consensus among guidelines supports beginning PSA screening at age 50 for average-risk men with no family history, and at age 45 for African American men.