What is the clinical relevance of Prostate-Specific Antigen (PSA) in prostate cancer screening?

Clinical Relevance of PSA in Prostate Cancer Screening

PSA testing is the best single test for early prostate cancer detection, though it has significant limitations including overdetection and overtreatment of prostate cancer, requiring thorough discussion of risks and benefits with patients before screening. 1, 2, 3

Role of PSA in Prostate Cancer Detection

• PSA is a glycoprotein secreted by prostatic epithelial cells that serves as the primary biomarker for prostate cancer screening and detection 4
• PSA testing has transformed prostate cancer diagnosis by enabling early detection on a global scale, contributing to the 30% decline in prostate cancer mortality in the United States 1, 5
• The American Urological Association no longer recommends a single threshold value of PSA to prompt prostate biopsy, instead advocating for consideration of multiple factors including age, family history, ethnicity, prior biopsy history, and comorbidities 2
• Traditionally, a cutoff value of 4.0 ng/mL has been used as the upper limit of normal, but cancer can be detected at all PSA levels, even below 1.0 ng/mL 3

Limitations of PSA as a Screening Tool

• PSA is not specific to cancer and can be elevated by multiple causes including prostatitis, benign prostatic hyperplasia (BPH), recent instrumentation, or trauma 3, 4
• Only approximately 25% of men with PSA levels between 4-10 ng/mL have prostate cancer on subsequent biopsy 3
• The balance of potential benefits (reduction of morbidity and mortality from prostate cancer) and harms (false-positive results, unnecessary biopsies, and possible complications) remains uncertain 1
• Screening leads to overdetection and overtreatment of some patients, which are significant concerns 1, 2

Current Screening Recommendations

• The American Cancer Society recommends that PSA screening should be considered in men with individual risk factors, with a thorough discussion of benefits and benefits 3
• For men between 45-75 years old with a life expectancy >10 years, consider baseline PSA at age 45, with repeat testing every 2-4 years if PSA <1 ng/mL, and more frequent follow-up (annually) if PSA ≥1 ng/mL 3
• Men at increased risk (African-American men and those with a first-degree relative with prostate cancer) should consider starting screening at age 45 1, 3
• The European Randomized Study of Screening for Prostate Cancer demonstrated a 20% relative reduction in prostate cancer deaths among those screened compared to those who were not at 9 years 1

Strategies to Improve PSA Specificity

• Free PSA percentage: lower values suggest a higher probability of cancer 3
• PSA density: relates PSA level to prostatic volume measured by transrectal ultrasound 3
• Age-adjusted PSA: considers different thresholds based on patient age 3
• PSA velocity: evaluates the rate of change of PSA over time, though its predictive value is controversial 3
• Newer biomarkers such as the Prostate Health Index (PHI) or the 4K score may be used to increase specificity and reduce unnecessary biopsies 6, 7

Technical Considerations in PSA Testing

• It is essential to use the same PSA assay for longitudinal monitoring as PSA assays are not interchangeable 2
• Laboratory variability can range from 20-25% depending on standardization method 2
• For accurate PSA velocity measurement, at least three PSA values over a time period of at least 18 months are recommended 2
• 5α-reductase inhibitors (finasteride, dutasteride) decrease PSA levels by approximately 50% in 6-12 months 3

Approach to PSA Screening

• Men should be informed of the risks and benefits of prostate cancer screening before biopsy 1, 2
• The option of active surveillance should be discussed for certain men diagnosed with prostate cancer to address concerns of overtreatment 1, 2
• The population most likely to benefit from screening will be men 50 to 70 years of age who are at average risk and men older than 45 years of age who are at increased risk 1
• Older men and men with significant medical problems who have a life expectancy of fewer than 10 years are unlikely to benefit from screening 1