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

The Role of PSA in Prostate Cancer Screening

PSA screening is not recommended as a routine test for all men; instead, shared decision-making is recommended for men aged 55-69 years, weighing the small potential mortality benefit against significant risks of overdiagnosis and overtreatment. 1

Current Screening Recommendations

Age-Based Recommendations

• Ages 55-69: Shared decision-making approach recommended, discussing potential benefits and harms 1
• Age ≥70: Screening generally not recommended due to increased risk of harms 1
• High-risk groups: Consider earlier screening (age 45-50) for:
  • African American men (higher baseline risk of prostate cancer) 1, 2
  • Men with family history of prostate cancer 1, 2

Benefits vs. Harms of PSA Screening

Benefits

• Small reduction in prostate cancer mortality (approximately 1.3 deaths prevented per 1000 men screened over 13 years) 1
• May prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened 1

Harms

• Overdiagnosis of indolent cancers that would never cause symptoms
• Complications from biopsies (bleeding, pain, infections, hospital readmissions) 1
• Complications from treatment (urinary incontinence, erectile dysfunction) 1
• Psychological burden (anxiety, uncertainty) 1

Improving PSA Testing Accuracy

Standard PSA testing has limited specificity. Several approaches can improve its diagnostic value:

PSA Derivatives

1. Free-to-Total PSA Ratio

   • Lower percentage of free PSA (<10%) associated with higher cancer risk 2, 3
   • Can reduce unnecessary biopsies by 30% without missing significant cancers 2

2. PSA Density

   • PSA level divided by prostate volume measured via ultrasound 1
   • Helps differentiate between BPH and cancer

3. PSA Velocity

   • Rate of PSA increase over time
   • Yearly increase >0.75 ng/mL may predict malignancy 1
   • Requires at least 3 measurements over 18 months 1

4. Age-Adjusted PSA

   • Recognizes that PSA naturally increases with age 1

Advanced Biomarker Tests

• Prostate Health Index (PHI): Combines total PSA, free PSA, and [-2]proPSA 2

  • PHI <27: Very low risk of significant cancer
  • PHI >35: Higher risk warranting biopsy consideration

• 4Kscore: Estimates probability of high-grade prostate cancer 2

Screening Algorithm

1. Initial Assessment:

   • Determine risk factors: age, race, family history
   • Discuss benefits and harms of screening

2. For men aged 55-69 who choose screening:

   • Perform PSA test
   • Consider risk-stratified screening intervals:
     • PSA <1 ng/mL: Rescreen every 2-4 years
     • PSA 1-3 ng/mL: Rescreen every 1-2 years
     • PSA >3 ng/mL: Consider additional testing 1, 4

3. For elevated PSA:

   • Repeat PSA test to confirm elevation
   • Consider free-to-total PSA ratio, PHI, or 4Kscore to improve specificity 2
   • Consider multiparametric MRI before biopsy to better target suspicious areas 2

4. For persistently elevated PSA:

   • Transrectal ultrasound-guided biopsy or MRI-targeted biopsy 1, 2

Special Considerations

Factors Affecting PSA Levels

• Conditions that can elevate PSA: Prostatitis, BPH, urinary catheterization 1
• Medications that can lower PSA: 5α-reductase inhibitors (finasteride, dutasteride) - multiply PSA by 2.3 to determine true value 1

Common Pitfalls

• Lower urinary tract symptoms are not associated with increased prostate cancer risk; they are typically due to benign prostatic enlargement 1
• Relying solely on PSA threshold without considering other factors can lead to unnecessary biopsies 2
• Ignoring risk factors in African American men and those with family history who may benefit from earlier screening 1

Cost-Effectiveness

PSA screening may only be cost-effective when:

• Screening frequency is low (every 4 years)
• Active surveillance is offered to men with low-risk prostate cancer (Gleason score ≤6 and stage ≤T2a) 1

The controversy around PSA screening stems from the modest mortality benefit weighed against substantial risks of overdiagnosis and treatment complications. The decision to undergo screening should be individualized through informed discussion of these factors.