What to do for an elevated Prostate-Specific Antigen (PSA) level?

Management of Elevated PSA Levels

For an elevated PSA level, repeat testing should be performed in 4-6 weeks to confirm the elevation before proceeding with further evaluation, as PSA can fluctuate naturally and may be elevated due to non-malignant causes. 1

Initial Evaluation of Elevated PSA

1. Confirm PSA elevation:

   • Repeat PSA test in 4-6 weeks to account for laboratory variability (20-25%)
   • Use the same laboratory and schedule testing at the same time of day to reduce circadian variations
   • Consider non-malignant causes of elevation:
     • Recent prostate biopsy
     • Prostatitis
     • Benign prostatic hyperplasia (BPH)
     • Urethral or prostatic trauma

2. Clinical assessment:

   • Perform digital rectal examination (DRE)
   • Calculate PSA velocity (requires at least 3 measurements over 3 months)
   • Consider age-specific PSA reference ranges
   • For patients on finasteride, PSA values should be doubled for comparison with normal ranges 2

Diagnostic Algorithm

1. If confirmed elevated PSA:

   • PSA <10 ng/mL with normal DRE: Consider multiparametric MRI before biopsy
   • PSA ≥10 ng/mL with Gleason score 4-5: Bone scan indicated
   • PSA >15 ng/mL with Gleason score ≥7: CT/MRI of abdomen/pelvis indicated
   • Locally advanced tumor or bone pain: Bone scan indicated

2. Biopsy considerations:

   • Combined approach of MRI-targeted biopsy plus systematic sampling is optimal
   • If PSA velocity >0.75 ng/mL per year: Higher likelihood of aggressive disease

Special Considerations

1. Patients on 5α-reductase inhibitors (e.g., finasteride):

   • Finasteride reduces serum PSA by approximately 50% within six months
   • Establish new PSA baseline after at least six months of treatment
   • Any confirmed increase from lowest PSA value while on finasteride should be evaluated, even if within normal range
   • For interpretation, PSA values should be doubled 2

2. Age considerations:

   • Men older than 75 years with comorbidities may have little benefit from aggressive evaluation
   • Consider life expectancy when determining evaluation approach

3. PSA fluctuations:

   • Natural variations in PSA levels are common
   • An isolated elevation should be confirmed before proceeding with biopsy 3
   • Rate of PSA rise is often more important than absolute value in predicting aggressive disease

4. Subclinical prostatitis:

   • Consider antibiotic treatment if laboratory signs of prostatitis are present
   • Approximately 30% of patients with subclinical prostatitis show PSA decrease >20% after antibiotics 4

Follow-up Recommendations

• If biopsy is negative: Continue PSA monitoring every 6 months for the first year, then annually if stable
• If biopsy reveals cancer: Follow treatment guidelines based on risk stratification
• After treatment:
  • Post-radical prostatectomy: PSA should be undetectable (<0.4 ng/mL)
  • Post-radiation therapy: Three consecutive PSA rises indicates biochemical recurrence

Common Pitfalls to Avoid

1. Rushing to biopsy after a single elevated PSA:

   • Up to 44% of men with PSA >4 ng/mL will have normal values on subsequent testing 3
   • Confirm elevation before invasive procedures

2. Ignoring PSA velocity:

   • Rapid increases correlate with higher likelihood of aggressive cancer
   • Calculate using at least 3 measurements over time

3. Overlooking medication effects:

   • 5α-reductase inhibitors significantly reduce PSA levels
   • Adjust interpretation accordingly for patients on these medications

4. Failing to consider age-specific reference ranges:

   • PSA naturally increases with age
   • Use age-appropriate thresholds for evaluation

By following this structured approach to elevated PSA, clinicians can avoid unnecessary biopsies while ensuring appropriate evaluation of potentially significant prostate cancer.