What to do if Prostate-Specific Antigen (PSA) is elevated?

Management of Elevated PSA Levels

For a patient with an elevated PSA level, repeat testing should be performed in 4-6 weeks to confirm the elevation before proceeding to further evaluation, as laboratory variability can range from 20-25%. 1

Initial Evaluation

1. Confirm the elevation with repeat testing:

   • Wait 4-6 weeks before repeating the PSA test
   • Ensure patient avoids ejaculation and vigorous cycling for 48 hours prior to repeat testing
   • Consider using the same laboratory and assay for consistency 1
   • A 20% decrease in repeat PSA levels is associated with a significantly lower risk of prostate cancer and high-grade disease 2

2. Evaluate for non-malignant causes of PSA elevation:

   • Recent prostate biopsy
   • Prostatitis
   • Benign prostatic hyperplasia (BPH)
   • Urethral or prostatic trauma 1
   • Medications like dutasteride can reduce PSA by approximately 50% 3

3. Perform a digital rectal examination (DRE):

   • Assess prostate size, consistency, and presence of nodules
   • Consider urinalysis to exclude urinary tract infection or hematuria 1

Decision Making Based on Repeat PSA Results

If PSA remains elevated:

1. Consider referral to urology for prostate biopsy if:

   • PSA velocity exceeds 0.75 ng/mL per year
   • DRE is abnormal
   • Free PSA percentage is low (≤25%) 1
   • Free PSA ≤10% indicates high risk of prostate cancer 1

2. Consider multiparametric MRI before biopsy:

   • Improves targeting of suspicious areas
   • A combined approach of MRI-targeted biopsy plus systematic sampling is optimal 1

If PSA decreases by ≥20% or returns to normal:

• Risk of prostate cancer and high-grade disease is significantly reduced 2
• Consider routine monitoring rather than immediate biopsy 1

Monitoring and Follow-up

1. If biopsy is performed and negative:

   • Continue PSA monitoring every 6 months for the first year
   • Then annually if stable 1
   • Consider repeat MRI and biopsy if PSA continues to rise, especially if velocity exceeds 0.75 ng/mL/year 1

2. If biopsy is not performed:

   • Repeat PSA every 6 months to monitor for significant changes 1
   • Be vigilant for PSA velocity >0.75 ng/mL per year 1

3. If biopsy reveals cancer:

   • Follow treatment guidelines based on risk stratification from the National Comprehensive Cancer Network (NCCN) 1
   • Treatment options depend on cancer stage, grade, and patient factors 1

Special Considerations

• Age-specific PSA reference ranges should be considered when interpreting PSA values 1
• Men with <15 years life expectancy are unlikely to benefit from aggressive diagnostic workup 1
• Patients on testosterone replacement therapy (TRT):
  • Hold TRT and refer to urology for evaluation if PSA increases by >1.0 ng/mL during first six months of treatment 1
  • Do not restart TRT without urologic clearance 1
• Dutasteride effects on PSA:
  • Reduces PSA by approximately 50%
  • Any confirmed increase in PSA while on dutasteride should be evaluated, even if values are within normal range for untreated men 3
  • May increase risk of high-grade prostate cancer 3

Common Pitfalls to Avoid

1. Do not rely on a single PSA measurement for clinical decisions due to potential laboratory variability 1
2. Do not interpret PSA in isolation without considering age, DRE findings, and PSA kinetics 1
3. Remember that not all PSA elevations indicate cancer, as benign conditions can cause significant elevations 1
4. Do not ignore rising PSA even if absolute values are within normal range, especially in patients on 5-alpha reductase inhibitors like dutasteride 3
5. Avoid delaying evaluation in patients with significant PSA velocity, even if absolute PSA values are only moderately elevated 1

By following this structured approach to elevated PSA levels, clinicians can ensure appropriate evaluation while minimizing unnecessary biopsies and interventions.