Management of Elevated PSA on Repeat Testing
After a repeat PSA test confirms elevation, the next step should be a prostate biopsy, preceded by consideration of multiparametric MRI for better targeting of suspicious areas. 1
Confirmation of PSA Elevation
When a patient presents with an elevated PSA level, it's important to understand that:
- A repeat PSA test is recommended to confirm the elevation before proceeding to more invasive procedures 1
- Short-term decreases in PSA may occur in men with prostate cancer (including high-grade cancer) and should not necessarily deter further evaluation 2
- However, a significant decrease (≥20%) in PSA on repeat testing is associated with a lower risk of prostate cancer and particularly high-grade disease 3
Decision Algorithm for Confirmed Elevated PSA
1. Evaluate PSA Characteristics
- PSA level range matters:
- PSA 4.0-10.0 ng/mL: 25-35% positive predictive value for cancer
- PSA >10.0 ng/mL: 43-65% positive predictive value for cancer 1
- PSA velocity: The rate of PSA rise is often more important than the absolute value in predicting aggressive disease 1
- PSA density: Consider prostate volume in relation to PSA level 1
2. Proceed to Imaging
- Multiparametric MRI: Should be considered before biopsy to improve targeting of suspicious areas 1
- Imaging indications based on PSA level:
- PSA ≥10 ng/mL with Gleason score 4-5: Bone scan
- PSA >15 ng/mL with Gleason score ≥7: CT/MRI of abdomen/pelvis 1
3. Prostate Biopsy
- Technique: Transrectal ultrasound-guided biopsy under antibiotic coverage and local anesthesia
- Sampling: Minimum of 10-12 cores required for adequate sampling
- Optimal approach: Combined MRI-targeted biopsy plus systematic sampling 1
Special Considerations
Risk Factors That May Lower the Threshold for Biopsy
- Family history of prostate cancer
- African American ethnicity
- Free/total PSA ratio (lower ratio increases cancer risk)
- Age (consider age-specific PSA reference ranges) 1
Factors That May Affect PSA Levels
- Recent ejaculation (abstain for 48 hours before testing)
- Infection or inflammation
- Recent instrumentation
- 5α-reductase inhibitors (finasteride, dutasteride) - typically cause ~50% decrease in PSA within 6-12 months of starting therapy 4
Follow-up After Decision
- If biopsy is negative: Continue PSA monitoring every 6 months for the first year, then annually if stable 1
- If biopsy reveals cancer: Treatment depends on risk stratification based on cancer stage, grade, and patient factors 1
Common Pitfalls to Avoid
Ignoring PSA decreases: A decrease in PSA on repeat testing does not rule out cancer - 43% of men with prostate cancer show a PSA decrease below their baseline level 2
Over-relying on absolute PSA cutoffs: The decision to proceed to prostate biopsy should be based on multiple factors, not just PSA level 1
Failing to consider age: Men older than 75 years with other medical problems may have little to gain from aggressive evaluation and treatment 1
Not accounting for medications: 5α-reductase inhibitors significantly affect PSA levels and must be considered when interpreting results 4
The evidence clearly supports proceeding to prostate biopsy after confirmation of elevated PSA, with consideration of multiparametric MRI to improve targeting and diagnostic accuracy.