What is the appropriate workup for a patient with elevated Prostate-Specific Antigen (PSA)?

Workup for Elevated PSA

The appropriate workup for a patient with elevated PSA should include verification of the elevated PSA with a second measurement, followed by multiparametric MRI prior to prostate biopsy, with consideration of PSA density to help distinguish between malignant and benign causes. 1

Initial Evaluation of Elevated PSA

Confirmation of Elevated PSA

• Repeat PSA testing to confirm elevation before proceeding to invasive procedures 1
  • Note: Even if repeat PSA shows a decrease, this should not deter further workup as 43% of men with prostate cancer may show a PSA decrease below their baseline level 2
• Ensure proper pre-test conditions for accurate PSA measurement:
  • Abstain from ejaculation for 48 hours before testing
  • Avoid testing during active prostatitis or urinary tract infection
  • Avoid recent urinary instrumentation
  • Use the same laboratory and assay for serial measurements 3, 1

Risk Assessment Factors

• Consider PSA density (PSA divided by prostate volume)
  • Optimal cutoffs: 0.10 ng/ml² in biopsy-naïve patients and 0.15 ng/ml² in patients with previous negative biopsy 4
  • Helps distinguish between prostate cancer and intraprostatic inflammation 4
• Evaluate free-to-total PSA ratio
  • Ratio <0.18 has 95% sensitivity and 80% specificity for prostate cancer 5
  • Particularly useful in the PSA range of 4-10 ng/mL 1, 5
• Consider PSA velocity (rate of change over time) 3, 1

Imaging Studies

Multiparametric MRI

• Recommended before biopsy to improve targeting of suspicious areas 1
• Most accurate imaging method for detecting local recurrence 3
• Helps identify lesions that require targeted biopsy 1

Bone Scan

• Not routinely recommended with PSA <10 ng/mL and Gleason score <7 3, 1
• Consider when:
  • PSA ≥10 ng/mL with Gleason score 4-5
  • PSA >15 ng/mL with Gleason score ≥7
  • Presence of bone pain
  • Locally advanced tumor 1

CT Scan

• Limited value in detecting early recurrence in the prostate bed 3
• Consider CT of abdomen/pelvis when PSA >15 ng/mL with Gleason score ≥7 1
• Not effective until PSA reaches high levels (mean of 27.4 ng/mL for positive CT) 3

Advanced Imaging

• Consider PSMA-PET/MRI for patients with suspicious lesions on multiparametric MRI
  • High accuracy (90%) for detecting significant prostate cancer 6
  • May reduce unnecessary biopsies 6

Biopsy Approach

Indications for Biopsy

• Confirmed elevated PSA (typically >4.0 ng/mL)
• Abnormal digital rectal examination
• Suspicious lesions on multiparametric MRI 1

Biopsy Technique

• Combined approach of MRI-targeted biopsy plus systematic sampling is optimal 1
• Minimum of 10-12 cores required for adequate sampling 1
• Perform under antibiotic coverage and local anesthesia 1

Common Pitfalls to Avoid

• Do not rely solely on a single PSA measurement for clinical decisions
• Do not dismiss elevated PSA due to a subsequent decrease on repeat testing 2
• Do not automatically proceed to biopsy without considering PSA density and free-to-total PSA ratio, which can reduce unnecessary biopsies 5, 4
• Do not order bone scans or CT scans for patients with mildly elevated PSA (<10 ng/mL) and no other risk factors, as yield is very low 3, 1
• Avoid interpreting PSA values without considering medications that affect PSA levels (e.g., 5α-reductase inhibitors typically cause ~50% decrease in PSA) 1