What is the recommended next step for a 60-year-old man with a slightly elevated Prostate-Specific Antigen (PSA) level, a free PSA of 0.65, % free PSA of 13.7, and a Prostate Health Index (PHI) score of 22.7?

Management of 60-Year-Old Man with Elevated PSA and PHI Score of 22.7

This patient should proceed with repeat PSA testing and clinical evaluation, but does NOT require immediate prostate biopsy based on his PHI score of 22.7, which falls below the threshold of 35 that significantly increases probability of high-grade cancer. 1

Risk Stratification Based on PHI Score

The PHI score of 22.7 places this patient in a low-risk category for clinically significant prostate cancer:

• PHI scores <25 are associated with only 0.6% risk of high-grade prostate cancer over 6 years of follow-up 2
• At 90% sensitivity, a PHI cutoff of <28.6 can spare 30.1% of patients from unnecessary biopsy for benign disease or insignificant cancer 3
• The National Comprehensive Cancer Network recommends that PHI >35 significantly increases probability of detecting high-grade cancer, making biopsy more appropriate at that threshold 1

His % free PSA of 13.7% provides additional reassurance:

• Free PSA between 10-25% represents intermediate risk, not the high-risk category (<10%) that would mandate immediate biopsy 4
• This percentage suggests lower probability of aggressive disease compared to men with free PSA <10% 4

Recommended Management Algorithm

Step 1: Exclude Confounding Factors

• Rule out active urinary tract infection or prostatitis, as these can dramatically elevate PSA and typically normalize within 14 days of treatment 4
• Confirm no recent ejaculation, vigorous physical activity, or prostate manipulation (DRE, catheterization) within 48-72 hours of testing 4
• Verify patient is not on 5-alpha reductase inhibitors (finasteride/dutasteride), which reduce PSA by ~50% 4

Step 2: Perform Digital Rectal Examination

• Any nodule, asymmetry, or increased firmness requires immediate urology referral regardless of PSA or PHI values 5, 4
• DRE should not be used as stand-alone test but must be performed when PSA is elevated 4

Step 3: Repeat PSA Testing

• Routinely repeating PSA in patients with elevated levels is independently associated with 58% decreased risk of unnecessary biopsy (relative risk 0.42) 6
• Use the same PSA assay for longitudinal monitoring, as assays are not interchangeable due to different calibration standards 4
• If repeat PSA normalizes (<4.0 ng/mL), continue surveillance with PSA testing at 2-4 year intervals 4

Step 4: Calculate PSA Velocity

• PSA velocity ≥1.0 ng/mL per year requires immediate urology referral even if absolute PSA remains in "normal" range 4
• Rapidly growing cancers may have "normal" PSA levels; velocity is crucial for detecting aggressive disease 4

When to Proceed to Biopsy

Biopsy should be considered if:

• PHI score rises to ≥35 on repeat testing (11.7% risk of high-grade cancer) 2
• PHI density (PHI/prostate volume) ≥1.2 (21% risk of high-grade cancer) 2
• PSA velocity ≥1.0 ng/mL per year 4
• Any abnormality on digital rectal examination 5, 4
• Free PSA drops to <10% 4

If biopsy is pursued, multiparametric MRI should be obtained first:

• MRI has high sensitivity for clinically significant prostate cancer and should be ordered before biopsy in most cases 1, 4
• MRI-guided targeted biopsy combined with systematic sampling (minimum 8-12 cores) improves detection rates 1
• PHI density combined with MRI PI-RADS scoring achieves superior performance (AUC 0.85) compared to PSA density alone (AUC 0.81) 7

Follow-Up Strategy for This Patient

Given PHI <25, this patient should:

• Repeat PSA and PHI testing in 6-12 months with DRE 1, 2
• Men with PHI <25 or PHI density <0.4 can have less frequent follow-up compared to higher-risk patients 2
• Continue monitoring at 2-4 year intervals if PSA remains stable and <4.0 ng/mL 4

Critical Pitfalls to Avoid

• Don't assume negative biopsy excludes cancer: Prostate biopsies miss cancer in 20-30% of cases; repeat biopsy should be considered if clinical suspicion remains high despite negative initial results 4
• Don't focus only on absolute PSA values: This patient's PSA of 4.7 ng/mL is only modestly elevated, but velocity changes are more predictive of aggressive disease 4
• Don't delay referral for significant velocity changes: Even with low PHI, PSA velocity ≥1.0 ng/mL/year warrants urology evaluation 4
• Don't ignore DRE findings: Any palpable abnormality requires immediate referral regardless of biomarker values 5, 4