What are the next steps for a patient with a moderately hypertrophic prostate gland and rising PSA levels, but no evidence of prostate tumor on MRI?

Management of Moderately Hypertrophic Prostate with Rising PSA and Negative MRI

For a patient with moderately hypertrophic prostate (45-50cc), rising PSA levels, and negative MRI findings, continued PSA monitoring with consideration of PSMA-PET/CT if PSA continues to rise is recommended.

Current Clinical Picture

• The MRI shows a moderately hypertrophic prostate gland (45-50cc) with no evidence of prostate tumor based on MRI criteria 1
• Multilobular high T2W foci consistent with age-related hypertrophic changes rather than malignancy 1
• Negative staging parameters with no evidence of extracapsular disease, neurovascular bundle invasion, seminal vesicle involvement, or pelvic adenopathy 1
• Median lobe hypertrophy causing mild impingement on the bladder outlet 1

Recommended Next Steps

Continued PSA Monitoring

• Regular PSA monitoring every 6-12 months is recommended as the first step in follow-up 1, 2
• PSA testing should be performed more frequently (every 3 months) if the patient is at high risk of recurrence or has rapidly rising values 1
• PSA velocity (change over time) should be carefully monitored, as rapid rises (≥0.75 ng/mL per year) increase concern for cancer 2

When to Consider Additional Imaging

• If PSA continues to rise despite negative MRI findings, next-generation imaging (NGI) should be considered 1
• PSMA-PET/CT is specifically recommended as the preferred next imaging modality when conventional imaging is negative but clinical suspicion remains high 1
• Other options include 11C-choline or 18F-fluciclovine PET/CT if PSMA imaging is unavailable 1

Role of Repeat Biopsy

• Consider repeat prostate biopsy if PSA continues to rise despite negative imaging 1
• Anteriorly directed biopsy should be considered if PSA remains persistently elevated, as anterior tumors may be missed on standard biopsy approaches 1
• Multiparametric MRI can help identify regions of cancer missed on prior biopsies and should be used to guide targeted biopsies 1

Importance of PSA Density and MRI Findings

• PSA density (PSA level divided by prostate volume) should be calculated to improve risk stratification 3, 4
• Patients with PSA density ≤0.10 and negative MRI have a high negative predictive value (95%) for clinically significant prostate cancer 3
• The combination of negative MRI and low PSA density could potentially reduce unnecessary biopsies 4

Considerations for Benign Prostatic Hyperplasia (BPH)

• The moderate prostate hypertrophy (45-50cc) with bladder outlet impingement suggests BPH, which may contribute to PSA elevation 1
• Consider workup for benign disease if PSA elevation is modest and consistent with BPH 1
• Addressing BPH symptoms may be warranted regardless of cancer concerns, particularly if there is bladder outlet obstruction 1

Common Pitfalls to Avoid

• Do not rely solely on MRI to exclude prostate cancer, as false negatives can occur, especially with small anterior tumors 5
• Reader experience significantly impacts MRI accuracy; consider second opinion readings for difficult cases 5
• Do not dismiss rising PSA solely based on negative imaging, as persistent PSA elevation warrants continued vigilance 1
• Avoid unnecessary biopsies in patients with stable PSA, negative MRI, and low PSA density, as these patients have low risk of clinically significant cancer 6, 3

Long-term Surveillance Strategy

• For patients with negative MRI and stable PSA, follow-up with PSA and DRE at 6-12 month intervals is appropriate 1, 6
• If PSA velocity increases significantly (>0.5 ng/mL per month), consider more aggressive evaluation despite negative imaging 1
• Consider PSMA-PET/CT as the next step if PSA continues to rise, as it has superior detection capability for small volume disease compared to conventional imaging 1