What is the best course of treatment for a patient with Benign Prostatic Hyperplasia (BPH) and elevated Prostate-Specific Antigen (PSA) levels, with abnormal findings on PET/CT PSMA scan?

Management of Elevated PSA with Abnormal PSMA PET/CT After Brachytherapy

This patient requires repeat prostate biopsy targeting the PSMA-avid area in the left prostate bed, as the rising PSA trend (8.23→12.30→10.39 ng/mL over 4 months) combined with PSMA uptake indicates possible clinically significant prostate cancer recurrence that warrants tissue diagnosis before initiating salvage therapy. 1

Critical Assessment of Current Findings

PSA Trend Analysis

• The PSA demonstrates a concerning rising pattern with values of 8.23 (3/27), 12.30 (6/17), and 10.39 (8/5), representing a significant increase over a short timeframe that meets criteria for biochemical recurrence evaluation 1
• While the absolute PSA values fluctuate, the overall upward trend from the baseline of 8.99 (1/20) warrants investigation, particularly in the context of prior brachytherapy where PSA should remain suppressed 1
• The PSA velocity and pattern suggest active disease rather than benign prostatic tissue, especially given the PSMA PET findings 1

PSMA PET/CT Interpretation

• The "mild to moderate radiotracer uptake" in the lateral left prostate bed on PSMA PET/CT has high clinical significance, as PSMA-PET demonstrates pooled sensitivity of 0.89 for clinically significant prostate cancer detection 1
• PSMA-PET has superior detection rates compared to conventional imaging (79.7% versus 13.9%) for identifying recurrent disease, particularly in the prostate bed (69.6% versus 5.1%) 1
• The fact that this abnormality was "not well demonstrated" on the MRI does not exclude malignancy—PSMA-PET frequently detects MRI-invisible disease and can identify clinically significant cancer missed by MRI alone 1, 2
• Detection rates with PSMA-PET increase with higher PSA levels, and this patient's PSA range (8-12 ng/mL) falls within the optimal detection window 1

Recommended Diagnostic Algorithm

Immediate Next Steps

• Perform PSMA-PET/ultrasound-guided targeted biopsy of the left prostate bed lesion with 2-4 cores from the PSMA-avid area, as this approach detects clinically significant prostate cancer in 80-88% of PSMA-positive patients with prior negative biopsies 3, 4
• Add systematic template biopsy (12 cores) to the targeted approach, as the combined method increases detection of ISUP grade ≥2 cancers by approximately 40-50% in the repeat-biopsy setting compared to targeted biopsy alone 1
• The presence of brachytherapy seeds should not preclude biopsy—use transperineal approach if transrectal access is difficult 1

Biopsy Timing Considerations

• Proceed with biopsy promptly given the rising PSA trend and positive PSMA-PET findings, as earlier detection and treatment of biochemical recurrence improves outcomes 1
• Do not wait for further PSA rises or additional imaging, as the current evidence already warrants tissue diagnosis 1

Critical Pitfalls to Avoid

Common Errors in This Clinical Scenario

• Do not dismiss the PSMA-PET findings simply because the MRI was unremarkable—PSMA-PET has higher sensitivity for detecting recurrent disease and frequently identifies lesions not visible on MRI 1, 2
• Do not attribute rising PSA solely to BPH in a patient with prior brachytherapy and positive PSMA-PET, as this combination strongly suggests malignancy rather than benign disease 1
• Do not perform conventional imaging (CT/bone scan) instead of acting on the PSMA-PET results, as PSMA-PET is superior and should guide management decisions 1
• Do not delay biopsy to "watch and wait" with serial PSA monitoring, as the current findings already meet criteria for tissue diagnosis 1

Specific Technical Considerations

• Ensure the biopsy targets the exact location of PSMA uptake using fusion guidance, as cognitive targeting may miss small lesions 1
• Obtain at least 2-4 cores from the PSMA-avid area specifically, not just systematic sampling 3, 4
• Document the Gleason grade group (ISUP grade) if cancer is found, as this determines salvage therapy options 1

Post-Biopsy Management Framework

If Biopsy Confirms Clinically Significant Cancer (ISUP Grade ≥2)

• Proceed with multidisciplinary discussion regarding salvage radiation therapy to the prostate bed, as early salvage RT (at PSA <0.5 ng/mL ideally, but certainly at current levels) improves 4-year failure-free survival (75.5% versus 51.2% with delayed treatment) 1
• Consider androgen deprivation therapy in conjunction with salvage RT for high-grade disease 1
• Repeat PSMA-PET after salvage therapy to assess treatment response 1, 5

If Biopsy Shows Low-Grade Cancer (ISUP Grade 1) or Negative

• If ISUP grade 1: Consider active surveillance with PSA every 3 months and repeat PSMA-PET in 6 months 1
• If negative biopsy: Repeat PSA in 6-8 weeks to confirm trend, and consider repeat PSMA-PET/biopsy if PSA continues rising, as sampling error can occur even with targeted biopsies 1
• Monitor PSA doubling time—if <6 months, this indicates aggressive disease requiring treatment even with negative biopsy 1

Monitoring Protocol

• PSA testing every 3 months after biopsy regardless of results 1
• Repeat PSMA-PET if PSA rises by ≥0.4 ng/mL from post-biopsy nadir 1
• Digital rectal examination at each follow-up visit 6