Efficacy of Lu-177 PSMA for Patients with High PSMA Expression and No Other Tumors on FDG Scan
Lu-177 PSMA therapy is highly effective for asymptomatic patients with high PSMA expression and no PSMA-negative lesions on imaging, with clinical trials demonstrating significant improvement in overall survival (15.3 vs 11.3 months) and progression-free survival (8.7 vs 3.4 months) compared to standard of care. 1
Patient Selection Criteria
Lu-177 PSMA therapy is indicated for patients with:
- Confirmed metastatic castration-resistant prostate cancer (mCRPC)
- High PSMA expression on PET imaging
- No dominant PSMA-negative metastatic lesions
- Previous treatment with androgen receptor-directed therapy and taxane-based chemotherapy 1
For asymptomatic patients with high PSMA expression and no other tumors on FDG scan, the absence of PSMA-negative lesions is particularly favorable for treatment response, as these lesions would not take up the radiopharmaceutical.
Efficacy Data
The VISION trial provides the strongest evidence for Lu-177 PSMA efficacy:
- Median overall survival: 15.3 months with Lu-177 PSMA + standard of care vs 11.3 months with standard of care alone (HR 0.62, p<0.001) 1
- Median progression-free survival: 8.7 months vs 3.4 months (HR 0.40, p<0.001) 1
- PSA response rate (≥50% decline): 57% in the LuPSMA trial 2 and 66% in the TheraP trial 3
The TheraP trial demonstrated superiority of Lu-177 PSMA over cabazitaxel with:
- Higher PSA response rate (66% vs 37%, p<0.0001)
- Fewer grade 3-4 adverse events (33% vs 53%) 3
Treatment Protocol
The standard Lu-177 PSMA-617 regimen consists of:
- 7.4 GBq (200 mCi) administered intravenously
- Every 6 weeks
- For 4-6 cycles 1
Predictors of Response
Several factors predict better response to Lu-177 PSMA therapy:
- Higher baseline SUVmax values (>10.50) in bone metastases correlate with better treatment response 4
- Higher PSMA tumor volume (>1.50 cm³) and total lesion PSMA (>8.50 g) also predict favorable outcomes 4
- Lymph node metastases tend to respond better than bone metastases 4
Safety Profile
Lu-177 PSMA therapy has a manageable toxicity profile:
- Grade ≥3 adverse events: 52.7% with Lu-177 PSMA vs 38% with standard of care alone 1
- Most common adverse events:
- Dry mouth (87%, mostly grade 1)
- Transient nausea (50%, grade 1-2)
- Fatigue (50%, grade 1-2)
- Thrombocytopenia (13%, grade 3-4) 2
Extended Therapy Considerations
For patients who respond well initially:
- Extended therapy beyond 6 cycles appears safe with no significant increase in grade 3-4 toxicity
- Patients receiving extended treatment have shown favorable median survival of 31.3 months from first administration 5
- Treatment can be continued uninterrupted or as a rechallenge after a break 5
Quality of Life Impact
Lu-177 PSMA therapy maintains or improves quality of life:
- Clinically meaningful improvements in pain severity and interference scores
- 37% of patients experience ≥10 point improvement in global health score by the second treatment cycle 2
Conclusion
For asymptomatic patients with high PSMA expression and no other tumors on FDG scan, Lu-177 PSMA therapy offers significant survival benefits with manageable toxicity. The absence of PSMA-negative lesions is particularly favorable for treatment response, making these patients ideal candidates for this targeted radiopharmaceutical therapy.