How soon after the first Lutetium-177 (LU-177) infusion for metastatic prostate cancer can improvement on a Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) scan be expected?

Timing of Improvement on PSMA PET Scan After First LU-177 Infusion for Metastatic Prostate Cancer

Improvement on PSMA PET scan can typically be expected no earlier than 12 weeks after the first LU-177 infusion for metastatic prostate cancer. 1

Evaluation Timeline and Response Assessment

• The Prostate Cancer Clinical Trials Working Group (PCWG2) advises to "ignore early rises (prior to 12 weeks) in determining PSA response" and recommends evaluating for response no earlier than 12 weeks after treatment initiation 1
• Standard LU-177 PSMA therapy protocol includes:
  • Dosage of 7.4 GBq (200 mCi) administered intravenously every 6 weeks
  • Typical treatment duration of 4-6 cycles 1
  • Evaluation after at least 2 cycles (12 weeks) for meaningful assessment

Evidence for Response Timing

• In the TheraP trial, imaging responses were assessed 8 weeks after cycle 1 and 12 weeks after cycle 2, with more definitive responses observed at the later timepoint 2
• Recent research using same-day post-therapy SPECT/CT imaging shows that quantitative analysis of tumor volume reduction becomes more reliable after multiple cycles, with meaningful assessment requiring at least the third cycle to mitigate potential treatment-related flare-up effects 3
• Early imaging (1-2 hours post-infusion) can be performed but has limitations in detecting small tumor lesions and may not accurately predict long-term response 3

Response Rates and Patterns

• PSA response rates (≥50% decline) of 57-66% have been observed in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving LU-177 PSMA therapy 1
• Patients with PSA decline have significantly longer progression-free survival compared to non-responders 1
• The VISION trial demonstrated:
  • Median progression-free survival of 8.7 months with LU-177 PSMA therapy versus 3.4 months with standard of care alone
  • Median overall survival of 15.3 months versus 11.3 months 4, 1

Important Considerations for Imaging Assessment

• PSMA PET imaging is superior to conventional imaging for identifying sites of prostate cancer with higher specificity and sensitivity 4
• Patient selection for LU-177 therapy should be based on confirmed mCRPC, high PSMA expression on PET imaging, and no dominant PSMA-negative metastatic lesions 1
• In a recent study, 66% of patients showed >30% reduction in LU-177 PSMA-positive total tumor volume, which was associated with significantly improved overall survival and PSA progression-free survival 3

Monitoring Recommendations

• Regular assessment of hematological parameters (hemoglobin, platelets, leukocytes) before each cycle to monitor for toxicity 1
• Common side effects include hematological toxicities (anemia, thrombocytopenia, lymphopenia), fatigue, dry mouth, and nausea 1
• Grade 3-4 adverse events occur in approximately 52.7% of patients receiving LU-177 PSMA therapy compared to 38.0% with standard care alone 1

Clinical Pitfalls to Avoid

• Do not rely on very early imaging (before 12 weeks) to determine treatment efficacy, as early PSA rises may occur and are not necessarily indicative of treatment failure 1
• Be aware that treatment-related flare phenomena can occur, potentially confounding early imaging interpretation 3
• Recognize that small metastatic lesions may be missed on early post-therapy imaging 3

In conclusion, while some changes may be detected earlier, meaningful and reliable assessment of response to LU-177 PSMA therapy on PSMA PET imaging should be performed no earlier than 12 weeks after the first infusion, preferably after at least 2 treatment cycles have been completed.