After two Lutetium-177 (LU-177) treatments, are changes in Prostate-Specific Antigen (PSA) levels or Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) scans better for determining efficacy of Lutetium-177 (LU-177) therapy?

Evaluation of LU-177 Treatment Efficacy: PSMA PET Scans vs PSA Levels After Two Treatments

PSMA PET scans are superior to PSA level changes for determining the efficacy of LU-177 therapy after two treatments, as PSMA PET quantitative parameters more accurately predict progression-free survival and treatment response.

Imaging Recommendations for LU-177 Treatment Monitoring

• PSMA PET imaging is strongly recommended for monitoring response to LU-177-PSMA-617 therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) 1
• The American Urological Association (AUA) and Society of Urologic Oncology (SUO) guidelines recommend PSMA PET imaging for patients considering 177Lu-PSMA-617 therapy 1
• PSMA PET imaging should be performed at least annually for mCRPC patients without PSA progression or new symptoms 1

PSMA PET Advantages for Treatment Response Assessment

• PSMA PET imaging can identify sites of prostate cancer with superior specificity and sensitivity compared to conventional imaging 1
• Quantitative analysis of 177Lu SPECT/CT at baseline and week 6 (after second treatment) provides valuable prognostic information 2:
  • Any increase in SPECT total tumor volume (TTV) between baseline and week 6 is associated with significantly shorter PSA progression-free survival (HR 2.5; 95% CI, 1.5-4.2) 2
  • Median PSA PFS in patients with increased SPECT TTV was only 3.7 months versus 6.7 months in those with no increase 2

PSA Response Limitations

• While PSA decline ≥50% after the first cycle correlates with improved overall survival (21.0 months vs 8.0 months), approximately 20% of non-responders after the first cycle can become responders after completing additional cycles 3
• PSA response alone may not capture the complete treatment effect, as radiographic progression can occur in 24.5% of patients without PSA progression 1
• Combined assessment using both PSA and PSMA imaging provides more comprehensive evaluation than either modality alone 2

Practical Approach to Monitoring LU-177 Treatment Response

• Perform baseline PSMA PET/CT prior to initiating LU-177 therapy to confirm PSMA expression and establish baseline disease burden 1
• Conduct quantitative 177Lu SPECT/CT imaging 24 hours after first and second treatments 2
• Evaluate changes in SPECT total tumor volume (TTV) between first and second treatments (week 6) 2
• Monitor PSA levels before each treatment cycle and 6-8 weeks after treatment 3
• Consider treatment modification or intensification if:
  • PSMA SPECT TTV increases between first and second treatments 2
  • Both PSA and SPECT TTV increase (associated with very short median PFS of 2.8 months) 2

Predictive Value of Early Imaging Assessment

• Patients with both increased PSA and increased SPECT TTV after second treatment have significantly shorter progression-free survival (median 2.8 months) compared to those with reduced SPECT TTV and PSA (median 9.0 months) 2
• Artificial intelligence-based analysis of baseline PSMA PET/CT images may further improve patient selection and outcome prediction 4

Common Pitfalls and Caveats

• PSA levels can fluctuate and may not always correlate with imaging findings 1, 2
• PSMA expression can be heterogeneous and change during treatment, affecting imaging results 5
• Baseline PSMA expression levels in metastatic lesions may predict treatment response, with higher baseline SUVmax values (>10.50) associated with better response in bone metastases 5
• Treatment-induced changes in PSMA expression can occur and should be considered when interpreting follow-up scans 5

In conclusion, while both PSA monitoring and PSMA PET imaging provide valuable information, quantitative PSMA imaging after the second LU-177 treatment offers superior predictive value for treatment efficacy and patient outcomes. The combination of both modalities provides the most comprehensive assessment.