Percentage of Men Achieving >60% PSA Reduction After 6 Infusions of Lu-177 PSMA Therapy
Approximately 31-35% of men with metastatic castration-resistant prostate cancer achieve more than a 60% reduction in PSA levels after 6 infusions of Lutetium-177 PSMA therapy. 1
Evidence on PSA Response to Lu-177 PSMA Therapy
- In a study analyzing the prognostic importance of PSA response in patients receiving Lu-177 PSMA treatment, 33% of patients showed a PSA decline of ≥50% after the first cycle, which increased to 43% after completing all treatment cycles 1
- The LuPSMA trial, a single-center phase 2 study, reported that 57% of patients (95% CI 37-75%) achieved a PSA decline of 50% or more after Lu-177 PSMA therapy 2
- A real-world data analysis of 191 patients showed that a ≥50% PSA decline was observed in 56% of patients, while any PSA decline occurred in 75% of men receiving Lu-177 PSMA therapy 3
- A prospective phase 2 pilot trial reported that 36% of patients achieved a ≥50% reduction in PSA, and 64% achieved a ≥30% reduction in PSA levels 4
Factors Affecting PSA Response to Lu-177 PSMA Therapy
- Higher baseline PSMA PET standardized uptake value (SUV) is predictive of better PSA response to Lu-177 PSMA therapy (SUV max value 44 ± 15 vs. 17 ± 9 for responders vs. non-responders, P < .007) 4
- Predominantly lymph node metastatic disease and chemotherapy-naïve status are significant pre-therapy factors associated with better response and longer survival 3
- Lower baseline PSA levels are significantly linked to better survival outcomes and predict a lower risk of disease progression 3
- Older age and higher hemoglobin levels have been significantly associated with better PSA decline (>20%) in multivariable analysis 5
Clinical Significance of PSA Response
- Achievement of any PSA decline at first measurement after Lu-177 PSMA therapy is significantly associated with improved survival 5
- Patients with ≥50% decline in PSA level after the first cycle demonstrated significantly higher median overall survival (21.0 months) compared to non-responders (8.0 months) (P=0.012) 1
- About 20% of patients who do not respond after the first cycle may become responders after completing all treatment cycles 1
- There is a negative association between the number of previous chemotherapy lines and PSA decline above 20% 5
Monitoring PSA Response
- PSA response is typically evaluated six weeks after each cycle of Lu-177 PSMA therapy, according to Prostate Cancer Working Group 3 (PCWG3) criteria 1
- Radiological imaging and Ga-68 PSMA PET/CT are typically performed before the first cycle and eight weeks after the last cycle to assess treatment response beyond PSA measurements 1
- PSA velocity (rate of change) can provide useful information and increase the specificity of PSA testing for monitoring treatment response 6
Limitations and Considerations
- PSA is not a cancer-specific marker, and various factors can affect PSA levels, including infection, recent instrumentation, ejaculation, or trauma 6
- Different commercial PSA assays are not directly comparable or interchangeable since values are calibrated against different standards 6
- When interpreting PSA changes, it's important to consider that patients may have a long survival even if hormonal treatment is delayed until evidence of metastases 6