PSA Decline After One Infusion of Lu-177 PSMA Therapy
A PSA decline is expected in approximately 50-66% of patients after a single infusion of Lu-177 PSMA therapy, with about 33% of patients achieving a PSA decline of ≥50% after the first cycle.
Evidence for PSA Response After First Lu-177 Infusion
The evidence from multiple studies demonstrates consistent PSA response patterns after initial Lu-177 PSMA therapy:
According to a retrospective study of 30 patients receiving Lu-177 PSMA therapy, a decline in serum PSA of ≥50% was detected in 33% of patients while a decline of any amount was observed in 50% of patients after the first cycle 1.
In another study of 71 patients receiving Lu-177 PSMA therapy, some PSA decline occurred in 66% of patients after treatment, with 56% achieving a PSA decline ≥50% 2.
The LuPSMA trial, a single-center phase 2 study, reported that 57% of patients achieved a PSA decline of 50% or more after Lu-177 PSMA therapy 3.
Factors Affecting PSA Response
Several factors influence the likelihood and magnitude of PSA response:
Tumor Dose: A significant correlation exists between whole-body tumor dose and PSA response. Patients receiving a tumor dose of at least 10 Gy are more likely to achieve a PSA decline of ≥50% 4.
PSMA Expression: Higher PSMA expression on pre-treatment imaging correlates with better absorbed dose and subsequent PSA response 4.
Baseline PSA: Higher baseline PSA levels and faster PSA doubling times are associated with positive PET scans and potentially better response to therapy 5.
Delayed Response Phenomenon
It's important to note that some patients who don't respond to the first cycle may show a delayed response:
Approximately 20% of patients who do not respond after the first cycle may become responders after completing additional cycles 1.
In one study, 12 out of 41 non-responders (29%) after the first cycle responded to further therapy cycles 2.
Clinical Implications
The PSA response after a single infusion has prognostic significance:
Patients with ≥50% PSA decline after the first cycle demonstrated significantly longer median overall survival (21.0 months) compared to non-responders (8.0 months) 1.
The NCCN guidelines recognize Lu-177 PSMA-617 as an effective therapy option for metastatic castration-resistant prostate cancer, with a category 1 recommendation based on the VISION trial results 5, 6.
Monitoring Recommendations
For patients receiving Lu-177 PSMA therapy:
PSA levels should be evaluated approximately six weeks after each cycle 1.
Response evaluation with radiological imaging and Ga-68 PSMA PET/CT should be performed before the first cycle and eight weeks after the last cycle 1.
Even if PSA response isn't seen after the first infusion, continuing therapy may be beneficial as delayed responses can occur 2.
Conclusion
While a PSA decline is expected in the majority of patients after a single Lu-177 PSMA infusion, the absence of an immediate response does not preclude benefit from continued therapy. The correlation between PSA response and survival outcomes underscores the importance of monitoring PSA levels throughout the treatment course.