What rate of decline in Prostate-Specific Antigen (PSA) levels would be considered a good response during treatment with Lutetium-177 (LU-177) for recurrent castration-resistant metastatic prostate cancer?

PSA Response Rates During Lu-177 PSMA Therapy for Castration-Resistant Metastatic Prostate Cancer

A PSA decline of ≥50% from baseline is considered a good response during Lu-177 PSMA therapy for recurrent castration-resistant metastatic prostate cancer, with approximately 43-46% of patients achieving this benchmark after completion of treatment cycles. 1

Expected PSA Response Patterns

• PSA response to Lu-177 PSMA therapy may be delayed, with guidelines recognizing that favorable effects on PSA may take up to 12 weeks or more to manifest, even with cytotoxic treatments 2, 1
• Some patients may experience a "PSA bounce" phenomenon where PSA rises temporarily before declining 3
• Guidelines recommend monitoring PSA by cycle but continuing treatment through early rises for a minimum of 12 weeks unless there is other evidence of progression 2, 1

Response Rates by Treatment Course

• After the first cycle of Lu-177 PSMA:

  • Approximately 33-57% of patients achieve a PSA decline of ≥50% 4, 5
  • About 50-75% of patients show any decline in PSA 4, 6

• After completion of all treatment cycles (typically 3-6 cycles):

  • 43-56% of patients demonstrate a PSA decline of ≥50% 1, 4, 7
  • 46-66% of patients show some PSA decline 4, 7

Delayed Response Phenomenon

• Approximately 20% of patients who do not respond after the first cycle (no PSA decline ≥50%) may become responders after completing all treatment cycles 4, 7
• Of patients showing no PSA decline at all after the first cycle, about 20% may still achieve some PSA decline after completing therapy 4
• In one study, 12 out of 41 initial non-responders (29%) responded to further therapy cycles 7

Prognostic Significance of PSA Response

• Patients achieving a ≥50% PSA decline after the first cycle have significantly longer median overall survival (21.0 months) compared to non-responders (8.0 months) 4
• After completion of all treatment cycles, median overall survival is significantly better for:
  • Patients with any PSA decline: 13.0 months vs. 6.0 months for non-responders 4
  • Patients with ≥50% PSA decline: 21.0 months vs. 6.0 months for non-responders 4

Treatment Protocol Considerations

• Standard treatment protocol involves 3-5 cycles of Lu-177 PSMA at 6-12 week intervals 3
• Each cycle typically delivers 5.55-7.4 GBq (150-200 mCi) of Lu-177 PSMA 3
• Lu-177 PSMA therapy has shown improved overall survival compared to standard of care (15.3 vs 11.3 months) in metastatic castration-resistant prostate cancer 3, 8

Important Caveats

• Patients with predominantly lymph node metastases and those who are chemotherapy-naïve tend to have better responses 6
• Lower baseline PSA levels are associated with better survival outcomes 6
• Non-responders after completion of all cycles should be closely monitored as they have significantly shorter survival 4
• About 24.5% of patients may have radiographic progression without PSA progression, highlighting the importance of routine imaging in addition to PSA monitoring 8