Will Prostate-Specific Antigen (PSA) levels decrease 2 weeks after the first Lutetium-177 (Lu-177) infusion?

PSA Response After First Lu-177 PSMA Infusion

PSA levels typically do not show significant decline just 2 weeks after the first Lu-177 PSMA infusion, and early PSA measurements should not be used to determine treatment response.

Understanding PSA Response Patterns with Lu-177 PSMA Therapy

Lu-177 PSMA therapy is a targeted radioligand treatment for metastatic castration-resistant prostate cancer (mCRPC). When evaluating its effectiveness, it's important to understand the timeline of PSA response:

Early PSA Response (First 2-4 Weeks)

• PSA levels may fluctuate during the first few weeks after treatment
• Guidelines recommend against using early PSA changes to determine treatment response
• The Prostate Cancer Clinical Trials Working Group (PCWG2) specifically advises to "ignore early rises (prior to 12 weeks) in determining PSA response" 1

Appropriate Timing for PSA Assessment

• PSA should be monitored by cycle but evaluated for response no earlier than 12 weeks after treatment initiation 1
• The American Urological Association recommends formal response assessment after every 2 cycles (approximately every 12-16 weeks) 2
• Early PSA measurements at 2 weeks post-infusion have limited prognostic value

Evidence on PSA Response Patterns

Research studies have established specific patterns of PSA response to Lu-177 PSMA therapy:

• In clinical studies, PSA response is typically evaluated 6 weeks after each cycle, not at 2 weeks 3
• The LuPSMA trial showed that 57% of patients achieved a PSA decline of ≥50% during the course of treatment, but this was not observed within the first 2 weeks 4
• The TheraP trial demonstrated PSA responses in 66% of patients receiving Lu-177 PSMA therapy, but these were measured at standard intervals (not at 2 weeks) 5

Factors Affecting PSA Response

Several factors influence PSA response to Lu-177 PSMA therapy:

• Age and baseline hemoglobin levels are significantly associated with PSA decline 6
• Prior chemotherapy exposure may negatively impact PSA response 6
• Approximately 20% of patients who don't respond after the first cycle may become responders after completing additional cycles 3

Clinical Recommendations for PSA Monitoring

For optimal monitoring of treatment response:

1. Obtain baseline PSA before starting treatment
2. Monitor PSA regularly throughout treatment, but don't make treatment decisions based on 2-week values
3. Wait until at least 12 weeks (or after 2 cycles) to formally assess PSA response 1, 2
4. Consider that a favorable effect on PSA may be delayed for 12 weeks or more, even with effective therapy 1
5. Recognize that PSA patterns can vary, including initial rise followed by decline, plateau, or delayed response 1

Conclusion

While PSA is an important biomarker for monitoring response to Lu-177 PSMA therapy, measurements taken just 2 weeks after the first infusion are premature for determining treatment effectiveness. Guidelines clearly recommend waiting at least 12 weeks before formally assessing PSA response, as early fluctuations may not reflect the ultimate treatment outcome.