What is the next step in treatment for a patient with declining Prostate-Specific Antigen (PSA) levels after Docetaxel (Taxotere) and Lutetium-177 (LU-177) infusions?

Management of Prostate Cancer with Declining PSA After Docetaxel and LU-177 Therapy

Response Assessment and Recommendation

Continue with the current treatment regimen of LU-177 therapy as the PSA decline from 0.43 to 0.28 indicates a favorable treatment response that should be maintained. 1

The observed PSA decline of 35% two weeks after LU-177 infusion is encouraging, especially considering the patient's previous aggressive disease with a 30-day PSA doubling time before the second Docetaxel infusion.

Understanding PSA Response Patterns

• PSA decline is a positive indicator of treatment response, with studies showing that patients who experience PSA decline have significantly longer progression-free survival (PFS) and overall survival (OS) compared to those without PSA reduction 2
• The Prostate Cancer Clinical Trials Working Group advises against making treatment decisions based on early PSA values (prior to 12 weeks), as favorable effects on PSA may be delayed 1
• PSA patterns can vary, including initial rise followed by decline, plateau, or delayed response 1

Monitoring Recommendations

1. Continue PSA monitoring:

   • Obtain regular PSA measurements every 4-6 weeks
   • Avoid making definitive treatment decisions based on 2-week values alone
   • Formally assess PSA response after at least 12 weeks (or after 2 cycles) 1

2. Imaging surveillance:

   • PSMA PET imaging after every 2 cycles of therapy (approximately every 12-16 weeks)
   • Post-therapy imaging 1-24 hours after each LU-177 infusion using SPECT/CT to document radiopharmaceutical distribution 1
   • More frequent imaging if PSA begins rising again or new symptoms develop

Treatment Continuation Protocol

• Standard LU-177 PSMA therapy: 7.4 GBq (200 mCi) administered intravenously every 6 weeks 1
• Treatment duration: Typically 4-6 cycles, with potential for extended therapy in responding patients 1, 3
• Monitoring for toxicity: Regular assessment of hematological parameters (hemoglobin, platelets, leukocytes) before each cycle 2

Evidence for Continued Treatment

• In patients receiving standardized LU-177 PSMA therapy, 79% showed PSA decrease, with 58% demonstrating >50% PSA decline 2
• Patients with PSA decline had significantly longer PFS (27 vs. 15 weeks) and OS (median survival not reached vs. 52 weeks) compared to non-responders 2
• Extended therapy with LU-177 PSMA (beyond 6 cycles) has shown favorable safety profiles without increased grade 3-4 toxicity in appropriate candidates 3

Potential Next Steps Based on Future Response

1. If continued response:

   • Complete planned course of LU-177 therapy (typically 4-6 cycles)
   • Consider maintenance therapy or extended treatment in case of continued response 3

2. If PSA stabilizes:

   • Continue therapy as scheduled with close monitoring
   • Reassess with imaging to confirm disease control

3. If PSA rises after initial response:

   • Consider treatment intensification or modification
   • Options may include shortened interval between LU-177 cycles, combination with other agents, or switch to alternative therapy 4

Cautions and Considerations

• Hematological toxicities are common with LU-177 PSMA therapy, including anemia, thrombocytopenia, and leukopenia 1, 2
• Monitor renal function throughout treatment, as patients with renal impairment may require dose adjustments 1
• Dry mouth and salivary gland dysfunction can occur and should be monitored 1

The current PSA decline suggests a favorable response to the combination of Docetaxel followed by LU-177 therapy. Recent evidence supports the efficacy of this sequential approach in metastatic prostate cancer 5. Continuing with the current treatment regimen is appropriate, with regular monitoring of PSA and imaging to assess ongoing response.