Prompt PSA changes as a prognostic marker for response to PSMA-radioligand therapy

Area of Science:

• Oncology
• Nuclear Medicine
• Radiopharmaceutical Therapy

Background:

• Prostate-specific-membrane-antigen radioligand therapy (PSMA-RLT) with [177Lu]Lu-PSMA-617 is a treatment for metastatic castration-resistant prostate cancer (mCRPC).
• Predicting treatment response and survival early in the course of PSMA-RLT is crucial for patient management.

Purpose of the Study:

• To investigate if early changes in prostate-specific-antigen (PSA) levels within two days after the first PSMA-RLT cycle can predict treatment response and overall survival.
• To establish correlations between early PSA dynamics and long-term outcomes in mCRPC patients.

Main Methods:

• A retrospective analysis of 76 mCRPC patients treated with [177Lu]Lu-PSMA-617 was conducted.
• Pretreatment PSA values and relative PSA changes (dPSA) at two days post-cycle 1 were evaluated.
• Correlations between dPSA and biochemical response (BCR) using Prostate-Cancer-Working-Group (PCWG3) criteria were assessed.

Main Results:

• 42% of patients showed a PSA decrease, with 59% achieving partial response (PR).
• Among patients with stable PSA (46%), 17 (46%) achieved PR.
• Patients with PSA decrease or stable PSA lived longer (399 and 405 days, respectively) compared to those with PSA increase (225 days).

Conclusions:

• Decreased or stable PSA levels two days after the first [177Lu]Lu-PSMA-617 cycle are associated with favorable biochemical response.
• Early PSA dynamics following PSMA-RLT can serve as a predictive biomarker for treatment efficacy and overall survival in mCRPC patients.