Metastatic lesion location and avidity on baseline PSMA PET/CT as predictor of duration of Lu177 treatment in men with metastatic castrate resistant prostate cancer.

188 Background: 177 Lu-PSMA-617 PSMA is a prostate-specific membrane antigen (PSMA) targeted radioligand therapy, which has been shown to improve progression-free survival in men with metastatic castrate-resistant prostate cancer (mCRPC). PSMA avidity on pretreatment PET/CT has been consistently linked to improved progression-free survival following treatment with Lu177, possibly translating to fewer required treatment cycles. In contrast, patients with low PSMA expression may need additional cycles to achieve therapeutic benefit or may require transition to alternative therapies due to inadequate response. This study seeks to clarify the predictive value of PSMA uptake on pretreatment PET/CT for determining treatment duration. Methods: We conducted a HIPAA-compliant, IRB-approved retrospective review of patients with mCRPC who received Lu-177 therapy between December 31, 2023, and February 29, 2024. Pretreatment PSMA PET scans were analyzed to identify sites of disease, and maximum and mean standardized uptake values (SUV) were measured for the most avid lesions in the viscera (liver and lung), lymph nodes, and bones using the SyngoVia VOI tool. Patients were stratified by treatment exposure (>3 vs. ≤3 Lu-177 cycles), and associations between SUV metrics and treatment duration were assessed using Fisher’s exact test. Results: 98 patients were included, with a median age of 73 years at Lu177 initiation. Disease distribution included lung (n=10), liver (n=16), lymph node (n=67), and bone (n=87). Due to limited sample sizes, analyses were restricted to lymph node and bone metastases. When PSMA uptake was analyzed by quartiles, mean SUV was not associated with the number of treatment cycles. However, a higher max SUV in bone and lymph node lesions correlated with a greater likelihood of patients completing more than three cycles (Table 1). Conclusions: Higher maximum SUV uptake in bone and lymph node metastases on pretreatment PSMA PET/CT was associated with a greater likelihood of prolonged treatment duration. These results suggest that tumors with high PSMA expression may derive increased benefit from extended Lu-177 therapy compared to tumors with low PSMA avidity. Lu177 treatment duration by PSMA avidity in lymph node and bone lesions. Number of Lu177 Cycles ≤3 >3 All p-value N % N % N % Lymph node SUV max ≤14.22 13 25 4 8.7 17 17.35 0.0361 ≤33.17 9 17.31 7 15.22 16 16.33 ≤61.36 6 11.54 11 23.91 17 17.35 >61.36 5 9.62 11 23.91 16 16.33 Lymph node SUV mean ≤20.0 9 17.31 7 15.22 16 16.33 0.0673 ≤37.8 6 11.54 10 21.74 16 16.33