Baseline PSMA PET/CT as a predictive biomarker for toxicity and patient-reported outcomes in mCRPC patients undergoing <sup>177</sup>Lu-PSMA radioligand therapy.
Authors: Vishnu Murthy, Ojaswita Lokre, Timothy G. Perk, Lucia Chen, Pan Thin, Kathleen Nguyen, Stephanie Lira, Rejah M. Alano, Andrei Gafita, Johannes Czernin, Jeremie Calais
Journal: Journal of Clinical Oncology (2024)

e17058 Background: The phase III VISION trial demonstrated that 177 Lu-PSMA-617 (PSMA-RLT) prolonged overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Common side effects of PSMA-RLT include xerostomia, bone pain, and myelosuppression. The objective of this study is to evaluate the role of baseline PSMA PET/CT (bPET) in predicting hematologic toxicity and patient-reported outcomes in mCRPC patients undergoing PSMA-RLT. Methods: Patients treated with 177 Lu-PSMA-617 in the Expanded Access Program at UCLA with available bPET, toxicity data, and patient-reported outcomes (BPI, FACT-P, and Xerostomia Questionnaire) were included in this retrospective analysis. TRAQinform IQ technology (AIQ Solutions-Madison, WI) was used to conduct region of interest (ROI)-based analyses at bPET. SUV mean , SUV max , volume (cm 3 ), and total lesion PSMA (TLP; SUV mean x volume) of the whole-body tumor burden, healthy bone, and the salivary glands were extracted. We evaluated the following associations: 1) Whole-body tumor parameters on bPET with time to worsening of FACT-P scores (defined as a decrease of &gt;10 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 2) Healthy bone parameters on bPET with time to worsening of BPI Pain Severity and Pain Interference scores (defined as a 30% increase or at least 2 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 3) Salivary gland parameters on bPET with Xerostomia Questionnaire scores (Mixed-effect linear regression model). Results: 61 mCRPC patients were included. When evaluating associations between healthy bone SUV mean , SUV max , and TLP with time to first occurrence of Grade 3 or 4 hematologic toxicity, baseline hemoglobin was associated with a longer time to first occurrence (HR = 0.61, p = 0.005; HR = 0.59, p = 0.002; HR = 0.62, p = 0.005 respectively). When evaluating associations between bPET and time to worsening of FACT-P scores, whole-body tumor SUV mean , SUV max , and TLP were associated with a longer time to worsening (HR = 0.74, p = 0.033; HR = 0.82, p = 0.01; HR = 0.91, p = 0.028 respectively). When evaluating associations between salivary gland SUV mean , volume, SUV max , and TLP with Xerostomia Questionnaire scores, the number of cycles was associated with higher scores (mean estimate: 0.63, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.63, p = 0.003 respectively). Conclusions: In this retrospective analysis of 61 mCRPC patients treated with PSMA-RLT, bPET parameters were generally not predictive of hematologic toxicity or patient-reported outcomes. Of note, whole-body tumor SUV was associated with a longer time to worsening of FACT-P scores. Validation in a larger, prospective cohort is warranted.