Linking Baseline PSMA PET–Derived Parameters to Toxicity, Adverse Events, Pain, and Quality of Life in Patients Treated with [ ¹⁷⁷ Lu]Lu-PSMA-617: A Single-Center Retrospective Study

This study aimed to investigate whether quantitative parameters derived from baseline prostate-specific membrane antigen (PSMA) PET imaging can predict hematologic toxicity and patient-reported outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with ¹⁷⁷Lu-PSMA-617. <b>Methods:</b> This retrospective study analyzed data from the U.S. expanded-access program at UCLA (NCT04825652). We included 61 patients with mCRPC who received ¹⁷⁷Lu-PSMA-617 between May 2021 and March 2022 and had available baseline PSMA PET scans, hematologic toxicity data, and patient-reported outcomes. Questionnaires included the Functional Assessment of Cancer Therapy-Prostate (FACT-P), the Brief Pain Inventory-Short Form (BPI-SF), and a xerostomia assessment, all completed at each treatment cycle. Baseline PSMA PET parameters-including volume, SUV_mean, SUV_max, and total lesion PSMA (TLP; calculated by multiplying SUV_mean by volume) for whole-body disease, bone disease, and salivary glands-were quantified using TRAQinform IQ. Associations between these imaging metrics and clinical outcomes were assessed using univariate and multivariate models. <b>Results:</b> Multivariate Cox regression analysis showed that higher baseline bone tumor SUV_mean was significantly associated with delayed onset of grade 3 or 4 hematologic toxicity (hazard ratio [HR], 0.59; 95% CI, 0.36-0.98; <i>P</i> = 0.040), suggesting a protective effect. Conversely, higher bone TLP was associated with earlier onset of severe toxicity (HR, 1.31; 95% CI, 1.00-1.71; <i>P</i> = 0.049). Elevated whole-body SUV_mean at baseline was predictive of delayed deterioration in both FACT-P total scores (HR, 0.59; 95% CI, 0.43-0.83; <i>P</i> = 0.002) and BPI-SF pain intensity (HR, 0.66; 95% CI, 0.46-0.93; <i>P</i> = 0.019). Additionally, higher salivary gland SUV_mean, SUV_max, and TLP were significantly associated with increased xerostomia severity (<i>P</i> = 0.002, <i>P</i> = 0.006, and <i>P</i> = 0.015, respectively) in multivariate linear mixed-effects modeling. <b>Conclusion:</b> In this retrospective analysis of patients with mCRPC treated with ¹⁷⁷Lu-PSMA-617, baseline quantitative PSMA PET parameters were associated with both treatment-related toxicities and patient-reported outcomes. Validation in a larger, prospective, multicenter cohort is warranted.