Linking Baseline PSMA PET-Derived Parameters to Toxicity, Adverse Events, Pain, and Quality of Life in Patients Treated with [177Lu]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.

Methods

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, SUVmean, SUVmax, and total lesion PSMA (TLP; calculated by multiplying SUVmean 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.

Results

Multivariate Cox regression analysis showed that higher baseline bone tumor SUVmean was significantly associated with delayed onset of grade 3 or 4 hematologic toxicity (hazard ratio [HR], 0.59; 95% CI, 0.36-0.98; P = 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; P = 0.049). Elevated whole-body SUVmean at baseline was predictive of delayed deterioration in both FACT-P total scores (HR, 0.59; 95% CI, 0.43-0.83; P = 0.002) and BPI-SF pain intensity (HR, 0.66; 95% CI, 0.46-0.93; P = 0.019). Additionally, higher salivary gland SUVmean, SUVmax, and TLP were significantly associated with increased xerostomia severity (P = 0.002, P = 0.006, and P = 0.015, respectively) in multivariate linear mixed-effects modeling.

Conclusion

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.