⁶⁸Ga-PSMA PET/CT for Response Evaluation of²²³Ra Treatment in Metastatic Prostate Cancer

CT and bone scintigraphy are not useful for response evaluation of bone metastases to ²²³Ra treatment in metastatic castration-resistant prostate cancer (mCRPC). PET using ⁶⁸Ga prostate-specific membrane antigen 11 (⁶⁸Ga-PSMA) is a promising tool for response evaluation of mCRPC. The aim of this study was to determine the utility of ⁶⁸Ga-PSMA PET/CT for response evaluation of ²²³Ra treatment in patients with mCRPC. Methods: Within this prospective, multicenter, imaging discovery study, 28 patients with mCRPC, eligible for ²²³Ra treatment, were included between 2019 and 2022. Patients received ²²³Ra according to the standard of care. Study procedures included CT, bone scintigraphy, and ⁶⁸Ga-PSMA PET/CT at baseline, after 3 and 6 cycles of ²²³Ra treatment, and on treatment failure. Response to ²²³Ra treatment was visually assessed on all 3 imaging modalities. Total tumor volume within bone (TTV_bone) was determined on ⁶⁸Ga-PSMA PET/CT. Intrapatient heterogeneity in response was studied using a newly developed image-registration tool for sequential images of PET/CT. Results were compared with failure-free survival (good responders vs. poor responders; cutoff, 24 wk) and alkaline phosphatase (ALP) response after 3 cycles. Results: Visual response assessment criteria could not distinguish good responders from poor responders on ⁶⁸Ga-PSMA PET/CT and bone scintigraphy. For ⁶⁸Ga-PSMA PET/CT, TTV_bone at baseline was lower in good responders than in poor responders, whereas TTV_bone increased in both groups during treatment. TTV_bone was higher in patients with new extraosseous metastases during ²²³Ra treatment. Although TTV_bone and ALP correlated at baseline, changes in TTV_bone and ALP on treatment did not. ⁶⁸Ga-PSMA response of TTV_bone showed intrapatient heterogeneity in most patients. Conclusion: mCRPC patients with lower TTV_bone on ⁶⁸Ga-PSMA PET/CT have the best clinical outcome after ²²³Ra treatment. Response is highly heterogeneous in most patients. A decrease in ALP, which occurred in most patients, was not correlated with a decrease in TTV_bone, which might make one question the value of ALP for disease monitoring during ²²³Ra treatment in clinical practice.