<sup>68</sup>Ga-PSMA PET/CT for Response Evaluation of<sup>223</sup>Ra Treatment in Metastatic Prostate Cancer
Anouk C. de Jong, Marcel Segbers, Sui Wai Ling, Laura H. Graven, Niven Mehra, Paul Hamberg, Tessa Brabander, Ronald de Wit, Astrid A.M. van der Veldt
Abstract
CT and bone scintigraphy are not useful for response evaluation of bone metastases to <sup>223</sup>Ra treatment in metastatic castration-resistant prostate cancer (mCRPC). PET using <sup>68</sup>Ga prostate-specific membrane antigen 11 (<sup>68</sup>Ga-PSMA) is a promising tool for response evaluation of mCRPC. The aim of this study was to determine the utility of <sup>68</sup>Ga-PSMA PET/CT for response evaluation of <sup>223</sup>Ra treatment in patients with mCRPC. <b>Methods:</b> Within this prospective, multicenter, imaging discovery study, 28 patients with mCRPC, eligible for <sup>223</sup>Ra treatment, were included between 2019 and 2022. Patients received <sup>223</sup>Ra according to the standard of care. Study procedures included CT, bone scintigraphy, and <sup>68</sup>Ga-PSMA PET/CT at baseline, after 3 and 6 cycles of <sup>223</sup>Ra treatment, and on treatment failure. Response to <sup>223</sup>Ra treatment was visually assessed on all 3 imaging modalities. Total tumor volume within bone (TTV<sub>bone</sub>) was determined on <sup>68</sup>Ga-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. <b>Results:</b> Visual response assessment criteria could not distinguish good responders from poor responders on <sup>68</sup>Ga-PSMA PET/CT and bone scintigraphy. For <sup>68</sup>Ga-PSMA PET/CT, TTV<sub>bone</sub> at baseline was lower in good responders than in poor responders, whereas TTV<sub>bone</sub> increased in both groups during treatment. TTV<sub>bone</sub> was higher in patients with new extraosseous metastases during <sup>223</sup>Ra treatment. Although TTV<sub>bone</sub> and ALP correlated at baseline, changes in TTV<sub>bone</sub> and ALP on treatment did not. <sup>68</sup>Ga-PSMA response of TTV<sub>bone</sub> showed intrapatient heterogeneity in most patients. <b>Conclusion:</b> mCRPC patients with lower TTV<sub>bone</sub> on <sup>68</sup>Ga-PSMA PET/CT have the best clinical outcome after <sup>223</sup>Ra 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<sub>bone</sub>, which might make one question the value of ALP for disease monitoring during <sup>223</sup>Ra treatment in clinical practice.