Clinical Impact of Changes in Tumor Uptake and Volume on PSMA PET/CT During [ ¹⁷⁷ Lu]Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer

Although tumor volume and new lesions (NLs) have been investigated previously as measures of response, the clinical impact of changes in tumor uptake on prostate-specific membrane antigen (PSMA) PET remains largely unknown. <b>Methods:</b> This multicenter retrospective study investigated the clinical impact of changes in tumor uptake and volume on PSMA PET during [¹⁷⁷Lu]Lu-PSMA in metastatic castration-resistant prostate cancer (mCRPC). The primary outcomes were the associations of changes in SUV_max (ΔSUV_max) and SUV_mean(ΔSUV_mean), changes in total tumor volume (ΔTTV), and occurrence of NLs with prostate-specific antigen (PSA) progression-free survival (PSA-PFS) and overall survival (OS). The study included patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA between 2014 and 2019. PSMA PET/CT was performed at baseline and after 2 cycles of therapy. Whole-body analyses (SUV_max, SUV_mean, TTV, and NLs) were performed and calculated using qPSMA software. <b>Results:</b> In total, 124 patients with mCRPC (median age, 73 y; interquartile range, 67–76 y) were included in the study. Whole-body ΔTTV and the occurrence of NLs were significantly associated with shorter PSA-PFS (hazard ratio [HR], 5.7; 95% CI, 3.59–9.06; and HR, 1.6; 95% CI, 1.4–1.8; <i>P</i> &lt; 0.0001) and with OS (HR, 2.3; 95% CI, 1.61–3.43; and HR, 1.3; 95% CI, 1.1–1.4; <i>P</i> &lt; 0.001). Patient-based analysis showed that ΔSUV_max and ΔSUV_mean were not associated with outcome (HR, 1.00; 95% CI, 0.99–1.00; <i>P</i> = 0.30; and HR, 0.90; 95% CI, 0.99–1.00; <i>P</i> = 0.11). Region-based analysis found that only ΔSUV_max in visceral lesions was significantly associated with PSA-PFS (<i>P</i> = 0.007) but not with OS. <b>Conclusion:</b> Only ΔTTV and the occurrence of NLs provided significant prognostic value and should be considered when evaluating treatment response to [¹⁷⁷Lu]Lu-PSMA therapy.