Dynamic Changes in Tumor Burden in Patients Undergoing PSMA RLT.

We evaluated quantitative changes in total metastatic tumor burden in patients with metastatic castration-resistant prostate cancer undergoing prostate-specific membrane antigen radioligand therapy (PSMA RLT) using single photon emission computed tomography/computed tomography (SPECT/CT). This retrospective two-center study included 331 patients treated with PSMA RLT. SUVmean, SUVmax, and total tumor volume (TTV) were measured using post-treatment SPECT/CT, and median percentage changes were calculated. Patients received a median of 3 RLT doses, and the prostate-specific antigen (PSA50) response rate was 58.4%. Early responders (≥30% TTV reduction between cycles 1 and 2; n = 187, 56.5%) demonstrated a 61.3% TTV reduction at cycle 2, with continued reductions in subsequent cycles. Minimal responders (<30% TTV reduction; n = 144, 43.5%) showed modest, gradual decreases across cycles (-1.4% at cycle 2, -26.5% at cycle 3, and -67.6% at cycle 6). A modest positive correlation was observed between PSA and TTV changes (r = 0.318, p < 0.001); however, 43.6% of patients exhibited PSA-TTV discordance. Early responders experienced smaller reductions in tumor burden in later cycles than minimal responders. These findings suggest that dynamic changes in TTV on SPECT/CT can be used to guide RLT strategy.