Evaluating Interim Progression: First Posttherapy ¹⁷⁷ Lu-PSMA SPECT/CT Relative to Baseline PSMA PET/CT

Prostate Cancer Working Group 4 recommends using prostate-specific membrane antigen (PSMA) PET for response assessment of patients with androgen pathway receptor modulator–resistant prostate cancer treated with ¹⁷⁷Lu-PSMA-617. For that purpose, the time interval between baseline PSMA PET and initiation of therapy is critical as interim disease progression may influence the performance of PET as a response assessment tool. <b>Methods:</b> We visually assessed the frequency of interim disease progression seen on the first posttherapy ¹⁷⁷Lu-PSMA-617 SPECT/CT in 87 patients with androgen pathway receptor modulator–resistant prostate cancer. The time interval between baseline PSMA PET and initiation of therapy, pretherapy prostate-specific antigen (PSA) measures, and treatment outcomes between patients with or without interim progression on SPECT/CT were also compared. <b>Results:</b> For the 32 patients (36.8%) with interim progression, the PET to therapy interval (88 d) was significantly greater than those without progression (42 d, <i>P</i> &lt; 0.001) despite adjusting for age, Gleason grade, and PSA doubling time. A time interval between baseline PSMA PET and initiation of therapy exceeding 30 d was seen in approximately 94% of patients with interim progression. PSA response and overall survival were not impacted by interim progression. <b>Conclusion:</b> Baseline PSMA PET may not represent the true disease status if the first cycle of ¹⁷⁷Lu-PSMA-617 occurs more than 30 d after baseline PET.