SPECT Versus PET for [¹⁷⁷Lu]Lu-PSMA Response Assessment Using Quantitative RECIP 1.0

Prostate-specific membrane antigen (PSMA) PET/CT is widely used to monitor response during [¹⁷⁷Lu]Lu-PSMA radiopharmaceutical therapy (RPT) in metastatic castration-resistant prostate cancer (mCRPC), but access and cost limit its routine use. The aim of this study was to compare cycle 2 [¹⁷⁷Lu]Lu-PSMA SPECT/CT versus PSMA PET/CT in terms of response status and prognostic significance in patients with mCRPC treated with [¹⁷⁷Lu]Lu-PSMA RPT. Methods: Patients with mCRPC receiving [¹⁷⁷Lu]Lu-PSMA RPT and undergoing SPECT/CT 24 h after therapy and PSMA PET/CT at baseline and after 2 treatment cycles were included. Visual and quantitative analyses were performed. PSMA-avid lesions were segmented with both imaging techniques, using an SUV threshold of 3. Response status was defined in accordance with RECIP 1.0. Changes in prostate-specific antigen levels at 12 wk were characterized in accordance with Prostate Cancer Working Group 3 criteria. Categoric agreement of response classification between the 2 modalities was determined using Cohen κ. Patients were followed for progression-free survival (PFS) and overall survival (OS). Survival analysis was conducted using Cox hazard ratios (HRs) and Kaplan-Meier curves. C-indices measuring the prognostic discrimination of each modality were compared. Results: In total, 102 patients were included. Progressive disease was identified in 13 of 102 patients using SPECT and in 32 patients using PET (exact agreement, 63%; κ = 0.67). When combined with prostate-specific antigen measures, the gap narrowed to 32 versus 40 patients, respectively (exact agreement, 87%; κ = 0.93), with discordances limited to adjacent categories. A response on SPECT never corresponded to progression on PET, and progression on SPECT was always confirmed by PET. Progressive disease identified by either modality was associated with shorter PFS (SPECT: HR, 3.3; 95% CI, 1.8-6.0; PET: HR, 4.1; 95% CI, 2.6-6.6) and OS (SPECT: HR, 4.7; 95% CI, 2.3-9.6; PET: HR, 3.0; 95% CI, 1.8-4.8; all P < 0.001). PET provided higher prognostic accuracy for PFS than did SPECT (C-index, 0.66 vs. 0.57, respectively; P < 0.001) but not OS (C-index, 0.63 vs. 0.58, respectively; P = 0.055). Conclusion: Response evaluation with RECIP 1.0 on cycle 2 SPECT showed substantial agreement with interim PSMA PET and achieved comparable prognostic accuracy for OS. SPECT response always excluded progression on PET, and SPECT progression was always confirmed by PET. These findings support the use of cycle 2 SPECT/CT for early response assessment of patients treated with [¹⁷⁷Lu]Lu-PSMA RPT.