Prognostic Value of Initial Imaging and PSA Change with [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A ProsTIC Registry Analysis.

[177Lu]Lu-PSMA-617 radiopharmaceutical therapy improves survival and quality of life in patients with metastatic castration-resistant prostate cancer. We assessed whether patients who did not achieve an early prostate-specific antigen (PSA) decline after the first cycle (C1) benefited from further [177Lu]Lu-PSMA-617.

Methods

We analyzed patients with metastatic castration-resistant prostate cancer participating in a registry of [177Lu]Lu-PSMA-617 (ProsTIC registry, NCT04769817). Patients with a PSA either rising (≥25% increase from baseline) or stable (30% decrease to 25% increase from baseline) within 28 d of starting treatment (C1) and consequently received a second dose (cycle 2) were included. Biochemical response was defined as a PSA decline of more than 50% from baseline (PSA-50) within 20 wk after C1. Quality of life was assessed on 2 validated scales. We evaluated the effect of PSA change and 3 imaging parameters (pretreatment PSMA PET SUVmean, pretreatment [18F]FDG PET metabolic tumor volume, and mean total tumor dosimetry on SPECT/CT after C1) with these outcomes and survival time after cycle 2.

Results

Of 195 patients, 103 met inclusion criteria between January 5, 2021, and March 30, 2023, with an early PSA rise in 31 patients (30%) or stable PSA in 72 patients (70%). Of 103 patients, 45 (44%) achieved PSA-50 by 140 d after C1. Seven of 31 patients (23%) and 38 of 72 patients (53%) with early rising and stable PSA, respectively, had achieved a PSA-50 by 140 d after C1. A PSMA SUVmean of 10 or more versus an SUVmean of less than 10 conferred a higher chance of PSA-50 (59% vs. 37%; odds ratio, 2.53; 95% CI, 1.08-5.95). In total, 59 deaths were recorded with a median overall survival of 11.3 mo after cycle 2. [18F]FDG metabolic tumor volume was the only variable to have a meaningful association with overall survival. Patients with baseline pain scores of 10 or greater according to EORTC QLQ-C30 pain or 2 or greater according to BPI-SF had clinically meaningful reductions in pain in 39 of 55 patients (71%) and 17 of 37 patients (46%), respectively.

Conclusion

Discontinuing [177Lu]Lu-PSMA-617 based solely on PSA response after just 1 cycle is not advisable as a substantial number of patients achieve PSA-50 or a reduction in pain. Baseline imaging parameters have prognostic utility and can assist in patient counseling and clinical decision-making.