Dual-tracer PET/CT with [⁶⁸Ga]Ga-PSMA-617 and [⁶⁸Ga]Ga-RM26 improves early prediction of biochemical failure in prostate cancer: a prospective phase II trial.

Abstract

Prostate-specific membrane antigen (PSMA) and Gastrin-releasing peptide receptor (GRPR) PET demonstrate hopeful results in initial staging of prostate cancer (PCa), offering potential to support precision treatment decisions. We investigated whether the dual-tracer PET/CT with [⁶⁸Ga]Ga-PSMA-617 and [⁶⁸Ga]Ga-RM26 could enhance prediction of biochemical recurrence (BCR) after radical prostatectomy (RP) in PCa. 102 patients from prospective cohort NCT05073653 underwent preoperative [⁶⁸Ga]Ga-PSMA-617 and [⁶⁸Ga]Ga-RM26 PET/CT. Tumor uptake was quantified by maximum standardized uptake value (SUVmax), with optimal cutoffs determined using maximally selected rank statistics. Biochemical recurrence-free survival (BRFS) was estimated by Kaplan-Meier analysis, and the correlations between BRFS and predictors were examined using Cox regression. Predictive values were assessed using time-dependent receiver-operating characteristic (ROC) curves. We additionally used transcriptomic data (GSE70770, n = 198) for external validation. 52 patients (51.0%) experienced BCR within the follow-up (median, 22.3 months). High PSMA-SUVmax (> 6.6) was associated with shorter BRFS (hazard ratio [HR] 3.17, p = 0.004), as was low GRPR-SUVmax (≤ 13.0) (HR 0.51, p = 0.026). Both were identified as independent predictors for BRFS. PSMA-SUVmax correlated with most of conventional clinicopathological factors (p < 0.005), whereas GRPR-SUVmax did not (p > 0.200). The combined PSMA + GRPR-SUVmax model achieved a superior time-dependent AUC of 0.73, compared with PSMA (AUC 0.63) or GRPR alone (AUC 0.62). External transcriptomic analysis corroborated that PSMA_high/GRPR_low phenotype was associated with poorer BRFS (p = 0.029). This study provides first clinical evidence that [⁶⁸Ga]Ga-RM26 PET/CT adds independent prognostic value to PSMA PET/CT for early prediction of BCR after RP. Dual-tracer PET/CT may enable more accurate risk stratification and guide personalized management in PCa patients.