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Background  Both prostate-specific membrane antigen (PSMA) uptake and tumour blood flow (TBF) correlate with International Society of Urological Pathology (ISUP) Grade Group (GG) and hence prostate cancer (PCa) aggressiveness. The aim of the present study was to evaluate the potential synergistic benefit of combining the two physiologic parameters for separating significant PCa from insignificant findings.    Methods  From previous studies of [ 82 Rb]Rb positron emission tomography (PET) TBF in PCa, the 43 patients that underwent clinical [ 68 Ga]Ga-PSMA-11 PET were selected for this retrospective study. Tumours were delineated on [ 68 Ga]Ga-PSMA-11 PET or magnetic resonance imaging. ISUP GG was recorded from 52 lesions.    Results  [ 68 Ga]Ga-PSMA-11 maximum standardized uptake value (SUVmax) and [ 82 Rb]Rb SUVmax correlated moderately with ISUP GG (rho = 0.59 and rho = 0.56, both p < 0.001) and with each other (r = 0.65, p < 0.001). A combined model of [ 68 Ga]Ga-PSMA-11 and [ 82 Rb]Rb SUVmax separated ISUP GG > 2 from ISUP GG 1–2 and benign with an area-under-the-curve of 0.85, 96% sensitivity, 74% specificity, and 95% negative predictive value. The combined model performed significantly better than either tracer alone did (p < 0.001), primarily by reducing false negatives from five or six to one (p ≤ 0.025).    Conclusion  PSMA uptake and TBF provide complementary information about tumour aggressiveness. We suggest that a combined analysis of PSMA uptake and TBF could significantly improve the negative predictive value and allow non-invasive separation of significant from insignificant PCa.

Potential synergy between PSMA uptake and tumour blood flow for prediction of human prostate cancer aggressiveness