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

Mads Ryø Jochumsen,Jens Sörensen,Michael Borre,Kirsten Bouchelouche,Jørgen Frøkiær,Bodil Ginnerup Pedersen,Lars Poulsen Tolbod

doi:10.1186/s13550-021-00757-y

Abstract

BackgroundBoth 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.MethodsFrom previous studies of [82Rb]Rb positron emission tomography (PET) TBF in PCa, the 43 patients that underwent clinical [68Ga]Ga-PSMA-11 PET were selected for this retrospective study. Tumours were delineated on [68Ga]Ga-PSMA-11 PET or magnetic resonance imaging. ISUP GG was recorded from 52 lesions.Results[68Ga]Ga-PSMA-11 maximum standardized uptake value (SUVmax) and [82Rb]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 [68Ga]Ga-PSMA-11 and [82Rb]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).ConclusionPSMA 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.

Highlights

Both prostate-specific membrane antigen (PSMA) uptake and tumour blood flow (TBF) correlate with International Society of Urological Pathology (ISUP) Grade Group (GG) and prostate cancer (PCa) aggressiveness
The uptake of PSMA in the primary tumour have been proposed as a marker of PCa aggressiveness in a number of studies [6,7,8,9]; in a recent large study on high-risk patients, we have demonstrated a large overlap in tumour PSMA uptake between
The present study suggests that a combined analysis of [68Ga]Ga-PSMA-11 uptake and TBF provides a synergetic effect that reduces the number of false negatives and gives a high accuracy for separation of clinically significant PCa from insignificant findings

Summary

Introduction

Both prostate-specific membrane antigen (PSMA) uptake and tumour blood flow (TBF) correlate with International Society of Urological Pathology (ISUP) Grade Group (GG) and prostate cancer (PCa) aggressiveness. Two studies by Yao et al showed that PSMA expression was associated with a higher cellular folate uptake [12, 13]. This could provide a rationale behind a correlation between PSMA expression and PCa aggressiveness, as folate is necessary for DNA synthesis and cell division, and a higher accessibility may give a proliferative advantage. Whether the enhanced availability of the glutamate neurotransmitter plays any role for PCa remains unanswered

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