Accuracy of [68Ga]Ga-RM2-PET/CT for diagnosis of primary prostate cancer compared to histopathology

Abstract

Introduction: Prostate cancer (PCa) often shows an overexpression of the gastrin-releasing peptide receptor (GRPr). Therefore, GRPr is a possible theragnostic target. An interesting antagonist GRPr-ligand is RM2 or BAY86-7548. This study examines the accuracy of positron emission tomography (PET) with [⁶⁸Ga]Ga-RM2 for diagnostic imaging of primary PCa (pPCa) compared to histopathology in patients undergoing radical prostatectomy (RP).

Methods: [⁶⁸Ga]Ga-RM2-PET examinations were performed in 15 patients before RP. All prostate specimens were histopathologically examined based on predefined spatial octants. Each prostate volume on PET was subdivided into octants, which were correlated to histopathology and evaluated according to presence of tumor by two experienced examiners. Additionally, PET data was evaluated by volume of interest (VOI) analyses in terms of maximum standardized uptake value (SUVmax) and normalized SUVmax relative to background activity (rSUVmax). Receiver operating characteristic (ROC) curves for SUVmax and rSUVmax were calculated.

Results: At least one focus of increased [⁶⁸Ga]Ga-RM2 uptake corresponding to a tumor manifestation on histology was found in 14 of 15 patients (93%). Spatial concordance of visual PET readings with histopathology was very variable. Intraindividual agreement reached from ≤2 octants in three, 3-5 octants in six to ≥6 octants in six patients, resulting in a relatively low correlation of visual PET readings with histopathology (accuracy = 0.63; p = 0.0018). Lesion-based analysis found a sensitivity of 69% and a positive predictive value of 73%. Concordantly, the octant-based ROC curves for SUVmax and rSUVmax indicated a relatively low diagnostic performance (area under the curve of 0.59 and 0.61, respectively).

Conclusions: [⁶⁸Ga]Ga-RM2-PET shows only a relatively low diagnostic accuracy for pPCa compared to histopathology on an octant basis, which may be explained to some extent by methodological weaknesses. Further studies need to explore, whether the observed high interindividual variability of agreement between [⁶⁸Ga]Ga-RM2-PET and histopathology can be explained by different tumor biologies or other coincident prostatic pathologies.

Keywords: Bombesin; GRPR; Histopathology; PET/CT; Prostate cancer; [(68)Ga]-RM2.