Improved Accuracy and Reliability of PRIMARY Scoring Using Delayed [68Ga] Ga-PSMA PET/CT Imaging.

Objectives: Delayed [⁶⁸Ga]Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) images show reduced PSMA uptake in benign lesions and increased PSMA uptake in malignant lesions. This study investigated the efficacy of PRIMARY scoring on [⁶⁸Ga]Ga-PSMA PET/CT images at standard versus delayed time points and assessed the potential added value of delayed imaging in PRIMARY scoring.

Methods: A total of 140 patients with biopsy results of International Society of Urological Pathology grade groups (ISUP) 1-2 who had standard (median 60 min) and delayed images (median 138 min) with [⁶⁸Ga]Ga-PSMA PET/CT before radical prostatectomy were included. Results were confirmed in pathological reports. For diagnostic parameters, two experienced nuclear medicine physicians, who were blinded to clinical data, independently reviewed the images, and a third physician provided consensus in cases of disagreement. PRIMARY scoring was also conducted by four nuclear medicine physicians on both images, with a 1-month interval between assessments for intraobserver agreement analyses.

Results: The percentage of lesions scored as 1-2 in PRIMARY scoring decreased from 29% to 10% in delayed images compared with standard images, whereas lesions scored as 3-5 increased from 71% to 90%. Additionally, agreement between two experienced nuclear medicine physicians regarding scoring was 66% for standard imaging and 77% for delayed imaging. The number of patients with PRIMARY score 5 increased from 31 to 46 in delayed imaging. All patients were confirmed to have clinically significant prostate cancer (csPCa). Furthermore, no csPCa of ISUP grade 3 or higher was detected in patients with a delayed PRIMARY score (dPRIMARY). The sensitivity of standard PRIMARY scoring was 71%, which increased to 92% with dPRIMARY scoring, with a consistent positive predictive value of 87% for both. Intraobserver agreement Cohen's kappa values for all observers were higher for delayed images than for standard images. Inter-observer agreement, assessed by Fleiss kappa, was 0.47 and 0.52 for standard images in rounds 1 and 2, respectively, and 0.61 and 0.72 for delayed images, respectively.

Conclusion: Decreased background activity and increased primary tumor uptake in delayed images improved differentiation between primary tumors and benign lesions, leading to better primary tumor identification. Enhanced reliability was also observed in both intraobserver and interobserver assessments of delayed images.