Pathological and radiological features of false-positive lesions on [68Ga]Ga-PSMA-11 PET/CT in primary staging of prostate cancer: a radio-pathology matching analysis

Purpose The aim of this study was to investigate the radiological and pathological characteristics of false-positive lesions on [Ga-68]Ga-PSMA-11 PET/CT during the primary staging of prostate cancer. Methods This study retrospectively analyzed 216 prostate cancer patients who had [Ga-68]Ga-PSMA-11 PET/CT before radical prostatectomy. False-positive lesion was defined as suspicious lesion with PRIMARY score >= 3 on PET/CT but benign on whole-mount pathology. To analyze the radiological and pathological features of false-positive lesions, no-uptake areas on PSMA PET/CT with benign pathology on the whole-mount specimen were randomly delineated and defined as true-negative lesions. The pathological features of false-positive and true-negative lesions were compared using Fisher's exact test. The differences of SUVmax and SUVmean between false-positive and true-positive lesions were determined and compared using the Wilcoxon matched-pairs signed-ranks test. In addition, PSMA expression in false-positive lesions was assessed by immunohistochemistry. Results A total of 36 false-positive lesions were identified on [Ga-68]Ga-PSMA-11 PET/CT: 25 (69.44%) were simple atrophy with cyst formation, 7 (19.44%) were prostatic nodular hyperplasia, 3 (8.33%) were inflammation and 1 (2.78%) was normal glands. A comparable number of 36 true-negative lesions were delineated: 21 (58.33%) were normal glands, 8 (22.22%) were simple atrophy with cyst formation, 6 (16.67%) were prostatic nodular hyperplasia, and 1 (2.78%) were inflammation. The Fisher's exact test revealed a statistically significant difference in the prevalence of simple atrophy with cyst formation between false-positive and true-negative lesions (69.44% vs. 22.22%; P < 0.001). Differences in SUVmax and SUVmean between false-positive and true-positive lesions were also statistically significant (both P < 0.001). PSMA expression in false-positive lesions was confirmed via immunohistochemistry. Conclusion This study determined that simple atrophy with cyst formation is a distinctive pathological feature of false-positive lesions on [Ga-68]Ga-PSMA-11 PET/CT. This observation is likely attributable to the elevated PSMA expression in simple atrophy with cyst formation, as confirmed by histological analysis. Additionally, false-positive lesions were found to have significantly lower SUV compared to true-positive lesions.