Equivocal bone lesions on PSMA PET/CT: systematic review and meta-analysis on their prevalence and malignancy rate

Purpose Prostate-specific membrane antigen (PSMA) PET/CT has an established reliable diagnostic performance for detecting metastases in prostate cancer. However, there are increasing instances of scans demonstrating equivocal bone lesions, with non-specific uptake and without a definite benign or malignant CT correlate. To date, the prevalence, malignancy rate, and relationship with radioligand type ([ 18 F] PSMA-1007 vs. others ([ 68 Ga]Ga-PSMA-11 and [ 18 F] DCFPyL) for these equivocal lesions have not been extensively established. Methods A systematic review and meta-analysis was conducted on equivocal bone lesions. Pubmed and EMBASE were searched up to December 11, 2023. Quality of the studies was evaluated using QUADAS-2. The following proportions were pooled using random-effects model: (1) prevalence of equivocal bone lesions (i.e., number of patients with one or more equivocal bone lesions/number of patients with PSMA PET/CT) and (2) their malignancy rates (i.e., number of metastases/number of equivocal bone lesions). Subgroup analyses based on radioligand type, clinical setting, and definition of equivocal bone lesion were performed. Results Twenty-five studies (4484 patients) were included. Pooled prevalence of equivocal bone lesions was 20% (95%CI, 12–31%). [ 18 F]PSMA-1007 was associated with a greater prevalence of equivocal lesions compared with other radioligands: 36% (95%CI 26–48%) vs. 8% (95%CI, 4–14%), respectively, p < 0.01. Pooled malignancy rate of equivocal bone lesions was 14% (95%CI, 7–25%). [ 18 F]PSMA-1007 was associated with a lower malignancy rate compared to other radioligands: 8% (95%CI, 3–19%) vs. 29% (95%CI, 17–44%), respectively, p = 0.01. There were no signficant difference in prevalence or malignancy rate between subgroups stratified to clinical setting or definition of equivocal bone lesions ( p = 0.32–0.60). Conclusions Equivocal bone lesions are often encountered on PSMA PET/CT but exihibit a low malignancy rate. Compared to other radioligands, [ 18 F]PSMA-1007 requires special attention as it is associated with a higher frequency and lower rate of metastasis.