Factors Predicting Metastatic Disease in ⁶⁸Ga-PSMA-11 PET–Positive Osseous Lesions in Prostate Cancer

Abstract

Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen (PSMA) uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on ⁶⁸Ga-PSMA-11 PET. The purpose of this study was to evaluate the diagnostic accuracy of ⁶⁸Ga-PSMA-11 PET for osseous prostate cancer metastases and improve bone uptake interpretation using semiquantitative metrics. Methods: Fifty-six prostate cancer patients (18 before prostatectomy and 38 with biochemical recurrence) who underwent ⁶⁸Ga-PSMA-11 PET/MRI or PET/CT examinations with osseous PSMA-ligand uptake were included in the study. Medical records were reviewed retrospectively by board-certified nuclear radiologists to determine true or false positivity based on a composite endpoint. For each avid osseous lesion, we measured biologic volume; size; PSMA Reporting and Data System (RADS) rating; SUV_max; and ratio of lesion SUV_max to liver, blood pool, and background bone SUV_max. Differences between benign and malignant lesions were evaluated for statistical significance, and cutoffs for these parameters were determined to maximize diagnostic accuracy. Results: Among 56 participants, 13 (22.8%) had false-positive osseous ⁶⁸Ga-PSMA-11 findings and 43 (76.8%) had true-positive osseous ⁶⁸Ga-PSMA-11 findings. Twenty-two patients (39%) had 1 osseous lesion, 18 (32%) had 2–4 lesions, and 16 (29%) had 5 or more lesions. Cutoffs resulting in statistically significant (P < 0.005) differences between benign and malignant lesions were a PSMA RADS rating of at least 4, an SUV_max of at least 4.1, and SUV_max ratios of at least 2.11 for lesion to blood pool, at least 0.55 for lesion to liver, and at least 4.4 for lesion to bone. These measurements corresponded to a lesion-based ⁶⁸Ga-PSMA-11 PET lesion detection rate of 80%, 93%, 89%, 21%, and 89%, respectively, for malignancy, and a specificity of 73%, 73%, 73%, 93%, and 60%, respectively. Conclusion: PSMA RADS rating, SUV_max, and SUV_max ratio for lesion to blood pool can help differentiate benign from malignant lesions on ⁶⁸Ga-PSMA-11 PET. An SUV_max ratio of more than 2.2 for lesion to blood pool is a reasonable parameter to support image interpretation and presented a superior lesion detection rate and specificity when compared with visual interpretation by PSMA RADS. These parameters hold clinical value by improving diagnostic accuracy for metastatic prostate cancer on ⁶⁸Ga-PSMA-11 PET/MRI and PET/CT.