Quantitative Assessment of Early [¹⁸F]Sodium Fluoride Positron Emission Tomography/Computed Tomography Response to Treatment in Men With Metastatic Prostate Cancer to Bone

Abstract

Purpose [F]Sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) is a promising radiotracer for quantitative assessment of bone metastases. This study assesses changes in early NaF PET/CT response measures in metastatic prostate cancer for correlation to clinical outcomes. Patients and Methods Fifty-six patients with metastatic castration-resistant prostate cancer (mCRPC) with osseous metastases had NaF PET/CT scans performed at baseline and after three cycles of chemotherapy (n = 16) or androgen receptor pathway inhibitors (n = 40). A novel technology, Quantitative Total Bone Imaging, was used for analysis. Global imaging metrics, including maximum standardized uptake value (SUV) and total functional burden (SUV), were extracted from composite lesion-level statistics for each patient and tracked throughout treatment. Progression-free survival (PFS) was calculated as a composite end point of progressive events using conventional imaging and/or physician discretion of clinical benefit; NaF imaging was not used for clinical evaluation. Cox proportional hazards regression analyses were conducted between imaging metrics and PFS. Results Functional burden (SUV) assessed midtreatment was the strongest univariable PFS predictor (hazard ratio, 1.97; 95% CI, 1.44 to 2.71; P < .001). Classification of patients based on changes in functional burden showed stronger correlation to PFS than did the change in number of lesions. Various global imaging metrics outperformed baseline clinical markers in predicting outcome, including SUV and SUV. No differences in imaging response or PFS correlates were found for different treatment cohorts. Conclusion Quantitative total bone imaging enables comprehensive disease quantification on NaF PET/CT imaging, showing strong correlation to clinical outcomes. Total functional burden assessed after three cycles of hormonal therapy or chemotherapy was predictive of PFS for men with mCRPC. This supports ongoing development of NaF PET/CT-based imaging biomarkers in mCRPC to bone.

Loss of dihydrotestosterone-inactivation activity promotes prostate cancer castration resistance detectable by functional imaging

“…tumors that are spatially and temporally separated. No such imaging modalities are currently employed in standard clinical practice, which are usually instead employed to determine tumor size and/or localization (27,28).…”

Association Between New Unconfirmed Bone Lesions and Outcomes in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide

“…Uptake of F18-labeled fluordeoxyglucose allows more direct visualization of the tumor, but interpretation may be confounded by the presence of osteoblastic remodeling within the responding tumor microenvironment. 16 Additional tumor-specific positron emission tomography probes, such as prostate-specific membrane antigen, choline, fluciclovine, or dihydrotestosterone, 17,18 may provide useful discrimination in this clinical setting, where bone imaging results are disconnected from PSA, soft-tissue imaging, and patient symptoms, provided that proper analytic and clinical validation studies are performed in this mCRPC setting. Our work highlights this unmet need for functional bone imaging over time to more fully assess patient benefits.…”

Functional and Hybrid Imaging of Bone Metastases

“…The measurement of total skeletal metastatic burden is possible with 18F‐fluoride PET as there is generally high contrast between metastases and normal bone. In prostate cancer, a number of studies have shown that global quantitative metrics can predict treatment response and progression‐free survival or overall survival …”