Impact of Anatomic Location of Bone Metastases on Prognosis in Metastatic Castration-Resistant Prostate Cancer

Patients with metastatic castration-resistant prostate cancer can develop bone lesions throughout their skeleton. Previously the distribution of lesions and its impact on survival have been explored using Tc-99m-methylene diphosphonate planar scintigraphy (bone scans), but not using the more sensitive F-18-NaF positron emission tomography/computed tomography. Several regional standard uptake values metrics were more prognostic of progression-free survival than their whole-body counterparts. Background: Whole-body assessments of F-18-NaF positron emission tomography (PET)/computed tomography (CT) provide promising quantitative imaging biomarkers of metastatic castration-resistant prostate cancer (mCRPC). This study investigated whether the distribution of metastases across anatomic regions is prognostic of progression-free survival. Patients and Methods: Fifty-four mCRPC patients with osseous metastases received baseline NaF PET/CT. Patients received chemotherapy (n = 16) or androgen receptor pathway inhibitors (n = 38). Semiautomated analysis using Quantitative Total Bone Imaging software extracted imaging metrics for the whole, axial, and appendicular skeleton as well as 11 skeletal regions. Five PET metrics were extracted for each region: number of lesions (N-L), standardized maximum uptake value (SUVmax), average uptake (SUVmean), sum of uptake (SUVtotal), and diseased fraction of the skeleton (volume fraction). Progression included that discovered by clinical, biochemical, or radiographic means. Univariate and multivariate Cox proportional hazard regression analyses were performed between imaging metrics and progression-free survival, and were assessed according to their hazard ratios (HR) and concordance (C)-indices. Results: The strongest univariate models of progression-free survival were pelvic N-L and SUVmax with HR = 1.80 (N-L: false discovery rate adjusted P = .001, SUVmax: adjusted P = .001). Three other region-specific metrics (axial N-L: HR = 1.59, adjusted P = .02, axial SUVmax: HR = 1.61, adjusted P = .02, and skull SUVmax: HR = 1.58, adjusted P = .04) were found to be stronger prognosticators relative to their whole-body counterparts. Multivariate model including region-specific metrics (C-index = 0.727) outperformed that of whole-body metrics (C-index = 0.705). The best performance was obtained when region-specific and whole-body metrics were included (C-index = 0.742). Conclusion: Quantitative characterization of metastatic spread by anatomic location on NaF PET/CT enhances potential prognostication. Further study is warranted to optimize the prognostic and predictive value of NaF PET/CT in mCRPC patients. (C) 2019 Elsevier Inc. All rights reserved.