Impact of anatomic location of bone metastases on prognosis in mCRPC

Abstract Patients with metastatic castrate-resistant prostate cancer (mCRPC) can develop bone lesions throughout their skeleton. Previously the distribution of lesions and its impact on survival has been explored using 99m Tc-methylene diphosphonate planar scintigraphy (bone scans), but not on the more sensitive 18 F-NaF PET/CT. We found that several regional SUV metrics were more prognostic of progression-free survival (PFS) than their whole-body counterparts. Background Background: Whole-body assessments of 18 F-NaF PET/CT provide promising quantitative imaging biomarkers of metastatic castrate-resistant prostate cancer (mCRPC). This study investigates whether the distribution of metastases across anatomic regions is prognostic of progression-free survival (PFS). Methods Fifty-four mCRPC patients with osseous metastases received baseline NaF PET/CTs. Patients received chemotherapy (N=16) or androgen-receptor (AR) pathway inhibitors (N=38). Semi-automated QTBI analysis extracted imaging metrics for the whole-, axial-, and appendicular-skeleton and 11 skeletal regions. Five PET metrics were extracted for each region: number of lesions (N L ), maximum uptake (SUV max ), average uptake (SUV mean ), sum of uptake (SUV total ), and diseased fraction of the skeleton (volume fraction, VF). Progression included clinical, biochemical, or radiographic. Univariate and multivariate Cox proportional-hazard regression analyses were performed between imaging metrics and PFS and were assessed according to their hazard ratios (HR) and concordance (C) indices. Results The strongest univariate models of PFS were pelvic N L and SUV max with HR=1.80 (N L : false discovery rate adjusted p-value=0.003, SUV max : adjusted p-value=0.005). Three other region-specific metrics (axial N L : HR=1.59, adjusted p-value=0.02, axial SUV max : HR=1.61, adjusted p-value=0.02, and skull SUV max : HR=1.58, adjusted p-value=0.04) 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.