Bone Metastasis Distribution Matters: Prognostic Effect of the Axial‐to‐Peripheral Ratio in Metastatic Hormone‐Sensitive Prostate Cancer

ABSTRACT Background Bone metastases represent the dominant pattern of spread in metastatic hormone‐sensitive prostate cancer (mHSPC). Current prognostic classifications mainly rely on metastatic burden defined by lesion number or volume, while the prognostic significance of anatomical distribution within the skeleton remains insufficiently explored. This study aimed to investigate the prognostic impact of axial and peripheral bone metastasis patterns and to evaluate the clinical relevance of the axial‐to‐peripheral bone metastasis ratio in mHSPC. Methods This multicenter retrospective study included 209 patients with radiologically confirmed bone‐metastatic mHSPC treated between January 2018 and November 2025. Bone metastases were classified as axial, peripheral, or combined according to anatomical location using conventional imaging and PSMA PET/CT. Metastatic burden was quantified separately for axial and peripheral compartments, and an axial‐to‐peripheral bone metastasis ratio was calculated. Results Axial skeletal involvement was present in 94.7% of patients, while 81.3% exhibited peripheral metastases. Patients with combined axial and peripheral involvement demonstrated inferior survival compared with those with isolated axial disease. The axial‐to‐peripheral metastasis ratio emerged as a significant prognostic factor (log‐rank p = 0.004). Patients with a balanced distribution (ratio = 1) had markedly worse survival (median OS 15.0 months) compared with those with axial‐predominant disease (ratio = 2; median OS 40.0 months). Increasing axial metastatic burden was associated with a stepwise increase in mortality risk. Conclusions The axial‐to‐peripheral bone metastasis ratio represents a novel and clinically applicable prognostic marker in mHSPC.