Skeletal metastatic burden as a strong prognostic factor of survival in advanced NSCLC treated with chemo-immunotherapy: An exploratory imaging-based analysis

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Background Metastatic burden is a key determinant of prognosis in advanced solid tumors, yet current RECIST 1.1-based assessment does not fully capture total or site-specific disease extent. Emerging evidence suggests that quantitative imaging-derived metrics may improve prognostic stratification beyond binary metastatic classification. Methods We retrospectively analyzed 52 patients with advanced non-oncogene-addicted lung cancer. Baseline clinical variables and imaging-derived metastatic lesions were assessed across multiple organ sites (lung, lymph nodes, bone, brain, liver and adrenal glands). Lesion area was calculated using an elliptical approximation and summed per organ and globally. Overall survival was evaluated using multivariable Cox regression models with restricted cubic splines to account for non-linear effects. Analyses included: binary metastatic status, continuous site-specific tumor burden, and relative contribution of each site to total metastatic load. Results Median age was 67 years, and bone (53%) and brain (27%) were frequent metastatic sites. Across all analytical levels, bone metastases consistently showed the strongest prognostic impact. Bone involvement was associated with worse overall survival both as a binary variable (HR 2.93, p = 0.020) and as continuous tumor burden (HR 2.82, p = 0.014). A higher relative contribution of bone disease to total tumor burden was also significantly associated with poorer survival (HR 3.01, p = 0.016). Other metastatic sites did not demonstrate consistent statistically significant associations with survival in this exploratory cohort, although these findings should not be interpreted as evidence of absence of prognostic relevance. Histological subtype and age remained independent prognostic factors across models. Conclusion Quantitative assessment of metastatic burden identified skeletal disease as a consistent prognostic signal in this exploratory cohort, supporting further investigation of imaging-derived measures of metastatic burden and spatial disease distribution.

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