Objective:To develop and validate a radiomics prognostic scoring system (RPSS) for prediction of progression-free survival (PFS) in patients with stage Ⅳ non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stage Ⅳ NSCLC patients treated with platinum-based chemotherapy were included for model construction and validation (Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography (CT) images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method (LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts (All P＜0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status (PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95％ confidence interval (95％ CI):0.765-0.779],internal validation (C-index:0.738,95％ CI:0.730-0.746),external validation (C-index:0.750,95％ CI:0.734-0.765),and mutation validation (C-index:0.739,95％ CI:0.720-0.758).Decision curve analysis revealed that RPSS significandy outperformed the clinicopathologic-based model in terms of clinical usefulness (All P＜0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniendy used to achieve individualized prediction of PFS probability for stage Ⅳ NSCLC patients treated with platinum-based chemotherapy,which holds promise for guiding personalized pre-therapy of stage Ⅳ NSCLC.