Résumé : This study aimed to validate the prognostic value of baseline whole-body metabolically active tumor volume (WB-MATV) and total lesion glycolysis (WB-TLG) measured with 18F-FDG PET/CT in a large cohort of chemorefractory metastatic colorectal cancer (mCRC) patients treated with multikinase inhibitors. The secondary objective of this study was to compare WB-MATV and WB-TLG respective prognostic values with commonly used clinical prognostic factors. Methods: Of 238 patients pooled from 2 successive prospective multicenter trials investigating multikinase inhibitors in chemorefractory mCRC, 224 were considered suitable for analysis. The patients were retrospectively randomly assigned to a development set (n 5 155 patients) or a validation set (n 5 69 patients). WB-MATV and WB-TLG optimal cutoffs for prediction of overall survival (OS) were determined by Contal and O’Quigley’s method. Univariate analyses were performed to assess the prognostic values of WB-MATV and WB-TLG. Multivariate analyses were performed for WB-MATV and WB-TLG along with clinical factors to identify the independent prognostic factors of OS. The prognostic weight for each parameter was obtained from the Cox model. Results: WB-MATV and WB-TLG optimal cutoffs for OS prediction were 100 cm3 and 500 g, respectively. Univariate analyses showed that WB-MATV and WB-TLG parameters were strongly related to outcome in both the development and the validation sets. In the validation set, the median OS was 5.2 mo versus 12.8 mo for high versus low WB-MATV (hazard ratio [HR], 3.12; P, 0.001) and 4.7 mo versus 13.9 mo for high versus low WB-TLG (HR, 3.67; P, 0.001). The multivariate analyses found that both high WB-MATV and high WB-TLG were independent negative prognostic parameters for OS, having the highest prognostic weight among the well-known clinical prognostic factors (HR, 2.46 and 2.23, respectively; P, 0.001). Conclusion: Baseline WB-MATV and WB-TLG parameters were validated as strong prognosticators of outcome in a large cohort of chemorefractory mCRC patients treated with multikinase inhibitors. These parameters were identified as independent prognostic imaging biomarkers with the highest prognostic values among the commonly used clinical factors. These biomarkers should therefore be used to support the optimal therapeutic strategy.