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Background: The aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose–positron emission tomography (FDG–PET) for early assessment of chemotherapy response in patients with advanced colorectal cancer. Methods: Dynamic FDG–PET was carried out before and at 2 (n = 50) and 6 months (n = 19) after the start of treatment. Quantitative Patlak analysis [metabolic rate of glucose (MRGlu)] and a simplified method to measure glucose metabolism [standardized uptake value (SUV)] were evaluated. The predictive value of changes in glucose metabolism was assessed with Cox proportional regression analysis. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan–Meier estimates. Results: There was an increase in the rates of death (P = 0.049 for ΔMRGlu PET1–2; P = 0.017 for ΔSUV PET1–2; P = 0.032 for ΔMRGlu PET1–3; P = 0.048 for ΔSUV PET1–3) and progression (P = 0.026 for ΔMRGlu PET1–2; P = 0.035 for ΔSUV PET1–2; P = 0.041 for ΔMRGlu PET1–3; P = 0.081 for ΔSUV PET1–3) associated with worse response as assessed by PET on Cox proportional regression analysis. The OS and PFS analysis showed a significant predictive value at broad ranges of ΔMRGlu and ΔSUV cut-off levels. Conclusion: The degree of chemotherapy-induced changes in tumor glucose metabolism is highly predictive for patient outcome. The use of FDG–PET for therapy monitoring seems clinically feasible since simplified methods (SUV) are sufficiently reliable. [ABSTRACT FROM AUTHOR]