301 Background: The purpose of this study was to investigate sequential FDG PET-CT as a correlative marker in metastatic clear cell renal cancer (mRCC) patients treated with first line sunitinib. Three sequential scans were performed to determine the importance of the timing of scans. METHODS Forty-four untreated mRCC patients with MSKCC intermediate risk and poor risk disease were enrolled into a prospective study. FDG PET-CT scans were performed before (n=44), after 4 weeks (n=43) and 16 weeks (n=40) of sunitinib given at standard doses as the translational aspect of this trial ( NCT01024205 ). The primary endpoint was to determine whether 18F-FDG PET-CT response (defined as a 20% reduction in SUVmax) correlated with survival. RESULTS Forty-three (98%) patients had FDG PET-CT avid lesions at diagnosis (median SUVmax 6.8 range: <2.5-18.4). In multivariate analysis a high SUVmax and increased number of PET positive lesions correlated with worse overall survival (OS) (HR: 3.30 (95%CI: 1.36-8.45) and 3.67 (95%CI: 1.43-9.39) respectively[p<0.05]). After 4 weeks of sunitinib, metabolic responses occurred in 24 (57%) patients at 4 weeks, but this did not correlate with progression-free survival [PFS] (HR for responders= 0.87 [95%CI: 0.40-1.99]) or OS (HR for responders= 0.80 [95%CI: 0.34-1.85]) (p>0.05 for both). After 16 weeks of treatment, FDG PET-CT demonstrated disease progression in 28% (n=12) patients. At this time point, the FDG PET-CT correlated with both OS and PFS (HR 5.96 [95%CI: 2.43-19.02] and HR 12.13 [95%CI: 3.72-46.45] respectively). CONCLUSIONS Baseline FDG PET prior to sunitinib yields prognostically significant data. FDG PET response at 16 weeks predicts outcome, which is not the case at 4 weeks. This subsets of patients with a poor prognosis at 16 weeks could be investigated within the context of a randomized clinical trial. [Table: see text].