44 Chapter 3 ABSTRACT Purpose Watchful waiting (WW) can be considered for patients with metastatic clear cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with <2 International Metastatic RCC Database Consortium criteria and ≤2 metastatic sites (referred to as watch and wait (“W&W”)-criteria). The IMPACT-RCC study objective was to assess the predictive value of [18F]FDG- and [89Zr]Zr-DFO-girentuximab-PET/CT for WW-duration in patients with mccRCC. Patients and methods Between February 2015 and March 2018, 48 patients were enrolled, including 40 evaluable patients with good (n=14) and intermediate (n=26) prognosis. Baseline ceCT, [18F]FDG and [89Zr]Zr-DFOgirentuximab-PET/CT were performed. Primary endpoint was the time to disease progression warranting systemic treatment. Maximum standardized uptake values (SUVmax) were measured using lesions on CT-images co-registered to PET/CT. High and low-uptake groups were defined based on median geometric mean SUVmax of RECIST-measurable lesions across patients. Results The median WW-time was 16.1 months (95%CI 9.0-31.7). The median WW-period was shorter in patients with high [18F]FDG-tumor-uptake than those with low-uptake (9.0 versus 36.2 months, HR 5.6;95%CI 2.4-14.7; p<0.001). Patients with high [89Zr]Zr-DFO-girentuximab-tumor-uptake had a median WW-period of 9.3 months versus 21.3 months with low-uptake (HR 1.7;95%CI 0.93.3; p=0.13). Patients with “W&W-criteria” had a longer median WW-period of 21.3 compared with patients without: 9.3 months (HR 1.9;95%CI 0.9-3.9; pone-sided=0.034). Adding [ 18F]FDG-uptake to the “W&W-criteria” improved the prediction of WW-duration (p<0.001); whereas [89Zr]ZrDFO-girentuximab did not (p=0.53). Conclusions In patients with good or intermediate risk mccRCC, low [18F]FDG-uptake is associated with prolonged WW. This study shows the predictive value of the “W&W-criteria” for WW duration and shows the potential of [18F]FDG-PET/CT to further improve this.