5079 Background: In metastatic clear cell renal cell carcinoma (mccRCC), the number of International Metastatic Database Consortium (IMDC) risk factors plus metastatic sites may identify patients with rapid or slow disease progression in a period of watchful waiting (WW) (median WW of 8.4 vs 22.2 months; Rini et al. Lancet Oncol. 2016). We aimed to validate this and prospectively assess the added value of baseline PET with [18F]FDG and [89Zr]Zr-DFO-girentuximab to predict the WW-period in the multicenter IMaging PAtients for Cancer drug selecTion (IMPACT)-RCC cohort study. (NCT02228954). Methods: Between February 2015 and March 2018, 40 treatment-naïve mccRCC patients with a good (n=13) or intermediate prognosis (n=25) according to IMDC, were enrolled. Following baseline CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab-PET, CT scans (RECIST1.1) were acquired at 2, 4, 6, 9, 12 months and thereafter every 4 months. Primary endpoint was time to radiological and/or clinical disease progression, requiring systemic treatment. Patients were assigned to a favorable (<2 IMDC risk factors and <3 metastatic sites) or unfavorable for WW-group (all others; Rini et al). Maximum standardized uptake values (SUVmax) were measured in PET-positive lesions measuring ≥10mm, or 15mm in lymph nodes. High and low-uptake groups were defined based on median geometric mean (gm) SUVmax across patients. A one-sided test was used to validate observations by Rini et al; other tests were two-sided. Results: The median WW-period was 9.3 months in the unfavorable WW-group (n=19) vs 20.4 months in the favorable WW-group (n=21) (HR 1.89 95%CI 0.94-3.89; p=0.037), confirming observations of Rini et al. Patients with high [18F]FDG uptake had a median WW-period of 8.5 months compared to 25.2 months in the low-uptake group (HR 4.08 95%CI 1.89-9.28; p=0.0002). Patients with high [89Zr]Zr-DFO-girentuximab uptake had a median WW-period of 10.7 versus 16.4 months in the low-uptake group (HR 1.37; 95%CI 0.69-2.76; p=0.37). [18F]FDG uptake groups improved a Cox-model for WW based on the prognostic groups of Rini et al (p=0.0015); [89Zr]Zr-DFO-girentuximab did not (p=0.98). Conclusions: The IMPACT-RCC study validated the observations by Rini et al. and shows that adding baseline [18F]FDG PET further improves the prediction of the duration of the WW-period in mccRCC patients. Clinical trial information: NCT02228954 .
GFOD1 and peejar are promising markers for clear-cell renal cell carcinoma disease progression
