142 Chapter 8 FUTURE PERSPECTIVES Position of molecular imaging in mccRCC In the IMPACT-RCC study, both [18F]FDG PET/CT and [89Zr]Zr-DFO-girentuximab PET/CT have shown their additional value in detecting more metastases compared to standard CT. While the number or lesions which could be detected increased, the potential prognostic value of this finding has not yet been determined. Therefore, we cannot elaborate on the role of either techniques as diagnostic tool at this point. The heterogeneous tracer-uptake between lesions is suggestive of differences in phenotype of the individual tumor lesions. Further investigation of the individual lesion could be of interest to choose local treatment of a metastasis over systemic treatment based on the biologic phenotype. This could ultimately delay the start of systemic treatment. [18F]FDG PET/CT In agreement with previous studies reporting a prognostic value of [18F]FDG PET/CT in cancer patients, we showed that [18F]FDG PET/CT could discriminate between indolent and aggressive disease in a subset of newly diagnosed patients with mccRCC. Subsequently, early knowledge on the total tumor metabolism could be essential to steer the initial treatment strategy in patients with mccRCC. Patients considered for a period of WW could be provided more information regarding the duration of this WW-period. Our data have shown that WW could still be considered a valuable treatment option in selected patients, even with the current alterations in the 1st line treatment options for patients with mccRCC. While our data should be externally validated, we do not expect more prospective clinical trials to study WW in light of the developments in 1st line treatment options (e.g., combination targeted and immunotherapy. Nevertheless, we have shown the value of WW as initial treatment option in a subset of mccRCC patients, who can be better identified with the help of [18F]FDG PET/CT. Since the response to first line (combination) immunotherapy is less prominent in patients with a good prognosis according to IMDC criteria, those patients should be considered for WW. We recommend the use of [18F]FDG PET/CT in those patients to improve the selection of patients with a predicted long period of WW. [89Zr]Zr-DFO-girentuximab PET/CT The prognostic value of CAIX expression has been most studied for hypoxia-induced CAIX, compared to the VHL-mutation-induced CAIX. Studies reporting a prognostic value of CAIX in ccRCC, use different cut-offs for high or low CAIX-expression and do not consistently report the presence of VHL-mutation13,14. In the IMPACT-RCC study, we performed [89Zr]Zr-girentuximab PET/CT to study whether this technique could predict WW time in patients with recently diagnosed mccRCC and showed inter-and intra- patient heterogeneity. In the absence of histologic confirmation, we cannot elaborate on the grounds of this heterogeneity. This could be the result of variable CAIX-expression or local differences in e.g., local vasculature affecting perfusion of the tracer. Future studies should analyze [89Zr]Zr-DFO-girentuximab accumulation and CAIX expression on a lesion level to determine the origin of the interlesional heterogeneity. Additionally, the assessment of the prognostic value of [89Zr]Zr-DFO-girentuximab on a lesion level would complement our data on [89Zr]Zr-DFO-girentuximab on a patient level. Based on our data, there
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