Presentation Authors: Mark Ball*, Rabindra Gautam, Christopher Ricketts, Cathy Vocke, Laura Schmidt, Maria Merino, Marston Linehan, Bethesda, MD
Introduction: Genetically-defined renal cell carcinomas (RCC), including those associated with von Hippel-Lindau (VHL; clear cell RCC, VHL gene), Hereditary Papillary Renal Carcinoma (HPRC, Type 1 Papillary RCC, MET gene) Birt-Hogg-DubÃ© (BHD, chromophobe RCC, FLCN gene), Hereditary Leiomyomatosis and Renal Cell Carcinomas (HLRCC; Type 2 Papillary RCC, FH gene), Succinate Dehydrogenase RCC (SDHRCC, eosinophilic RCC, SDHB gene) and BAP1 RCC (clear cell, BAP1 gene) are managed at our institution based on genotype. Active surveillance (AS) until 3 cm is employed for VHL, FLCN, and MET-altered tumors, while immediate surgical resection is used for FH and SDHB tumors. BAP1-associated tumors are a more recently described entity that is associated with high grade, high stage RCC, and while we do not routinely perform AS for these lesions, some patients have undergone a period of AS prior to being diagnosed with BAP1 alterations. We sought to characterize the growth of genetically-defined tumors during AS.
Methods: Patients managed on prospective National Cancer Institute Institutional Review-approved protocols with germline alterations in VHL, FLCN, MET, and BAP1 and multiple cross-sectional imaging studies were identified. Renal tumor size was measured as the largest single-dimension diameter on imaging. Growth rates were calculated using linear regression. Kruskal-Wallis test was used to compare growth rates among genetically-defined groups.
Results: A total of 340 with genetically-defined tumors were identified, including 240 VHL-deficient, 71 FLCN-deficient, 27 MET-amplified, and 2 BAP1-deficient. There were significant differences in growth rates by genetic alteration (Figure 1). BAP1 had the fastest median growth rate (.7 cm/year, interquartile range [IQR] .6-.9), followed by VHL (0.4, IQR .3-.6), FLCN (0.09, IQR .02-.2), and MET (0.08, IQR .04-.2), p < 0.001.
Conclusions: In a cohort of genetically defined tumors, there were statistically and clinically different growth rates that varied by genetic alteration. These findings may have broad applicability for the management of both hereditary and non-hereditary genetically defined renal tumors regarding AS imaging schedules and triggers for intervention.