Growth Rates of Genetically Defined Renal Tumors: Implications for Active Surveillance and Intervention.

Abstract

Published series of growth rates of renal tumors on active surveillance largely consist of tumors without pathologic or genetic data. Growth kinetics of genetically defined renal tumors are not well known. Here, we evaluate the growth of genetically defined renal tumors and their association with patient clinical and genetic characteristics. We evaluated patients with an inherited kidney cancer susceptibility syndrome as a result of a pathologic germline alteration of <i>VHL, MET, FLCN,</i> or <i>BAP1</i> with at least 1 solid renal mass managed with active surveillance at our institution. Tumor growth rates (GR) were calculated and patients were stratified by genetic alteration and other clinical and genetic factors to analyze differences in growth rates using linear regression and comparative statistics. A total of 292 patients with 435 genetically defined tumors were identified, including 286 <i>VHL</i>-deficient, 91 <i>FLCN</i>-deficient, 52 <i>MET</i>-activated, and 6 <i>BAP1</i>-deficient tumors. There were significant differences in GRs when stratified by genetic alteration. <i>BAP1</i>-deficient tumors had the fastest median GR (0.6 cm/y; interquartile range [IQR], 0.57-0.68 cm/y), followed by <i>VHL</i>-deficient tumors (GR, 0.37 cm/y; IQR, 0.25-0.57 cm/y), <i>FLCN</i>-deficient tumors (GR, 0.10 cm/y; IQR, 0.04-0.24 cm/y), and tumors with <i>MET</i> activation (GR, 0.15 cm/y; IQR, 0.053-0.32 cm/y; <i>P</i> < .001). Tumors from the same patient had similar GRs. Younger age was independently associated with higher GR (<i>P</i> = .005). In a cohort of genetically defined tumors, tumor growth rates varied in a clinically and statistically different manner according to genetic subtype. Rapid growth of <i>BAP1</i>-deficient tumors indicates that these patients should be managed with caution. The faster growth of tumors in younger patients may support more frequent imaging, whereas the slower growth of other tumors may support extended surveillance beyond annual imaging in some instances.