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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Longitudinal Evaluation of Clear-cell Renal Cell Carcinoma in von Hippel-Lindau Disease
W Marston Linehan1, Cathy Anne Pinto2, Yanfang Liu2
1National Cancer Institute, Bethesda, MD, USA.
Background And Objective:
An understanding the natural history of von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) is critical to the development of optimal clinical management approaches and interpretation of trial results for comparable populations and endpoints. Our aim was to describe the natural progression of disease in patients with VHL RCC.
Methods:
This was a natural history study involving 244 patients with VHL with ≥10-mm renal tumor(s) who were evaluated and managed at the US National Cancer Institute between 2004 and 2020. We analyzed radiographic outcomes, renal surgeries, metastasis, sequalae of surgery, including chronic kidney disease (CKD), and mortality. Radiographic outcomes were assessed according to Response Evaluation Criteria in Solid Tumours v1.1. The primary analyses were descriptive in nature.
Key Findings And Limitations:
Among 178 patients with at least three serial tumor assessments and up to 5 yr of follow-up, the rate of spontaneous tumor regression (≥30% decrease) was 1.8% (95% confidence interval [CI] 0.4-5.2%). The probability of not having disease progression in the presence of competing risks at 5 yr was 37% (95% CI 30-44%). During follow-up, 186/244 patients had one or more renal surgeries, and 108/244 had two or more. RCC metastasis was reported for 12 patients. Among patients who underwent surgery, 41% developed postprocedure CKD. Potential limitations include selection bias and misclassification of outcomes.
Conclusions And Clinical Implications:
Our study demonstrates that RCC is a significant burden for VHL patients, with high rates of disease progression, surgery, and metastasis development, even in a closely monitored, multidisciplinary clinical environment, and identifies CKD as an underappreciated aspect of VHL. These findings can provide a context for the antitumor activity of new treatments for RCC.
