Longitudinal Evaluation of Clear-cell Renal Cell Carcinoma in von Hippel-Lindau Disease

IF 25.3 1区医学 Q1 UROLOGY & NEPHROLOGY

European urology Pub Date : 2025-04-23 DOI:10.1016/j.eururo.2025.03.002

W. Marston Linehan, Cathy Anne Pinto, Yanfang Liu, Kristin Choo, Rabindra Gautam, Claire Fox, Ananya Roy, Mengying Li, Rafia Bosan, Deborah Nielsen, Beth Ryan, Zoe Blake, Krista Reynolds, Alexis Rompre-Brodeur, Peter A. Pinto, Cathy Vocke, Sandeep Gurram, Mark W. Ball, Rodolfo Perini, Ramaprasad Srinivasan

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Abstract

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.

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冯-希佩尔-林道氏病中透明细胞肾细胞癌的纵向评估

背景和目的了解与冯-希佩尔-林道（Von Hippel-Lindau，VHL）病相关的肾细胞癌（RCC）的自然病史对于制定最佳临床管理方法以及解释可比人群和终点的试验结果至关重要。我们的目的是描述VHL RCC患者疾病的自然进展情况。方法这是一项自然史研究，涉及2004年至2020年间在美国国立癌症研究所接受评估和管理的244名肾肿瘤≥10毫米的VHL患者。我们分析了放射学结果、肾脏手术、转移、手术后遗症（包括慢性肾病（CKD））和死亡率。放射学结果根据《实体瘤反应评估标准》（Response Evaluation Criteria in Solid Tumours v1.1）进行评估。主要研究结果和局限性在178名至少接受过三次连续肿瘤评估、随访时间长达5年的患者中，肿瘤自发消退率（下降≥30%）为1.8%（95%置信区间[CI] 0.4-5.2%）。在存在竞争风险的情况下，5年后疾病不再恶化的概率为37%（95% CI 30-44%）。在随访期间，186/244 名患者接受了一次或多次肾脏手术，108/244 名患者接受了两次或两次以上手术。据报告，12 名患者发生了 RCC 转移。在接受手术的患者中，41%在术后出现了慢性肾功能衰竭。我们的研究表明，RCC是VHL患者的一个重大负担，即使在严密监测的多学科临床环境中，疾病进展、手术和转移的发生率也很高。这些发现可为RCC新疗法的抗肿瘤活性提供一个背景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European urology 医学-泌尿学与肾脏学

CiteScore

43.00

自引率

2.60%

发文量

1753

审稿时长

23 days

期刊介绍： European Urology is a peer-reviewed journal that publishes original articles and reviews on a broad spectrum of urological issues. Covering topics such as oncology, impotence, infertility, pediatrics, lithiasis and endourology, the journal also highlights recent advances in techniques, instrumentation, surgery, and pediatric urology. This comprehensive approach provides readers with an in-depth guide to international developments in urology.