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肾细胞癌辅助免疫治疗及复发管理的现状:一项欧洲德尔菲研究的见解

Current status of adjuvant immunotherapy and relapse management in renal cell carcinoma: Insights from a European delphi study.

作者信息

Grünwald Viktor, Bex Axel, Rottey Sylvie, Suárez Cristina, Procopio Giuseppe, Velasco Guillermo, Melichar Bohuslav, Bedke Jens, Pickering Lisa, Fontes-Sousa Mário, Schmidinger Manuela, Bamias Aristotelis, Gross-Goupil Marine, Porta Camillo, Barthélémy Philippe, Escudier Bernard, Albiges Laurence

机构信息

Department of Medical Oncology, University Hospital Essen, Essen, Germany.

Division of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

出版信息

Eur J Cancer. 2025 Jul 25;225:115569. doi: 10.1016/j.ejca.2025.115569. Epub 2025 Jun 7.

Abstract

INTRODUCTION

Adjuvant immunotherapy has remarkably advanced the management of localized renal cell carcinoma (RCC) in patients at high risk of post-surgery recurrence. This Delphi study aimed to establish expert consensus on its use and subsequent management of relapse.

METHODS

Fifteen RCC experts participated in a two-round Delphi process between July and November 2024. The study included 43 core survey items, divided into 67 components for comprehensive evaluation.

RESULTS

Consensus, defined as ≥ 75 % agreement, was achieved for 39 of 67 items (58.2 %). Experts agreed on using the Leibovich score for selecting patients for adjuvant pembrolizumab (79 %), initiating therapy within 90 days post-surgery (86 %), and not restricting treatment to programmed death ligand-1 (PD-L1)-positive tumors (100 %). Plasma kidney injury molecule-1 (KIM-1) was considered by the experts as a potential useful recurrence risk biomarker (93 %). Immune checkpoint inhibitor (ICI)-refractory disease was defined as relapse within 6 months post-adjuvant therapy (80 %). Focal therapies for oligometastatic recurrence (80 %), and targeted therapies or clinical trial enrollment for ICI-refractory patients (87 %) were supported. Belzutifan was recommended for fourth-line or later use after ICI therapy and multiple tyrosine kinase inhibitors (93 %). By contrast, no consensus was reached on ICI salvage therapy in specific subgroups, including patients with clear-cell RCC (60 %), without bone/brain metastases (60 %), good performance status (60 %), low tumor burden (47 %), or papillary RCC (36 %).

CONCLUSIONS

This Delphi study provides insights into the evolving role of adjuvant immunotherapy in localized RCC and relapse management. A multidisciplinary approach and periodic review are essential to optimizing treatment strategies.

摘要

引言

辅助免疫疗法显著推进了术后复发高风险局部肾细胞癌(RCC)患者的管理。这项德尔菲研究旨在就其使用及后续复发管理达成专家共识。

方法

15名RCC专家参与了2024年7月至11月期间的两轮德尔菲流程。该研究包括43项核心调查项目,分为67个组成部分进行综合评估。

结果

67项中的39项(58.2%)达成了共识(定义为≥75%的一致意见)。专家们一致同意使用莱博维奇评分来选择接受辅助派姆单抗治疗的患者(79%),在术后90天内开始治疗(86%),并且不将治疗局限于程序性死亡配体-1(PD-L1)阳性肿瘤(100%)。专家们认为血浆肾损伤分子-1(KIM-1)是一种潜在有用的复发风险生物标志物(93%)。免疫检查点抑制剂(ICI)难治性疾病被定义为辅助治疗后6个月内复发(80%)。支持对寡转移复发进行局部治疗(80%),以及对ICI难治性患者进行靶向治疗或纳入临床试验(87%)。推荐在ICI治疗和多种酪氨酸激酶抑制剂之后将贝佐蒂凡用于四线或更晚治疗(93%)。相比之下,在特定亚组中,包括透明细胞RCC患者(60%)、无骨/脑转移患者(60%)、良好体能状态患者(60%)、低肿瘤负荷患者(47%)或乳头状RCC患者(36%),关于ICI挽救治疗未达成共识。

结论

这项德尔菲研究为辅助免疫疗法在局部RCC及复发管理中不断演变的作用提供了见解。多学科方法和定期评估对于优化治疗策略至关重要。

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