Society for Immunotherapy of Cancer (SITC) Clinical Practice Guideline on Immunotherapy for the Treatment of Renal Cell Carcinoma - Version 3.0

Sep 23, 2026

Uploaded by Jake

Immunotherapy is a core pillar of renal cell carcinoma (RCC) treatment, with earlier agents such as interleukin-2 and interferon-alpha producing complete responses in only a small fraction of patients. Immune checkpoint inhibitors (ICIs) have improved response rates and prolonged survival, reshaping standard care in both first-line and subsequent-line settings and expanding into adjuvant use for selected high-risk patients. The SITC convened an expert panel to produce evidence-based, consensus recommendations, addressing therapy selection across adjuvant and metastatic contexts, special populations, response monitoring, and patient education and quality-of-life considerations.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Abstract

Introduction

RCC epidemiology and treatment landscape

Role of immunotherapy and ICIs

Clinical challenges and unanswered questions

Biomarkers and risk stratification

Selection, sequencing, and special patient considerations

Open access Position article and guidelines Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of renal cell carcinoma, version 3.0 Rana R McKay,1 Archana Ajmera,2 Michael B Atkins ,3 Pedro C Barata ,4 Cristiane Bergerot,5 Laura Bukavina,6 Toni K Choueiri ,7 Arpita Desai,8 A Ari Hakimi,9 Susan Poteat,10 Thomas Powles,11 Brian I Rini ,12 Brian Shuch,13 Sabina Signoretti,14 Shankar Siva,15 Wenxin Xu,7 Wesley Yip,16 Tian Zhang ,17 Sumanta K Pal 18 To cite: McKay RR, Ajmera A, Atkins MB, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of renal cell carcinoma, version 3.0. Journal for ImmunoTherapy of Cancer 2026;14:e013788 . doi:10 . 1136/ jitc-2025-013788 Accepted 01 February 2026 © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. For numbered affiliations see end of article. Correspondence to Dr Rana R McKay; [rmckay@health.ucsd.edu](rmckay@health.ucsd.edu) ABSTRACT Immunotherapy has been a pillar of the renal cell carcinoma (RCC) treatment landscape for over three decades. Some of the earliest cancer immunotherapies available, such as interleukin 2 and interferon-alpha, have resulted in complete responses, but only in a small number of patients. Immune checkpoint inhibitors (ICIs), however, have demonstrated improved response rates and prolonged survival for a greater number of patients, fully transforming the standard of care in firstline and subsequent-line settings. More recently, ICIs are also being used in the adjuvant setting for high-risk patients. However, treatment with ICIs requires a nuanced understanding of topics such as patient selection, histology and risk considerations, and integration with local therapies. As such, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline (CPG) on immunotherapy for the treatment of RCC. Drawing from published data and clinical experience, the Expert Panel developed evidencebased and consensus-based recommendations. Topics include therapy selection in the adjuvant and metastatic settings, considerations for special patient populations, response monitoring, and patient education and quality of life considerations, among others, with the goal of improving patient care by providing guidance to the oncology community. INTRODUCTION Kidney cancer accounts for 4%–5% of all cancers diagnosed in the USA,1 with an increasing incidence.2 Fortunately, mortality rates have steadily declined 1%–2% annually.2 While much of the improved survival outcomes over the past 50 years are related to incidental identification of small renal masses, advances in treatment regimens may have contributed, with immunotherapy currently at the forefront of this dynamic treatment landscape. Renal cell carcinoma (RCC) is a subset of kidney cancer that is typically not responsive to chemotherapy,3 and therefore, treatment modalities include surgical intervention, local radiation, targeted agents, and immunotherapy. RCC is a highly immune-infiltrated tumor, enabling immunotherapy approaches to reactivate suppressed antitumor immune responses.4 In fact, some of the earliest approved immunotherapies, interleukin 2 (IL-2) and interferon-alpha (IFN-alpha), were long the standard of care (SOC) and often the only therapeutic options for patients with metastatic RCC before 2004.5 6 Response rates to these early immunotherapies were modest, however, often limited to 5%–20% of patients.5 6 The use of angiogenesis-targeting agents, such as vascular endothelial growth factor receptor (VEGFR)-directed tyrosine kinase inhibitors (TKIs), has demonstrated improved clinical benefit for many patients with advanced/metastatic RCC.7 However, developing resistance and absence of treatment alternatives have limited the benefit

FAQs

What led to the development of this SITC clinical practice guideline for RCC immunotherapy?

The guideline was created by a SITC expert panel to translate published data and clinical experience into evidence-based, consensus recommendations for immunotherapy in RCC, including adjuvant and metastatic settings.

How have immune checkpoint inhibitors changed RCC standard of care?

ICIs improved response rates and prolonged survival for more patients than earlier immunotherapies, transforming standard care in first-line and subsequent-line settings, with later incorporation into adjuvant treatment for selected high-risk patients.

What challenges remain when using ICIs in RCC treatment decisions?

Key challenges include limited clinical utility of biomarkers for guiding ICI selection, constrained usefulness of VEGFR-based risk models in ICI trials, absence of head-to-head comparisons among FDA-approved metastatic immunotherapies, and complexity in integrating and sequencing immunotherapy with local therapies for resistant disease.

Sep 23, 2026

Uploaded by Jake