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Adjuvant therapy options in renal cell carcinoma — targeting the metastatic cascade

Nature Reviews Urology volume 20, pages 179–193 (2023)Cite this article

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Abstract

Localized renal cell carcinoma (RCC) is primarily managed with nephrectomy, which is performed with curative intent. However, disease recurs in ~20% of patients. Treatment with adjuvant therapies is used after surgery with the intention of curing additional patients by disrupting the establishment, maturation or survival of micrometastases, processes collectively referred to as the metastatic cascade. Immune checkpoint inhibitors and vascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitors (TKIs) have shown efficacy in the treatment of metastatic RCC, increasing the interest in the utility of these agents in the adjuvant setting. Pembrolizumab, an inhibitor of the immune checkpoint PD1, is now approved by the FDA and is under review by European regulatory agencies for the adjuvant treatment of patients with localized resected clear cell RCC based on the results of the KEYNOTE-564 trial. However, the optimal use of immunotherapy and VEGFR-targeting TKIs for adjuvant treatment of RCC is not completely understood. These agents disrupt the metastatic cascade at multiple steps, providing biological rationale for further investigating the applications of these therapeutics in the adjuvant setting. Clinical trials to evaluate adjuvant therapeutics in RCC are ongoing, and clinical considerations must guide the practical use of immunotherapy and TKI agents for the adjuvant treatment of localized resected RCC.

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Fig. 1: Sequential steps of the renal cell carcinoma metastatic cascade.
Fig. 2: Adjuvant systemic therapies in renal cell carcinoma disrupt multiple steps of the metastatic cascade.

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Acknowledgements

The authors thank the National Institute of Health Clinical and Translational Science Awards Program, grant number UL1TR00457. They are also grateful for the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant P30 CA008748.

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  1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Kelly N. Fitzgerald, Robert J. Motzer & Chung-Han Lee

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K.N.F. and R.J.M. researched data for the article. All authors contributed substantially to discussion of the content. All authors wrote the article. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Chung-Han Lee.

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R.J.M. reports grants from Bristol Myers Squibb, grants and personal fees from Pfizer, Novartis, Eisai, Exelixis, Merck and Genentech/Roche, and personal fees from Lilly, Incyte, EMD Serono Research and Development Institute, AVEO Pharmaceuticals and Takeda. C.-H.L reports honoraria from Intellisphere, Research to Practice and AiCME, consulting or advisory role with Amgen, Bristol Myers Squibb, Eisai, Exelixis, Merck and Pfizer/EMD Serono, institutional research funding from Bristol Myers Squibb, Calithera Biosciences, Eisai, Exelixis, Lilly, Merck and Pfizer, and travel/accommodation expenses from Calithera Biosciences and Eisai. K.N.F. declares no competing interests.

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Fitzgerald, K.N., Motzer, R.J. & Lee, CH. Adjuvant therapy options in renal cell carcinoma — targeting the metastatic cascade. Nat Rev Urol 20, 179–193 (2023). https://doi.org/10.1038/s41585-022-00666-2

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