Shaping the Future of Adjuvant RCC Therapy

Thomas E. Hutson, DO, PharmD

Texas Tech University Health Science Center School of Medicine Lubbock, Texas 79415

Correspondence to: Thomas Hutson, DO, PharmD

The Kidney Cancer Journal is pleased to receive and review the expert consensus manuscript stemming from the IKCSEU24 Think Tank, a timely and critical contribution to the evolving discourse on adjuvant therapy for renal cell carcinoma (RCC). Full article link is available here . Despite the significant advancements in systemic therapies for metastatic disease, the adjuvant setting remains an area of active investiga- tion and considerable unmet need, as evidenced by the limited number of FDA approvals for tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in this space. The collaborative effort of 26 leading experts to define future research priorities is precisely the kind of strategic foresight required to navigate the complexities and accelerate progress in this crucial area of kidney cancer management.

The recommendations put forth by the IKCSEU24 Think Tank resonate deeply with the current trajectory of oncology: a relentless pursuit of precision and patient-centricity. The call to move beyond traditional TNM staging for patient selection and to develop robust, tumor-based biomarkers of response is paramount. This aligns perfectly with the broader shift towards identifying which patients truly benefit from adjuvant therapy, thereby maximizing efficacy while minimizing unnecessary exposure to toxicity. Furthermore, the emphasis on detecting minimal residual disease (MRD) through novel approaches like circulating tumor DNA (ctDNA) holds immense promise for limiting overtreatment, allowing for more tailored and dynamic treatment decisions post-surgery. The established role of adjuvant pembrolizumab, based on the KEYNOTE-564 trial, has been a significant milestone, providing the first clear evidence of an overall survival benefit in this setting. This success underscores the potential of immunotherapy to impact long-term outcomes for patients with high-risk RCC. Equally commendable is the advocacy for novel clinical trial endpoints, such as time to first-line therapy for metastatic disease (TTFT), which could significantly speed up clinical development by providing more relevant and earlier indicators of long- term benefit. Crucially, the manuscript underscores the often-overlooked yet vital importance of patient- centered outcomes, including quality of life and functional status. This holistic perspective ensures that advancements not only prolong survival but also preserve the well-being of individuals living with and beyond kidney cancer. We wholeheartedly concur with the conclusion that future advancements hinge on collaborative efforts across institutions and industry, fostering data sharing, streamlining protocols, and embracing drugs with new mechanisms of action, all while prioritizing enhanced patient selection and minimizing long-term toxicity. This manuscript serves as an invaluable roadmap, charting a course towards a more effective and individualized approach to adjuvant RCC therapy.

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