New breakthroughs and future trends in renal cell carcinoma therapy: Highlights from the 2025 European Society for Medical Oncology Annual Congress

Abstract

The 2025 European Society for Medical Oncology Annual Meeting unveiled pivotal advances across the therapeutic spectrum of renal cell carcinoma, marking a decisive shift towards precision medicine. In localized disease, adjuvant therapy is being refined through risk stratification, as demonstrated by the RAMPART trial, which showed significant benefit for dual immune-checkpoint inhibition specifically in high-risk patients. The Neoadjuvant Study With Combination Immuno-oncology for Primary Clear Cell Renal Cell Cancer study further demonstrated that even a short course of neoadjuvant dual immunotherapy could induce meaningful pathological responses in locally advanced clear-cell renal cell carcinoma. For advanced stages, the treatment paradigm is rapidly evolving beyond standard immuno-tyrosine kinase inhibitor combinations. Investigational triple therapies, such as adding a hypoxia-inducible factor 2-alpha inhibitor to first-line regimens, show promise for deeper and more durable responses. A central theme of the conference was the parallel development of predictive biomarkers—including molecular classifiers, dynamic plasma markers, tumor microenvironment signatures, and AI-based histology analysis—to guide individualized treatment selection and avoid ineffective therapy. Following disease progression on first-line treatment, the management landscape is expanding with new evidence from direct comparative trials (e.g., LenCabo), novel drug combinations, and emerging modalities like stereotactic radiotherapy.

Keywords: Renal cell carcinoma; Precision medicine; European Society for Medical Oncology 2025; Immunotherapy; Biomarkers

Core Tip: This timely review synthesizes pivotal advances in renal cell carcinoma management presented at the 2025 European Society for Medical Oncology Annual Congress. It highlights the shift towards precision medicine, evidenced by risk-stratified adjuvant immune checkpoint inhibitor therapy, promising short-course neoadjuvant immune checkpoint inhibitor strategies, and the evolution towards triple-combination regimens in advanced disease. A parallel focus is the critical development of predictive biomarkers—from molecular classifiers to artificial intelligence-based pathology tools—to guide individualized treatment selection and optimize outcomes across the disease spectrum, marking a decisive move beyond a one-size-fits-all therapeutic approach.