Advancements of investigational agents for renal cell carcinoma: what clinical progress have we seen in the last 5 years?

Introduction: RCC management has evolved toward immunotherapy-based strategies, with adjuvant anti-PD-1 therapy after nephrectomy and immune-VEGF TKI combinations in the metastatic setting now representing standards of care. Outcomes remain variable because of biological heterogeneity, treatment resistance, and the limited performance of currently available biomarkers. Areas covered: This review synthesizes contemporary standards of care together with advances in tumor biology and biomarker development, and appraises investigational modalities across immune, targeted, and cellular platforms. We analyze how standards of care and translational insights have evolved in recent years, outlining the principal directions of current and investigational treatments. Expert opinion: The field is moving toward biology-informed treatment selection. Priorities include prospective validation of biomarker strategies, standardization of assay platforms, and integration of dynamic response measures to refine treatment selection, sequencing, and combinations. Molecularly defined subsets and less common histologies warrant dedicated, adequately powered studies. With rigorous methodology and standardized testing methods, emerging approaches have the potential to translate current signals into more consistent and durable clinical benefits in RCC.