Next‑generation sequencing‑guided personalized therapy in renal cell carcinoma

Abstract

Abstract Purpose The WHO’s classification of renal cell carcinoma (RCC) has transitioned from solely morphologic to an integrated molecular-defined classification with genotyping based on driver genes. One-third of patients with localized diseases eventually develop metastases. First-line treatments with tyrosine kinase inhibitors and immunotherapies have shown promise in improving patient outcomes. This study aims to assess the efficacy of next-generation sequencing (NGS) guided therapy for patients with metastatic renal cell carcinoma (mRCC). Methods We evaluated a cohort of 77 mRCC patients. In the context of first-line systemic treatment, 35 patients were administered NGS-guided personalized therapy, while 42 received empirical therapy. We subsequently compared the progression-free survival (PFS) of both groups and reported the objective response rate (ORR) for the NGS-guided group. Results Over the past three years, the application rate of NGS post-nephrectomy in West China Hospital averaged 21%. The NGS-guided group showed a significantly better PFS (P = .01) compared to the empirical therapy group. The NGS-guided group also exhibited an ORR of 41.9% and a disease control rate (DCR) of 90.3%. Conclusions Our data highlights NGS as a crucial, clinically accessible genotyping method suitable for broader adoption. This study underscores that NGS-guided therapy can significantly enhance outcomes for mRCC patients, particularly for specific driving mutations, such as FH.