Dr Vento on the Clinical Significance of Somatic NGS in Guiding Treatment Decisions for Non–Clear Cell RCC

“[NGS] helps develop precision medicine approaches and would [help us find abnormalities that] we’re not frequently finding—like ALK fusions—that are targetable.”

Joseph Vento, MD, an assistant professor in the Department of Internal Medicine at the University of Texas Southwestern Medical Center; as well as a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center, discussed the clinical significance of using somatic next-generation sequencing (NGS) to guide treatment decisions for patients with non–clear cell renal cell carcinoma (non-ccRCC).

Given the heterogeneity of non–clear cell subtypes—including papillary, chromophobe, and unclassified histologies—Vento emphasized the importance of precision oncology approaches to improve outcomes in this population. In his practice, Vento routinely orders somatic NGS for patients with advanced or metastatic non-ccRCC to identify actionable genomic alterations that could inform treatment selection. Although targetable findings, such as ALK fusions, are uncommon, their detection can be clinically meaningful, offering additional therapeutic opportunities and potentially life-prolonging benefits with ALK-directed agents. He highlighted a case series demonstrating the value of this approach and noted that even infrequent discoveries across the field can substantially affect individual patient care.

Beyond rare gene fusions, Vento explained that NGS provides broader insights into tumor biology and may uncover other actionable pathways, such as MET-driven papillary RCC. These findings could support the use of targeted agents in select patients, he emphasized. Additionally, as tumor-agnostic drug approvals expand, identifying genomic alterations with relevance across tumor types has become increasingly important, he stated. Accumulating molecular data from NGS testing also contributes to a growing evidence base that can refine future therapeutic strategies for non-ccRCC and beyond, he noted. According to Vento, incorporating somatic NGS into routine care is most relevant for patients with advanced or metastatic disease, who represent most of the cases managed at tertiary cancer centers.