Rethinking High-Risk EGFR-Mutant NSCLC

Jonathan Riess, MD, MS, and Nicholas Villanueva, MD, discuss the evolving definition of high-risk EGFR-mutant NSCLC, including factors such as brain and liver metastases, TP53 co-mutations, circulating tumor DNA status, and overall disease burden. They explore whether molecular complexity is becoming a stronger driver of treatment intensification than clinical features alone, and caution against over-interpreting co-mutations without prospective validation.