Treatment Sequencing in Resectable Lung Cancer: The Good and the Bad of Adjuvant Versus Neoadjuvant Therapy

The treatment scenario for patients with resectable non–small cell lung cancer has changed dramatically with the incorporation of immunotherapy. The introduction of immunotherapy into treatment algorithms has yielded improved clinical outcomes in several phase II and III trials in both adjuvant (Impower010 and PEARLS) and neoadjuvant settings (JHU/MSK, LCMC3, NEOSTAR, Columbia/MGH, NADIM, and CheckMate-816), leading to new U.S. Food and Drug Administration approvals in this sense. Different treatment options are now available for patients, making the optimal treatment scenario a matter of intense debate. In this review, we summarize the main results concerning treatment sequencing in resectable non–small cell lung cancer from the past 30 years in the preimmunotherapy era, focusing on recent advances after incorporation of immunotherapy. Finally, the utility of several parameters (PD-L1, tumor mutational burden, radiomics, circulating tumor DNA, T-cell receptor, and immune populations) as predictive biomarkers for therapy personalization is discussed.