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Improving neoadjuvant and perioperative therapy in non-small-cell lung cancer
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DOI：10.1038/s41571-026-01174-7.png)
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Abstract
En 中文
Neoadjuvant chemoimmunotherapy, comprising an anti-PD-(L)1 antibody and platinum-doublet chemotherapy, given alone or as part of a perioperative regimen with the addition of adjuvant anti-PD-(L)1 therapy, has become the standard of care for patients with early-stage, resectable non-oncogene-driven non-small-cell lung cancer (NSCLC). This approach has demonstrated substantial increases in pathological response rates and improvements in long-term outcomes, including overall survival. However, these advances have largely been achieved through uniform treatment application across biologically heterogeneous tumours. As a result, a central challenge in contemporary perioperative management is how to identify which patients require escalation or de-escalation of treatment following surgery and which individuals could safely avoid unnecessary treatment. In this Review, we summarize current evidence supporting pathological response, and particularly pathological complete response (pCR), as a robust and clinically meaningful surrogate for durable benefit in patients with NSCLC. We then consider how complementary tools, including circulating tumour DNA, radiomics and metabolic imaging approaches, and baseline molecular and immune biomarkers, can be integrated to refine patient selection and dynamically adapt perioperative strategies. Finally, we describe potential therapeutic strategies to intensify perioperative treatment in biologically high-risk populations, with the dual objective of increasing the likelihood of a pCR and improving disease control in patients with an insufficient pathological response. Perioperative chemoimmunotherapy, comprising platinum-doublet chemotherapy plus an anti-PD-(L)1 antibody, has become the standard-of-care approach for patients with resectable non-small-cell lung cancer without an actionable driver alteration. However, the development of this approach has thus far been largely empirical, with limited capacity for adaptation of treatment strategies to better meet the needs of individual patients. In this Review, the authors discuss the potential for improvements in the current approach to perioperative therapy, including de-escalation for those with a pathological complete response, the capacity of various baseline and/or dynamic biomarkers to optimize outcomes, and the potential for escalation in patients with early evidence of a lack of responsiveness in the perioperative setting.
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