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Clinical investigation of immune checkpoint inhibitors (ICIs) has expanded from indications in metastatic non–small cell lung cancer (NSCLC) to add to the treatment of early-stage or resectable NSCLC.

Although completed randomized trials supported the approvals of some ICIs as perioperative therapies (i.e., adjuvant, neoadjuvant, or neoadjuvant followed by adjuvant), ongoing trials are evaluating other anti–PD-(L)1 antibodies for similar indications, or in combination with stereotactic body radiotherapy (SBRT).

The incorporation of immunotherapy brings potential to improve outcomes of patients with resectable NSCLC, but these advances have also increased the complexity of the treatment landscape and created important knowledge gaps.

This article reviews the current standards for local therapies in NSCLC, describes the clinical trials exploring the combination of ICIs to SBRT, and explains the recent approvals of ICIs as perioperative therapies.

A discussion follows to highlight three important areas of uncertainty: (1) the contribution of ICIs given in each treatment phase (neoadjuvant and adjuvant) to the overall effect of neoadjuvant chemoimmunotherapy followed by adjuvant ICIs; (2) the selection of regimens to serve as comparators in future randomized trials of perioperative therapies; and (3) the role of pathologic complete response as an intermediate end point and aid for selection of patients for adjuvant therapy.

Moving forward, stakeholders will need to engage in concerted research efforts to address the relevant clinical questions regarding the optimal management of resectable NSCLC.

Read a Q&A related to the review here.