The integration of immune checkpoint inhibitors has transformed the therapeutic landscape for patients with resectable and potentially resectable stage Ⅲ non-small cell lung cancer, providing unprecedented opportunities for curative treatment. Several trials have investigated immune checkpoint inhibitors, either alone or in combination with chemotherapy or radiotherapy, as neoadjuvant and/or adjuvant approaches for resectable and potentially resectable stage Ⅲ non-small cell lung cancer. This comprehensive review elaborates and deeply analyzes the evolving evidence from landmark clinical trials and emerging treatment strategies. Despite these promising outcomes, significant challenges remain, including optimal treatment modality selection, controversy about adjuvant immunotherapy for patients who have already achieved a pathologic complete response, appropriate endpoint evaluation, and biomarker identification. This review also discusses future directions for optimizing immunotherapy integration in patients with resectable stage Ⅲ non-small cell lung cancer, emphasizing the need for personalized treatment approaches to maximize patient benefit while addressing unanswered clinical questions.

As the leading cause of cancer-related deaths, lung cancer remains a noteworthy threat to human health. Although immunotherapies, such as immune checkpoint inhibitors (ICIs), have significantly increased the efficacy of lung cancer treatment, a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance. Bispecific antibodies (bsAbs) bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles, thus attracting increasing attention as novel antitumor therapies. At present, in addition to the approved bsAb, amivantamab, three novel bsAbs (KN046, AK112, and SHR-1701) are being evaluated in phase 3 clinical trials and many bsAbs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer (NSCLC). Herein we present the structure, classification, and mechanism of action underlying bsAbs in NSCLC and introduce related clinical trials. Finally, we discuss challenges, potential solutions, and future prospects in the context of cancer treatment with bsAbs.

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). The efficacy of pembrolizumab without chemotherapy in stage Ⅳ NSCLC has incited interest in similar approaches for LA-NSCLC. Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy (iRT) have generated encouraging results. This review discusses the existing studies and prospective directions of chemotherapy-free iRT strategies in unresectable LA-NSCLC. Although the initial findings of chemotherapy-free iRT strategies have shown promising efficacy, we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free iRT. These challenges include determining the optimal dose and fractionation, precise target volume delineation, and identification of additional suitable patient cohorts. Furthermore, the feasibility of chemotherapy-free iRT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase Ⅲ trials.