Neoadjuvant Immunotherapy for NSCLC: Current Concepts and Future Approaches

Lung cancer is the leading cause of cancer-related deaths worldwide. Patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy. However, these patients continue to have a high risk of recurrence and death. Unfortunately, there has been little progress in the treatment of resectable NSCLC over the past several decades. Neoadjuvant therapy, which has been considered as an approach to improve survival in patients with resectable NSCLC, is a hotly debated topic. A systematic review of 32 randomized trials involving 10,000 patients revealed that there was no difference in survival between preoperative and postoperative chemotherapy. Because of such results and the theoretical concern about resectable tumors progressing on relatively ineffective neoadjuvant chemotherapy, and thus becoming unresectable, neoadjuvant chemotherapy fell out of favor, and many clinicians preferred adjuvant chemotherapy after surgery. However, neoadjuvant therapy has been revived in the past couple of years, with emerging data from various ongoing trials suggesting that neoadjuvant immunotherapy may have significant efficacy and could potentially improve the survival of patients with resectable NSCLC. In this review article, we discuss the evidence supporting the role of neoadjuvant immunotherapy in the multimodal management of resectable NSCLC. We summarize early results of ongoing clinical trials and highlight the challenges in adopting a uniform definition of treatment "success." We address hurdles to be overcome for seeking regulatory approval for neoadjuvant immunotherapy and establishing it as a standard of care. Finally, we provide some perspectives for the future.