Perioperative Chemo/Immunotherapies in Lung Cancer: A Critical Review on the Value of Perioperative Sequences

Resectable non-small cell lung cancer (NSCLC) continues to pose significant challenges with high recurrence and mortality rates, despite traditional platinum-based chemotherapy yielding only an approximate 5% improvement in 5-year overall survival when administered preoperatively or postoperatively. In recent years, the integration of immune checkpoint inhibitors (ICIs), such as nivolumab, durvalumab and pembrolizumab, with platinum-based regimens in the perioperative setting has emerged as a transformative strategy. Our comprehensive review, based on a systematic bibliographic search of PubMed, Google Scholar, EMBASE, Cochrane Library, and clinicaltrials.gov, targeting pivotal clinical trials from the past two decades, examines the impact of these neoadjuvant and adjuvant chemoimmunotherapy approaches on major pathological response rates and overall survival in early-stage NSCLC. Although these perioperative strategies represent a paradigm shift in treatment, promising durable responses are offset by persistent recurrence, emphasizing the necessity for optimized treatment sequencing, duration, and the identification of predictive biomarkers. Collectively, our findings underscore the critical role of the perioperative schema, particularly the neoadjuvant component, which enables the evaluation of novel biomarkers as surrogates for overall survival, in improving patient outcomes and delineating future research directions aimed at reducing mortality and enhancing the quality of life for patients with resectable NSCLC.