Neoadjuvant therapy in early-stage non-small cell lung cancer—pros, cons and future promise: a narrative review

Background and Objective: Lung cancer is one of the most prevalent cancers worldwide and the leading cause of cancer-related mortality. Early-stage non-small cell lung cancer (NSCLC) is traditionally treated with up front surgical resection, but high rates of relapse have raised interest in optimizing systemic therapies. In recent years, neoadjuvant therapy has gained increasing popularity primarily in patients with borderline resectable or locally advanced disease. In this review, we aim to summarize the advantages, disadvantages, current and evolving applications of neoadjuvant therapy particularly in early-stage I–II NSCLC where its role is less defined. Methods: The PubMed and ClinicalTrials.gov databases were queried on June 10, 2025 to identify pertinent studies using keywords related to neoadjuvant therapy and lung cancer. Only English language articles were included. The relevant key findings and information were summarized with a focus on outcomes related to stage I–II disease. Key Content and Findings: Neoadjuvant therapy has various advantages including decreasing tumor burden preoperatively, providing time for patient medical optimization, early prognostication based on observed tumor response, and early treatment of micro-metastatic disease. Several important disadvantages also exist—the most significant drawback being complications of systemic therapy resulting in delay or cancellation of curative surgery. Neoadjuvant therapy can also increase surgical difficulty. Multidisciplinary teams should collaborate early on to evaluate if a patient may benefit from systemic therapy and optimize timing of proposed regimens in relation to resection. Tumor-specific factors, such as size or presence of actionable genetic alterations, should be considered and highlights the importance of completing staging and obtaining molecular markers in a timely fashion. Patient-specific factors, such as autoimmune conditions and functional status, are also of great consideration and highlight the importance of a comprehensive history and exam. Conclusions: At present, neoadjuvant therapy should be considered in all patients with early-stage resectable NSCLC. It is the amalgamation of patient and tumor factors, along with current available guidelines that can help inform a recommendation for the use of neoadjuvant therapy in early-stage NSCLC. Additional studies evaluating long-term outcomes and survival are needed further define the optimal timing and utilization of this promising treatment modality.