A narrative review of pathologic response in non-small cell lung cancer: challenges, implications, and future directions

Abstract

Background and Objective: The increasing use of neoadjuvant therapy in non-small cell lung cancer (NSCLC) has magnified the importance of pathologic response as a treatment endpoint. However, there are persistent challenges in its assessment and interpretation. This review aimed to synthesize current methods and challenges in evaluating pathologic response in patients with NSCLC, summarize available assessment techniques and biomarkers, and collate current data on pathologic response to neoadjuvant treatments and the association with survival outcomes. Methods: We selected and reviewed articles proposing guidelines or approaches to the pathologic assessment of NSCLC, articles describing challenges in assessing pathologic response in NSCLC, and studies reporting pathologic response to neoadjuvant treatment and/or the association between pathologic response and survival outcomes. Data were extracted and summarized descriptively. Key Content and Findings: In this review, we summarize methods for evaluating pathologic response in patients with resectable NSCLC and highlight current challenges, including variability in pathologic response assessment, the limited standardization of techniques and biomarkers, and the difficulty of interpreting pathologic response. We also review current clinical data on pathologic response to neoadjuvant chemotherapy, radiotherapy, immunotherapy, tyrosine kinase inhibitors (TKIs), and antiangiogenic therapies, and the association between pathologic response and survival outcomes. Finally, we review and discuss the selection of optimal treatment strategies for patients who achieve a pathologic response to neoadjuvant therapy. Conclusions: Pathologic response is a valuable indicator of early response to treatment, but its current limitations necessitate a cautious and balanced approach in treatment decision-making for patients with early-stage resectable NSCLC, with consideration also given to other factors such as long-term survival and quality of life.