Pathological Response and Immune Biomarker Assessment in Non-Small-Cell Lung Carcinoma Receiving Neoadjuvant Immune Checkpoint Inhibitors

SIMPLE SUMMARY: Recently, the U.S. Food and Drug Administration (FDA) approved neoadjuvant immunotherapy plus chemotherapy for the treatment of resectable non-small-cell lung carcinoma (NSCLC) due to the clinical benefits reported in several clinical trials. In these settings, the pathological assessment of the tumor bed to quantify a pathological response has been used as a surrogate method of clinical benefit to neoadjuvant therapy. In addition, several clinical trials are including the assessment of tissue-, blood-, or host-based biomarkers to predict therapy response and to monitor the response to neoadjuvant treatment. In this manuscript, we provide an overview of current recommendations for the evaluation of pathological response and describe potential biomarkers used in clinical trials of neoadjuvant immunotherapy in resectable NSCLC. ABSTRACT: Lung cancer is the leading cause of cancer incidence and mortality worldwide. Adjuvant and neoadjuvant chemotherapy have been used in the perioperative setting of non-small-cell carcinoma (NSCLC); however, the five-year survival rate only improves by about 5%. Neoadjuvant treatment with immune checkpoint inhibitors (ICIs) has become significant due to improved survival in advanced NSCLC patients treated with immunotherapy agents. The assessment of pathology response has been proposed as a surrogate indicator of the benefits of neaodjuvant therapy. An outline of recommendations has been published by the International Association for the Study of Lung Cancer (IASLC) for the evaluation of pathologic response (PR). However, recent studies indicate that evaluations of immune-related changes are distinct in surgical resected samples from patients treated with immunotherapy. Several clinical trials of neoadjuvant immunotherapy in resectable NSCLC have included the study of biomarkers that can predict the response of therapy and monitor the response to treatment. In this review, we provide relevant information on the current recommendations of the assessment of pathological responses in surgical resected NSCLC tumors treated with neoadjuvant immunotherapy, and we describe current and potential biomarkers to predict the benefits of neoadjuvant immunotherapy in patients with resectable NSCLC.