Current status and future perspectives on immunotherapy in neoadjuvant therapy of resectable non-small cell lung cancer

Abstract

Resectable non–small cell lung cancer (NSCLC) is defined as stage I-II, and some locally advanced (stage III) tumor. Despite the associated relatively high recurrence rates after surgery, surgical treatment remains the standard treatment for patients with early-stage NSCLC. At present, neoadjuvant therapy is becoming an increasingly popular therapeutic strategy for resectable NSCLC. However, studies have reported that neoadjuvant chemotherapy only slightly improves recurrence rates, making it inadequate for extending patient survival. The significant survival benefits of immunotherapy in advanced NSCLC have greatly stimulated researchers’ interests in applying immune checkpoint inhibitors (ICIs) for treating early-stage resectable NSCLC. A few recent phase II radomized clinical trials suggested that ICIs yield better major pathologic response (MPR) rates than neoadjuvant chemotherapy alone, demonstrating their potential as alternatives to the existing fixed therapy pattern for early-stage NSCLC. Most initial studies regarding neoadjuvant immunotherapy selected MPR and pathologic complete response (pCR) as primary or secondary endpoints, leading to a significant reduction in the time and cost of research and development compared with the use of overall survival time and median survival time as endpoints. Meanwhile, to confirm these benefits, more phase III clinical trials are being conducted, and there is a growing demand for research on related problems, including the screening of population, formulation of treatment strategies, duration and course of immunotherapy, influence of neoadjuvant immunotherapy on the safety of surgery, standardization of treatment effect evaluation and pathologic evaluation, and ways to effectively identify pseudoprogression and avoid resultant misjudgment in surgery and adjuvant therapy.