Pathological response and tumor regression grading following neoadjuvant chemo‑immunotherapy and chemotherapy in resectable non‑small cell lung cancer

Recent neoadjuvant trials in lung cancer have demonstrated meaningful survival advantages, highlighting the need for standardized assessment of pathologic response in resected specimens. Only two systems are currently recommended for evaluating post‑treatment response, namely the International Association for the Study of Lung Cancer (IASLC) tumor regression grading system and the immune‑related pathologic response criteria (irPRC). The present study aimed to review and apply histopathologic parameters for assessing tumor regression in non‑small cell lung carcinoma (NSCLC) specimens resected after neoadjuvant therapy. A total of 30 NSCLC resections obtained after neoadjuvant therapy between 2022 and 2025 were analyzed. Gross and microscopic evaluations were performed according to IASLC recommendations. Residual viable tumor, fibrosis, inflammation and necrosis were semi‑quantitatively assessed according to IASLC and irPRC principles. Major pathologic response (mPR) was defined as ≤10% viable tumor and pathologic complete response (pCR) as 0% viable tumor. Associations with demographic features, treatment modalities and survival outcomes were analyzed. Compared with chemotherapy (CT) alone, chemo‑immunotherapy (CIT) exhibited a trend toward a deeper pattern of tumor regression, reflected by lower median viable tumor percentages (7.5 vs. 55.0%) and higher mPR rates (62.5 vs. 22.7%), although these differences did not reach statistical significance. pCR occurred in 37.5% of patients treated with CIT and in 13.6% of patients treated with CT. CIT specimens demonstrated more prominent immune‑mediated stromal changes, including greater intratumoral inflammation (32.5 vs. 10.0%) and more frequent lymphocytic patterns. Fibrosis strongly correlated with response (P<0.001), whereas necrosis did not. Spread through air spaces positivity was found to be significantly reduced in cases of mPR (P<0.001). Therefore, neoadjuvant CIT may be associated with deeper pathologic regression compared with CT, characterized by increased fibrosis and immune activation. Major pathologic response remains a potential prognostic indicator and integration of IASLC and irPRC criteria, together with tumor microenvironment assessment, may improve the evaluation of treatment response in resectable NSCLC.