Pathological response and survival after neoadjuvant therapy in pulmonary adenosquamous carcinoma: a comparative study

Lung adenosquamous carcinoma (ASC) is a rare and aggressive subtype. This exploratory study aimed to evaluate the real-world clinical, pathological, and survival outcomes of patients with ASC receiving neoadjuvant therapy compared to adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). We retrospectively screened 702 lung cancer patients treated with neoadjuvant therapy between January 2018 and February 2025. Finally, 19 ASCs, 75 LUADs, and 208 LUSCs met the inclusion criteria. All LUAD/LUSC patients received neoadjuvant immunochemotherapy (NIC). ASC patients received chemotherapy ( n = 3), targeted therapy ( n = 3), or NIC ( n = 13). Pathological response, surgical safety, and survival (OS and PFS) were analyzed. ASC in NIC group exhibited a significantly higher residual tumor percentage compared to LUAD and LUSC ( P = 0.014). The Major Pathological Response (MPR) rate was markedly lower in ASC (23.1%) than in LUAD (50.7%) and LUSC (58.7%) ( P = 0.030). Crucially, Kaplan-Meier analysis showed no significant differences in OS ( P = 0.907) or PFS ( P = 0.627) among the three histological groups. Within the ASC cohort, the recurrence rates for patients receiving NIC and NTC were only 7.7% (1/13) and 0.0% (0/3), compared to 66.7% (2/3) for those receiving chemotherapy alone. In this small exploratory cohort, NIC and NTC achieved superior pathological regression and systemic control over chemotherapy alone in ASC. Despite relative resistance to NIC versus LUAD/LUSC, survival was comparable. High‑quality R0 resection may offset suboptimal pathological responses. Collectively, these findings hint at a potential pathological‑survival paradox in ASC, warranting prospective validation.