Patients with rare lung adenosquamous carcinoma who received neoadjuvant therapy achieved overall and progression-free survival rates comparable to those observed in lung adenocarcinoma and lung squamous cell carcinoma, despite experiencing lower rates of major pathological response. According to an exploratory comparative analysis, patients receiving neoadjuvant immunochemotherapy exhibited a significantly higher percentage of residual tumor tissue, yet their long-term survival trajectories showed no statistically significant divergence from more common non-small cell lung cancer subtypes.

Lung adenosquamous carcinoma is recognized as an aggressive and rare histological subtype of lung malignancy. The exploratory investigation was designed specifically to evaluate and compare the real-world clinical features, pathological regression, and survival outcomes of patients with adenosquamous carcinoma against patients diagnosed with lung adenocarcinoma and squamous cell carcinoma who underwent neoadjuvant therapy.

The research team conducted a retrospective screening of 702 lung cancer patients who were treated with neoadjuvant regimens between January 2018 and February 2025. Following the application of strict inclusion criteria, the final study population comprised 302 patients: 19 individuals with lung adenosquamous carcinoma, 75 patients with lung adenocarcinoma, and 208 patients with lung squamous cell carcinoma. This multi-cohort selection enabled comparative assessments across distinct histological classifications treated during the same seven-year evaluation window.

Treatment protocols differed according to tumor histology and clinical management decisions. All 75 patients in the adenocarcinoma group and all 208 patients in the squamous cell carcinoma group received neoadjuvant immunochemotherapy. In contrast, the 19 patients within the adenosquamous carcinoma cohort were managed with three distinct therapeutic modalities: 13 patients received neoadjuvant immunochemotherapy, three patients were treated with targeted therapy, and three patients received chemotherapy alone. The study authors systematically tracked pathological responses, surgical safety, progression-free survival, and overall survival across these patient subsets.

Pathological evaluations revealed that adenosquamous carcinoma tumors had diminished histological responses to preoperative immunochemotherapy relative to other lung cancer subtypes. The adenosquamous carcinoma cohort treated with neoadjuvant immunochemotherapy exhibited a significantly higher residual tumor percentage than the adenocarcinoma and squamous cell carcinoma groups, reaching statistical significance with a P value of 0.014. Furthermore, the major pathological response rate was markedly lower in adenosquamous carcinoma at 23.1 percent, compared to 50.7 percent in lung adenocarcinoma and 58.7 percent in lung squamous cell carcinoma, representing a statistically significant difference with a P value of 0.030.

Despite the pronounced disparity in tumor clearance, Kaplan-Meier survival analyses demonstrated no significant differences in survival across the three histological groups. The comparative analysis yielded an overall survival P value of 0.907 and a progression-free survival P value of 0.627 among adenosquamous carcinoma, adenocarcinoma, and squamous cell carcinoma cohorts. Additionally, within the adenosquamous carcinoma cohort, disease recurrence occurred in only 7.7 percent (one of 13 patients) of those receiving neoadjuvant immunochemotherapy and 0.0 percent (zero of three patients) of those receiving neoadjuvant targeted therapy, compared to 66.7 percent (two of three patients) among patients who received chemotherapy alone.

The authors concluded that neoadjuvant immunochemotherapy and neoadjuvant targeted therapy achieved superior pathological regression and systemic tumor control over chemotherapy alone in this small exploratory cohort of adenosquamous carcinoma. Although the tumors demonstrated relative resistance to neoadjuvant immunochemotherapy when contrasted with adenocarcinoma and squamous cell carcinoma, patient survival remained equivalent. The investigators suggested that high-quality R0 surgical resection may offset suboptimal pathological responses, highlighting a potential pathological-survival paradox in lung adenosquamous carcinoma that warrants future prospective validation.

Subject of Research: Neoadjuvant therapy outcomes in pulmonary adenosquamous carcinoma

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

Article References: Li, D., Chen, Z., Shi, Y., Jiang, W., Sun, F., & Yin, J. (2026). Pathological response and survival after neoadjuvant therapy in pulmonary adenosquamous carcinoma: a comparative study. BMC Pulmonary Medicine. https://doi.org/10.1186/s12890-026-04885-w

Image Credits: AI Generated

DOI: 10.1186/s12890-026-04885-w

Keywords: pulmonary adenosquamous carcinoma, lung adenosquamous carcinoma, neoadjuvant therapy, neoadjuvant immunochemotherapy, neoadjuvant targeted therapy, lung adenocarcinoma, lung squamous cell carcinoma, major pathological response, residual tumor percentage, overall survival, progression-free survival, R0 resection, pathological regression, Kaplan-Meier analysis, tumor recurrence rate, surgical safety, exploratory cohort study