Survival impact of pathologic features after salvage lung resection following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer

Purpose: Salvage surgery for non-small cell lung cancer (NSCLC) is expected to become increasingly more common; however, the association between pathologic features and the postoperative prognosis remains unclear. This study aimed to clarify the survival impact of pathologic characteristics after salvage lung resection. Methods: Twenty-three patients who underwent salvage surgery following definitive chemoradiotherapy or systemic therapy for initially unresectable NSCLC from 2010 to 2020 were enrolled in this study. The tumor slides were reviewed to determine the size of the tumor bed and the proportions of viable tumor, necrosis, and stroma according to the recent recommendations from the International Association for the Study of Lung Cancer (IASLC). Results: Initially, 18 patients (79%) had clinical stage IIIB-IV disease. Six (26%) received chemoradiotherapy and 17 (74%) received systemic therapy alone. A major pathologic response (MPR, ≤10% of viable tumor) was observed in 6 patients, and 4 patients achieved a pathological complete response. The 3-year overall and recurrence-free survival rates (OS and RFS) were 78.6% and 59.2%, respectively. There was no significant difference in OS between patients with and without MPR, and even non-MPR patients achieved a favorable 3-year OS of 70.2%. Meanwhile, patients with high (≥30%) stroma showed significantly better OS than those with low (<30%) stroma (3-year OS: 100% vs. 23.3%, p < 0.001). Conclusion: The proportion of stroma based on the recent IASLC recommendations was an important feature for predicting long-term survival after salvage lung resection. A low-stroma signature may serve as an indicator for considering proactive postoperative therapies after salvage surgery. Trial registration number and date of registration This study was approved by the institutional ethics committee of Keio University School of Medicine on September 16 th , 2020 (registration no. 20200092).