Conversion Surgery After Induction Therapy for Initially Unresectable Stage III Non-small Cell Lung Cancer: A Proof-of-Concept Trial.

[BACKGROUND] To prove the concept of conversion surgery after induction therapy in initially unresectable stage III non-small-cell lung cancer (NSCLC), we conducted this single-arm, open label, prospective study.

[PATIENTS AND METHODS] In this proof-of-concept prospective study, patients with initially unresectable stage III NSCLC who had received induction therapy and evaluated radically resectable were included and underwent surgery. The primary outcome was perioperative morbidity. Bulk-RNA sequencing of baseline and post-treatment samples from patients receiving immunochemotherapy (ICT) as induction therapy was conducted to explore the transcriptomic characteristics of therapeutic response. This study was registered with ClinicalTrials.gov, NCT04945928.

[RESULTS] From August 2021 to January 2024, 30 patients were enrolled. The R0 resection rate was 93.3% (28/30). Postoperative morbidity was reported in ten patients (33.3%). The rate of major pathologic response and pathological complete response were 66.7% (20/30) and 26.7% (8/30). In a median follow-up time of 17 months (10.2-21.0 months), the rate of 1-year event-free survival and overall survival were 87.5% and 96.7%, respectively. Transcriptomic analysis found a significant association of B cell immunity with MPR after ICT. A gene set derived from the enriched B cell immune-related pathways predicted better survival in patients treated with immunotherapy.

[CONCLUSIONS] Conversion surgery after induction therapy was safe and feasible, with encouraging 1-year survival outcomes for selected patients with initially unresectable stage III NSCLC. These foregrounded the role of radical surgery in the treatment strategy in this setting. A B cell immune-related gene set with potential predictive value was also identified within the ICT cohort.

[CLINICAL TRIAL REGISTRY NUMBER] ClinicalTrials.gov, NCT04945928.