Objective  To explore the feasibility and clinical significance of repeated biopsy after lung cancer progression and provide a reference for the treatment of advanced lung cancer.

  Methods  The clinical data of 28 patients with lung cancer who had undergone repeated biopsies of the lesion tissue at Zhongda Hospital, Southeast University from November 2019 to June 2020, including the pathological types and driver oncogenes in the first and repeated biopsies of the lesion tissue, were retrospectively analyzed.

  Results  The pathological types of lung cancer in the 28 patients were non-small cell lung cancer (NSCLC) in 27 patients and small cell lung cancer (SCLC) in 1 patient. On repeated biopsy after treatment, the pathological type changed from adenocarcinoma to small-cell carcinoma in 3 patients, and the adenocarcinoma showed sarcomatous differentiation in 3 patients. The time period for the change from NSCLC to SCLC was 18-41 months. Repeated biopsy also showed changes in lung cancer driver oncogenes in 2 patients:1 epidermal growth factor receptor (EGFR)-negative patient developed EGFR Exon 19del after chemotherapy and 1 patient with EGFR Exon 19del developed drug resistance gene EGFR T790M after EGFR-tyrosine kinase inhibitor (TKI) treatment.

  Conclusion  Repeated biopsy after lung cancer progression is very important for assessing the histopathology and changes in driver oncogenes and selecting appropriate treatment methods.