Histological transformation of non-small cell lung cancer: Clinical analysis of nine cases

BACKGROUND: Histological transformation is one of the numerous mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Given its rarity, the underlying transformational mechanisms, clinical features, and therapeutic prognoses are only studied through limited case reports. AIM: To analyze the clinical characteristics and underlying mechanisms in non-small cell lung cancer (SCLC) patients with histological transformation after treatment with EGFR-TKIs. METHODS: We retrospectively investigated nine patients diagnosed with non-SCLC transforming to SCLC, large-cell neuroendocrine carcinoma (LCNEC), or squamous cell carcinoma on re-biopsy after first- or third-generation EGFR-TKIs. RESULTS: The median age of nine patients was 60 years. Among them, six patients had the EGFR 19del mutation, one had the L858R mutation, and one had wild-type EGFR. The level of plasma NSE was measured in six patients with SCLC or LCNEC transformation when transformation occurred, and five patients had elevated plasma NSE levels. All patients received standard chemotherapy after transformation with the exception of one patient who received chemotherapy and anlotinib. CONCLUSION: Tumor re-biopsy should be performed routinely when EGFR-TKI therapy fails in lung cancer patients to avoid ignoring histological transformation and to select a subsequent therapeutic strategy. The transformed tumor retained the original EGFR mutation, indicating that histological transformation represents an evolution from the initial tumor.