Published online Jun 26, 2021. doi: 10.12998/wjcc.v9.i18.4617
Peer-review started: January 26, 2021
First decision: February 25, 2021
Revised: March 11, 2021
Accepted: April 12, 2021
Article in press: April 12, 2021
Published online: June 26, 2021
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 prognosis are only studied through limited case reports.
The study of non-small cell lung cancer (SCLC) patients with histological transformation after treatment with EGFR-TKIs can improve our understanding of the clinical features and underlying mechanisms in this type of patient. This finding can remind us of the importance of re-biopsy when targeted drug resistance occurs.
The main objective of this study was to analyze the clinical characteristics and underlying mechanisms in non-SCLC (NSCLC) patients with histological transformation after treatment with EGFR-TKIs.
We retrospectively investigated nine patients diagnosed with NSCLC transforming to SCLC, large-cell neuroendocrine carcinoma (LCNEC), or squamous cell carcinoma on re-biopsy after first- or third-generation EGFR-TKIs.
The median age of the nine patients in this study was 60 years old. Among them, six patients had the EGFR 19del mutation, one had the L858R mutation, and one had wild-type EGFR. In six patients with SCLC or LCNEC transformation, plasma NSE levels were detected when transformation occurred, and five patients had elevated plasma NSE levels. All patients received standard chemotherapy after transformation except one patient who received chemotherapy and anlotinib.
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, which indicates that histological transformation represents an evolution from the initial tumor. Plasma pro-gastrin-releasing peptide and NSE levels could represent valuable and significant biomarkers to predict histological transformation.
Due to the limited cases in this study, it is difficult to draw reliable conclusions. However, our study suggests that the plasma NSE levels potentially represent a valuable biomarker to predict histological transformation, and re-biopsy should be performed to avoid ignoring the occurrence of histological transformation. Furthermore, to a large extent, histological transformation represents an evolution from the initial tumor.