From the Guidelines
Lung adenocarcinoma with neuroendocrine differentiation is a subtype of non-small cell lung cancer with a poor prognosis, generally worse than pure adenocarcinoma due to its aggressive behavior and frequent metastasis. The definition of this tumor is a hybrid combining adenocarcinoma and neuroendocrine characteristics, as noted in studies focusing on neuroendocrine tumors 1. Key points to consider include:
- Definition: It's a hybrid tumor combining adenocarcinoma and neuroendocrine characteristics.
- Diagnosis: Confirmed through biopsy and immunohistochemistry showing both adenocarcinoma markers (e.g., TTF-1, Napsin A) and neuroendocrine markers (e.g., synaptophysin, chromogranin A) 1.
- Treatment: Typically involves a combination of surgery (if possible), chemotherapy, and radiation therapy, with somatostatin analogs considered for carcinoid syndrome and as first-line systemic antiproliferative treatment in unresectable cases 1.
- Prognosis: Generally poor, with a median survival that can vary but is often reported in the range of 12-18 months for similar neuroendocrine tumors, though specific data for lung adenocarcinoma with neuroendocrine differentiation may vary.
- Monitoring: Regular follow-ups with CT scans every 3-6 months for the first two years, then annually, are crucial for detecting recurrence or metastasis early.
The poor prognosis is due to the tumor's aggressive nature, combining the invasive properties of adenocarcinoma with the rapid growth and metastatic potential of neuroendocrine tumors. Early detection and a multidisciplinary approach to treatment are crucial for improving outcomes, as emphasized by the European Neuroendocrine Tumor Society expert consensus 1. Systemic chemotherapy, including platinum-based drugs and temozolomide, may be used for progressive disease, although effects can be limited 1.
From the Research
Definition of Lung Adenocarcinoma with Neuroendocrine (NE) Differentiation
- Lung adenocarcinoma with neuroendocrine differentiation (LANED) is a rare histologic character of lung cancer, with clinical significance that remains unclear 2.
- Neuroendocrine tumors (NET) of the lung are a slowly growing subtype of lung cancer that has a different treatment paradigm than aggressive and more common forms of lung neuroendocrine neoplasms (NEN) like small cell lung cancer (SCLC) 3.
- Tumors with no evidence of neuroendocrine transformation histologically but harbouring neuroendocrine features are collectively referred to as non-small cell lung cancer (NSCLC) with neuroendocrine differentiation (NED) 4.
Prognosis of Lung Adenocarcinoma with Neuroendocrine (NE) Differentiation
- The prognosis of large cell neuroendocrine carcinoma of the lung (LCNEC) is poor, with a median overall survival of 8-12 months 5.
- For patients with advanced stages of LANED, the overall survival ranged from 11.0 to 46.7 months 2.
- A higher NEDI (NED index) correlated with better prognosis in patients with lung adenocarcinoma (LUAD) 4.
- The prognosis and treatment outcomes of LANED may be associated with molecular markers such as RET expression, EGFR mutation, ALK translocation, and PD-L1 expression 2.
Treatment of Lung Adenocarcinoma with Neuroendocrine (NE) Differentiation
- Surgery is advocated for early stage tumors, but surgery alone does not appear to be sufficient and adjuvant chemotherapy, consisting of platinum/etoposide, likely prevents recurrence in patients with completely resected LCNEC 6.
- For advanced disease, treatment modalities varied and the overall survival ranged from 11.0 to 46.7 months 2.
- Etoposide-based chemotherapy might be more effective in the treatment of LUAD with high NEDI values, while tumours with low NEDI values had better responses to immunotherapy than those with high NEDI values 4.
- Current guidelines for metastatic lung NET advocate a handful of treatment options, including somatostatin analogs (SSA), everolimus, temozolomide- or platin-based chemotherapy, and peptide receptor radionuclide therapy (PRRT) 3.