Abstract
Background and Objectives: Large cell neuroendocrine cancer is characterised by poor prognosis. The standard of treatment is still not established. The aim of this study was to assess the predictive factors of overall survival (OS) and progression-free survival (PFS) of pulmonary large cell neuroendocrine carcinoma (LCNEC) and combined LCNEC. Materials and Methods: All patients had confirmed pathology stage I-IV disease recorded between period 2002–2018. Survival curves were estimated by Kaplan–Meier method. Uni- and multivariable analysis was conducted using Cox-regression analysis. Results: A total of 132 patients with LCNEC and combined LCNEC were included. Half of them had clinical stage IIIB/C-IV. Patients were treated with radical (n = 67, including surgery alone; resection with neo-adjuvant or adjuvant chemotherapy, radiochemotherapy, or adjuvant radiotherapy; patients treated with radiochemotherapy alone), palliative (n = 41) or symptomatic (n = 24) intention. Seventeen patients were treated with resection margin R1 or R2. Non-small cell carcinoma (NSCLC) chemotherapy (platinum-vinorelbine; PN schedule) and small-cell lung carcinoma (SCLC) chemotherapy approaches (platinum/carboplatinum-etoposide; PE/KE schedule) were administered in 20 and in 55 patients, respectively. The median (95% Confidence Interval (CI)) OS and PFS were 17 months (9.0–36.2 months) and 7 months (3.0–15.0 months), respectively. Patients treated with negative resection margin, with lower clinical stage, without lymph node metastasis, and with size of primary tumour ≤4 cm showed significantly better OS and PFS. The main risk factors with an adverse effect on survival were advanced CS and positive resection margin. Conclusions: Patients with LCNEC characterized poor prognosis. Independent prognostic factors influencing PFS were initial clinical stage and resection margin R0 vs. R1-2.
Highlights
Neuroendocrine tumours of the lung are a diverse group of malignant neoplasms in terms of morphology, clinical characteristics, and etiology and represent 20% of all lung cancers [1]
Half of the patients were in IIIB/C-IV clinical stage, Ki67 > 55, and most patients (71%) had lymph node metastasis and size of tumour >4 cm (62%)
Radical treatment was administrated in 51% of patients, including surgery alone (45%), resection with neo- or adjuvant chemotherapy, radiochemotherapy or adjuvant radiotherapy (45%), or radiochemotherapy (10%)
Summary
Neuroendocrine tumours of the lung are a diverse group of malignant neoplasms in terms of morphology, clinical characteristics, and etiology and represent 20% of all lung cancers [1]. According to WHO classification (2015), four main types are distinguished—typical carcinoids, atypical carcinoids (low-grade tumours), small-cell lung carcinoma (SCLC), and large-cell neuroendocrine carcinoma (LCNEC)—all of which represent a group of high-grade malignant tumours. The current WHO classification defines LCNEC as morphologically non-small cell carcinoma (NSCLC) with histopathological features of neuroendocrine cancer and immunohistochemical expression of neuroendocrine markers. Clinical LCNEC behaves biologically aggressively, to SCLC [2,3]. Pulmonary LCNECs are rare tumours of the lung and the incidence appears to be approximately 3% of all lung cancers [4]. Five-year survival rates range from 15% to 57% for patients with LCNEC and
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