Adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers as prognostic factors of early-stage large-cell neuroendocrine carcinoma

Background: We investigated whether adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers affected survival of patients with the early stage of large-cell neuroendocrine cancer. Methods: This was a retrospective multicenter study including consecutive patients undergoing resection of node negative large-cell neuroendocrine carcinoma. Five-year survival and disease-free survival rate were evaluated by the Kaplan–Meier method and the log-rank test in relation to adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers (synaptophysin, chromogranin A, and neuron-specific enolase). Results: Our study population included 117 patients; 47 (40%) of these received adjuvant chemotherapy. Patients treated with adjuvant chemotherapy had better survival (74% vs. 45%, p = 0.002) and disease-free survival (79% vs. 40%, p = 0.001) in all cases except patients with tumor <20 mm (79.5% vs. 57.4%, p = 0.43). Lobectomy compared to sublobar resection was associated with better survival (67% vs. 0.1%, p < 0.0001) and disease-free survival (65% vs. 0.1%, p < 0.0001) also in patients with tumor <20 mm (79% vs. 28%, p = 0.001). Patients with triple-positive neuroendocrine markers had better survival (79% vs. 35%, p = 0.0001) and disease-free survival (69% vs. 42%, p = 0.0008). Regression analysis showed that tumor size <20 mm, lobectomy, adjuvant chemotherapy, and triple-positive immunistochemical neuroendocrine markers were significant favorable prognostic factors for survival outcomes. Conclusions: Lobectomy seems to be the management of choice in patients with large-cell neuroendocrine cancer <20 mm while adjuvant chemotherapy should be administered only in patients with tumor >20 mm.