Surgical treatment of neuroendocrine tumors of the lung*1

Abstract
Objective: This report reviews the pattern of neuroendocrine (NE) differentiation, lymph-node involvement, extension of surgery, and survival in 125 NE lung tumor patients. Methods: Standard diagnostic workup included CT scan, bronchoscopy, bronchial biopsy or Fine Needle Aspiration Biopsy, 111In-pentetreotide scan (OctreoScan) and mediastinoscopy in selected patients. NE differentiation was assessed based on the morphology and immunohistochemical reactivity for pan-neuroendocrine markers NSE, CGA, and Synaptophysin. For small cell carcinoma (SCC), only clinical stage I and II patients underwent surgery. Several different surgical procedures were utilized, from limited resections to lobectomy, pneumonectomy, and bronchoplastic procedures. Survival was assessed using Kaplan–Meyer method at 5 years. Results: There were 79 typical carcinoid (TC), eight atypical carcinoid (AC), 18 large cell carcinoma (LCC) and 20 SCC patients. Mean age at diagnosis was 54.6±15.2 (ranges from 16 to 77 years) for TC, 68.5±9.1 (range 53–81) for AC, 68.7±4.6 (range 58–77) for LCC, 64.6±7.9 (range 48–82) for SCC. Male/female ratio was 1/1 for TC and AC, 2.6/1 for LCC and 9/1 for SCC. Lymph-node involvement was present in 14% of TC, 0% of AC, 31.5% of LCC, and 45% of SCC. Cancer specific survival was 96% for TC, 87.5% for AC, 37.5% for LCC, and 30% for SCC at 5 years from surgery. Presenting symptoms were invariably of respiratory-related. None had the carcinoid syndrome. History of tobacco abuse ranged from 46% for TC to 100% in SCC. Survival ranged from a minimum of 1 month for SCC to a maximum of 168 months with no evidence of disease for TC. Synchronous multicentric forms were found in 14% of TC. Twenty-one percent (4/19) of the patients with SCC treated by induction therapy and surgery, and in few cases by surgery and adjuvant chemotherapy are alive without the evidence of the disease for 5 years. Conclusions: Due to the high percentage of lymph-node involvement and multicentric forms found in our series lobectomy with radical lymph-node dissection appears, in our opinion, the most appropriate surgical treatment in well-differentiated forms, while more limited resection appears sub-optimal. Also, due to the finding of recurrences many years after surgery, the follow-up must be accurate and protracted in this subgroup. Only Small Cell Lung Carcinoma patients in clinical stage I and II underwent surgery with good long-term results.