PURPOSE: Our aims were to evaluate (1) the result of surgical treatment of limited-stage small cell lung cancer (SCLC) by examining long-term survival and prognostic factors, (2) the diagnostic role of surgery by comparing clinical and histopathological diagnoses and staging, and (3) the impact of preoperative diagnostic accuracy on survival.

METHODS: We retrospectively reviewed the clinical profiles of 37 patients treated at our institution between January 1990 and December 2007 for SCLC diagnosed using surgical specimens.

RESULTS: The median follow-up period was 41.2 months, and the 5-year survival rate was 57.5%. Lobectomy or wider resection was performed alone in 33 cases and with mediastinal dissection in 29 cases. Fifteen patients did not receive chemotherapy. SCLC was diagnosed preoperatively or intraoperatively in 75% and non-SCLC in 25%. Clinical stage 1 disease was diagnosed in 29 patients; however, pathological stage 1 was seen in only 20. Patients at pathological stage 1 disease showed better survival than those at stage 2, but a similar result was not obtained in the case of clinical stage of the disease. Tumor size and nodal stage were the only significant factors influencing survival in a multivariate analysis. The adequacy of preoperative clinical diagnosis of tumor extensiveness, nodal involvement, and clinical stage did not significantly influence survival.

CONCLUSION: Surgery for limited-stage SCLC was associated with a favorable survival rate and provided important pathological information that can help predict survival. Accuracy of preoperative diagnoses showed no apparent impact on survival for surgically treated SCLC patients.

Small cell lung cancer (SCLC) has been primarily classified as limited or extensive, with limited stage confined to the primary tumor and regional lymph nodes. In the future, the TNM staging system should be integrated into the classification of SCLC.

The appropriate staging work-up for patients with SCLC has traditionally included contrast-enhanced computed tomography (CT) scans of the chest and abdomen, bone scan, and magnetic resonance imaging or CT scan of the brain. Recent data suggest that positron emission tomography can improve both staging accuracy and treatment planning in patients with SCLC.

Treatment for limited-stage SCLC consists of chemotherapy plus radiotherapy, and such therapy can cure 20-25% of patients. Extensive-stage SCLC is incurable, but chemotherapy can improve quality of life and prolong life.

Circulating tumor cells (CTCs) may have utility as surrogate biomarkers and "virtual" biopsies. We report the clinical significance and molecular characteristics of CTCs and CTC clusters, termed circulating tumor microemboli (CTM), detected in patients with small-cell lung cancer (SCLC) undergoing standard treatment.

PATIENTS AND METHODS : Serial blood samples from 97 patients receiving chemotherapy were analyzed using EpCam-based immunomagnetic detection and a filtration-based technique. Proliferation status (Ki67) and apoptotic morphology were examined. Associations of CTC and CTM number with clinical factors and prognosis were determined.

Results : CTCs were present in 85% of patients (77 of 97 patients) and were abundant (mean ± standard deviation = 1,589 ± 5,565). CTM and apoptotic CTCs were correlated with total CTC number and were detected in 32% and 57% of patients, respectively. Pretreatment CTCs, change in CTC number after one cycle of chemotherapy, CTM, and apoptotic CTCs were independent prognostic factors. Overall survival was 5.4 months for patients with ≥ 50 CTCs/7.5 mL of blood and 11.5 months (P < .0001) for patients with less than 50 CTCs/7.5 mL of blood before chemotherapy (hazard ratio = 2.45; 95% CI, 1.39 to 4.30; P = .002). Subpopulations of apoptotic and of proliferating solitary CTCs were detected, whereas neither were observed within cell clusters (CTM), implicating both protection from anoikis and relative resistance to cytotoxic drugs for cells within CTM.

CONCLUSION : Both baseline CTC number and change in CTC number after one cycle of chemotherapy are independent prognostic factors for SCLC. Molecular comparison of CTCs to cells in CTM may provide novel insights into SCLC biology.

Introduction: Small cell lung cancer (SCLC) is a biologically complex tumor whose medical treatment has remained largely unchanged over the last 30 years. The frustration for the invariably negative results reported in the early 2000s in clinical studies investigating new agents for this disease have contributed to the little interest shown by pharmaceutical industries in funding SCLC research. However, recent advances in the molecular understanding of the oncogenic mechanisms underlying SCLC have renewed the attraction for the clinical development of novel active drugs for the treatment of this challenging disease.

Areas covered: The authors briefly touch on the most promising agents under clinical development for the treatment of SCLC, either chemotherapeutic or targeted drugs. Relevant and recent (2 years) studies obtained through Pubmed literature research or released at International scientific meetings are presented.

Expert opinion: The data discussed herein provide evidence in support of the fact that only rationally designed clinical trials including relevant translational research may lead to successful results. Therefore, a thoughtful change in trial construction is crucial for the approval of new active drugs for this orphan disease.