Surgery in Small-Cell Lung Cancer: Past, Present and Future

Abstract

Small-Cell Lung Carcinoma (SCLC) represents about 15% of all lung cancers diagnosed worldwide. Although its incidence is diminished in the last decades, SCLC continues to represent an almost fatal disease due to its propensity to local relapse and distant metastasis, despite initial responsiveness to therapies. Biological behaviour of SCLC has therefore lead to consider it as a systemic disease per se not amenable of surgical resection: the Veterans Administration Lung Study Group (VALSG) two-stage classification was in fact based on field irradiation criteria and has been applied to SCLC for long-time. The introduction of TNM staging system, the common recurrences of local disease despite initial complete response after chemo-radiation therapy, the lack of a valid maintenance therapy after remission or a second-line therapy after relapse renewed interest in surgery in a multimodal treatment setting. However, the second prospective randomized trial in 1994, did not confirm any significant advantage of surgery compared to chemo-radiation therapy and several retrospective studies published in the same years failed to provide strong evidences of surgery's benefits. Lack of homogeneity in design of clinical trials, which are mostly dated, patients selection and other confounding factors made results of metaanalysis too much inconsistent to be added to guidelines; for these reasons, nowadays, surgery is recommended only in small peripheral nodules without nodal involvement (proven by invasive preoperative staging). Advances in comprehension of biological pathways underlying carcinogenesis in SCLC are the next steps that could deeply modify the approach to disease (patients selection and prognostic stratification, chemosensitivity and treatment modality) beyond the mere histology. Molecular profile should lead to identify subsets of tumours with more favourable prognosis, especially in terms of systemic control of disease, which is actually a major issue in SCLC; these subsets could be overlapped to NSCLC regarding to natural history of disease, making their treatment similar, including indication to surgery. The aim of this review is to analyze literature to deduce which has been, is actually and could be the role of surgery on overall survival and pattern of recurrence of patients affected by SCLC.