Elsevier

The Lancet

Volume 366, Issue 9494, 15–21 October 2005, Pages 1385-1396
The Lancet

Seminar
Small-cell lung cancer

https://doi.org/10.1016/S0140-6736(05)67569-1Get rights and content

Summary

Small-cell lung carcinoma is an aggressive form of lung cancer that is strongly associated with cigarette smoking and has a tendency for early dissemination. Increasing evidence has implicated autocrine growth loops, proto-oncogenes, and tumour-suppressor genes in its development. At presentation, the vast majority of patients are symptomatic, and imaging typically reveals a hilar mass. Pathology, in most cases of samples obtained by bronchoscopic biopsy, should be undertaken by pathologists with pulmonary expertise, with the provision of additional tissue for immunohistochemical stains as needed. Staging should aim to identify any evidence of distant disease, by imaging of the chest, upper abdomen, head, and bones as appropriate. Limited-stage disease should be treated with etoposide and cisplatin and concurrent early chest irradiation. All patients who achieve complete remission should be considered for treatment with prophylactic cranial irradiation, owing to the high frequency of brain metastases in this disease. Extensive-stage disease should be managed by combination chemotherapy, with a regimen such as etoposide and cisplatin administered for four to six cycles. Thereafter, patients with progressive or recurrent disease should be treated with additional chemotherapy. For patients who survive long term, careful monitoring for development of a second primary tumour is necessary, with further investigation and treatment as appropriate.

Section snippets

Molecular biology

The specific sequence of genetic alterations leading to small-cell lung cancer is still unclear. However, several important genetic and molecular changes have been noted, including the identification of autocrine growth loops, proto-oncogene activation, and loss or inactivation of tumour-suppressor genes.

Presentation and diagnosis

Patients with small-cell lung cancer typically present with disseminated disease. Symptoms are related either to bulky, intrathoracic disease or to distant metastases; cough and dyspnoea are the most common findings (table 2).51 Small-cell lung cancer tends to be centrally located, with hilar masses and hilar and mediastinal adenopathy (figure 1). Bronchoscopy shows submucosal endobronchial lesions, which partly explain the low likelihood of finding tumour cells in cytological brushings or

Paraneoplastic syndromes

Small-cell lung carcinoma has long been associated with paraneoplastic syndromes. The endocrine paraneoplastic disorders are characterised by ectopic production of peptide hormones, and the neurological complications are related to antibody-mediated damage to the central nervous system (table 3).

Hyponatraemia can be found in up to 15% of patients with small-cell lung cancer at presentation.57 In many of these patients, ectopic production of antidiuretic hormone, also known as arginine

Staging

Patients with small-cell lung cancer rarely present with disease that is sufficiently localised for surgical resection to be possible, so the TNM staging system is generally not used. Instead, staging typically uses the Veterans Administration Lung Study Group system, which classifies patients as having either limited-stage or extensive-stage disease.75 The definition of limited-stage disease varies but is generally designed to include patients whose disease is limited to one hemithorax, with

Prognostic factors

Several pretreatment characteristics in patients with small-cell lung cancer have been associated with meaningful differences in survival that have also been noted in patients with non-small-cell lung cancer (panel).82, 83, 84, 85, 86 The identification of such factors allows physicians and investigators to compare different populations of patients and to interpret the contribution of treatment to differences in survival between different groups. For example, since women with small-cell lung

Treatment

Combination chemotherapy remains the cornerstone of treatment for both limited-stage and extensive-stage small-cell lung cancer. In general, the administration of etoposide and cisplatin plus chest radiotherapy for patients with good performance status and limited-stage disease should produce a complete-response rate of 80% or higher, median survival in excess of 17 months, and 5-year cancer-free survival of 12–25%.76, 87 Patients with extensive-stage disease given combination chemotherapy

Prophylactic cranial irradiation

Patients whose small-cell lung cancer has been successfully treated nonetheless have a 50–67% risk of developing metastases in the central nervous system.140, 141 Therefore, in patients who have had a complete response to chemotherapy, cranial irradiation is used prophylactically. The radiation is typically administered in doses of 24–46 Gy in eight to 15 fractions. A meta-analysis of randomised trials of prophylactic cranial irradiation showed that the intervention reduced the risk of brain

Search strategy and selection criteria

This seminar is based mainly on papers published during the past 5 years, although some classic papers have been cited. The search strategy selected articles from MEDLINE by use of the PubMed system. The key words used were “carcinoma, small cell lung” cross-referenced with key words such as “epidemiology”, “pathology”, “cytogenetics”, “molecular biology”, “diagnosis”, “antineoplastic agents”, “radiotherapy”, and “surgery”. Only papers with an abstract in English were considered.

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