Surgery for limited stage small cell lung cancer: time to fish or cut bait.

Small cell lung cancer (SCLC) accounts for only 15% of lung cancers overall,1 but this malignancy represents the fifth leading cause of cancer mortality in the United States when considered independently from non-SCLC.2 Because most patients with SCLC present with advanced nodal disease, with or without systemic involvement, SCLC represents less than 5% of cases in large surgical series.3 From a historical perspective, when Mountain4 reviewed the experience of the M.D. Anderson Hospital and Tumor Institute in the surgical management of 368 patients with pathologically proven SCLC, they reported 30 years ago that only one patient survived longer than 5 years compared with 15 to 25% of non-SCLC patients. The discrepancy can be explained by the biologic behavior of SCLC, which results in dissemination to regional lymph nodes and/or distant metastatic sites in more than 90% of patients at initial presentation, thereby precluding surgery. Even patients with apparently “limited-stage” or “operable” tumors probably have micrometastatic deposits at distant sites, which have the potential to proliferate if only local therapeutic modalities, such as surgery or radiotherapy, are used. This also explains the dismal results of the landmark randomized trial of the British Medical Research Council5 that compared surgical resection with “radical radiotherapy” (30 Gy). Median survivals were only 199 and 300 days in the radiotherapy and surgical arms, respectively, with only one and three patients alive at 5 years. The introduction of chemotherapy to the treatment of SCLC led to significant improvements in survival between the 1970s and 1990s,6 but recently, survival seems to have reached a plateau for both localized and advanced SCLC. For localized SCLC, chemotherapy and thoracic radiation represent a global standard of care, and there is general agreement that surgery has very little role to play in this malignancy.7 In the monumental staging initiative undertaken by the International Association for the Study of Lung Cancer (IASLC), there were 12,620 cases of SCLC8 in the database (8088 with complete tumor, node, and metastasis [TNM] staging information). Five-year survival rates for clinically staged patients with stages IA and IB tumors were 38% and 21%, respectively. Interestingly, 5-year survival rates for stages IIA and IIB were similar at 38% and 18%, respectively. It has long been recognized that clinical staging does not correlate with pathologic staging. The IASLC staging project also had complete pathologic TNM staging information for 349 cases of SCLC who had undergone surgical resection,9 making this the largest SCLC surgical series reported to date. Surgically treated SCLC represented only 1.3% of all fully staged resected cases in the database and only 2.8% of all SCLC cases. Concordance between clinical and pathologic TNM staging was only 58%. Five-year survival rates for pathologically staged patients with stages IA and IB tumors were 53% and 44%, respectively, and 43% and 35%, respectively, for stages IIA and IIB. In this issue of the Journal, Yu et al.10 have presented the results of their analysis of 247 patients from the National Cancer Institute Surveillance Epidemiology and End