Ann Thorac Surg 2006;81:1193
© 2006 The Society of Thoracic Surgeons
Original article: General thoracic
Invited commentary
Richard Whyte, MD
Department of Cardiothoracic Surgery, CVRB 205, Stanford University Medical Center, 300 Pasteur Dr, Stanford, CA 94305
(Email: riwhyte{at}stanford.edu).
In the retrospective study by Yoshino and colleagues [1], the authors principal conclusion is that smoking is an independent predictor of survival in stage I patients with adenocarcinoma of the lung. This conclusion is based on the observations that (1) smokers had disproportionate numbers of higher stage patients, and that (2) at least for stage I patients, smoking was an independent predictor of survival. In addition, the authors observed that stage IB conferred a worse prognosis than stage IA, but failed to address whether this was dependent or independent of smoking status. Based on the observations from this study and future prospective analysis, it may be beneficial to extend adjuvant chemotherapy post-surgery to smokers with stage IB disease. The rationale that smoking confers a worse prognosis is supported by biologic effects of smoking that include exposure to oncogenic substances for longer periods of time, larger amounts of lung parenchyma being exposed to these substances, and on a molecular level, a larger number of genetic mutations occurring, thereby leading to upregulation of oncogenes, or downregulation of tumor suppressor genes. But why does this only apply to adenocarcinoma and not squamous cell carcinoma, and why only in stage I patients? The latter observation could be explained by the fact that stage I represents the largest number of patients, and that the effect does in fact take place in the other stages, but that the sample size does not permit it to be detected. Alternatively it could be that metastasis is the key event that determines prognosis, and that the differences between stages II, III, and IV are only ones of degree rather than the presence or absence of metastasis. The observation that smoking affects prognosis in adenocarcinoma (independent of the bronchoalveolar subtype), but not squamous cell tumors, may be better explained if we understood the molecular basis of the histologic subtypes of nonsmall cell lung cancer. Further work with gene microarrays and proteomic analysis with biomarker identification may elucidate this, but for now we must begin to realize that even though we tend to combine these subtypes together for purposes of treatment, their biologies may be different, and that as new drugs become available, specifically targeted therapies may be more appropriate.
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References
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- Yoshino I, Kawano D, Oba T, Yamazaki K, Kometani T, Maehara Y. Smoking status as a prognostic factor in patients with stage I pulmonary adenocarcinoma Ann Thorac Surg 2006;81:1189-1193.[Abstract/Free Full Text]
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