PubMed · 8096301
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J P Pignon, R Arriagada. 1993-04-10. Meta-analysis.. https://pubmed.ncbi.nlm.nih.gov/8096301/
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The unique phenotype expressed by small cell lung cancer (SCLC) cells is responsible for the distinct clinical behavior of SCLC. Basic research of SCLC is aimed at identifying and characterizing the unique attributes of SCLC cells that distinguish SCLC from other forms of lung cancer and contribute to the malignant behavior of SCLC. This article summarizes recent scientific advances in this area. Specific issues which are addressed include our current understanding of how SCLC arises, the origin and consequences of the neuroendocrine phenotype expressed by SCLC cells, and the role of SCLC adhesion molecules in SCLC metastasis.
The clinical significance of a tumor classification rests in its usefulness to predict the natural history and response to therapeutic intervention of given tumor types. In this context, the importance of distinguishing between SCNC and neoplasms with which it has been confused is evident. In 1990, we re-evaluated a series of 50 patients who underwent a complete resection for tumors in which the diagnosis of small cell carcinoma was thought to have been established. Adjuvant therapy was given to nearly all patients, either pre- or postoperatively. We re-evaluated the histology of these tumors in light of the differential diagnosis described previously and correlated the diagnosis with the survival curves. We found that WDNC of any subtype has a much better prognosis than SCNC. Even locally advanced WDNC has a better prognosis than stage I completely resected SCNC (Fig. 9). Others have reported similar observations based on their own retrospective studies. Preliminary observations on completely resected chest wall PNETs suggest that these tumors also have a more favorable prognosis than SCNC. Given the difficulty in distinguishing SCNC from other tumors described previously, and the fact that most SCNC are treated without resection, the clinician should be familiar with certain features that are unusual for SCNC, and, therefore, suggest reconsideration of the diagnosis. In our patient population, SCNC is rarely seen in a lifetime nonsmoker and is distinctly unusual in an ex-smoker of 15 years of longer. T with chest wall invasion is a very unusual clinical stage for true SCNC. Small cell neuroendocrine carcinoma can invade the chest wall, but this is almost always in the presence of extensive mediastinal or distant metastases. Clinicians should also be wary of accepting the diagnosis of SCNC when serial radiographs suggest that the lesion is not growing or growing very slowly. Untreated SCNC usually demonstrates some growth over a 3-month period of observation. Finally, SCNC tends to be a chemosensitive neoplasm, at least initially. The occasional tumors that do not respond tend to enlarge and disseminate rapidly. If a tumor neither decreases nor increases in diameter over a 3-month period of presumably appropriate chemo- or radiotherapy, the diagnosis of SCNC should be questioned. Over the last 15 years, several reports have suggested a role for resection in the management of SCNC, especially for tumors diagnosed at an early stage. Other reports may have unwittingly exaggerated the long-term survival of SCNC treated by currently available chemo- and radiotherapy protocols. A careful re-evaluation of the diagnostic material in such cases may lead to more consistent results and the development of more rational therapeutic protocols.
Patients with SCLC should have a complete history and physical examination with particular attention paid to symptoms and signs of extensive disease and paraneoplastic syndromes. Hematology and biochemistry should be obtained at the initial assessment. A chest radiograph will usually have been performed prior to diagnosis. Further imaging should then be done to determine if the patient has limited or extensive disease. In the nonprotocol setting, extensive radiologic investigations are not required once a site of metastatic disease has been identified. If symptoms or signs are present to indicate a site of extensive disease, then this should direct the next test. In the absence of any specific findings then either bone scan or abdominal imaging with either US or CT scanning may be done based on the roughly equal likelihood of metastatic disease in liver or bone. Because a bone scan is less expensive, it is often the next test selected. If the bone scan is negative, abdominal imaging should then be performed, followed by brain CT scan. If these investigations are negative, the next study should be a thoracic CT scan. Bone marrow examination is probably unnecessary in the nonprotocol setting unless serum LDH levels are elevated. In the setting of a clinical trial, complete staging should be done and even more precise staging using the TNM system should be considered based on the improved survival of patients with proven stage I disease. Using more precise staging will allow accurate comparisons of clinical trials and eliminate or minimize the question of patient selection. Surgical staging with mediastinoscopy may come to have a role in accurately determining stage I or II disease.