Morphology, surface antigens, staging, and prognostic factors of small cell lung cancer

Morphologic as well as biologic properties of small cell lung cancer change under chemotherapy toward a non-small cell and well-differentiated neuroendocrine phenotype. These biologic changes may be partly responsible for the acquisition of drug resistance. With the lack of significant advances with currently available chemotherapy, the development of new treatment strategies has become a major focus of research. Among others, these could include the use of antibodies to small cell lung cancer antigens. Several antigens associated with small cell lung cancer have now been biochemically and molecularly defined in the International Workshop of Small Cell Lung Cancer Antigens. In vitro and in vivo models have demonstrated the selective cytotoxic effect of immunoconjugates with radionuclides and plant toxins. Since recent clinical studies suggested a survival advantage for the use of radiotherapy in limited disease small cell lung cancer, anatomical staging to exclude distant sites of metastasis is likely to continue in clinical practice. Studies with a focus on cost-effective ways of anatomic staging are therefore of great importance. Continued efforts are under way to analyze pretreatment prognostic factors. The likely association of female gender with good prognosis and the in vitro data on stimulation of proliferation of small cell lung cancer cells by androgens may lead to the investigation of new therapeutic approaches based on endocrine manipulation.