Overview: NCI Workshop on Investigational Strategies for Detection and Intervention in Early Lung Cancer.

The reason why the NCI Workshop on Investigational Strat egies for Detection and Intervention in Early Lung Cancer was convened in Annapolis, Maryland, relates to the growing ex citement over reports of clinical trials suggesting benefit with the retinoid chemointervention approach in the upper airway, tamoxifen intervention with breast cancer, and the perceived potential of the growing body of information elucidating the nature of the early steps of epithelial cancer. Annapolis, by virtue of its proximity to Bethesda and the National Institutes of Health, ensures a healthy representation of the National Institutes of Health program staff. In the course of the Workshop, the opportunity existed for scientists, clini cians, and NIH program staff to learn more about the exciting opportunities provided in the approaches to early lung cancer. Because this is a new area which requires the close collaboration of a broad range of professionals, a corresponding evolution will be required in the trial methodology for these new direc tions. An intention of the Organ System Program staff and the organizing committee was to foster a full exploration of the scientific issues related to applications of emerging knowledge of early cancers and to identify mechanisms to potentially catalyze progress in this area of work. In considering the possibility of developing effective secondary prevention tools, i.e., tools for early cancer detection or biochemical intervention, there are several classes of issues. First, there are questions regarding the science of understand ing early cancer. What are the sequences of critical genetic events or critical levels of genetic events leading to the emer gence of a malignant clone of cells? What are the critical promotion factors in the process of carcinogenesis? What are the relevant markers which map the field carcinogenesis process in a fashion which lends them to application as early detection or intermediate end point discriminants? These are significant scientific questions and with the powerful molecular tools which have been recently developed basic scientists can become totally immersed by the opportunities provided in studying this area. A second level of questions arises if one attempts to apply the fruit of the recently elucidated tumor biology. How dose one scale up a molecular probe for lung cancer screening applications? The long experience with cervical cancer screen ing, as well as the more recent experience with human immu nodeficiency virus screening, demonstrates the complexity of the process of screening. An assay must be validated with great precision to permit responsible population-based application. Standardization of methodology for specimen acquisition, proc essing, analysis, and assay interpretation are all aspects of cytological screening of the cervix which are still controversial events after 50 years of experience with that screening tool. Can a prior consideration of this issue permit more efficient resolution of these issues for the next generation of bimolecular