UICC World Cancer Congress 2006

Objective: To discuss the current evidence, policy positions, and on-going investigations related to the question of efficacy of lung cancer screening.

Methods: Discussion of the current state of knowledge about lung cancer screening in the context of Wilson and Junger's important work on criteria for introducing mass screening to the population at risk. (1)

Results: Lung cancer is the most common cancer diagnosed in the world (excluding skin cancers), and the most common cause of death from cancer (1.35 million new cases, and 1.15 million deaths estimated in 2002, respectively). (2) Lung cancer is relatively uncommon before age 50, with rates increasing rapidly after age 50. Overall, lung cancer has a very poor prognosis. The most recent 5-year survival statistics in the U.S. shows only 15% of cases surviving 5 years, with nearly 65% of patients succumbing within a year of diagnosis. (3) European survival data is even less favorable. (2) Five-year survival is measurably better (49%) when the disease is diagnosed while still localized, but only a small percentage of cases in the world (< 16%) are diagnosed without regional disease or distant metastases.

The majority of lung cancers develop in individuals with a history of cigarette smoking. Risk of lung cancer declines with cessation at any age compared with individuals who continue smoking, but the decline is greater among those who cease smoking early, and at least by middle age. (4) Clearly, there is no substitute for primary prevention of tobacco use, but hundreds of millions of adult in the world use tobacco, and hundreds of millions of adults are former smokers, with continuing excess risk. (5)

The observation that localized lung cancers had better survival led to several randomized trials of lung cancer screening with chest x-ray in the 1970's and 1980's, using combinations of chest X-ray and sputum cytology. (6-10) None of these studies showed a significant reduction in lung cancer mortality in the group invited to screening, although some results were suggestive of a survival benefit. (11-12) While results of prospective trials were disappointing, they also had such significant methodological limitations. (7) Newer technology for the early detection of lung cancer appears to be more promising than conventional chest x-rays. More recent results using low dose helical CT have renewed interest in lung cancer screening, most notably findings from the Early Lung Cancer Action Project (ELCAP), which demonstrated significantly superior performance of spiral CT compared with chest x-ray in finding small, resectable lung cancers. (13)These findings, and those from other similar investigations have led to the initiation of trals in Europe and the National Lung Screening Trial (NLST) in the U.S., initiated in September 20002. (14-15) However, given the very favorable performance of spiral CT compared with chest x-ray, and the apparent significant improvement in survival associated with diagnosis of a smaller tumor, many have expressed impatience with launching a prospective randomized trial, and postponing establishing health policy about lung cancer screening until the trials are completed. Do we know enough to begin screening for lung cancer now? Much remains to be learned before population based screening can be endorsed, but it can be learned at a more rapid pace.

Despite very favorable results from observational studies, (13, 16-17) broad consensus about policy depends, at a minimum, on results from a prospective randomized trial comparing lung cancer mortality in an experimental group with a control group. Ideally, this comparison is between a group invited to screening and a group receiving usual care. While early results were sufficiently promising to launch trials in the U.S. and Europe, one can only recall several decades of rancor over breast cancer screening questions, for which there was not consensus on the scientific evidence, to be reminded that absence of broad consensus about the scientific evidence was a major impediment to shaping consistent health policy. Further, screening must be thought of as having its own discrete chain of events, within a larger chain of events for the patient with lung cancer, the entirely of which is vulnerable to any break or weakness in the links. At this time, it is fair to say that we do not know with measurable confidence who should be invited to lung cancer screening based on age and risk, and at what intervals they should be screened. It also is fair to say that quality assurance protocols that have been demonstrated to be so essential to the success of breast cancer screening are not yet developed for lung cancer screening. There is no question that if lung cancer screening is shown to be efficacious, there will be a long learning curve for all involved before high quality services are commonplace. This is especially important because lung cancer screening has a relatively high likelihood of a positive result in individual patients at risk, and poor management of the process or reconciling an abnormality could result in significant harm to the patient.

Warner and Mulshine have proposed a vision for population-based lung cancer screening that offers the greatest potential for the population at risk, and the most effective use of heath resources. (18) They propose first, that we not wait until the conclusion of the trials to address a broad range of current concerns (overdiagnosis, cost-effectiveness, harms, etc.) and operational aspects of screening, specifically risk stratification and eligibility, test performance, diagnostic algorithms, and therapeutic strategies that are attentive to conservation of pulmonary reserve, especially considering that years of life gained are not years free of risk of secondary malignancies. Such a parallel strategy, i.e. conducting ongoing operational research and development concurrently with the trials, is possible in the U.S. since there is active promotion and uptake of testing for early lung cancer detection in the at-risk population outside of experimental settings. To the degree that these clinical programs can follow common algorithms and capture data for evaluation, such as the consortium of clinical centers organized by the Early Lung Cancer Action at the Weill Medical College of Cornell University, (19) much can be learned about best practices related to testing and integrated management of screen-detected lesions that the prospective randomized trials, with their greater emphasis on mortality endpoints, will not provide. Further, technology doesn't come to a standstill while trials are underway, and it is thus wiser to explore the potential and cost-effectiveness of evolving screening algorithms, new technologies, and diagnostic strategies since they are likely to be the ones in use at the conclusion of prospective studies. It is hard to defend the position that addressing the issue of how best to implement screening should await publication of trial end results.

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