Conflicting evidence in lung cancer screening: randomized controlled trials versus case-control studies☆

In today’s issue of Lung Cancer, we return to the issue of chest X-ray/sputum cytology screening for lung cancer. Sagawa et al. present the results of four recently published studies [1 /4] that addressed the question, and use meta-analysis techniques to provide a summary estimate of the relationship [5]. Their findings will be considered by many to be atypical: the four studies (referred to hereafter as the ‘‘Sagawa studies’’) observed a reduction (statistically significant in three) in lung cancer mortality with screening, and the summary result, which also was statistically significant, suggests a reduction on the order of 40%. Why do these studies show a benefit, while others have shown none [6 /9]? There may be very simple answers to this question. One simple answer may be that the Sagawa studies were conducted in Japan, while the studies that show no benefit were conducted in the United States (Memorial Sloan-Kettering study [6], Johns Hopkins study [7], Mayo Lung Project [8]) and Europe (Czechoslovakian study[9]). Another simple answer may be that the chest X-ray technology utilized in the Sagawa studies was superior to that employed in the aforementioned conflicting studies; the Sagawa studies were conducted in the 1990s, while the other studies were conducted in the 1970s and 1980s. Yet another simple answer may be that a different question was addressed in the Sagawa studies (attendance after invitation to a screening program vs. no attendance after invitation) as compared with the Mayo Lung Project [8] (prevalence screen for all, intense screening vs. a one-time recommendation for annual screening) and the Czechoslovakian study [9] (prevalence screen for all, screening at 6-month intervals for intervention arm participants, additional screen for controls 3 years after enrollment). In fact, some might argue that the Sagawa studies came closest to answering the most relevant question: does annual screening, compared with no screening, reduce the risk of lung cancer mortality. While it is plausible that the aforementioned explain the inconsistency in results, another difference must be considered. While the most prominent of the previous studies utilized a randomized controlled trial (RCT) design [6 /9], the Sagawa studies utilized the case-control study design. As the reader is well aware, RCTs are considered the ‘‘gold standard’’ in research [10], primarily because many biases are avoided due to random assignment of the study regimen. Casecontrol studies, on the other hand, assess relationships among individuals who have chosen their exposure (in this instance, their screening regimen) [11]. The case-control design is useful in situations where exposure cannot be assigned due to logistical or ethical issues, but in research fields like cancer screening, where RCTs can and have been done, the findings of case-control studies usually PII of linked article S0169-5002(03)00197-1 *For courier: 6130 Executive Blvd, Suite 3131, Rockville, MD 20852, USA. Tel.: /1-301-496-7468; fax: /1-301-402-0816. E-mail address: pm145q@nih.gov (P.M. Marcus). Lung Cancer (2003) 41, 37 /39