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LUNG CANCER: Gary M. Strauss, Lorenzo Dominioni, James R. Jett, Matthew Freedman, and Frederic W. Grannis, Jr Como International Conference Position Statement: Lung Cancer Screening for Early Diagnosis 5 Years After The 1998 Varese Conference Chest 2005; 127: 1146-1151 [Abstract] [Full text] [PDF]

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Premises and Precision

Jerome M Reich   (20 May 2005)

Premises and Precision 20 May 2005
Jerome M Reich, Physician Send letter to journal: Re: Premises and Precision Reichje{at}dnamail.com Jerome M Reich	Premises and Precision* London, 1770. Engrossed in conversation, two figures emerge from the Mitre Tavern, walking arm in arm eastward toward the Thames. Pausing momentarily to listen to two neighbors vociferously arguing over the fence separating their residences, the larger of the two (Johnson) addresses his companion (Boswell): “Depend on it Sir, that disputation will not be resolved!—They are arguing from different premises.” Basing their opinion principally on the premise that increased survival observed with lung cancer screening constitutes evidence of efficacy, the authors (1) suggest that radiographic imaging should be considered by individuals at risk. However, mortality reduction, not survival enhancement, is the goal of cancer screening. The premise that an increase in survival will translate into a reduction in mortality was shown to be invalid by Welch et al.(2), who reported that despite an impressive increase in lung cancer survival (from 6% to 14%) between 1950-54 and 1989-95, mortality was not reduced. In contradistinction to what might have been expected, mortality increased over this time interval, the increase (259%) outpacing the increase in incidence (249%). The authors (1) state, referencing the Mayo and Czech trials in the 70’s and 80’s, that these were: “ . . . interpreted as indicating that CXR screening was ineffective. This is because of a failure to demonstrate significant reductions in lung cancer mortality in populations that were randomized to CXR screening.” It would have been more precise to state that those populations randomized to screening experienced both a higher lung cancer and a higher all-cause mortality: Manser et al. (3) pooled the updated Mayo (4) and Czech (5) trials, and found a risk of death from lung cancer to be 11% higher in the intervention groups: relative risk (RR), 1.11; 95% confidence interval (CI), 1.00-1.23; p = .05. For all-cause mortality, they reported an intervention cohort RR of 1.03; 95% CI, .93-1.14 in the Mayo, and a RR of 1.16; 95% CI, 1.00-1.35 in the Czech trial. Lung cancer screening can reduce mortality only if it succeeds at interdicting growth at a resectable stage. Although the screened populations in both trials achieved the objective of identifying a larger number and proportion with resectable cancers, neither trial achieved a reduction in the absolute number of advanced cancers. One might speculate that some of the screen-identified resectable cancers lacked lethal biologic potential. This is germane because, augmenting surgical mortality, persons with lung cancer experience a much higher non-cancer mortality than obtains in persons with other common malignancies: Brown et al.(6), employing SEER database figures, reported that 10% of individuals with lung cancer died of non-cancer causes, and that the non-cancer relative hazard of death was nearly three-times the non-cancer hazard of death in age and gender matched persons. I fully agree with the authors: if one chooses to set aside the observations that survival improvement in plain radiographic screening has been accompanied by higher lung cancer and all-cause mortality; that ~90% of positive tests in low-dose computerized tomographic screening trials are false-positive, with an attendant psychological impact, radiation exposure from sequential examinations and risk of invasive interventions; that persons undergoing curative lung cancer surgery experience a high non-cancer mortality, which will, at least in part, offset any benefit; and that the costs involved are huge, then it is perfectly prudent to suggest to persons at risk that they undergo radiographic screening on the premise that the consequent increased survival will be reflected by a reduction in mortality. *Premises and Precision Chapter 1. It is a truth universally acknowledged that agreement on the validity of premises and precision of reportage will hasten resolution of disputes . . . Jayne Austin References (1)Strauss GM, Dominioni L, Jett JR, Freedman M, Grannis FW. Como International conference position. Chest 2005;127:1146-51 (2)Welch GH, Schwartz L, Woloshin S. Are increasing 5-year survival rates evidence of success against cancer? JAMA 2000;283(22):2975-78 (3)Manser RL, Irving LB, Byrnes G, Abramson MJ, Stone CA, Campbell DA. Screening for lung cancer: a systematic review and meta-analysis of controlled trials. Thorax 2003;58:784-89 (4)Marcus PM, Bergstralh E, Fagerstrom RM, et al. lung cancer mortality in the Mayo lung project: impact of extended followup. J Natl Cancer Inst 2000;92:1308-16 (5)Kubďk A, Parkin DM, Khlat M, Erban J, Polak J, Adamec M. Lack of benefit from semi-annual screening for cancer of the lung: follow-up report of a randomized controlled trial on a population of high-risk males in Czechoslovakia. Int J Cancer 1990; 45:26-33 (6)Brown BW, Brauner C, Minnotte MC. Noncancer deaths in white adult cancer patients. J Natl Cancer Inst 1993;85:979-87 Yours truly, Jerome Reich, MD, FCCP