Improved survival and higher mortality: the conundrum of lung cancer screening.

Abbreviations: CG control group; CR chest radiograph; ELCAP Early Lung Cancer Detection Project; FN false negative; FP false positive; HRCT high-resolution CT; IG intervention group; LC lung cancer; LCM lung cancer mortality; LDCT screening helical low-dose CT; MLP Mayo Lung Project; mSv millisieverts; NSCLC nonsmall cell lung cancer; SCR screening chest radiograph; TN true negative; TP true positive; TVDT tumor volume doubling time I mprovement in cancer survival rates constitutes such intuitively forceful evidence of progress in cancer treatment that its corollary, improvement in mortality rate, appears self-evident. However, Welch et al, 1 employing data from the nationally compiled Surveillance, Epidemiology, and End Results program, found no overall correlation between increased survival and mortality rates for 20 of the most common types of solid tumors. Survival (5year) is the percentage of individuals alive 5 years following a cancer diagnosis. Incidence and (causespecific) mortality rates are age-adjusted, population-based rates. Incidence is the number of new cases per 100,000 population per year, and the (cause-specific) mortality rate is the number of deaths (from the disease) per 100,000 population per year. Increased survival, with no change in mortality rate, is most often attributable to lead-time bias, in which improvements in ascertainment permit diagnosis at an earlier point in time without affecting longevity (outcome). Thus, earlier diagnosis of a highly lethal and untreatable neoplastic disorder would improve survival without affecting mortality rate. Less obviously, if an increase in longevity resulting from intervention in some individuals was offset by a delayed decrease in longevity in others, survival would improve and the mortality would remain unchanged. Survival and mortality are not complementary measures. Increased incidence may reflect a genuine secular trend, but it will be influenced by diagnostic improvements as well, particularly screening. In cancers with known effective treatments (eg, breast and testicular cancer), increased survival is, by definition, accompanied by decreased mortality, irrespective of an increased incidence attributable to improved diagnostics. Thus, compared with the period from 1950 to 1954, in the period from 1989 to 1995 the 5-year breast cancer For editorial comment see pages 1, 3 survival rate increased from 60 to 86%, incidence increased by 55%, and the mortality rate decreased by 8%. For the same periods, the 5-year survival rate for testicular cancer increased from 57 to 96%, incidence increased by 106%, and the mortality rate decreased by 73%. In contrast, although the 5-year survival rate for lung cancer (LC) more than doubled (from 6 to 14%) in the same periods, the increase in mortality rate (259%) exceeded the increase in incidence (249%). 1 An increase in LC incidence and survival are the expected consequences of the widespread employment of screening chest radiographs (SCRs) augmented by diagnostic and therapeutic advances. If this combination were effective, the mortality rate would necessarily decrease. If the observed increased LC mortality (LCM) rate reflected a secular trend in tumor aggressiveness, one would expect survival to decrease. Because increased survival is credited to therapeutic effectiveness, increased mortality and increased survival appear to be mutually exclusive outcomes. Two large, prospective, randomized, controlled, LC screening trials exhibited the same apparent