LDCT Screening Linked With Overdiagnosis of Lung Cancer Among Taiwanese Women

Low-dose CT (LDCT) screening of mostly nonsmoking Asian women was associated with considerable lung cancer overdiagnosis, according to findings of a population-based cohort study.

Results, published in JAMA Internal Medicine, also revealed 5-year survival is biased by LDCT detection of indolent early-stage lung cancers, leading researchers to conclude LDCT screening should be targeted only to heavy smokers unless randomized trials show value in low-risk groups.

In 2021, the US Preventive Services Task Force expanded lung cancer screening eligibility to those with 20 or more pack-years (down from the previous recommendation of 30 pack-years) based on modeling studies and a European trial.

Large proportions of lung cancer cases are attributable to smoking; however, not all are, and this proportion is expected to grow as cigarette smoking declines in some regions.

Opportunistic lung cancer screening has been popularized in Asian countries including Taiwan, China, and South Korea, where hospital-based programs routinely include nonsmokers, the authors explained.

In Taiwan, the practice has been offered “as a free charitable service to selected groups,” with women often featured in promotions for LDCT, a notable fact as women in Taiwan rarely smoke. Studies have shown prevalence among this population has been under 5% since 1980.

To elucidate the potential of lung cancer overdiagnosis following LDCT promotion, investigators assessed data from the Taiwan National Cancer Registry. Specifically, they sought evidence on “increased early-stage incidence, demonstrating that screening detects cancer early, and decreased late-stage incidence, demonstrating that screening leads to a reduction in the presentation of advanced cancer.”

Analyses were conducted on cases diagnosed between 2004 and 2018 while all incidence data were age adjusted to the 2000 world standard population, the researchers wrote.

Of the approximately 12 million women in the Taiwanese population, 57,898 received a lung cancer diagnosis diagnosed in this window.

Analyses revealed:

• After the introduction of LDCT screening, the incidence of early-stage (stages 0-I) lung cancer in women increased more than 6-fold, from 2.3 to 14.4 per 100,000 population (absolute difference, 12.1; 95% CI, 11.3-12.8) from 2004 to 2018
• There was no change in the incidence of late-stage (stages II-IV) lung cancer, from 18.7 to 19.3 per 100,000 (absolute difference, 0.6; 95% CI, –0.5 to 1.7)
• Because the additional 12.1 per 100,000 early-stage cancers were not accompanied by a concomitant decline in late-stage cancers, most of the additional cancers detected represent overdiagnosis
• Despite stable mortality, 5-year survival more than doubled from 2004 to 2013, from 18% to 40%, which is arguably the highest lung cancer survival rate in the world

The approaches used in this study suggest that overall, between 7000 and 12,2000 Taiwanese women have been overdiagnosed with lung cancer

Alternative explanations to overdiagnosis, including that the true occurrence of lung cancer is increasing in Taiwan, are possible but unlikely, the researchers explained. “It is difficult to imagine how such an increase in true disease occurrence would involve solely early-stage disease,” they wrote.

Findings also do not exclude the fact that LDCT screening may have had a small beneficial effect, as screening could have advanced the time of diagnosis of a few cancers on track to become late-stage disease. But “a possible beneficial effect of screening has no bearing on the question of whether overdiagnosis is occurring, because the 2 can coexist,” the authors said.

Additional data revealed a downstream effect of overtreatment based on overdiagnosis. The investigators also highlighted the role of the “popularity paradox” insofar as the more overdiagnosis and overtreatment that occur following screening, the more people feel the practice is beneficial and popularity of the service grows.

“Because the risk of lung cancer diagnosis is conflated with the risk of death due to lung cancer, widespread screening apparently diminishes the importance of cigarette smoking as a risk factor for lung cancer,” marking another unforeseen consequence of the screening initiative.

Due to the nature of the observational study, causal conclusions cannot be drawn and confounding bias may be present. However, “the pattern of incidence growth—dramatically rising early-stage incidence coupled with stable late-stage incidence—is difficult to explain as anything other than an effect of screening or incidental detection,” the authors concluded.

Reference

Gao W, Wen CP, Wu A, Welch HG. Association of computer tomographic screening promotion with lung cancer diagnosis among Asian women. JAMA Intern Med. Published online January 18, 2022. doi:10.1001/jamainternmed.2021.7769