Lung Cancer Screening Population in Real World May Be at Greater Risk for Harm

Lung cancer screening populations are older and sicker than those in the National Lung Screening Trial (NLST), a multicenter analysis showed, casting doubt on replicability in the real world.

As compared with the NLST, which launched programs across the country, the Personalized Lung Cancer Screening (PLuS) cohort study had a higher proportion of participants ages 65 and older (49% vs 26.6%), reported Dejana Braithwaite, PhD, MSc, of the University of Florida College of Medicine in Gainesville, and colleagues in JAMA Health Forum.

Rates of comorbidities in PLuS also exceeded those observed in the NLST. Prevalence rates were particularly high for chronic obstructive pulmonary disease (COPD; 32.7% vs 17.5%, respectively), diabetes (24.6% vs 9.7%), and heart disease (15.9% vs 12.9%).

“These findings suggest that many individuals screened for lung cancer may experience additional complications in conjunction with lung cancer diagnosis and treatment because of their age and underlying comorbid conditions and may not live long enough to benefit from LCS [lung cancer screening],” Braithwaite and team wrote. “Older patients and those with consequential comorbidity likely have different risk-benefit profiles, which may affect screening outcomes.”

“Our results underscore the importance of developing the evidence for advancing risk-based LCS,” they added. “The high prevalence of multimorbidity, frailty, and impaired cardiopulmonary function in the PLuS cohort suggests that the balance of benefits and harms observed in the NLST group may not translate to the clinical setting.”

The randomized NLST had shown that three rounds of annual screening with low-dose CT reduced lung cancer mortality by 20% among current and former smokers as compared with the same number of annual screens with chest radiography. However, there were risks as well: false positives, complications in procedures for benign nodules, and more.

Given the risk of those events, along with “the overall healthier status and younger age of NLST participants relative to screening-eligible adults in the clinical setting, and the higher procedure volumes and dedicated thoracic surgery support generally seen in NLST trial centers, it may prove difficult to replicate the relatively low risk of harms as LCS is implemented in clinical populations and settings,” Braithwaite and colleagues wrote.

The PLuS data appear to be more akin to the general U.S. population eligible for screening, which is nearly twice as likely to be 70 or older and significantly more likely to currently smoke tobacco than those in the NLST. About two-thirds have comorbid conditions that may diminish the overall benefit of screening.

PLuS included 31,795 patients who had low-dose CT lung cancer screening (but no lung cancer diagnosis in the 5 years prior) across three healthcare systems in California, Florida, and South Carolina between 2016 and 2021. Comorbidity and pulmonary function data were abstracted from electronic health records and from institutional and state registries, along with Surveillance, Epidemiology, and End Results (SEER) data. Comparator data in the NLST came from self-report in the low-dose CT arm of the trial.

The PLuS cohort was more diverse than the NLST patients, with 23.3% identifying as a racial and ethnic minority compared with 8.5%, which the researchers called “a meaningful step toward reducing disparities in outcomes.”

Severe comorbidities were common in the PLuS cohort. More than 19% had a Charlson Comorbidity Index score of 4 or higher, which makes favorable health outcomes less likely across the continuum from diagnostic testing to potentially curative surgery. “In addition, competing causes of death from diseases such as COPD, heart disease, and other cancers may attenuate the benefit of screening,” the researchers wrote.

Notably, multimorbidity and frailty were especially common among PLuS cohort patients ages 75 and older — a group not included at baseline in the NLST.

“There is an opportunity to develop and deploy new interventions that manage the complex health profiles of older LCS candidates with greater disease severity and target LCS in populations where it is likely to have the greatest impact,” Braithwaite’s group concluded.

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