Review Outlines Barriers to Widespread LDCT Lung Cancer Screening in Europe

In a recent review, authors outlined major factors inhibiting uptake of standardized, effective, and accessible low-dose CT (LDCT) screening for lung cancer throughout Europe.

Lung cancer accounted for 1.8 million deaths globally in 2020, and although promising therapeutics have been introduced for patients with late-stage disease, prognoses remain poor for most patients, researchers explained.

LDCT can help detect lung cancer early and reduce mortality. In the United States, CMS recently broadened its coverage for LDCT via a national coverage determination. Previously, Medicare beneficiaries could have the procedure covered beginning at age 55. Under the new rule, individuals aged 50 to 77 are eligible, while tobacco smoking history has been lowered from at least 30 packs per year to at least 20 packs per year.

However, large-scale European programs have yet to be implemented despite the practice’s proven benefits.

One study conducted in 2002 “reported an overall 20% (95% CI, 6.8%-26.7%; P = .004) reduction in lung cancer mortality after 6.5 years of follow-up when using LDCT compared to chest x-ray for lung cancer screening,” the authors wrote. Numerous other studies have since yielded encouraging results further supporting the use of LDCT in at-risk populations.

To reduce harms—including radiation exposure—and to ensure screening efficacy, appropriate trial population selection is imperative, the researchers stressed. Similar to inclusion criteria outlined by CMS, most LDCT lung cancer screening trials select participants based on age and smoking status.

But the authors cautioned these are not the only lung cancer risk factors, as family history, genetic polymorphisms, occupational hazards, and air pollution can all play roles in disease development. Thus far, only 1 randomized controlled trial has employed a lung cancer risk prediction model to select participants, and those investigators found it to have good discrimination and high sensitivity.

As a result, “the use of a risk-prediction model for participant selection in a lung cancer screening program could improve effectivity, and research should now be focused on further fine tuning and independent validation of existing risk prediction models,” the authors wrote.

An additional barrier to increased LDCT screening uptake for lung cancer is weighing its benefit-harm ratio, as participants can be exposed to radiation during the scans.

Although a short screening interval can lead to reductions in interval cancers and late-stage lung cancer, “a short interval does involve increased radiation exposure, costs, and a possible increase in false-positive results.”

Finding the appropriate balance can be challenging. Currently, the United States and Canada recommend annual screenings while other countries may opt for biennial screenings due to cost considerations. Different screening frequency can be based on a person’s lung cancer risk or presence of baseline lung nodules and new nodules detected; however, the latter option is not supported by evidence from existing trials.

Lung nodule assessment is also key when it comes to determining optimal LDCT screening implementation. Typically, these nodules are assessed based on size, growth, and type, but new evidence points to the benefits of also considering lung nodule volume.

“Nodule growth at follow-up screening can also be more accurately detected when using volumetric measurements in place of diameter, and can be used for the calculation of volume doubling time (VDT). VDT represents the exponential growth of a lung nodule and can subsequently be used for determining nodule management and follow-up,” the authors explained.

One additional barrier to LDCT screening uptake may be cost-effectiveness. Mixed findings have been published on this topic, with different conclusions relating to different at-risk populations.

Because of these variations, the researchers propose implementation of lung cancer screening strategies should be tailored to each specific country with regard to cost per quality-adjusted life-year.

“Cost-effectiveness analyses should therefore now be focused on country-specific health and social care infrastructure and perspectives,” they noted.

Increased workloads faced by radiologists—stemming from workforce shortages and higher demand—may also hinder implementation. However, new advancements in artificial intelligence (AI) may help ease some of these challenges.

For example, AI could assist a human scan reader, either as a first, second, or concurrent reader. But the risk of false-negatives and false-positives comes along with incorporation of AI into clinical practice, and a host of other potential hurdles.

“A different approach to the use of AI in LDCT-lung cancer screening is lung nodule classification using radiomics or deep learning models to distinguish between benign and malignant nodules,” researchers added. This could be used to determine new imaging biomarkers to help differentiate malignant and benign modules. It may also assist in determining individual-based lung cancer screening intervals.

Participant recruitment and adherence pose a challenge to successful implementation of screening trials. Several interventions have been proposed to meet this barrier, including introducing program coordinators, but further research is needed in this area, the authors said.

Importantly, improving trial implementation should not replace other lung cancer preventive measures such as smoking cessation programs, with some guidelines even calling for these programs to be built into screening trials. Previous research has also supported the concurrent implementation of abstinence and screening.

“To achieve optimal outcomes, research into factors associated with LDCT screening implementation is still necessary,” the researchers said.

“Shifting the focus to this type of research will help to achieve the fundamental goal of implementing accessible, affordable, and applicable CT screening programs in Europe for high-risk individuals. Once implemented, continuous monitoring of participant eligibility, LC detection rate, false-positive/negative rates, LC interval, adherence and referral rate, and CT radiation exposure will be required to ensure efficacy,” they concluded.

Reference

Lancaster HL, Heuvelmans MA, Oudkerk M. Low-dose CT lung cancer screening; clinical evidence and implementation research. J Intern Med. Published online March 6, 2022. doi:10.1111/joim.13480