Although the annual incidence of lung cancer is dropping in some countries, such as the US, lung cancer is still a leading cause of cancer-related death.1,2 An individual’s propensity to survive lung cancer largely depends on the stage at diagnosis. Therefore, early detection is a major strategy for improving population-level lung cancer statistics. Disseminating effective early detection programs creates a major opportunity to improve public health.
The National Lung Screening Trial (NLST), the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON), and the Multicentric Italian Lung Detection Trial (MILD) clearly demonstrated that low-dose computed tomographic (LDCT) screening for lung cancer saves lives.3,4,5 Unfortunately, implementation has been challenging, even in the US, where LDCT screening has been a covered healthcare benefit since 2015. In addition to LDCT screening for ostensibly healthy persons deemed to be at high risk, lung cancer can be detected early through programs designed to foster guideline-concordant management of incidentally detected lung nodules.6 These two approaches to early lung cancer detection have different resource requirements, eligibility criteria, healthcare policy support, and may provide access to different segments of the population at risk for lung cancer.
Current Problems with LDCT Lung Cancer Screening
The population-level impact of lung cancer screening is hindered by multiple factors. First is the implementation barrier. Since the Medicare Coverage Decision in 2015, it is estimated that only 5% of eligible people have undergone lung cancer screening in the US. This slow pace of adoption leaves LDCT lung cancer screening well behind approved screening tests for other cancers, such as mammography for breast cancer, Pap test for cervical cancer, and colonoscopy for colorectal cancer.7
However, even with full implementation, only a minority of the US lung cancer population would be eligible for screening. By one estimate, uniform adoption of the NLST eligibility criteria would have enabled detection of 27% of all individuals with lung cancer in the US.8 The population-level impact of lung cancer screening is inhibited by a mismatch between age- and tobacco-based risk definitions and true lung cancer risk within population subgroups. Women, Black people, and Native Hawaiians are at considerably higher risk for lung cancer at earlier ages and with lower levels of cigarette smoking than white males.9 Therefore, the ratio of lung cancer incidence to LDCT screening eligibility differs significantly by sex and race.9
Age, race, geographic, and socio-economic disparities in access to LDCT screening have also emerged. Paradoxically, the segments of the population most at risk for lung cancer are also the most likely to be disadvantaged in accessing LDCT screening. In an attempt to reduce these disparities, the US Preventive Services Task Force (USPSTF) expanded LDCT lung cancer screening eligibility criteria in 2021.10
Lung Nodule Programs—A Complementary Approach
In addition to LDCT screening, programs to promote guideline-concordant management of incidentally detected lung nodules provide an avenue to early lung cancer detection. We recently reported the impact of a lung nodule program implemented concurrently with a lung cancer screening program, the Detecting Early Lung Cancer (DELUGE) in the Mississippi Delta cohort.6 DELUGE is a prospective observational cohort study of individuals enrolled in LDCT and incidental lung nodule programs in a large community healthcare system covering counties in Mississippi, Arkansas, and Tennessee. These states have some of the highest lung cancer incidence and mortality rates in the US.1
The DELUGE lung nodule program was implemented to promote guideline-concordant management of lung lesions identified by radiologic studies performed for reasons other than suspected cancer or screening. From January 2015 to May 2021, the lung nodule program enrolled 15,461 individuals, 772 of which were subsequently diagnosed with lung cancer. During this time, for every one person diagnosed with lung cancer by LDCT screening, five people were diagnosed with lung cancer in the nodule program.
Both early detection programs succeeded in redistributing lung cancer diagnoses to earlier stages compared with the typical multidisciplinary lung clinic patient population. Earlier stage at diagnosis resulted in more curative-intent surgery in both early detection programs. Of note, most individuals diagnosed with lung cancer in the DELUGE nodule program would not have been eligible for LDCT lung cancer screening by current criteria at the time of diagnosis.
Expanding LDCT Screening Criteria
To address the noted race- and sex-based disparities in LDCT screening eligibility, the USPSTF expanded the recommendations for lung cancer screening in 2021. The expanded USPSTF 2021 criteria reduced the age of eligibility from 55 to 50 years and reduce the required lifetime smoking exposure from 30 pack-years to 20 pack-years.10 In a recent publication in the Journal of Thoracic Oncology, we used the DELUGE nodule cohort to examine how modifications of the USPSTF criteria could have impacted access to LDCT screening and the race- and sex-based differences over the previous six years.11
In the 17,421 individuals enrolled in the DELUGE nodule cohort from 2015 to 2021, the USPSTF 2021 criteria would have led to a 30% increase in screening eligibility compared to the USPSTF 2013 criteria. The additional cohort of individuals who were eligible for screening by applying the 2021 criteria were 27% Black and 55% female compared to the individuals eligible by USPSTF 2013 who were 17% Black and 48% female.
We also evaluated the potential impact of more expansive changes to lung screening criteria. When we reduced the pack-year requirement to 10 years, the overall eligibility increased an additional 13% over the USPSTF 2021 criteria and the proportion of eligible individuals who were Black or female increased further. Expanding the quit duration from 15 to 25 years, which resulted in similar proportions of eligible Black and female individuals compared to USPSTF 2021, led to a 9% increase in the total number eligible.
In this cohort of patients with pulmonary nodules identified, one lung cancer was diagnosed for every 4.5 individuals eligible by USPSTF 2013 criteria and 5.0 individuals by USPSTF 2021 criteria. The additional scenarios evaluated, with more liberal pack-year and quit duration criteria, yielded one lung cancer for every 5.0 to 5.3 individuals.
Data from the DELUGE cohort support the hypothesis that USPSTF 2021 criteria can increase access to Black individuals and women, and it would not result in a large increase in the number needed to screen. We also found some evidence to suggest that a further reduction in smoking exposure criteria should be considered.
The Path Forward
The lifesaving ability of lung cancer screening has been demonstrated in multiple clinical trials in multiple populations. Yet, the full societal benefit of early lung cancer detection remains elusive. The population-level impact is severely diluted by implementation barriers. Appropriately, a significant proportion of early detection effort is currently focused on improving the uptake of LDCT screening in populations eligible by current selection criteria. Necessary as this effort is, it is insufficient to achieve the full potential population-level benefit of early lung cancer detection.
Treatment of individuals with early-stage lung cancer can be highly successful with multidisciplinary decision-making, guideline-concordant management, and access to good quality curative-intent treatment. Early detection is the key that can open access to curative-intent treatment at a more cost-effective end of the risk-benefit equation. With early detection programs, a higher proportion of patients undergo surgical resection, fewer need neoadjuvant or adjuvant therapy, and survival is superior.6
Programs to promote guideline-concordant management of incidentally detected lung nodules provide a complementary approach, bringing access to a more socio-economically, racially, and potentially geographically diverse population than LDCT programs that demand implementation of de-novo infrastructure. There is great potential synergy in implementing both approaches to early lung cancer detection.
Even where LDCT screening is entirely inaccessible, for example in countries where it is not a covered healthcare benefit, leveraging pre-existing infrastructure and developing processes to ensure guideline-concordant management of incidentally detected lung nodules is a pragmatic approach that can provide meaningful population-level access to early lung cancer detection. By this means, lung cancer can be detected early, often, and everywhere.
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