Evidence shows more early lung cancer screening leads to better outcomes and less lung cancer mortality. "Working in a large community-based health care system at the heart of the U.S. lung cancer mortality belt, we have felt the need for pragmatic solutions and came up with the idea of a two-pronged approach to early detection of lung cancer," noted Raymond U. Osarogiagbon, MBBS, FACP, Chief Scientist at Baptist Memorial Health Care and principal investigator of The Mid-South Miracle Project. He and his colleagues investigated how conventional low-dose CT (LDCT) screening compares with guideline-concordant management of incidentally detected lung nodules when it comes to which patients get screened, what types of lung cancers are found, and patient outcomes after cancers are detected for each method. The researchers created two prospective observational databases as part of the ongoing Detecting Early Lung Cancer (DELUGE) in the Mississippi Delta project. The data show both approaches work and have led to increased early detection of lung cancer and improved outcomes (J Clin Oncol 2022; doi: 10.1200/JCO.21.02496).
1 Can you discuss the two lung cancer screening approaches?
"The two approaches are conventional LDCT screening and guideline-concordant management of incidentally detected lung nodules. LDCT has the advantage of high-level evidence based on the positive results of ... large randomized controlled trials (the National Lung Screening Trial [NLST], the Dutch-Belgian screening trial [NELSON], and the Italian trial [MILD], as well as a large meta-analysis). All of those trials reveal significant reduction in lung cancer (and in the case of the NLST, all-cause) mortality; however, implementation barriers mean that in the U.S. only an estimated 5-10 percent of eligible individuals have participated.
"The eligibility criteria for insurance coverage for LDCT (based on the clinical trials' eligibility criteria, which in turn are based on age and smoking history) are very imperfect. By most estimations, even with 100 percent adoption (and remember, we're at about 5 percent by most estimations), much fewer than 50 percent of all persons diagnosed with lung cancer in the U.S. would be eligible for screening.
"And add the fact that the eligibility criteria underestimate lung cancer risk in women and racial minorities, especially Black persons, who develop lung cancer at a younger age and with less tobacco exposure than White men. Therefore, LDCT screening as currently practiced runs the risk of exacerbating lung cancer disparities; while paradoxically, subset analyses of NLST and NELSON data suggest that women and Black persons stand to have even greater benefit from LDCT screening than men or White persons.
"Promoting guideline-concordant management of incidentally detected lung nodules has the advantage of bypassing some of the barriers to LDCT screening. Unlike LDCT screening, which requires multiple steps involving physicians, patients, and health care systems before a test is done, interpreted, and acted upon, incidental lung nodule programs start from the point of detection of an abnormal, potentially cancerous lesion on a test that has already been performed and interpreted.
"The program simply attempts to ensure that the abnormal finding is acted upon. Therefore, the challenges of eligibility criteria, insurance coverage, access to a test, the need for additional institutional infrastructure, and capacity are minimized.
"Nodule programs, also provide access to hard-to-reach segments of populations that typically do not seek preventive care, because a common point of origin of the abnormal radiologic study is the emergency room or other acute care setting, where such persons often seek care.
"Theoretical disadvantages of incidental lung nodule programs include delays in care while the immediate reason for imaging (the acute care problem that led to the test being done in the first place) is addressed; potentially higher competing risks for mortality (from the abnormality that led to the test being done in the first place); and some need for infrastructure to identify, systematically track, and ensure guideline-concordant management of a potentially large population of patients.
"Finally, the guidelines (whether those of the American College of Chest Physicians, British Thoracic Society, or Fleischner Society) are not based on the high level of evidence that LDCT screening is based on."
2 Your data shows both approaches work?
"Yes, for every lung cancer patient identified through the LDCT screening program, there were approximately five patients diagnosed through the incidental lung nodule program. The stage distribution of lung cancer was similar (61% and 60%, respectively, for Stage I or II) between programs, the proportion of patients able to undergo curative-intent treatment was similar, and overall survival was slightly better in the LDCT screening-detect lung cancer cohort compared with the incidental lung nodule program lung cancer cohort.
"Compared to a cohort of patients from our multidisciplinary thoracic oncology program, which we used to contextualize our findings in the two early detection programs, outcomes in both cohorts were significantly better than expected. We concluded that the two approaches are complementary. It's noteworthy that the racial distribution and risk factors for lung cancer were strikingly different. There were significantly more Black persons diagnosed in the nodule program (27%) than in the LDCT program (16%). And 13 percent of the lung cancer patients in the screening program had never smoked cigarettes, such persons, who represent up to 10-15 percent of lung cancer patients in the U.S. who currently have no pathway to early detection because they are ineligible for screening by all existing criteria. Furthermore, 20 percent of the patients with lung cancer in the nodule program had quit smoking more than 15 years before, so would have been ineligible for screening.
"Indeed, even if 100 percent of all patients eligible for screening in the whole cohort had participated in screening, the nodule program would still have detected 20 percent of all the early-stage lung cancers.
3 What are the implications of the findings?
"Even with the 2021 expanded USPSTF criteria, only 49 percent of the lung cancer patients in the Incidental Lung Nodule Program would have been eligible for LDCT screening. Although this was up from 43 percent with the 2013 USPSTF criteria, it still represents less than 50 percent of lung cancer patients in the nodule program. LDCT screening saves lives and needs better implementation, but it is not enough by itself. We need to implement both LDCT screening programs and programs to ensure guideline-concordant management of lung nodules detected on radiologic studies performed for other reasons."