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Lung cancer remains the leading cause of cancer-related mortality, in large part secondary to advanced stage at diagnosis (Chapter 41). Annual low-dose CT (LDCT) screening for lung cancer is recommended for those at high risk by multiple organizations, including the USPSTF, the American Cancer Society, the American College of Chest Physicians, and the National Comprehensive Cancer Network. In 2021, the USPSTF updated its criteria for LDCT screening. High-risk criteria include age 50–80 years, at least a 20-pack-year smoking history, and either current smoking or quit date within past 15 years. Screening should be stopped once 15 years have elapsed since quitting smoking or if a comorbid condition renders the benefits of screening null. Simulation models developed for the purposes of informing this recommendation found yearly screening using these parameters to be the most efficient in reducing lung cancer–related deaths, though more false-positive test results are expected compared to the original recommendation.

Annual CXRs are not recommended for lung cancer screening in current or former smokers as no mortality benefit has been demonstrated with serial exams in two large RCTs: the Prostate, Lung, Colorectal and Ovarian Randomized Trial (PLCO) and the National Lung Cancer Screening Trial (NLST). The PLCO randomized 154,901 adults (52% current or former smokers) between the ages of 55 and 74 years to receive either no screening or annual posterior-anterior CXRs for 4 consecutive years with follow up for a mean of 12 years. The results showed mortality benefit from four annual CXRs. The NLST enrolled 53,454 current or former smokers who were randomly assigned to three annual posterior-anterior CXRs or three LDCT scans and monitored for ad additional 6.5 years. Compared with chest radiography, LDCT detected more early-stage lung cancers and fewer advanced-stage lung cancers, indicating that LDCT screening systematically shifted the time of diagnosis to earlier stages, thereby providing more persons the opportunity for effective treatment. Furthermore, the cohort that received three annual LDCT scans had a statistically significant mortality benefit, with reductions in both lung cancer deaths (20.0%) and all-cause mortality (6.7%).

Trials of LDCT in the Netherlands and Belgium (NELSON), Germany (LUSI), Denmark (DLCST), the United Kingdom (UKLS), and Italy (MILD, DANTE, ITALUNG) have revealed variable findings depending on the risk profile of the included patients, but generally indicate that screening is most likely to be effective in reducing lung cancer-specific mortality if performed at short intervals in a high-risk population. Potential harms of LDCT screening include false positive findings, overdiagnosis, radiation, and anxiety and patient distress which ought to be discussed prior to patient’s referral for screening. Other issues that remain of concern include (1) Generalizability to practice: NLST-participating institutions demonstrated a high level of expertise in imaging interpretation and diagnostic evaluation. Ninety-six percent of findings on CT were false positives but the vast majority of patients were monitored with serial imaging. Invasive diagnostic evaluations were uncommon and were associated with a low complication rate (1.4%). (2) Duration of screening: The rate of detection ...

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