CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT

Abstract

Background The effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial. Methods 4104 men and women, healthy heavy smokers/former smokers were randomised to five annual low-dose CT screenings or no screening. Two experienced chest radiologists read all CT scans and registered the location, size and morphology of nodules. Nodules between 5 and 15 mm without benign characteristics were rescanned after 3 months. Growing nodules (>25% volume increase and/or volume doubling time<400 days) and nodules >15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice. Results Participation rates were high in both groups (screening: 95.5%; control: 93.0%; p<0.001). Lung cancer detection rate was 0.83% at baseline and mean annual detection rate was 0.67% at incidence rounds (p¼0.535). More lung cancers were diagnosed in the screening group (69 vs 24, p<0.001), and more were low stage (48 vs 21 stage IeIIB non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC), p¼0.002), whereas frequencies of high-stage lung cancer were the same (21 vs 16

Screening for Lung Cancer With Low-Dose Computed Tomography

“…One of the most remarkable features of the NLST is that benefit in terms of lower lung cancer mortality in the LDCT arm compared with the chest x-ray control arm began to accrue by the end of the first year after randomization and reached maximum benefit at 6 years. However, this early benefit has not been seen in three small European trials that have reported lung cancer mortality [2][3][4].…”

Lung Cancer Screening

“…Table 1 provides a list of select RCTs and highlights the differences in their respective inclusion criteria, screening intervals and definitions for positive screen results. [25][26][27][28][29][30][31] Since the ultimate objective of screening is to identify and treat early-stage LC, the participants' fitness for lung surgery is an important factor to consider when assessing eligibility for screening. [12] Accordingly, it is noteworthy that all the trials listed excluded those individuals with comorbidities that precluded them from curative LC surgery.…”

“…[30] The data from this trial will be pooled with those from the Danish LC Screening Trial before being published. [27] Unlike many of the other RCTs, the NELSON trial uses volumetric measurements to assess screen-detected nodules. This approach appears to be more specific than measurement of diameter and has a significantly lower positive screen rate (2.6% and 1.8%, respectively, in screening rounds 1 and 2), compared with the 26.4% across all rounds of screening in the NLST.…”

“…NLST [16] DANTE [26] DLCST [27] LUSI [28] ITALUNG [29] MILD [30] NELSON [ Table 2. Professional Societies' Guidelines for LC Screening [25] Society (Reference) Recommendation Grade NCCN [19] Annual LDCT in high-risk individuals Group 1: age 55 -79 y with >30 pack-years, current or former smokers who quit within the past 15 y Group 2: age >50 y with >20 pack-years and 1 additional risk factor * B USPSTF [12] Annual LDCT in high-risk individuals: age 55 -80 y with >30 pack-years, current or former smokers who have quit within the past 15 y † B ACCP/ASCO [17] Annual LDCT in high-risk individuals: age 55 -74 y with >30 pack-years, current or former smokers who quit within the past 15 y, but only in settings that can provide multidisciplinary care similar to that provided in the NLST 2B ACS [32] Annual LDCT in high-risk individuals: age 55 -74 y with >30 pack-years, current or former smokers who quit within the past 15 y, who are in good health B AATS [33] Annual Overdiagnosis refers to the detection of a cancer that would not otherwise have become clinically relevant during the patient's lifetime.…”

“…In addition, some required participants to demonstrate a specified baseline effort tolerance before undergoing screening. [27] The NLST is the largest RCT of LC screening to date. The study included 53 454 men and women at 33 tertiary centres across the USA.…”