Impact of lung cancer screening with low-dose chest computed tomography on an older population: a retrospective cohort study

Introduction

Background

Lung cancer (LC), the second most common cancer, is the leading cause of cancer-related mortality worldwide (1,2). The National Lung Screening Trial (NLST) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) study provided compelling evidence on the reduction of LC-related mortality among individuals aged 50–75 years with a significant smoking history who underwent lung cancer screening (LCS) using low-dose computed tomography (LDCT) compared to those undergoing chest radiography and those not undergoing screening, respectively (3,4).

The incidence of LC tends to increase with advancing age, particularly in the population aged 75–80 years (5). However, most LCS studies have primarily focused on patients aged ≤74 years (2-4,6,7). As a result, only a few studies have investigated the effectiveness of LCS with LDCT scans in patients aged >74 years (8). The current guidelines for LCS commonly recommend age restrictions. The US Preventive Services Task Force specifically advises LCS with LDCT scans for individuals aged 55–80 years. In addition to age, eligible patients should have a history of smoking of at least 20 pack-years, be current smokers, or have quit smoking within the last 15 years (9). In addition to the guidelines of the US Preventive Services Task Force, other recommendations are available regarding LCS with LDCT. The American Association for Thoracic Surgery suggests considering LCS with LDCT for patients aged 50–79 years. Similarly, the Chest journal recommends screening individuals aged 55–77 years (10,11). Meanwhile, based on the Korean Lung Cancer Screening Project (K-LUCAS), only patients aged 55–74 years with a current smoking history of more than 30 pack-years are eligible to undergo LCS with LDCT in the current National Cancer Screening Program of Korea (12).

Rationale and knowledge gap

In the older population, poor general condition, decreased cognitive function, and aging-related frailty are issues in active cancer diagnosis and treatment (13,14). Even with early LC diagnosis via LCS with LDCT, further pathologic diagnosis or treatment is not easily accessible by the older population. Considering the life expectancy, the survival gain from the LCS is unclear. Thus, LCS with LDCT has been considered complicated and rarely performed in the older population. However, there are concerns about the excess mortality caused by LC in an older population, and if left untreated, LC can be aggressive and lead to substantial morbidity and mortality, irrespective of age or comorbidity burden (15,16).

Objective

This study aimed to examine the results of LCS with LDCT on LC detection in the older population. This study also aimed to evaluate the trend of early-stage detection through screening. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-266/rc).

Methods

Study design and participants

This single-center retrospective cohort study was conducted at a teaching hospital, Veterans Health Service Medical Center (VHSMC), in Seoul. Two retrospective cohorts were used for the study. The first cohort consisted of patients who underwent LCS with LDCT, and the second cohort comprised patients with LC treated at the hospital, regardless of their screening status (Figure 1). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of the Veterans Health Service Medical Center (No. BOHUN 2023-02-004-001), the requirement for written informed consent was waived due to the retrospective nature of the study.

Figure 1 Flow chart of patient enrollment. LCS, lung cancer screening; LDCT, low-dose computed tomography; VHSMC, Veterans Health Service Medical Center; CT, computed tomography.

The VHSMC pulmonology clinic provides LCS using LDCT to veterans, regardless of their smoking history or age limits. Among participants who visited the pulmonologists’ clinic, only patients who had their first LCS with LDCT between January 2012 and June 2020 and whose age at the initial screening was between 70 and 80 years were included. To avoid including patients who underwent LDCT for purposes other than LCS, the following patient groups were excluded: those with a previous history of LC, those who underwent LDCT due to abnormalities found at an earlier chest radiography or other medical images (such as lung nodules, focal inflammation, haziness in the lung field, or other abnormalities suggestive of LC), and those who underwent LDCT for symptoms such as severe cough, dyspnea, hemoptysis, and weight loss.

Then, the patients were categorized into two age groups: the early 70s group, comprising individuals aged 70–74 years, and the late 70s group, comprising consisting of individuals aged 75–80 years. LC diagnosed in the screening cohort was defined as screening-detected lung cancer (SDLC). Among patients with LC in the LC cohort, which included all patients diagnosed with LC in VHSMC between January 1, 2012, and September 30, 2021, patients with non-screening-detected lung cancer (NSDLC) were selected. After excluding patients with SDLC from that cohort, using propensity score matching (PSM), the number of patients with NSDLC was selected five times, ensuring compatibility with the SDLC group. The PSM variables were age, sex, and year of LC diagnosis (Figure 1).

Data collection

The medical records of patients were retrospectively reviewed until death or September 30, 2021. The initial LDCT was performed based on the patient’s request for a health check or on the discretion of pulmonologists to perform LCS. Subsequent LDCT intervals were basically 1–2 years. The following data were collected: age, sex, smoking history, comorbidity with chronic obstructive pulmonary disease (COPD), body mass index, date of LDCT, LDCT interval, LDCT report and image, and number of LDCT scans taken. Nodules with a diameter of ≥4 mm were defined as non-calcified lumps (2,3). Moreover, lung nodules were evaluated using the Lung Imaging Reporting and Data System (Lung-RADS). In patients with nodules, subsequent LDCTs were performed based on the recommendations of the Lung-RADS (17). Patients with lung nodules with a RADS score of 3–4 points were considered positive on LCS with LDCT (18). In addition, survival data of all individuals in the screening cohort were collected from the medical records. All patients are veterans, and their medical records are linked to their survival data from the Ministry of Patriots and Veterans Affairs.

Patients were diagnosed with LC through pathological confirmation. However, for patients who cannot undergo a biopsy because of poor general condition, LC can be diagnosed based on imaging findings and multidisciplinary discussion. Data on LC pathology, diagnostic methods, and treatment modalities of patients with LC were gathered. Treatment was determined by each pulmonologist, oncologist, or surgeon according to National Comprehensive Cancer Network guidelines and decision from multidisciplinary discussions.

The screening rounds were defined based on the CT interval of patients who regularly underwent LCS. The initial LDCT was round 1 of screening. Round 2 was defined as subsequent screening with LDCT between 1 and 2 years after round 1. Round 3 was defined as subsequent screening with LDCT between 1 and 2 years after round 2, and rounds 4–7 were defined in the same way.

LCs detected during the screening were classified into three based on the screening round when the LC was diagnosed: prevalent cancer, subsequent screening-detected cancer, and interval cancer. Prevalent cancer referred to LC diagnosed based on lung abnormalities such as nodules detected in round 1. Subsequent screening-detected cancer was defined as LC diagnosed based on lung abnormalities or nodules detected in subsequent screening rounds except for round 1. Conversely, an interval cancer was defined as LC that arise between scheduled LCS, with the previous screening showing a negative or “normal” result. These cancers are detected in the interval period between screenings and may be cases that were either missed or not detectable in previous screenings (19).

Outcomes

The main outcome of this study is LC detection in the screening groups, and this outcome was compared between the early and late 70s groups. The cumulative LC detection rate was evaluated based on the follow-up duration and LC detection rate for each LDCT round. The characteristics of LC, biopsy methods, and treatments between the early and late 70s groups were compared in patients diagnosed with LC. In addition, differences in LC characteristics, such as stage, histology, and initial treatment, were evaluated between patients with SDLC and NSDLC.

Statistical analyses

Categorical variables were presented as numbers and percentages, and between-group comparisons were conducted using Pearson’s chi-square or Fisher’s exact test, as appropriate. Continuous variables were expressed as means and standard deviations and compared between the two groups using Student’s t-test.

LC detection rates were defined in two ways. First, it was defined as the ratio of total LC cases to the entire population screened. The LC detection ratio was calculated for each LDCT screening round and its subgroups. Second, the rate of LC events per person-years at risk for the event was analyzed. Person-years were measured from the time of the first screening to the date of LC diagnosis.

Kaplan-Meier estimation and log-rank tests were used to evaluate the cumulative estimated LC detection rate between the early and late 70s groups. Kaplan-Meier estimation was used to compare survival differences between the LC-diagnosed group and the non-diagnosed group within the screening cohort. It was performed for the total population and separately for the early and late 70s groups, respectively. Survival duration was defined as the time from the initial date of LDCT to the date of death.

To mitigate potential imbalances in factors between patients with SDLC and NSDLC, PSM was applied to reduce selection bias between the SDLC and NSDLC groups. PSM was performed using logistic regression models, with age, sex, and year of LC diagnosis as covariates. PSM was performed at a 1:5 ratio without replacement, with a caliper value of 0.005. Following PSM, the differences between the matched groups were <0.1, indicating a successful balancing of covariates.

All P values were two-sided, and a P value of <0.05 was considered statistically significant. All analyses were performed using Stata 17.0 (Stata Corp., College Station, TX, USA).

Results

Characteristics of the screened populations

Between January 2012 and June 2020, a total of 6,815 participants underwent LDCT at a pulmonary clinic. Among them, 5,494 participants whose purpose for screening was not LCS were excluded. In addition, 40 patients with a previous history of LC were excluded, resulting in the inclusion of 1,281 participants. Among these, 1,020 and 261 participants were included in the early and late 70s groups, respectively (Figure 1).

Table 1 shows the baseline characteristics of the participants undergoing LCS. Among the participants, 94.6% were men, and 39.8% had COPD. Moreover, 32.7% were current smokers, 55.0% were former smokers, and 10.5% were never-smokers, indicating that 87.7% of the participants had a history of smoking. Compared with the late 70s group, the early 70s group had a higher proportion of current smokers and a lower proportion of never-smokers (P=0.008). The median pack-years of smoking among smokers were 40, with the early and late 70s groups having median pack-years of 40 and 36, respectively (P=0.083).

Each participant had a median number of LDCT scans of 2. Among the participants, 889 (69.4%) underwent ≥2 LDCT scans, and 603 (47.1%) underwent ≥3 LDCT scans. Compliance with LCS was higher in the early 70s group than in the late 70s group. Specifically, 723 participants (70.9%) in the early 70s group and 166 participants in the late 70s group underwent ≥2 LDCT (63.6%) (P=0.023). Similarly, a higher proportion of participants in the early 70s group (48.5%) had undergone ≥3 LDCT scans compared with the late 70s group (41.4%) (P=0.039). The median follow-up durations from the initial LDCT were 3.7 years (25th/75th percentile: 2.7–5.7) in the early 70s group and 3.2 years (25th/75th percentile: 2.2–5.9) in the late 70s group (P=0.006).

In this study, the initial LDCT detected nodules in 708 (55.3%) patients. Among them, 569 (55.8%) in the early and 139 (52.3%) in the late 70s group had nodules, respectively, with no significant difference between the two groups (P=0.464) (Table 1). The initial Lung-RADS score, based on the characteristics of the lung nodules, is described in Table 1. According to the Lung-RADS score, no significant differences were found in the initial lung nodule characteristics between the early and late 70s groups (P=0.552).

LC detection during screening

In a median of 3.6 years of follow-up, 36 (2.8%) of 1,281 patients were diagnosed with LC. No statistically significant differences were found in the proportion of participants diagnosed with LC between the early and late 70s groups. Of the 1,020 participants in the early 70s group, 27 (2.7%) were diagnosed with LC, and of the 261 participants in the late 70s group, 9 (3.4%) were diagnosed with LC (P=0.485). The incidence of LC per 1,000 person-years in the overall group was 6.5. However, the incidence of LC per 1,000 person-years was slightly higher in the late 70s group (8.3) than in the early 70s group (6.1), and this difference was not statistically significant (P=0.428). In round 1, 14 (1.1%) patients were diagnosed with LC, which included 10 (1.0%) patients in the early 70s group and 4 (1.5%) in the late 70s group. However, no significant difference was found between the two groups (P=0.716) (Table 2).

The LC detection rate was analyzed for each round among patients who participated in subsequent regular screening programs. In round 2, a total of 812 patients (63.4% of the baseline participants) underwent LCS with LDCT. Among the baseline participants, 604 (47.2%) underwent round 3 of screening, and 372 (29.0%) and 189 (14.8%) patients completed rounds 4 and 5 of screening (Table 3). Table 3 shows the nodule-positive rates and LC detection rates in each round, and Figure 2 illustrates the initial nodule-positive rates and subsequent LC rates in each screening round. The lung nodule positivity rate in each round was 4.8–11.7% without any tendency to increase or decrease. In round 2, the late70s group showed higher nodule positivity rates (6.1% vs. 12.3%, P=0.008); however, the cancer detection rate was comparable between the age groups (1.1% and 0.6% in the early and late 70s groups, respectively, P=0.634). Table 3 and Figure 2 show the LC detection rates and the number of lung cancers detected, respectively, according to screening rounds and age groups, specifically the SDLC in rounds 2 and 3 in the early 70s group. However, no LC was detected in the subsequent screening in rounds 2 and 3 in the late 70s group, whereas two SDLCs were found in round 3. Regarding interval cancer, one interval cancer was found between rounds 1 and 2 in the early 70s group, and three interval cancers (1 between rounds 1 and 2, 1 between rounds 3 and 4, and 1 between rounds 4 and 5) were diagnosed in the late 70s group. In round 4, the LC detection rate in the late 70s group was higher than that in the early 70s group (4.6% vs. 0.0%, P<0.001), and one was an incident cancer. During the screening periods, the detection rate of interval cancer was higher in the late 70s group than in the early 70s group (P=0.014) (Table 4). In total, 21 of 27 (77.8%) participants were finally diagnosed with LC from the initial positive nodules in the early 70s group, whereas 4 of 9 (44.4%) were finally diagnosed with LC from initial positive nodulesin the late 70s group (Figure 2).

Figure 2 Classification based on the diagnosis time during screening and initial positive nodule in a group of 36 patients with lung cancer.

Figure 3A shows the cumulative probability of LC detection in the total population. During the screening, the cumulative probabilities of being diagnosed with LC within 1, 2, 4, and 6 years of follow-up were 1.33%, 1.65%, 2.44%, and 3.08%, respectively. Figure 3B shows the probabilities of LC detection according to the two age groups. At 4 years of follow-up, the cumulative LC detection rates were 2.35% and 2.94% in the early and late 70s group, respectively. However, the cumulative LC detection rates did not show a significant difference between the two groups (P=0.523, Figure 3B).

Figure 3 Cumulative lung cancer detection probability. (A) Estimated lung cancer detection probability in the overall population; (B) estimated lung cancer detection probability according to age. CI, confidence interval.

Table S1 and Table S2 present the LC detection rates and incidences, respectively, according to subgroups, including sex, smoking history, COPD, and emphysema. The analysis did not reveal any significant differences in the LC detection rates between the early 70s and late 70s groups across these subgroups.

Characteristics and treatment approaches for older individuals with SDLC

In total, 36 patients with LCs were identified in the screening cohorts, with 27 patients from the early 70s group and 9 from the late 70s group. Table 4 shows the cancer classification according to the screening round, LC diagnostic methods, LC stage, and types of treatment according to age groups. The cancer classification (prevalent, subsequent screening-detected, and interval cancer) is shown in Table 4. Four interval cancers were detected, 3 of 9 (33.3%) in the late 70s group and 1 of 27 (3.7%) in the early 70s group, with a higher proportion in the late 70s group than in the early 70s group (P=0.014). In the pathologic diagnoses, the four interval cancers included two small cell LC and one squamous cell carcinoma in the late 70s group and one adenocarcinoma in the early 70s group.

Among patients diagnosed with LC in the early 70s group, only one did not undergo biopsy because of poor general medical condition. All patients with LC in the late 70s group underwent biopsy. The proportion of patients who underwent biopsy was not statistically different between LCs detected in the early and late 70s groups (P=0.379). Among the patients in the early 70s group, 15 (55.6%) presented with adenocarcinomas, whereas 4 (44.4%) in the late 70s group presented with squamous cell carcinomas (P=0.442). Moreover, 15 (55.6%) and 4 (44.4%) patients in the early and late 70s groups were diagnosed with stage I LC, and 4 (14.8%) and 3 (33.3%) patients with LC in the early and late 70s groups were diagnosed with stage IV cancer, respectively. The stage distribution between the early and late 70s was not statistically different (P=0.666). Regarding the initial treatment, 16 (59.3%) and 2 (22.2%) patients in the early and late 70s groups received surgical treatment, respectively (P=0.054). Moreover, the proportion of patients who received appropriate LC treatment based on stage was higher in the early 70s group (n=23, 85.2%) than in the late 70s group (n=6, 66.7%), without a statistical difference (P=0.216) (Table 4).

Survival comparison between patients with LC and individuals without LC

When evaluating all-cause mortality, significantly lower survival was observed in screened patients with LC than in screened participants without LC. The Kaplan-Meier survival curves presented in Figure 4 demonstrate a substantial disparity in overall survival between patients diagnosed with LC and those without LC. This trend in survival was consistent across all subgroups, including the entire screened population, as well as the early and late 70s groups. Notably, the survival probability among patients with LC was consistently lower than in those without LC in each subgroup, with P values of <0.001. The estimated 5-year survival of the group with screening-detected LC was 69.1% in the total population, including 75.4% and 35.6% in the early and late 70s groups, respectively.

Figure 4 Survival comparisons between patients with and without lung cancer by age. (A) All participants; (B) 70≤ screened population <75 years (early 70s); (C) 75≤ screened population <80 years (late 70s). CI, confidence interval.

Differences in LC characteristics and treatment between the screened and non-screened groups

Regarding the baseline characteristics, the SDLC and NSDLC groups had comparable sex proportion and age after PSM; however, BMI was significantly higher in the SDLC group than in the NSDLC group (24.2 vs. 22.8, P=0.041). Table 5 presents the baseline characteristics of patients with LC and the cancer characteristics of these two groups, indicating that the SDLC group had higher rates of stage I LC (52.8% vs. 30.6%, P=0.010) and lower rates of stage IV (19.4% vs. 42.2%, P=0.010) than the NSDLC group. No significant differences were observed in the distributions of the pathological types of LC (P=0.204). Moreover, 18 (50.0%) and 64 (35.6%) patients with SDLC and NSDLC underwent surgery, respectively (P=0.103). In addition, 2 (5.6%) patients in the SDLC group and 23 (12.8%) in the NSDLC group received the best supportive care without any cancer treatment (P=0.216). In the SDLC group, 29 (80.6%) patients received appropriate treatment based on their cancer stage, and in the NSDLC group, 141 (78.3%) received appropriate treatment (P=0.766).

Discussion

Key findings

To our knowledge, this study is one of the few studies that have reported LCS results in older individuals. Specifically, this study focused on the group aged 75–80 years, which has not been adequately represented in previous randomized controlled trials (RCTs) such as the NLST or NELSON studies. This study recruited 1,281 older individuals in their 70s and retrospectively reviewed the results of LCS using LDCT, which was performed for a median of 2 and at a median follow-up duration of 3.6 years. Moreover, the LC detection rate was comparable between the early and late 70s groups; however, the incidence of interval cancer, which is diagnosed between screenings, was significantly higher in the late 70s group. The rates of stage I LC between the early and late 70s groups were comparable. This study provides a new insight into the characteristics of LC in the early and late 70s groups. The proportion of patients who received surgical treatment and best supportive care based on stage was lower in the late 70s group than in the early 70s group, without showing statistical significance. Moreover, the SDLC group had earlier LC stages than the NSDLC group. Thus, this study indicates that LC can be diagnosed in the early stage even in individuals in their late 70s through LCS, although LC survival data were not shown appropriately. This finding highlights the need for further research regarding LCS in this age group.

Strengths and limitations

Despite our efforts to include a diverse older population undergoing LCS, 90% of the participants were smokers, and 40% had COPD. The screening was primarily conducted at a pulmonologist’s clinic, and this study was conducted at the largest veteran health service center in Korea, resulting in a predominantly male group. As a result, the cohort primarily consisted of male participants who were smokers and had a higher prevalence of comorbidities compared with the general population, which introduces potential selection bias and limits generalizability. While this may not fully represent the characteristics of the general population, it aligns with previous LCS studies such as NLST, NELSON, and UKLS (3,4,20). Therefore, we are convinced that this study provides valuable insights into the outcomes of LCS, specifically in the older high-risk population.

This study has several limitations. Owing to the retrospective setting, no comparative control group such as non-screening population or chest radiography group was employed. To minimize selection bias, patients with respiratory symptoms were excluded. This led to the exclusion of a large number of participants, resulting in a small sample and statistical power. In addition, no data on the fitness/Eastern Cooperative Oncology Group (ECOG) performance status of the participants at the time of screening were analyzed, which hinders the comprehensive evaluation of the older population. Moreover, the median follow-up period of 3.7 years was relatively short, which is shorter than follow-up periods (7–11 years) in current LCS studies (3,4,21).

Comparison with similar researches

The overall LC incidence rate in the screening group was 6.5 per 1,000 person-years, with rates of 6.1 per 1,000 person-years in the early 70s group and 8.3 per 1,000 person-years in the late 70s group. These incidence rates are comparable to the findings of previous large RCTs, such as NLST with an incidence rate of 645 cases per 100,000 person-years (3), slightly higher than the incidence rate reported in the NELSON trial of 5.58 cases per 1,000 person-years, and in the ITALUNG trial of 49.9 per 10,000 person-year (4,7).

The LC detection rates observed in round 1 (prevalent cancer) of the present study were 1.1% in the total participant population and 1.5% in the early 75s group. These rates are comparable or slightly higher to the findings reported in previous well-powered RCTs such as the NELSON trial (0.9%), NLST trial (1.0%), and Asian studies such as K-LUCAS (0.7%), and study by Li et al. (0.7%) (3,4,12,22). The similarities in prevalent cancer rates in round 1 suggest that our study population, consisting of older individuals aged 70–80 years could be considered suitable for LCS. However, after round 1, the late 70s group showed a lower proportion of SDLC but higher rates of interval cancer than the early 70s group. This suggests that the subsequent LCS in this study might not have been as effective in diagnosing LC in the late 70s group. Further studies are warranted to assess the effectiveness of subsequent LCS using LDCT in this age group.

The late 70s group showed higher rates of interval cancer than the early 70s group. Two of 3 interval cancer cases in the later 70s group were small cell LC, and this is not surprising because of the high proportion of interval cancer in the late 70s group. Patients with small LC do not get any survival benefit from LCS (23); It is worth noting that in this study, the compliance was lower in the late 70s group than in the early 70s group, resulting in a higher proportion of interval cancers in the late 70s group. collectively ,we think our data are not sufficient to conclude that the late 70s group showed higher rates of interval cancer in general. Further research is needed to support the difference in the proportion of interval cancer between age groups.

In the total screening group, 50.0% of the patients were diagnosed with stage I LC, including 55.6% in the early 70s group and 44.4% in the late 70s group. These findings align with the results of a previous study, which reported stage I LC rates ranging from 36% to 67% (21,24). In the present study, 19.4% in the total screening group and 33.3% in the late 70s group had stage IV LC. These proportions are consistent with the range of 10–30% reported in previous studies for the diagnosis of stage IV LC (24). Importantly, in the present study, the proportion of patients diagnosed with stage I LC was higher in the SDLC group than in the NSDLC group. In addition, the proportion of patients diagnosed with stage IV LC in the SDLC group (19.4%) was considerably lower than that observed in the NSDLC group (42.7%). These findings suggest a potential change in the staging in this patient population undergoing LCS. More studies are needed to explore whether this change in stage distribution has any effect on survival outcomes.

The issue of overdiagnosis is widely discussed in the field of screening. Previous RCTs have reported varying proportions of overdiagnosis, ranging from 0% to 67% (25). However, our data are sufficient to assess the potential issue of overdiagnosis. Unfortunately, our study did not include a control group, which makes it challenging to calculate the exact proportion of overdiagnosis.

Our data show promising results of LC treatment in the older population. In this study, 81% of the patients in the SDLC group received treatment appropriate to their cancer stage. Pham et al. showed that 73.7% of patients aged 70s with LC were presented for treatment discussion at a multidisciplinary meeting (16). Walter et al. (26) showed that 79.8% of the patients with LC aged 75–84 years received any tumor-directed treatment. Ganti et al. showed that 75% of patients with LC aged >65 years received any tumor-directed treatment (27). Despite concerns regarding treatment toxicity, shorter expected life expectancy, treatment intolerability, and nihilism in an older population, the proportion of SDLC that received cancer treatment in our study was comparable to those in previous studies (15,26,27). Even though this could not guarantee survival gain from screening, at least, results show that a significant number of patients actively pursued aggressive treatment after screening.

In this study, 59% of the early 70s group underwent surgery, whereas only 20% of the late 70s group received surgical treatment. The lower rate of surgical interventions in the late 70s group suggests that the possibility of achieving complete recovery from LC may be lower in this group. However, in older patients, stereotactic ablative radiation therapy has been reported to have comparable treatment efficacy to surgery for early-stage LC (28-30). Therefore, it would be inappropriate to conclude solely based on the lower surgical rate that older patients who underwent screening have lower treatment rates.

Explanations of finding

Unfortunately, our data were not sufficient to estimate the LC mortality reduction between the screening group and the non-screened group. Because of the retrospective design, lead time bias is possible when we compare SDLC and NSDLC; thus, our data could not show the survival benefit of screening.

While poor adherence in the real world is a big issue, the recently published study by Silvestri et al. showed that 23.2% of the 70–77-year-old The U.S. Preventive Services Task Force (USPSTF)-eligible population underwent follow-up LDCT (31). We think that the relatively high adherence rate to follow-up CT in our study is a strength considering real-world data. Even though our adherence rate is lower than the rates reported in powered RCTs, comparing other real-world data with our data (63.4% of the participants in round 2) showed that our adherence rate was higher than that reported in previous studies (23–66% of the adherence rate) (31,32).

Conclusions

This study provides valuable insights into the detection of LC in the older population through LCS with LDCT. The findings highlight the comparable role of LCS with LDCT in identifying LC in patients in their early and late 70s, with LC detection rates comparable to those reported in previous studies. Moreover, a substantial proportion of the detected LCs was at an early stage, indicating potentially favorable treatment outcomes. Importantly, the majority of older patients diagnosed with LC through screening received appropriate treatment based on their individual LC stage. Further research on the survival benefits of LCS with LDCT in this older population is warranted.

Acknowledgments

This study was presented as a poster presentation at The IASLC World Conference on Lung Cancer(WCLC) 2023.

Funding: This study was supported by the VHS Medical Center Research Grant, Republic of Korea (No. VHSMC21009).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-266/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-266/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-266/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form. HRK received research grants from VHS Medical Center for this study and another project. JHS received a research grant from VHS Medical Center unrelated to this study. KBC received a consultant fee from KOLON PHARMA and honoraria for lectures from GSK and Hanmi Pharmaceutical. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of the Veterans Health Service Medical Center (No. BOHUN 2023-02-004-001), and the requirement for written informed consent was waived due to the retrospective nature of the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. [Crossref] [PubMed]
2. Jonas DE, Reuland DS, Reddy SM, et al. Screening for Lung Cancer With Low-Dose Computed Tomography: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2021;325:971-87. [Crossref] [PubMed]
3. National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395-409. [Crossref] [PubMed]
4. de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial. N Engl J Med 2020;382:503-13. [Crossref] [PubMed]
5. Malhotra J, Malvezzi M, Negri E, et al. Risk factors for lung cancer worldwide. Eur Respir J 2016;48:889-902. [Crossref] [PubMed]
6. Infante M, Lutman FR, Cavuto S, et al. Lung cancer screening with spiral CT: baseline results of the randomized DANTE trial. Lung Cancer 2008;59:355-63. [Crossref] [PubMed]
7. Paci E, Puliti D, Lopes Pegna A, et al. Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial. Thorax 2017;72:825-31. [Crossref] [PubMed]
8. International Early Lung Cancer Action Program Investigators. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006;355:1763-71. [Crossref] [PubMed]
9. US Preventive Services Task Force. Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2021;325:962-70. [Crossref] [PubMed]
10. Mazzone PJ, Silvestri GA, Souter LH, et al. Screening for Lung Cancer: CHEST Guideline and Expert Panel Report. Chest 2021;160:e427-94. [Crossref] [PubMed]
11. Jacobson FL, Austin JH, Field JK, et al. Development of The American Association for Thoracic Surgery guidelines for low-dose computed tomography scans to screen for lung cancer in North America: recommendations of The American Association for Thoracic Surgery Task Force for Lung Cancer Screening and Surveillance. J Thorac Cardiovasc Surg 2012;144:25-32. [Crossref] [PubMed]
12. Lee J, Kim Y, Kim HY, et al. Feasibility of implementing a national lung cancer screening program: Interim results from the Korean Lung Cancer Screening Project (K-LUCAS). Transl Lung Cancer Res 2021;10:723-36. [Crossref] [PubMed]
13. Gajra A, Akbar SA, Din NU. Management of Lung Cancer in the Elderly. Clin Geriatr Med 2016;32:81-95. [Crossref] [PubMed]
14. Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 2014;32:2595-603. [Crossref] [PubMed]
15. Fabrikant MS, Wisnivesky JP, Marron T, et al. Benefits and Challenges of Lung Cancer Screening in Older Adults. Clin Ther 2018;40:526-34. [Crossref] [PubMed]
16. Pham J, Conron M, Wright G, et al. Excess mortality and undertreatment in elderly lung cancer patients: treatment nihilism in the modern era? ERJ Open Res 2021;7:00393-2020. [Crossref] [PubMed]
17. Kastner J, Hossain R, Jeudy J, et al. Lung-RADS Version 1.0 versus Lung-RADS Version 1.1: Comparison of Categories Using Nodules from the National Lung Screening Trial. Radiology 2021;300:199-206. [Crossref] [PubMed]
18. Pinsky PF, Gierada DS, Black W, et al. Performance of Lung-RADS in the National Lung Screening Trial: a retrospective assessment. Ann Intern Med 2015;162:485-91. [Crossref] [PubMed]
19. Schabath MB, Massion PP, Thompson ZJ, et al. Differences in Patient Outcomes of Prevalence, Interval, and Screen-Detected Lung Cancers in the CT Arm of the National Lung Screening Trial. PLoS One 2016;11:e0159880. [Crossref] [PubMed]
20. Field JK, Vulkan D, Davies MPA, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. Lancet Reg Health Eur 2021;10:100179. [Crossref] [PubMed]
21. Oudkerk M, Liu S, Heuvelmans MA, et al. Lung cancer LDCT screening and mortality reduction - evidence, pitfalls and future perspectives. Nat Rev Clin Oncol 2021;18:135-51. [Crossref] [PubMed]
22. Li N, Tan F, Chen W, et al. One-off low-dose CT for lung cancer screening in China: a multicentre, population-based, prospective cohort study. Lancet Respir Med 2022;10:378-91. [Crossref] [PubMed]
23. Wang Q, Gümüş ZH, Colarossi C, et al. SCLC: Epidemiology, Risk Factors, Genetic Susceptibility, Molecular Pathology, Screening, and Early Detection. J Thorac Oncol 2023;18:31-46. [Crossref] [PubMed]
24. Sands J, Tammemägi MC, Couraud S, et al. Lung Screening Benefits and Challenges: A Review of The Data and Outline for Implementation. J Thorac Oncol 2021;16:37-53. [Crossref] [PubMed]
25. Heleno B, Siersma V, Brodersen J. Estimation of Overdiagnosis of Lung Cancer in Low-Dose Computed Tomography Screening: A Secondary Analysis of the Danish Lung Cancer Screening Trial. JAMA Intern Med 2018;178:1420-2. [Crossref] [PubMed]
26. Walter J, Tufman A, Holle R, et al. "Age matters"-German claims data indicate disparities in lung cancer care between elderly and young patients. PLoS One 2019;14:e0217434. [Crossref] [PubMed]
27. Ganti AK, Klein AB, Cotarla I, et al. Update of Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non-Small Cell Lung Cancer in the US. JAMA Oncol 2021;7:1824-32. [Crossref] [PubMed]
28. Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015;16:630-7. [Crossref] [PubMed]
29. Roesch J, Andratschke N, Guckenberger M. SBRT in operable early stage lung cancer patients. Transl Lung Cancer Res 2014;3:212-24. [Crossref] [PubMed]
30. Lee K, Kim HO, Choi HK, et al. Real-world treatment patterns for patients 80 years and older with early lung cancer: a nationwide claims study. BMC Pulm Med 2018;18:127. [Crossref] [PubMed]
31. Silvestri GA, Goldman L, Tanner NT, et al. Outcomes From More Than 1 Million People Screened for Lung Cancer With Low-Dose CT Imaging. Chest 2023;164:241-51. [Crossref] [PubMed]
32. Lopez-Olivo MA, Maki KG, Choi NJ, et al. Patient Adherence to Screening for Lung Cancer in the US: A Systematic Review and Meta-analysis. JAMA Netw Open 2020;3:e2025102. [Crossref] [PubMed]