REVIEW ARTICLE [Link]

2024S111

Lung cancer screening: a mini review of the major trials and guidelines
Wolfgang William Schmidt Aguiar1* , Daniel Oliveira Bonomi1 , Francisco Martins Neto1 ,
Clara de Andrade Pontual Peres2 , Arthur dos Santos Sena2
Brazilian Society of Thoracic Surgery

INTRODUCTION and mortality1,3. It is also important to implement secondary

Lung cancer remains a notable global health concern due to its prevention in people who are at high risk (current and former
high incidence and mortality rates. In 2020, there were an esti- heavy smokers) to detect lung cancer in its earliest stages, when
mated 1.8 million lung cancer-related deaths and 2.2 million treatment, mainly surgical, is most successful3.
new lung cancer cases, making it the leading cause of cancer In this sense, significant effort was made to enhance early
death (18% of all cancer deaths) and the second most frequently diagnosis and treatment for lung cancer in order to improve
diagnosed cancer in the world (11.4% of all cancer diagnoses)1. patient outcomes. Initially, in the 1970s, trials using chest
Lung cancer often goes undetected until its advanced stages, radiography and sputum cytology to detect early lung cancer
with these late diagnoses contributing immensely to a poor were performed, which proved to be ineffective in reducing its
prognosis. In most countries, the 5-year survival rate in patients mortality. Later, in the 1990s, low-dose spiral chest computed
with lung cancer is only 10–20%1. The presence of metastasis tomography (LDCT) was shown to have potential usefulness
upon first diagnosis, indicating advanced disease, is the main in lung cancer screening (LCS)2. Since then, multiple interna-
cause of treatment failure, while patients diagnosed at an earlier tional observational studies and randomized trials have been
stage, like stage IA, and adequately treated have significantly executed, confirming the efficacy of annual LDCT in reducing
higher 5-year survival rates, exceeding 70%2. This underscores lung cancer mortality and thus serving as the basis for current
the importance of early diagnosis and appropriate treatment guidelines concerning lung cancer prevention and screening1,2.
for better outcomes in lung cancer patients. In the present study, we aim to do a mini-review of the major
Exposure to risk factors is intimately linked to lung can- trials and guidelines concerning lung cancer screening (LCS).
cer etiology. The most important and prevalent risk factor is
tobacco smoking, which accounts for 80–90% of lung cancer
diagnoses, despite the fact that only about 15% of smokers METHODS
develop this neoplasm. Tobacco smoke contains many car- PubMed/MEDLINE and the Cochrane Library were searched
cinogens, causing the relative risk of lung cancer in a smoker for English-language articles published until August 2023,
to be around 20 times higher than the risk in a nonsmoker3. with the following descriptors: lung cancer; screening; diag-
The global pattern of lung cancer incidence is related to the nosis; smoking cessation; treatment. Our team also reviewed
tobacco epidemic, and since the disease has poor survival and reference lists of pertinent articles and studies suggested by
high fatality rates, its mortality is also associated with such an the review writers.
epidemic1. It is important to note that there are also other risk The aim was to find the most pertinent randomized con-
factors that can be associated with lung cancer, such as second- trolled trials regarding screening for lung cancer with LDCT
hand smoke, electronic cigarettes, pre-existing lung disease, and guidelines about the same topic, published by different
occupational exposures, and oncogenic viruses3. respected entities with a broad spectrum of different countries.
In this context, it is evident the importance of primary Two reviewers selected the trials and/or guidelines, taking
prevention of lung cancer, which consists of reducing smok- into consideration the relevance, methodology, impact in the
ing initiation, particularly in the younger population, and scientific community, quality of the journals, and range and
increasing smoking cessation, to achieve a reduction in risk respect of the entities when it came to the guidelines.

¹Brazilian Society of Thoracic Surgery – São Paulo (SP), Brazil.

2
University of Pernambuco – Recife (PE), Brazil.
*Corresponding author: wwsaguiar@[Link]
Conflicts of interest: the authors declare there is no conflicts of interest. Funding: none.
Received on September 21, 2023. Accepted on September 28, 2023.

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Lung cancer screening – an overview

RESULTS AND DISCUSSION performed in that matter, as shown in Table 1. It opened the
The first double-blind randomized controlled trial regarding door for discussion and research on early diagnosis and screening
LCS with statistically relevant results was the National Lung for lung cancer, considering that most of the research regard-
Screening Trial (NLST), which was also the largest trial ever ing that disease targets treatment options.

Table 1. Major trials about lung cancer screening and their results.
Number of Target group (age
Trial Study design Summary of findings Additional points
participants and smoking status)
Participants randomly
assigned to one of
55–74 years old, The results of the
NLST two screening groups:
with a history of study showed that
(National one group underwent
smoking for at least LDCT reduced lung
Lung LDCT annually for 3 >53,000 X
30 years or had quit cancer mortality by
Screening years, and the other
smoking within the 20% compared with
Trial) group underwent chest
past 15 years. chest X-ray.
X-ray annually for the
same period.
Participants were
40–74 years old,
randomly assigned to The primary endpoint
who were current or
either LDCT group of the study was lung
NELSON former smokers with
or the control group. cancer mortality. The
((NEderlands a smoking history of
The LDCT group LDCT group had a
Leuvens >15,000 at least 10 cigarettes X
received screening with significantly lower
Screening per day for at least
low-dose computed cancer mortality (up to
ONderzoek) 30 years or 15
tomography scans at 20%) rate compared
cigarettes per day for
baseline and after 1, 2, with the control group.
at least 25 years.
and 4 years.
Screening with LDCT resulted in
While the UKLS
Participants were a high proportion of lung cancers
showed benefits
randomly assigned being detected at early stages.
50–75 years in early detection,
to LDCT screening In the screened group, 87.8% of
UKLS (UK old with the risk the study was not
(periodicity defined diagnosed cancers were at stage
Lung Screen 4,055 score Liverpool sufficiently large or
according to the Wald I or II. The trial shows, however,
Trial) Lung Project long term to determine
Single Screen Design) a proportion of false-positive
(LLPv2)≥4.5% a direct impact on
or no screening (usual results of 18.5% (nodules that
lung cancer mortality
care). were initially suspicious but later
reduction.
confirmed as benign).
50–69 years old,
with eligibility
criteria being defined Modeling by sex
by at least 25 years showed a statistically
Participants were smoking of at least significant reduction in
recruited from the 15 cigarettes per lung cancer mortality
LUSI (Lung
general population and day or at least 30 among women
Screening
randomly assigned to 4,052 years smoking of at (HR=0.31 [95%CI X
Intervention
LDCT screening or least 10 cigarettes 0.10–0.96], p=0.04),
Trial)
no screening during 5 per day, including but not among men
years. ex-smokers who had (HR=0.94 [95%CI
stopped smoking not 0.54–1.61], p=0.81)
more than 10 years screened by LDCT.
before invitation to
screening.
LDCT screening
was associated with
Participants were 49–75 years old, The biennial LDCT arm showed
a significant 39%
randomized to annual current or formers a similar overall mortality (HR
MILD reduction in lung
or biennial LDCT, with smokers (<10 years 0.80, 95%CI 0.57–1.12) and LC
(Multicentric cancer mortality at 10
a median screening 4,099 of quitting) of ≥20 specific mortality at 10 years
Italian Lung years (HR 0.61; 95%CI
period of 6.2 years or packs/year without (HR 1.10, 95%CI 0.59–2.05),
Detection) 0.39–0.95; p=0.017), as
no screening (usual history of cancer in as compared with annual LDCT
well as a nonsignificant
care). ≤5 years. arm.
20% decrease in all-
cause mortality.

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 Aguiar WWS et al.

Those trials have all come to similar findings, showing that Another aspect shown in the trials was that, in patients
LDCT is a great choice for LCS, and it has the capability of who were current smokers during screening, the smoking ces-
reducing up to 20%, in some trials even more, of lung can- sation rate was extremely higher compared to those that didn’t
cer-related mortality. That comes up as extremely enthusiastic undergo screening.
for the scientific community that had, and still has, witnessed Considering all that, important societies and entities
the dramatic cases of advanced lung cancer. started publishing guidelines based on those trials; they can
The trials showed, however, some points that need to be be seen in Table 2. Most of the guidelines have similar rec-
analyzed carefully before implementing a screening program, ommendations, with annual LDCT screening for risk groups
such as the presence of false-positives, which lead to unneces- as the standard. Also, specialized centers are recommended,
sary surgical intervention and patient-family anxiety, and the as described.
detection of lesions that may never become cancer, leading to Those guidelines evaluated important aspects of LCS, such
overdiagnosis and overtreatment. Smaller trials in low- to mid- as the difference in all-cause mortality, lung cancer mortality,
dle-income countries have shown that the rate of false-positives and quality of life; effectiveness in different subgroups; effec-
increases significantly in tuberculosis-endemic areas. Those out- tiveness associated with frequency of screening; accuracy of
comes were minimized, though, with the performance of the screening with LDCT; harms associated with that; and other
screening in specialized centers with highly defined protocols, practices that should be encouraged to diminish the incidence
the analysis of an experienced multidisciplinary team, and the of lung cancer, being able to minimize, in the future, the num-
presence of a thoracic radiologist. ber of people in the risk groups.
Alongside that, much has been speculated about the One of those practices, encouraged by most of the
cost-effectiveness of LCS with LDCT, considering the cost guidelines, takes place in smoking cessation programs that
of that screening for large populations. A systematic review should have a broad range for all the population, with mul-
from the Lung Cancer Journal, published in 2022, evalu- tidisciplinary teams involving mental health care profes-
ates that matter. The review looked at 45 studies, includ- sionals and multiple strategies for smokers to quit smok-
ing trials and modeling studies. 86.7% of the studies found ing, as well as educational programs for nonsmokers. That
screening with LDCT to be cost-effective, being optimal increases tremendously the cost-effectiveness of screening,
between the ages of 55 and 75 years, with a history of at considering that the risk groups would become smaller and
least 20 packs per year. smaller with time.

Table 2. Guidelines for screening for lung cancer.

Guideline Recommendations
Screening with annual LDCT in individuals between the ages of 50 and 80 years with a
USPSTF (United States Prevention Taskforce), 2021 history of smoking at least 20 packs/year. The screening must be done in specialized centers
with highly defined protocols, to minimize the rate of false positives and overdiagnosis.
Screening with LDCT in individuals aged 50–75 years with a smoking history of at least
European Society of Radiology+European
20 packs/year and a quit time of less than 10 years. Should be done yearly for at least 3
Respiratory Society, 2020
years. The results must be interpreted by radiologists with expertise in thoracic imaging.
Brazilian Society of Pneumology and
Phthisiology+Brazilian Society of Thoracic LDCT annually in individuals between 50 and 80 years old, who are current smokers or
Surgery+Brazilian College of Radiology and Imaging quit smoking in the last 15 years, with a smoking history of at least 20 packs/year.
Diagnosis, 2023
Screening with LDCT in individuals aged 55–74 years with at least a 30 packs/year
smoking history, who currently smoke or quit less than 15 years ago. Annual screening
Canadian Task Force on Preventive Health Care, 2016
with LDCT up to three consecutive years. Screening should only be carried out in health
care settings with expertise in early diagnosis and treatment of lung cancer.
LCDT screening in individuals aged between 55 and 77 years, with a >30 packs/year smoking
National Comprehensive Cancer Network, 2022 history, who are current smokers or quit in the past 15 years. Or individuals with more than
50 years old, with a smoking history of > 20 packs/year, with additional risk factors.
Age between 50 and 74 years; 20 or more packs/year history of smoking tobacco; and, if
Royal Australian and New Zealand College of former smoker, have quit within 20 years should undergo helical LDCT. To be involved in
Radiologists (RANZCR), 2021 the program, participants should also be willing to receive counseling and participate in
shared decision-making before screening.

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Lung cancer screening – an overview

CONCLUSION strategies such as public-private partnerships and the employ-

Even though the benefits of LDCT in LCS have been proven, ment of mobile CT scanners.
the implementation of such programs still faces important chal- At last, the results shown here must be seen with extreme
lenges. The first one concerns continuing medical education hope that, in the future, hopefully in the short term, our com-
programs, so all of the medical society becomes aware of the munity will be able to see fewer advanced lung cancer cases,
need for LCS, as it already happens in other neoplasms, such with more early diagnosis, and an exponential reduction in
as breast cancer and colorectal cancer. smoking levels.
Another concern regards the stigma still present in the face
of a lung cancer diagnosis, considering the intimate relation-
ship with smoking and the consequent guilt and stress that the AUTHORS’ CONTRIBUTIONS
diagnosis may trigger in the patient and their family. WWSA: Conceptualization, Supervision, Writing – review &
Also, understanding and developing culture-sensitive screen- editing. DOB: Methodology, Writing – review & editing. FMN:
ing approaches is essential, especially when it comes to low- Methodology, Writing – review & editing. CAPP: Data cura-
and middle-income countries, where infrastructure and access tion, Writing – review & editing. ASS: Data curation, Writing
to healthcare may be a problem, and that must be faced with – original draft, Writing – review & editing.

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