# Lung cancer screening by low-dose CT scan in France: final results of the DEP KP80 study after three rounds

Olivier Leleu, Nicolas Storme, Damien Basille, Marianne Auquier, Valerie Petigny, Pascal Berna, Alexia Letierce, Sebastien Couraud, Julie de Bermont, Bernard Milleron, et al.

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Olivier Leleu, Nicolas Storme, Damien Basille, Marianne Auquier, Valerie Petigny, et al. Lung cancer screening by low-dose CT scan in France: final results of the DEP KP80 study after three rounds. EBioMedicine, 2024, 109, pp.105396. 10.1016/j.ebiom.2024.105396. hal-04743008

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# Lung cancer screening by low-dose CT scan in France: final results of the DEP KP80 study after three rounds

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Olivier Lelev,<sup>a,*</sup> Nicolas Storme,<sup>b</sup> Damien Basille,<sup>b,c</sup> Marianne Auquier,<sup>d</sup> Valerie Petigny,<sup>e</sup> Pascal Berna,<sup>f</sup> Alexia Letierce,<sup>g</sup> Sebastien Couraud,<sup>h</sup> Julie de Bermont,<sup>h</sup> Bernard Milleron,<sup>l</sup> and Vincent Jounieaux<sup>b,c</sup>

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## Summary

**Background** In prior randomised controlled trials, lung cancer screening using low-dose computed tomography (LDCT) has been shown to reduce lung cancer mortality and overall mortality. Despite these results, organised screening in France remains a challenge.

This study assessed the feasibility and efficacy of lung cancer screening within a real-life context in a French administrative territory.

**Methods** DEP KP80 was a single-arm prospective study. Participants aged between 55 and 74 years, smokers or former smokers of ≥30 pack-years, were recruited. An annual LDCT scan was scheduled and three rounds were performed. Subjects were selected by general practitioners or pulmonologists, who checked the inclusion criteria and prescribed the CT scan.

**Findings** Between March 2016 and February 2020, 1254 participants were enrolled. Overall, 945 (75.4%) participants underwent baseline LDCT (T0), 376 (42.8%) completed the first round (T1) and 270 (31%) the second (T2) one. Forty-two lung cancers were diagnosed, 30 cancers (71.4%) were stage I or II and 34 cancers (80.9%) were treated surgically. In this study, the overall positive predictive value for a positive screening was 48% (95% CI 37–59) and the negative predictive value 100% (95% CI 100–100).

**Interpretation** This study demonstrated the feasibility and efficacy of lung cancer screening in a real-life context with most lung cancers diagnosed at an early stage and surgically removed. Our results also highlighted the importance of participation in each round, underlining the fact that optimising organisation is a major goal.

**Funding** Agence Régionale de Santé de Picardie, La Ligue contre le cancer, le Conseil Départemental de la Somme, and AstraZeneca.

**Copyright** © 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

**Keywords:** Screening; Lung cancer; Early detection; Low-dose computed tomography (LDCT) scan; Real life

## Introduction

Despite major therapeutic advances in recent years, lung cancer remains the world's leading cause of cancer-related death, accounting for almost 2 million deaths every year, which is more than deaths related to breast and colon cancer combined.¹ The most powerful

prognostic factor in lung cancer is its tumour, node, metastasis (TNM) classification, with 5-year survival rates ranging from 92% for Stage IA to 10% for Stage IVA.²,³ Unfortunately, lung cancer is usually diagnosed at an advanced stage. The recent French KBP-2020 study showed that, out of 8999 new lung cancer cases, only

eBioMedicine
2024;109: 105396

Published Online 12
October 2024

https://doi.org/10.
1016/j.ebiom.2024.
105396

<footnote><sup>a</sup>Department of Pulmonology and Thoracic Oncology Centre Hospitalier Abbeville, Abbeville Cedex, France</footnote>

<footnote><sup>b</sup>Department of Pulmonology and Thoracic Oncology CHU Amiens, Amiens, France</footnote>

<footnote><sup>c</sup>AGIR Unit, University of Picardie Jules Verne, Amiens, France</footnote>

<footnote><sup>d</sup>Department of Radiology CHU Amiens, Amiens, France</footnote>

<footnote><sup>e</sup>CRCDC 6 Rue Colbert Amiens, France</footnote>

<footnote><sup>f</sup>Department of Thoracic Surgery CHU Amiens, France</footnote>

<footnote><sup>g</sup>Biostatistician, QualityStat, Morangis, France</footnote>

<footnote><sup>h</sup>Respiratory Medicine Department, CHU Lyon Sud, Lyon, France</footnote>

<footnote><sup>l</sup>Intergroupe Francophone de Cancérologie Thoracique, Paris, France</footnote>

<footnote>*Corresponding author.
E-mail address: lelev.olivier@ch-abbéville.fr (O. Lelev).</footnote>
Research in context

Evidence before this study

Lung cancer is a major public health problem. It is the leading
cause of cancer mortality worldwide. The most powerful
prognostic factor for this cancer is its TNM stage
classification. While 5-year survival in localised IA stages is
92%, it is less than 10% for metastatic IV stages.
Unfortunately, diagnosis of early-stage lung cancer is often by
chance, as the disease only develops symptoms later on.
Although lung cancer screening is emerging as a new
paradigm, its implementation remains a matter of debate. We
searched PubMed and the Cochrane Library with
combinations of the search terms "lung cancer" and
"screening" OR "early detection", with no language
restrictions for articles published before August 15, 2023.
In several randomised controlled trials, lung cancer screening
using low-dose computed tomography (LDCT) has proven
effective in reducing specific lung cancer mortality and overall
mortality in high-risk individuals. However, to this day,

despite the recommendations of various learned societies,
lung cancer screening has still not been implemented in many
countries, including France.

Added value of this study

The aim of our prospective multicentric study was to assess
the feasibility and efficacy of a lung cancer screening program
in a real-life setting.
The LDCT screening carried out as part of our DEP KP80 study
enabled the diagnosis of 71% of localised lung cancers (I-II).
Overall, 95% of patients diagnosed with cancer received
curative treatment, with a surgical resection rate of 81%.

Implications of all the available evidence

Our real-life study showed that, by adapting to the existing
healthcare system, it is now possible to implement effective
lung cancer screening using LDCT in high-risk individuals.

21.5% were diagnosed at Stages I and II compared with 78.5% at Stages III and IV.⁴

There is now a strong rationale for lung cancer
screening using low-dose computed tomography
(LDCT). It is particularly based on three positive rand-
omised trials: the U.S. based National Lung Screening
Trial (NLST), the Dutch-Belgian lung cancer screening
trial (Nederlands–Leuvens Longkanker Screenings
Onderzoek [NELSON]), and Multicentric Italian Lung
Detection (MILD) studies.⁵⁻⁷ In the recent Cochrane
meta-analysis, this screening reduced lung cancer
mortality by 20% and overall mortality by 5%.⁸

Like many international learned societies,⁹⁻¹¹ a
group of French experts recommended lung cancer
screening by LDCT for at-risk populations back in
2013, with an update in 2021.¹²,¹³ In 2022, the French
Health Authority (*Haute Autorité de Santé Française*,
HAS) recognised the efficacy of LDCT in lung cancer
screening, and supported the implementation of real-
life studies before initiating nationwide organised
screening.¹⁴

To assess the feasibility and real-life efficacy of a
lung cancer screening program using LDCT, we con-
ducted a multicentre prospective cohort study (DEP
KP80) consisting of three rounds of annual LDCT
screening (T0, T1, and T2) in a high-risk lung cancer
population. The study took place in the Somme
department, a French administrative territory. The
design of the DEP KP80 study, the recruitment pro-
cedure, and the intermediate results of the first and
second rounds have been reported previously.¹⁵⁻¹⁷ In
this article, we present the results of the three study
rounds, 3 years after the inclusion of the last
participant.

Methods

Screening protocol

Participants in the DEP KP80 study were recruited be-
tween March 2016 and February 2020 by the study's
investigating general practitioners (GPs) or pulmonolo-
gists (PNs). The inclusion criteria were those of the
NLST study: men or women, aged between 55 and 74,
with a smoking habit of more than 30 packs/year, cur-
rent smokers or former smokers who quit less than 15
years ago, with no apparent symptoms, informed about
possible ways of assisting smoking cessation, agreeing
to the screening procedures with accurate information
on the results and on the consequences that may result
from them (non-invasive explorations: thoracic scanner
at 3 months, positron emission tomography (PET), or
invasive explorations: CT-guided biopsy, bronchial
fibroscopy, surgical exploration, etc.). Exclusion criteria
included a history of cancer within the last 5 years,
significant impairment of general health, and cardiac or
respiratory comorbidities contraindicating thoracic
surgery.

All GPs, PNs, and radiologists in the Somme
department were invited by letter to be investigators in
the study. If they accepted, they were required to attend
training meetings designed to present the study and
increase their knowledge of bronchopulmonary cancer
screening. Public information campaigns were carried
out via press articles, radio and TV broadcasts, posters,
and leaflets. The study was coordinated by ADEMA 80,
the departmental structure that manages organised
breast and colon cancer screening.

According to France's National Institute of Statistics
and Economics Studies (INSEE), a governmental insti-
tution collecting and publishing data pertaining to the
French population, the population of the Somme department comprised 572,000 inhabitants at study initiation. Based on these data, we estimated that 14,360 people from the Somme department were eligible for lung cancer screening, depending on the inclusion criteria defined by our study protocol. This estimation was based on a previously published lung cancer screening model.¹⁸ The number of subjects required for this feasibility study was calculated based on lung cancer prevalence data in the general population, expected LDCT sensitivity, and desired precision of its 95% confidence interval, considering a bilateral first-order risk of 5%.¹⁹ Therefore, while taking as references the sensitivity and prevalence data from the NELSON study,²⁰ which reported a 85% sensitivity and 2.7% lung cancer prevalence, along with a 12% precision of its 95% confidence interval (half-interval amplitude), we needed 1260 subjects, plus 10% to compensate for those lost to follow-up, resulting in a total number of 1386 individuals to be included.

The investigating GP or PN prescribed the low-irradiation thoracic CT scan on a specific 3-part carbonless prescription pad provided by the coordinating centre: one part was a prescription for the patient to book an appointment for the scan, one part was returned to ADEMA 80 in a pre-stamped envelope for traceability, and the last part was for the prescriber. The prescribing physician checked the inclusion and exclusion criteria, explained the screening protocol, and informed the patient of the possibility of discovering an abnormality on the CT scan, as well as the possibility of further explorations. During this consultation, smoking cessation and/or an anti-smoking consultation were suggested.

Recruitment of participants by GPs or PNs limited the selection bias and confounding factors by making sure that subjects complied with the inclusion criteria and did not present any symptomatology suggestive of lung cancer (cough, haemoptysis, general condition alteration, etc.). The expertise of ADEMA 80 regarding screening and their method for collecting and entering information also limited measurement bias, with no missing data for LDCT scan results in the different screening rounds and demographic characteristics of participants and non-participants. ADEMA 80 collected personal data from each participant: age, sex, address, and smoking history using Zeus® software. Of note, this is the management software used by the French regional coordination centres for organised breast and colon cancer screening. Written information was provided on the screening procedures, expected benefits, and possible drawbacks. Informed consent was signed during the consultation. Sex identification was self-reported by study participants. The LDCT scan was performed in the radiological centres participating in the study without contrast injection in volume mode on a multi-slice machine (≥16 slices) with a nominal slice thickness of less than 1.5 mm and iterative

reconstructions. Subsequent scans were preferentially performed in the same radiological centre with identical acquisition constants.

A standardised interpretation report (Supplemental Figure S1) was sent by the radiologist to the coordinating centre, who forwarded it to the GP and/or PN who managed the patient according to the predefined algorithms for solid nodules and subsolid or ground-glass nodules (Supplemental Figures S2 and S3). If no suspicious nodule was found, the screening was considered negative and the patient was invited back the following year for a new LDCT, for a period of 2 years. If a nodule measuring more than 10 mm was detected, the screening was positive and the patient's file was presented at a MultiDisciplinary Team (MDT). For nodules between 5 and 10 mm, screening was indeterminate and an intermediate low-irradiation scan was performed 3 months later. Comparison between the initial scan and the second scan was used to calculate the nodule's doubling time. When it was less than 400 days, screening was definitively considered positive, with presentation of the case to the MDT. On the other hand, when it was more than 400 days, screening was negative and the annual follow-up continued. Participants eligible for the second and third rounds received their T0 results by postal mail, with an invitation to consult their GP for the prescription of T1 and T2. Subjects diagnosed with cancer did not participate in subsequent rounds (Fig. 1).

Lung cancer diagnosis was obtained by the anatomo-pathological study of biopsy and/or surgical specimens. The World Health Organization classification of lung cancers was used.²¹ Cancer stage was defined using the TNM classification (8th edition) of the International Association for the Study of Lung Cancer Staging Guidelines.³

In order to detect interval cancers, our database was cross-referenced from the first screening scan to the last screening round with that of the Somme Cancer Registry, which exhaustively records all cancers in the department.²² As in the NLST study, we defined interval cancer as a case diagnosed within 1 year after a negative CT scan and before the next annual screen.²³

## Ethics

This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. It has been approved by the French national drug safety agency (Agence Nationale de Sécurité du Médicament Reference: 160048-B81) and the Abbeville Hospital ethics committee (Reference: 23032018). DEP KP80 is registered on ClinicalTrials.gov: NCT03853967. Written informed consent was obtained during patient consultation.

## Statistics

Categorical variables were expressed as numbers and percentages, while quantitative variables were expressed
<figure><img src="image_3.png" /><figcaption>Fig. 1: Organisation of lung cancer screening in the DEP KP80 study.</figcaption></figure>

as means with standard deviations or medians and quartiles. The 95% confidence intervals (95% CI) of proportions were calculated using the Clopper-Pearson method.

Sensitivity was estimated by dividing the number of true positive screens by the numbers of true positive and false negative screens, and specificity by dividing the number of true negative screens (negative screens in the absence of lung cancer) by the numbers of true negative and false positive screens (positive screens in the absence of lung cancer). The positive predictive value was estimated by dividing all subjects with a true positive screening by all subjects with positive screening and negative predictive value by dividing all subjects with a true negative screening by all subjects with negative screening.

No adjustment for multiplicity of tests was done. Analyses were performed using R Studio® software version 2023.03.0.

## Role of funders

The funders were not involved in study design, data collection, analysis, interpretation of data, preparation of manuscript, or decision to publish.

## Results

### Results of three screening rounds (T0, T1, and T2), adherence, and demographic characteristics of the participants

The revision of the database for this final report showed that, of the 1254 participants included in the DEP KP80 study, 945 completed their initial scan, (i.e., participation rate of 75.4% at T0) and 309 did not attend their appointment (24.6%). Moreover, 376 and 270 participants completed their second and third rounds, respectively, including twelve participants at T1 who did not participate at T0 or were lost to follow-up at T0 and one participant at T2 who did not participate at T0. Thus, the participation rate was 42.8% at T1 (n = 376/878) and 31.1% at T2 (n = 270/869). The mean age of participants was 62.4 ± 4.9 years, and there were 33.1% of women. During the three rounds, 1591 screening LDCT scans were performed: 5.5% were positive (n = 87), 90.9% were negative (n = 1447), and 3.6% were lost to follow-up (n = 57). There were 12.9% indeterminate screenings (n = 206), finally considered after the 3-month follow-up scan as positive in 6.3% (n = 13) and negative in 66.0% (n = 136) of cases, 27.7% (n = 57) did not attend their 3-month follow-up scan appointment
(Fig. 2). There was a reduction in the rate of indeterminate screenings among the different time points (T0: 18.6%, T1: 2.6%, and T2: 7.4%), as well as in the rate of positive screenings (T0: 6.8%, T1: 4.8%, and T2: 1.9%). There was no difference in the rate of participation during the different rounds in terms of sex ratio. However, age and screening result during the previous round appeared to be major factors influencing participation. The oldest subjects participated more in the different rounds and the subjects with false positive screening results participated less in the subsequent rounds, especially at the third round (Table 1). GPs were responsible for referring 81% of subjects to our study, and PNs for 19%.

Incidence, stage, treatment, and histology of
diagnosed cancers

Lung cancer was diagnosed in 42 participants, corre-
sponding to 2.6% over all the CT scans or 4.4% over the
total participants (n = 945) having at least one CT scan.
The cancers were mostly diagnosed at an early stage: 4.8%
carcinoma *in situ* (n = 2/42), 64.3% stage I (n = 27/42),
7.1% stage II (n = 3/42), 21.4% stage III (n = 9/42), and
2.4% stage IV (n = 1/42) (Fig. 3). The mean age of patients
with lung cancer was 63.5 ± 4.8 years. Overall, 64% were
men (n = 27/42) and 36% women (n = 15/42). Indeter-
minate or false positive screening results in previous
rounds did not appear to be predictive of lung cancer in
subsequent rounds. Most cancers detected at T0 (76.7%)
followed an initial positive screening (n = 23/30), and the
majority of patients with cancer diagnosed at T1 or T2
(66.6%) had negative screenings in previous rounds
(n = 8/12) (Fig. 4).

Regarding the treatments, 80.9% of patients under-
went thoracic surgery (n = 34/42), 4.8% stereotactic
radiotherapy (n = 2/42), 9.5% combined radio-
chemotherapy (n = 4/42), 2.4% chemotherapy (n = 1/
42), and 2.4% comfort treatment (n = 1/42) (Fig. 5).

Of the 34 patients who underwent surgery, 79.4% had surgery only (n = 27/34), 5.9% had adjuvant chemotherapy (n = 2/34), and 14.7% had additional radio-chemotherapy (n = 5/34). Thoracic surgery consisted of 79.4% lobectomies (n = 27/34), 11.8% segmentectomies (n = 4/34), and 8.8% pneumonectomies (n = 3/34 including two right pneumonectomies).

A 63-year-old male patient who underwent right
pneumonectomy and developed mesenteric ischemia
with septic shock died within 60 days of surgery. It was
the only procedure associated with death in our study
(2.9% surgical mortality). In this patient, an unplanned
extended pneumonectomy up to the superior vena cava
and carina with sleeve resection was necessary in order
to enable a R0 resection of a cT3 neoplastic lesion. The
second right pneumonectomy was a total pneumonec-
tomy after R1 lobectomy for a cT1 neoplastic lesion.
Arterial sleeve resection was not possible given the

postoperative inflammatory response of the pre-tumour
tissues. In terms of histological analyses, there were
59.5% adenocarcinomas (n = 25/42), 16.7% squamous
cell carcinomas (n = 7/42), 11.9% neuroendocrine car-
cinomas (n = 5/42), 4.8% carcinoid tumours (n = 2/42)
and 7.1% unidentified results. (n = 3/42) (Table 2).

Investigation of false positives

During the three rounds of screening, 45 subjects were
screened positive but were not subsequently diagnosed
with cancer, giving a false positive rate of 2.8% (n = 45/
1591). A total of 72 complementary explorations were
performed in these 45 patients.

Most investigations carried out were non-invasive: 37.5% PET scans (n = 27/72), 25% complementary CT scans (n = 18/72), and 1.4% magnetic resonance imaging (MRI) scans (n = 1/72). Regarding invasive explorations, there were 30.5% flexible endoscopies (n = 22/72), 1.4% rigid bronchoscopies (n = 1/72), 1.4% endobronchial ultrasounds (n = 1/72) and 2.7% video-assisted thoracic surgeries (VATSs) (n = 2/72). Invasive explorations were performed on 55.5% of subjects with false positive screening results (n = 25/45): 48.9% underwent bronchial endoscopy (n = 22/45), 2.2% rigid bronchoscopy and endobronchial ultrasound (n = 1/45) and 4.4% underwent VATS (2/45). The rate of invasive investigations (excluding surgery) in those without lung cancer was 1.9% (n = 24/1212). The two VATS procedures were performed on benign lesions (an adenoma-toid cystic malformation and a hamartochondroma) and involved 0.16% of participants without lung cancer (n = 2/1212). These additional investigations did not result in any severe complications. Of note, no diagnostic transthoracic needle biopsy was performed before surgery in our study. The most frequent final diagnoses were infectious pathology (24.4%, n = 11/45), hamar-toma (13.3%, n = 6/45), and bronchiectasis (13.3%. n = 6/45) (Table 3). Retrospectively, one participant diagnosed with Stage I lung cancer at T2 had a nodule visible at T1, labelled false positive. By cross-referencing our data with that of the Somme cancer registry, we found no interval cancer. The sensitivity for the three study rounds was 100% (95% CI 92–100), the specificity 97% (95% CI 96–98), the negative predictive value 100% (95% CI 100–100) and the positive predictive value 48% (95% CI 37–59) (Table 4). By applying these sensitivity and specificity values and by varying the prevalence, the corresponding predictive negative and positive values were calculated (Supplemental Table S4).²⁴ If the negative predictive value did not change and remained at 100%, the positive predictive value was only 1% for a prevalence of 0.04% (never smoker with no risk factors)²⁵ and increased between 40% and 64% for a prevalence comprised between 2.1% and 5.2% (detection rates in selected lung cancer screening randomised trials)⁵,⁶,²⁶⁻²⁹
<figure><img src="image_4.png" /><figcaption>Fig. 2: Diagram showing flow of participants through the screening service. T0 = baseline screen, T1 = year 1 screen, T2 = year 2 screen.</figcaption></figure>
<table><thead><tr><th>Subjects invited</th><th>T0 n = 1254</th><th>T1 n = 878</th><th>T2 n = 869</th><th>T0-T2</th></tr></thead><tbody><tr><td>LDCT performed</td><td>945 (75.4)</td><td>376 (42.8)</td><td>270 (31.0)</td><td>1591</td></tr><tr><td>Sex in participants (%)</td><td></td><td></td><td></td><td></td></tr><tr><td>Male</td><td>67.3</td><td>67.3</td><td>66.7</td><td></td></tr><tr><td>Female</td><td>32.7</td><td>32.7</td><td>33.3</td><td></td></tr><tr><td>Sex in non-participants (%)</td><td></td><td></td><td></td><td></td></tr><tr><td>Male</td><td>65.7</td><td>67.5</td><td>68.0</td><td></td></tr><tr><td>Female</td><td>34.3</td><td>32.5</td><td>32</td><td></td></tr><tr><td>Age in participants</td><td>61.8 [58.5; 66.1]</td><td>63.5 [60.1; 67.8]</td><td>64.8 [61.4; 68.9]</td><td></td></tr><tr><td>Age in non-participants</td><td>61.1 [58.1; 64.9]</td><td>62.5 [59.3; 66.9]</td><td>63.6 [60.4; 68.2]</td><td></td></tr><tr><td>Negative Test</td><td>832 (88.0)</td><td>358 (95.2)</td><td>257 (95.2)</td><td>1447 (90.9)</td></tr><tr><td>Indeterminate Test</td><td>176 (18.6)</td><td>10 (2.6)</td><td>20 (7.4)</td><td>206 (12.9)</td></tr><tr><td>Negative test (before check at 3 months)</td><td>717 (75.9)</td><td>348 (92.6)</td><td>246 (91.1)</td><td>1311 (82.4)</td></tr><tr><td>Positive test (before check at 3 months)</td><td>52 (5.5)</td><td>18 (4.8)</td><td>4 (1.5)</td><td>74 (4.7)</td></tr><tr><td>Positive Test</td><td>64 (6.8)</td><td>18 (4.8)</td><td>5 (1.9)</td><td>87 (5.5)</td></tr><tr><td>Lung Cancer</td><td>30 (3.2)</td><td>10 (2.7)</td><td>2 (0.7)</td><td>42 (2.6)</td></tr><tr><td>Participants with a false positive result in the previous round</td><td></td><td>13 (3.5)</td><td>11 (5.1)</td><td>24 (4.1)</td></tr><tr><td>Non participants with a false positive result in the previous round</td><td></td><td>21 (4.2)</td><td>29 (18.0)</td><td>50 (7.5)</td></tr></tbody><tfoot><tr><td colspan="5">Quantitative variables are presented by median, 1st and 3rd quartiles, denoted: median [Q1-Q3]. Categorical variables are presented with frequency and percentage, denoted n (%) or percentage only as indicated in the table. LDCT: low-dose computed tomography.</td></tr><tr><td colspan="5"><b>Table 1:</b> Participation rates and results for the three rounds.</td></tr></tfoot></table>

<figure><img src="image_5.png" /><figcaption>**Fig. 3:** Cancer stages diagnosed in the three rounds (n = 42).</figcaption></figure>
<figure><img src="image_6.png" /><figcaption>Fig. 4: Screening results at T0, T1, and T2 for 42 patients with lung cancer. LDCT: low-dose computed tomography.</figcaption></figure>

<figure><img src="image_7.png" /><figcaption>Fig. 5: Treatments for cancers diagnosed in the three rounds (n = 42).</figcaption></figure>
<table><thead><tr><th>Subject</th><th>Round</th><th>Sex</th><th>Age</th><th>Stage</th><th>Histology</th><th>Treatment</th></tr></thead><tbody><tr><td>1</td><td>T0</td><td>M</td><td>69</td><td>I</td><td>Squamous cell</td><td>Left upper lobe segmentectomy</td></tr><tr><td>2</td><td>T0</td><td>F</td><td>68</td><td>I</td><td>Adenocarcinoma</td><td>Left upper lobectomy</td></tr><tr><td>3</td><td>T0</td><td>M</td><td>59</td><td>I</td><td>Adenocarcinoma</td><td>Right lower lobe segmentectomy</td></tr><tr><td>4</td><td>T0</td><td>M</td><td>60</td><td>IIIB</td><td>Adenocarcinoma</td><td>Radio-chemotherapy</td></tr><tr><td>5</td><td>T0</td><td>M</td><td>57</td><td>I</td><td>Squamous cell</td><td>Right pneumonectomy</td></tr><tr><td>6</td><td>T0</td><td>F</td><td>65</td><td>IIIA</td><td>Adenocarcinoma</td><td>Right upper lobectomy</td></tr><tr><td>7</td><td>T0</td><td>M</td><td>65</td><td>I</td><td>Carcinoid</td><td>Right upper lobectomy</td></tr><tr><td>8</td><td>T0</td><td>M</td><td>68</td><td>I</td><td>Squamous cell</td><td>Lobectomy + segmentectomy</td></tr><tr><td>9</td><td>T0</td><td>M</td><td>64</td><td>I</td><td>Adenocarcinoma</td><td>Right upper lobectomy</td></tr><tr><td>10</td><td>T0</td><td>F</td><td>60</td><td>I</td><td>Adenocarcinoma</td><td>Left lower lobectomy</td></tr><tr><td>11</td><td>T0</td><td>M</td><td>70</td><td>I</td><td>SCC</td><td>Right lower lobectomy then RC</td></tr><tr><td>12</td><td>T0</td><td>M</td><td>60</td><td>IIIA</td><td>Adenocarcinoma</td><td>Left lower lobectomy then RC</td></tr><tr><td>13</td><td>T0</td><td>F</td><td>60</td><td>Tis</td><td>Adenocarcinoma</td><td>Right upper lobectomy</td></tr><tr><td>14</td><td>T0</td><td>F</td><td>66</td><td>I</td><td>Adenocarcinoma</td><td>Left upper lobectomy</td></tr><tr><td>15</td><td>T0</td><td>M</td><td>66</td><td>IIIB</td><td>Squamous cell</td><td>Left lower lobectomy then RC</td></tr><tr><td>16</td><td>T0</td><td>M</td><td>59</td><td>II</td><td>Clinical</td><td>Stereotactic radiotherapy</td></tr><tr><td>17</td><td>T0</td><td>F</td><td>57</td><td>Tis</td><td>Adenocarcinoma</td><td>Right upper lobectomy</td></tr><tr><td>18</td><td>T0</td><td>F</td><td>57</td><td>II</td><td>Adenocarcinoma</td><td>Right upper lobectomy then RC</td></tr><tr><td>19</td><td>T0</td><td>F</td><td>71</td><td>IIIB</td><td>SCC</td><td>Radio-chemotherapy</td></tr><tr><td>20</td><td>T0</td><td>M</td><td>74</td><td>IV</td><td>Adenocarcinoma</td><td>Chemotherapy</td></tr><tr><td>21</td><td>T0</td><td>F</td><td>60</td><td>I</td><td>Clinical</td><td>Stereotactic radiotherapy</td></tr><tr><td>22</td><td>T0</td><td>M</td><td>68</td><td>I</td><td>Adenocarcinoma</td><td>Left upper lobectomy</td></tr><tr><td>23</td><td>T0</td><td>M</td><td>63</td><td>I</td><td>Adenocarcinoma</td><td>Left upper lobe segmentectomy</td></tr><tr><td>24</td><td>T0</td><td>M</td><td>71</td><td>I</td><td>Adenocarcinoma</td><td>Supportive care only</td></tr><tr><td>25</td><td>T0</td><td>M</td><td>66</td><td>IIIC</td><td>Adenocarcinoma</td><td>Radio-chemotherapy</td></tr><tr><td>26</td><td>T0</td><td>M</td><td>57</td><td>IIIA</td><td>NSCLC</td><td>Neoadjuvant chemotherapy followed by right lower lobectomy</td></tr><tr><td>27</td><td>T0</td><td>M</td><td>62</td><td>II</td><td>Adenocarcinoma</td><td>Right pneumonectomy</td></tr><tr><td>28</td><td>T0</td><td>F</td><td>56</td><td>I</td><td>Carcinoid</td><td>Medium lobectomy</td></tr><tr><td>29</td><td>T0</td><td>M</td><td>64</td><td>I</td><td>Adenocarcinoma</td><td>Right upper lobectomy</td></tr><tr><td>30</td><td>T0</td><td>M</td><td>56</td><td>I</td><td>Adenocarcinoma</td><td>Left lower lobar segmentectomy</td></tr><tr><td>31</td><td>T1</td><td>F</td><td>64</td><td>I</td><td>Squamous cell</td><td>Right upper lobectomy</td></tr><tr><td>32</td><td>T1</td><td>F</td><td>58</td><td>IIIA</td><td>LCLC</td><td>Left lower lobectomy followed by adjuvant chemotherapy</td></tr><tr><td>33</td><td>T1</td><td>M</td><td>61</td><td>IIIA</td><td>Squamous cell</td><td>Left pneumonectomy then RC</td></tr><tr><td>34</td><td>T1</td><td>F</td><td>63</td><td>I</td><td>SCC</td><td>Radio-chemotherapy</td></tr><tr><td>35</td><td>T1</td><td>F</td><td>55</td><td>I</td><td>Adenocarcinoma</td><td>Right upper lobectomy</td></tr><tr><td>36</td><td>T1</td><td>M</td><td>62</td><td>I</td><td>Adenocarcinoma</td><td>Right lower lobectomy</td></tr><tr><td>37</td><td>T1</td><td>M</td><td>56</td><td>I</td><td>Adenocarcinoma</td><td>Right upper lobectomy</td></tr><tr><td>38</td><td>T1</td><td>M</td><td>64</td><td>I</td><td>Adenocarcinoma</td><td>Right lower lobectomy</td></tr><tr><td>39</td><td>T1</td><td>M</td><td>61</td><td>I</td><td>Squamous cell</td><td>Left upper lobectomy</td></tr><tr><td>40</td><td>T1</td><td>M</td><td>68</td><td>I</td><td>SCC</td><td>Left upper lobectomy</td></tr><tr><td>41</td><td>T2</td><td>M</td><td>61</td><td>I</td><td>Adenocarcinoma</td><td>Left lower lobectomy</td></tr><tr><td>42</td><td>T2</td><td>F</td><td>55</td><td>I</td><td>Adenocarcinoma</td><td>Right upper lobectomy</td></tr></tbody><tfoot><tr><td colspan="7">F: female, M: male, SCC: squamous cell carcinoma, RC: radio-chemotherapy, LCLC: large cell lung carcinoma, NSCLC: non-small cell lung cancer.</td></tr></tfoot></table>

Table 2: Detected lung cancers-clinical features, stage, treatments, and histology.

Discussion

DEP KP80 is a French study evaluating the implementation of organised lung cancer screening on a territorial scale, under real-life conditions.

Lung cancers detected in DEP KP80 were localised in 71.4% of cases (Stage I/II) and 4.8% were carcinoma in situ (CIS). Our results are close to the 68% of localised Stage I/II reported in the NELSON trial and the 70% mentioned in the NLST study.⁵,⁶ They are higher than those of the European MILD, DANTE,

LUSI, ITALUNG and DLCT studies, in which the rate of Stage I/II varied from 54% to 69%.⁷,²⁶,²⁷,³⁰,³¹ Only the UK Lung Cancer Screening (UKLS) study presented a higher rate, with 83% of Stage I/II cases.²⁸

Overall, 80.9% of patients diagnosed with lung cancer underwent thoracic surgery, limited in eight cases out of 10 to a lobectomy. Our high thoracic surgery rate, which remains the standard treatment for localised cancers, is comparable to that of the MILD and PanCan studies,³² in which 80% and 75% of patients underwent
<table><thead><tr><th>Subject</th><th>Round</th><th>Sex</th><th>Age</th><th>CT scan</th><th>PET</th><th>Fibroscopy</th><th>Surgery</th><th>Final diagnosis</th></tr></thead><tbody><tr><td>1</td><td>T0</td><td>M</td><td>73</td><td>X</td><td>X</td><td>X</td><td></td><td>Infection</td></tr><tr><td>2</td><td>T0</td><td>M</td><td>66</td><td></td><td>X</td><td></td><td></td><td>Infection</td></tr><tr><td>3</td><td>T0</td><td>M</td><td>60</td><td>X</td><td>X</td><td>X</td><td></td><td>Infection</td></tr><tr><td>4</td><td>T0</td><td>M</td><td>60</td><td></td><td>X</td><td></td><td>X</td><td>Cystic adenomatoid malformation</td></tr><tr><td>5</td><td>T0</td><td>F</td><td>61</td><td></td><td></td><td></td><td></td><td>Lost to follow-up</td></tr><tr><td>6</td><td>T0</td><td>F</td><td>66</td><td>X</td><td></td><td></td><td></td><td>Unknown</td></tr><tr><td>7</td><td>T0</td><td>M</td><td>66</td><td>X</td><td>X</td><td></td><td></td><td>Bronchiectasis</td></tr><tr><td>8</td><td>T0</td><td>M</td><td>63</td><td></td><td>X</td><td></td><td></td><td>Infection</td></tr><tr><td>9</td><td>T0</td><td>F</td><td>58</td><td></td><td>X</td><td>X</td><td></td><td>Unknown</td></tr><tr><td>10</td><td>T0</td><td>M</td><td>65</td><td>X</td><td></td><td>X</td><td></td><td>Unknown</td></tr><tr><td>11</td><td>T0</td><td>F</td><td>67</td><td>X</td><td></td><td></td><td></td><td>Bronchiectasis</td></tr><tr><td>12</td><td>T0</td><td>M</td><td>55</td><td></td><td>X</td><td>X</td><td></td><td>Emphysema</td></tr><tr><td>13</td><td>T0</td><td>M</td><td>69</td><td>X</td><td></td><td></td><td></td><td>Infection</td></tr><tr><td>14</td><td>T0</td><td>M</td><td>60</td><td>X</td><td>X</td><td>X</td><td></td><td>Infection</td></tr><tr><td>15</td><td>T0</td><td>F</td><td>65</td><td>X</td><td></td><td></td><td></td><td>Unknown</td></tr><tr><td>16</td><td>T0</td><td>M</td><td>67</td><td>X</td><td></td><td>X</td><td></td><td>Infection</td></tr><tr><td>17</td><td>T0</td><td>F</td><td>55</td><td>X</td><td></td><td></td><td></td><td>Unknown</td></tr><tr><td>18</td><td>T0</td><td>M</td><td>57</td><td></td><td></td><td></td><td></td><td>Lost to follow-up</td></tr><tr><td>19</td><td>T0</td><td>F</td><td>58</td><td>X</td><td></td><td></td><td></td><td>Unknown</td></tr><tr><td>20</td><td>T0</td><td>M</td><td>70</td><td></td><td></td><td>X<sup>a</sup></td><td></td><td>Hamartoma</td></tr><tr><td>21</td><td>T0</td><td>M</td><td>62</td><td></td><td>X</td><td>X</td><td></td><td>Infection</td></tr><tr><td>22</td><td>T0</td><td>F</td><td>60</td><td>X</td><td>X</td><td>X</td><td></td><td>Bronchiectasis</td></tr><tr><td>23</td><td>T0</td><td>M</td><td>56</td><td></td><td>X</td><td>X</td><td></td><td>Emphysema</td></tr><tr><td>24</td><td>T0</td><td>M</td><td>62</td><td></td><td>X</td><td></td><td></td><td>Atelectasis</td></tr><tr><td>25</td><td>T0</td><td>M</td><td>57</td><td></td><td>X</td><td>X</td><td></td><td>Infection</td></tr><tr><td>26</td><td>T0</td><td>M</td><td>62</td><td></td><td>X</td><td>X</td><td></td><td>Pancreatic cancer</td></tr><tr><td>27</td><td>T0</td><td>M</td><td>58</td><td></td><td>X</td><td>X</td><td></td><td>Infection</td></tr><tr><td>28</td><td>T0</td><td>M</td><td>56</td><td></td><td></td><td></td><td></td><td>Lost to follow-up</td></tr><tr><td>29</td><td>T0</td><td>M</td><td>58</td><td></td><td>X</td><td>X</td><td></td><td>Infection</td></tr><tr><td>30</td><td>T0</td><td>F</td><td>73</td><td>X</td><td></td><td></td><td></td><td>Infection</td></tr><tr><td>31</td><td>T0</td><td>M</td><td>62</td><td></td><td>X</td><td></td><td></td><td>Unknown</td></tr><tr><td>32</td><td>T0</td><td>M</td><td>61</td><td></td><td>X</td><td>X</td><td></td><td>Bronchiectasis</td></tr><tr><td>33</td><td>T0</td><td>M</td><td>60</td><td>X</td><td></td><td>X</td><td></td><td>Infection</td></tr><tr><td>34</td><td>T0</td><td>F</td><td>67</td><td>X<sup>b</sup></td><td>X</td><td></td><td></td><td>Interstitial lung disease</td></tr><tr><td>35</td><td>T1</td><td>F</td><td>62</td><td></td><td>X</td><td>X</td><td></td><td>Infection</td></tr><tr><td>36</td><td>T1</td><td>M</td><td>62</td><td>X</td><td></td><td></td><td></td><td>Infection</td></tr><tr><td>37</td><td>T1</td><td>M</td><td>55</td><td></td><td>X</td><td></td><td>X</td><td>Hamartochondroma</td></tr><tr><td>38</td><td>T1</td><td>M</td><td>62</td><td></td><td>X</td><td>X</td><td></td><td>Infection</td></tr><tr><td>39</td><td>T1</td><td>F</td><td>55</td><td></td><td></td><td></td><td></td><td>Cancer at T2</td></tr><tr><td>40</td><td>T1</td><td>M</td><td>67</td><td></td><td>X</td><td>X</td><td></td><td>Bronchiectasis</td></tr><tr><td>41</td><td>T1</td><td>M</td><td>58</td><td></td><td>X</td><td>X</td><td></td><td>Interstitial lung disease</td></tr><tr><td>42</td><td>T1</td><td>M</td><td>57</td><td></td><td></td><td></td><td></td><td>Lost to follow-up</td></tr><tr><td>43</td><td>T2</td><td>M</td><td>59</td><td>X</td><td></td><td></td><td></td><td>Infection</td></tr><tr><td>44</td><td>T2</td><td>M</td><td>66</td><td></td><td>X</td><td>X</td><td></td><td>Unknown</td></tr><tr><td>45</td><td>T2</td><td>M</td><td>63</td><td></td><td>X</td><td>X</td><td></td><td>Infection</td></tr></tbody><tfoot><tr><td colspan="9">F: female, M: male, PET: positron emission tomography. <sup>a</sup>Rigid bronchoscopy + EBUS: Endobronchial ultrasound. <sup>b</sup>MRI: Magnetic resonance imaging.</td></tr><tr><td colspan="9">Table 3: False-positives: investigation and diagnosis.</td></tr></tfoot></table>

surgery, respectively. However, it is higher than the 60.6% of thoracic surgery in the NLST study and the 67.7% reported in the NELSON trial.⁵,⁶

These results, in terms of diagnostic stage and surgical treatment, confirm the real-life efficacy of lung cancer screening, the main aim of which is to diagnose early stages accessible to curative treatment.

One of the frequently cited drawbacks of cancer screening is overdiagnosis, which corresponds to the detection of indolent pre-cancerous or cancerous lesions which, if undiagnosed, would have remained clinically silent until death from another cause. This overdiagnosis is mostly linked to the discovery of ground-glass lesions corresponding to adenocarcinomas in
<table><thead><tr><th>T0</th><th colspan="2">Cancer</th><th></th></tr></thead><tbody><tr><td>Screening</td><td>Yes</td><td>No</td><td>Sensitivity = 1.00 (0.88-1.00)</td></tr><tr><td>Positive</td><td>30</td><td>34</td><td>Specificity = 0.96 (0.95-0.97)</td></tr><tr><td>Negative</td><td>0</td><td>832</td><td>PPV = 0.47 (0.34-0.60)</td></tr><tr><td></td><td></td><td></td><td>NPV = 1.00 (1.00-1.00)</td></tr></tbody></table>

<table><thead><tr><th>T1</th><th colspan="2">Cancer</th><th></th></tr></thead><tbody><tr><td>Screening</td><td>Yes</td><td>No</td><td>Sensitivity = 1.00 (0.69-1.00)</td></tr><tr><td>Positive</td><td>10</td><td>8</td><td>Specificity = 0.98 (0.96-0.99)</td></tr><tr><td>Negative</td><td>0</td><td>358</td><td>PPV = 0.56 (0.31-0.78)</td></tr><tr><td></td><td></td><td></td><td>NPV = 1.00 (0.99-1.00)</td></tr></tbody></table>

<table><thead><tr><th>T2</th><th colspan="2">Cancer</th><th></th></tr></thead><tbody><tr><td>Screening</td><td>Yes</td><td>No</td><td>Sensitivity = 1.00 (0.16-1.00)</td></tr><tr><td>Positive</td><td>2</td><td>3</td><td>Specificity = 0.99 (0.97-1.00)</td></tr><tr><td>Negative</td><td>0</td><td>257</td><td>PPV = 0.40 (0.05-0.85)</td></tr><tr><td></td><td></td><td></td><td>NPV = 1.00 (0.99-1.00)</td></tr></tbody></table>

<table><thead><tr><th>T0-T2</th><th colspan="2">Cancer</th><th></th></tr></thead><tbody><tr><td>Screening</td><td>Yes</td><td>No</td><td>Sensitivity = 1.00 (0.92-1.00)</td></tr><tr><td>Positive</td><td>42</td><td>45</td><td>Specificity = 0.97 (0.96-0.98)</td></tr><tr><td>Negative</td><td>0</td><td>1447</td><td>PPV = 0.48 (0.37-0.59)</td></tr><tr><td></td><td></td><td></td><td>NPV = 1.00 (1.00-1.00)</td></tr></tbody></table>

LDCT: Low-dose computed tomography. PPV: Positive Predictive Value. NPV: Negative Predictive Value.

<caption>**Table 4:** Performance of lung cancer screening with LDCT. 2 by 2 tables and estimates with 95% confidence intervals (Clopper-Pearson method) rounded to two decimal places.</caption>

situ. After being initially estimated at 18.5% in the NLST study,⁵ this rate was finally re-evaluated at 3% after a follow-up of 11 years.³¹ The CISNET modelling of the updated USPSTF criteria for lung cancer screening estimates this overdiagnosis at 6%.³⁴ In our study, we found only two in situ cancers (4.8%), both corresponding to ground-glass lesions.

Another potential drawback of lung cancer screening is the false positive rate. In our study, it was estimated at 2.8%. This rate is significantly lower than the 23.3% false positive rate noted in the three rounds of the NLST study, and is close to the 2.6% false positive rate in the first round of the NELSON trial.⁵,⁶ The positive predictive value observed in DEP KP80 was 48% (95% CI 37–59), comparable to the 43.5% of the NELSON trial, and better than the 3.8% of NLST study. The concordance of our results with those of the NELSON trial is explained by the use of similar algorithms integrating the concept of indeterminate screening for nodules between 5 and 10 mm, volumetry, and doubling time measurement, and confirms the value of this screening strategy. Moreover, the sensitivity (100% [95% CI 92–100]), specificity (97% [95% CI 96–98]), and negative predictive value (100% [95% CI 100–100]) of the DEP KP80 study were within the average of the corresponding values in previous studies. Jonas DE et al. reported in their literature review for the US Preventive Services Task Force recommendations on lung cancer screening that LDCT sensitivity ranged from 59% to 100%, specificity from 26.4% to 99.7%, negative predictive value from 97.7% to 100%, and positive predictive value from 33% to 43.5%.¹⁰ The variability of these results is most probably due to differences among studies regarding

inclusion criteria, decision-making algorithms, and screening protocols.

As in the NLST study, most investigations carried out on subjects with false positive screening results consisted of non-invasive explorations, with complementary imaging tests performed in 63.6% of cases. Only two VATS procedures were carried out for benign lesions (an adenomatoid cystic malformation and a hamartochondroma), representing 5.5% of surgical procedures, and involving 4.4% of subjects with false positive screening results. The rate of minor invasive investigations (excluding surgery) in those without lung cancer was only 1.9%. No patient in our study suffered from severe complications following invasive exploration. The rate of thoracic surgery for benign lesions is a quality criterion for lung cancer screening. In our study, it was particularly low. Indeed, in the five main European randomised controlled trials, surgery revealed between 8.9% and 27.2% of benign lesions detected by LDCT⁷,²⁶,³⁰ and this rate was 24.3% in the NLST study. Despite being low, our rate of futile thoracic surgery could possibly have been optimised by performing transthoracic needle biopsies. The absence of this technique in our study is justified by the fact that most patients with a positive screening result were suspected of having stage I or II cancer and did not require biopsies before surgery, as stated in the guidelines published by the British Thoracic Society and the National Comprehensive Cancer Network.³⁵,³⁶

The lung cancer detection rate in DEP KP80 was 2.6% at the end of three rounds. This rate is in line with the average of the main randomised controlled trials, in which it varies between 2.1% and 5.2%.⁵,⁶,²⁶⁻²⁹ The decrease in the detection rate observed between the first and third rounds justifies the latest French recommendations proposing LDCT screening 2 years in a row, followed by biennial screening in subjects whose first two screenings were negative in the absence of chronic obstructive pulmonary disease (COPD) or emphysema. Furthermore, the MILD study showed a comparable reduction in lung cancer mortality between annual and biennial screenings, with similar Stage I and surgery rates.⁷

It should also be noted that most patients with lung cancer screened in the second or third round had tested negative in previous rounds. Therefore, it appears that a false positive or intermediate screening result is not predictive of cancer risk in following rounds, and that, conversely, a negative screening should not be falsely reassuring and should encourage participation in subsequent rounds. The discovery of cancers at each annual screening scan in the NLST study (1% at T0, 0.7% at T1, and 0.9% at T2), the detection of 0.8% cancers in the NELSON trial in the fourth round 5.5 years after initial inclusion, and the results of the MILD study showing a reduction in mortality when screening is continued for
10 years justify the regular continuation of screening regardless of the results of previous rounds.⁵⁻⁷

We noted an important drop in participation from the first round (75.4%) to the second (42.8%) and third rounds (31%). Participation is the cornerstone of the efficacy of organised screening campaigns. In fact, the relatively low uptake in the second and third rounds is in line with data found in the real-life literature. Indeed, while participation is usually high in randomised controlled trials (over 90% for the four rounds of the NELSON trial and over 95% for the three rounds of the NLST study), the situation is quite different outside clinical trials.

Lopez-Olivo et al., in their systematic review and meta-analysis of participation in lung cancer screening in the USA outside randomised trials, found an overall participation rate of 55% regardless of the follow-up period.³⁷ The participation rate was 30% (95% CI [18%, 44%]) 12 months after the initial scan. Only one study reported a participation rate at 24 and 36 months of 38% and 28%, respectively.³⁸ In this meta-analysis, the barriers to participation were active smoking and race (non-white subjects). Subjects aged between 65 and 73 years and those with a higher level of education had a better participation rate. In our study, we noted that older subjects participated more in the different rounds. In DEP KP80, the absence of a reminder letter for the second and third rounds, as well as the need to consult one's GP to obtain the prescription for the screening scan at T1 and T2, were probably obstacles to participation. Informing and raising awareness among healthcare professionals and the general public regarding the importance of screening and its continuation after the initial scan until non-compliance with the inclusion criteria is essential to optimise participation and the efficacy of lung cancer screening. Particular attention should be paid to raising awareness among the youngest subjects (aged 50–60) and participants with false positive screening results, as these patients seem less likely to attend the various screening rounds. Reminder and re-invitation strategies in the English SUMMIT cohort have proved effective in improving participation.³⁹ Montes U et al. also showed that the availability of a lung cancer screening coordinator is associated with an increased compliance rate, most likely thanks to reminders and follow up contacts with participants.⁴⁰

While the involvement of GPs in lung cancer screening is considered essential in many countries,⁴¹ the organisation of lung cancer screening cannot be left to health professionals alone. The European Respiratory Society and the European Society of Radiology have recently recommended that lung cancer screening should be centralised within identified multidisciplinary structures bringing together PNs, radiologists, GPs, tobaccologists, thoracic surgeons, etc., respecting standardised protocols for nodule interpretation and

management, as well as quality criteria for LDCT scans.¹¹ In France, centres managing existing organised screening programs (breast, colon, and cervix) should be integrated into these structures, bringing in their expertise in terms of logistics and database management. Ideally, mobile teams, whose efficacy has been demonstrated in the United Kingdom in particular, should be involved in the system. They enable us to get as close as possible to the most at-risk populations, thus avoiding inequalities in access to screening.⁴²,⁴³

Nevertheless, the DEP KP80 study had some limitations. This observational cohort study was inherently subject to bias, which we reduced by using appropriate statistical methods and models. For this study, we did not collect data from the patients who did not attend their appointments, on ethnicity, smoking status (number of pack-years, current or former smokers), level of experience and number of readings performed by radiologists. However, these missing data were not essential to the main research question and their absence was unlikely to significantly affect our results. The study was non-randomised, uncontrolled, and the sample size was relatively small. However, we did not seek to evaluate the impact of screening on mortality, which has previously been done in the NLST and NELSON trials, but rather to investigate the feasibility and effectiveness of this screening method on a regional scale in France. The strengths of our study resided in its multicentric nature and the fact that existing patient pathways were respected, and screening participants were managed by their usual healthcare professionals (GPs, PNs, radiologists, thoracic surgeons, oncologists, etc.). No dedicated MDT or specific management circuit was set up for this study. The files of participants with positive screening results were presented during existing MDTs. The radiologists participating in DEP KP80 were general radiologists, not necessarily specialised in thoracic imaging, but who had signed a charter of good practice for LDCT and were committed to following the decision-making algorithms for the management of pulmonary nodules.

Our study, based on an existing healthcare system, enabled us to assess the feasibility and efficacy of organised lung cancer screening under real-life conditions, and to draw pragmatic conclusions from the results and any organisational difficulties.

In summary, the DEP KP80 study showed the real-life efficacy of lung cancer screening by LDCT in diagnosing a majority of early tumours that are candidates for surgery.

The design of our study, using existing healthcare circuits, showed the feasibility and possible rapid implementation of this screening. The drop in participation in the second and third rounds highlighted the need to optimise the organisation, particularly through dedicated multidisciplinary structures. In the future, the contribution of artificial intelligence, biomarkers, and
risk prediction models may improve the efficiency of healthcare professional resources and thus optimise participation, which remains the cornerstone of any screening program.

### Contributors

Leleu Olivier: conceptualisation, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, supervision, validation, visualisation, writing—original draft, writing—review & editing. Storme Nicolas: investigation, writing—original draft, writing—review & editing. Basille Damien: writing—review & editing. Auquier Marianne: writing—review & editing. Petigny Valerie: data curation, writing—review & editing. Berna Pascal: writing—review & editing. Letierce Alexia: methodology, data curation, formal analysis, writing—review & editing. Couraud Sébastien: writing—review & editing. de Bermont Julie: writing—review & editing. Milleron Bernard: writing—review & editing. Jounieaux Vincent: conceptualisation, writing—review & editing. Letierce Alexia and Couraud Sébastien accessed and verified the underlying data. All authors read and approved the final version of the manuscript.

### Data sharing statement

Data collected for the study, including deidentified individual participant data will be made available to others until December 2025, upon request to the corresponding author (leleu.olivier@ch-abbbeville.fr), and with a signed data access agreement.

### Declaration of interests

NS, DB, VJ, JdB, VP, BM, PB, MA and AL declare no potential conflicts of interest.

SC declares grants from AstraZeneca, Amgen, Adene, BDBio-science, BMS, Boeringher, Chugai, Janssens, Laidet, Lilly, MSD, Novartis, Roche, Pfizer, Takeda, Volition and Transdiag, royalties from Volition, payment for expert testimony from Amgen, Astra Zeneca, Boeringher, Health Event, MSD, Novartis, Pfizer and Sanofi, and support for attending meetings from Amgen, Astra Zeneca, BMS, Chugai, Janssens, Laidet and Takeda.

OL declares grants from Chiesi, AstraZeneca, BMS and Amgen, and support for attending meetings from France Oxygene and Aeris.

### Acknowledgements

This work was supported in part by grant from the Regional Health Agency of Picardie, La Ligue contre le cancer, the Conseil Départemental de la Somme and educational grants from AstraZeneca. The sponsors were not involved in the management and interpretation of the study. The authors would like to thank patients, GPs, PNs, and radiologists of the French Somme administrative territory who participated in our study. They likewise thank Gabrielle Cremer for expert English-language editing.

### Appendix A. Supplementary data

Supplementary data related to this article can be found at https://doi.org/10.1016/j.ebiom.2024.105396.

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