The proposed screening age was inconsistent across published clinical trials (Table 1), with starting ages ranging from 49 to 55 years and the end of screening ranging from 69 to 75 years. Although a recent economic evaluation of the implementation of LCS showed that screening patients aged 50 years and older is cost-effective,15 a higher cost-effectiveness ratio is obtained as the maximum age decreases. Additionally, most European trials begin screening at 50 years of age. Therefore, the task force proposes a screening age group between 50 and 75 years.

A smoking load ≥20 pack years was chosen for tobacco consumption. Most European and worldwide studies have selected this cutoff value. However, it is worth noting that the NELSON trial did not use the terminology of pack years and defined different smoking loads according to the duration of smoking habits. This methodology is not compatible with the population-based LCS in Portugal, as the required information cannot be automatically retrieved from national data sources. Regarding ex-smokers, while the relative risk of LC decreases with the years since quitting, the risk of LC among those who have quit in the last 15 years remains high compared with never-smokers.24Therefore, the task force recommends screening smokers with a smoking history of ≥20 pack years and ex-smokers of less than 15 years with the same smoking history.

The task force recommends that individuals with current or recent (within 5 years) treatment of advanced-stage non-lung cancer should not be included in a national LCS process.25 These particular populations are already subject to specific monitoring and have an increased risk of LC compared with the defined eligible population. Those with comorbid conditions that substantially limit life expectancy and those incapable of giving informed consent should also be excluded. Furthermore, screening should be postponed for at least 3 months if the person has symptoms of an active respiratory infection or a recent history of respiratory infection (e.g. pneumonia, tuberculosis, or viral infection) to reduce false-positive LDCT results.26

The selected sources are the most robust available. It should be highlighted that they only identify persons with a valid Sistema Nacional de Saúde (SNS) number and with a General Practitioner or Family Doctor attributed. According to the Transparency Portal of the National Health Service, about 10 % of the population may not fulfil these requirements, which may be a limitation, similar to what happens with other screening programs; for this reason, self-identification should be accepted.27

Step 2 – Invitation and Information

The ideal recruitment method is a matter of debate and can be highly resource-consuming.28–31

There is robust evidence from other implemented population-based screening programs that customised invitation letters are more effective when they include the following information: i) the patient´s name; ii) a comprehensive description of the screening program; iii) details about the inclusion and exclusion criteria; iv) information about the risks and benefits of patient participation in the screening program; v) a brief intervention promoting smoking cessation and referral to cessation programs; vi) a predefined date, time, and location for the screening test; and vii) an informed consent form. All documents must display the identification of the promoting entities. The screening program should also include an opt-out mechanism that allows individuals who do not wish to participate to inform the organisers of their decision.32

After receiving the invitation letter, individual participants should receive a confirmatory phone call from a dedicated healthcare professional affiliated with the screening program. This professional should conduct an eligibility assessment by applying a checklist that includes all inclusion and exclusion criteria. Additionally, the first screening round should be scheduled. It is important to note that a brief intervention for smoking cessation should be included during the phone call as part of the transversal smoking cessation approach.

Step 3 – Testing: Radiological requirements and protocols

The LDCT Protocol should be consistent and standardized across institutions and through the screening rounds.

Although the risk of radiation-induced cancer and the resulting mortality are low compared to the benefits of LDCT, the radiation dose should not be ignored, as the risk of radiation-induced cancer increases with the radiation doses used.33,34 The reliability and reproducibility of volumetric measurements depend on the appropriate and consistent use of acquisition and reconstruction parameters.35

To ensure the implementation of a reproducible screening program with sufficient image quality for the detection of small nodules while minimizing radiation dose, the following requirements must be met:

• •

  Centre-related requirements: An experienced radiologist should lead the implementation and monitor screening tests.33,34

• •

  Scanner-related requirements: A multi-detector row tomography equipment with 64 or more detector rows is preferable. If this is not possible, a 32-multidetector row equipment can be used.36 Using a mobile unit is an innovative practice already implemented in some countries that can provide added value by promoting adherence and ensuring equitable access to hard-to-reach populations.37

• •

  Technical standards for examination technique: The LDCT Protocol recommended by the European Society of Thoracic Imaging (ESTI) is described in Appendix B.38

The volume of the nodules, rather than their diameters, should be measured. Nodule volume is a more reliable predictor of early growth and plays a crucial role in reducing false-positive results, defining optimal management of patients with lung nodules, and improving outcomes.39 Nodule volume measurement is currently recommended by the British Thoracic Society Guidelines, Fleishner Society Guidelines, European Position Statement Expert Group, and the latest version of Lung-RADS.40–42 When applied to the NLST with a threshold of 6 mm, Lung-RADS allowed a 52 % reduction in false positives and a recall rate reduction to 12.8 % versus 26.3 % in round 1, and had good acceptance among radiologists.43

We recommend the use of a structured report and the Lung-RADS classification for the conclusion of the LCS report to standardise reporting and management of abnormal findings detected in LDCT.42 Board-certified radiologists with experience in pulmonary nodule imaging should be encouraged to pursue LCS Certification.34

Given that the implementation of an LCS program results in a significant increase in the workload of radiologists with the need for detailed nodule assessments, including volume duplication time, artificial intelligence (AI) solution aid is now widely recognised as beneficial for LCS programs.44

The optimal interval between two screening CT scans remains a subject of debate. In the NELSON trial, incremental intervals between screening tests were used: 1, 2, and 2 ½ years.8 When compared with the first round of screening (with a 1-year interval), the examination at 2 and ½ years resulted in a significantly lower detection rate of stage IA cancers (60.9% vs. 75.9 %, p = 0.02), a higher rate of stage IIIB/IV cancers (17.3% vs. 6.8 %, p = 0.02), and an increase in the number of interval cancers.45 Thus, a 2.5-year interval does not seem to be the most appropriate. The analysis of the two-year interval did not show a significant increase in the incidence of advanced stages compared to the 1-year interval (p = 0.09). However, there is insufficient evidence to support a 2-year interval.45

Therefore, the task force proposes a 1-year interval between two CT scans. This screening interval should be re-evaluated based on the diagnostic yield and incidence of interval cancers during the screening program and on the results of other studies that are currently underway. The screening should be continued as long as individuals meet the inclusion criteria.

Step 4 – Reporting and Referral of screening results

Screening results should inform the Lung-RADS classification and provide follow-up recommendations (Fig. 1).

Fig. 1.

Flowchart illustrating the information and the patient pathway according to the LUNG-RADS classification of lung cancer screening (This image is original and was generated by an author of the manuscript). CT – computed tomography.

(0.15MB).

Negative screening results should be communicated to the patient via text message and to the family doctor via national electronic medical records. The next screening round should be automatically scheduled.

Positive screening test results should be communicated to patients via text messages and written letters explaining the results. The results should also be sent to family doctors via national electronic medical records. Scheduling of additional examinations should be determined based on the results of the diagnostic workup outlined in Step 5.

Other clinically significant findings should be communicated to the patient via text messages and to the family doctor via national electronic medical records.

Step 5 – Diagnosis

Individuals with a positive screening test (Lung-RADS 3 or 4) should be promptly referred to a specialised pulmonology consultation.

Patients with a Lung-RADS score 3 should repeat the CT scan after 6 months. If the size of the nodule does not increase on the subsequent CT scan, the patient should be reintegrated into the regular screening program. However, if suspicious findings are detected, the management protocol should follow the Lung-RADS 4 protocol.

Patients with a Lung-RADS score of 4 should be referred to a Multidisciplinary Team that may include Pulmonologists, Radiologists, Interventional Radiologists, and Thoracic Surgeons. The team should discuss the appropriate management strategy for the patient and establish a follow-up plan (Fig. 1).

Diagnostic strategies for establishing the diagnosis of lung cancer usually include transthoracic biopsies and or bronchoscopy.

Pulmonary nodes, mainly if peripheral, can be diagnosed with a transthoracic pulmonary biopsy, which has a very high diagnostic yield for malignancy, although with an overall pooled incidence for pneumothorax of 25.9 % and chest drain insertion of 6.9 %.46 Currently, there is a trend to combine lung cancer diagnosis with lymph node endosonographic guided using endobronchial ultrasound (EBUS) ± endoscopic ultrasound (EUS) for mediastinal staging in an all-in-one procedure. Solitary pulmonary nodules constitute a challenge for the bronchoscopist. The sensitivity of bronchoscopy in detecting malignancy is highly variable, depending on factors such as nodule size, the nodule´s relation to the bronchial wall, the presence of CT- bronchus sign, complementary use of image systems, operator skills, and the prevalence of cancer in the population being screened.47 Image-guided techniques, such as EBUS with radial probe, fluoroscopy, cone-beam and electromagnetic navigation bronchoscopy, facilitate sampling peripheral lesions and improve the detection of such lesions. Moreover, a better yield can be achieved with combined modalities. Robotic bronchoscopy is also a promising developing technology.

Bronchoscopic sampling methods can also be improved with the use of cryobiopsies, allowing for larger and better-preserved samples, alongside with conventional biopsies forceps, brushings, and washes.48

Step 6 – Treatment

It is crucial to ensure that all individuals who require treatment receive the best possible care within the specified timeframe, following the European Society for Medical Oncology guidelines adjusted to the National Authority of Medicines and Health Products (Infarmed) indications. Timely and equal access to thoracic surgery, radiotherapy, and systemic oncological treatments must be guaranteed.

Step 7 – Pilot Testing, Monitoring, and Evaluation

The task force recommends the implementation of a pilot LCS program in Portugal based on the established effectiveness and cost-effectiveness of LCS in populations with similar characteristics at an international level.

This pilot program is expected to be conducted in at least two distinct primary healthcare areas, following a population-based approach and the recommendations of this task force, as mentioned above. A random sample of the eligible population should be selected for this pilot study.

The monitoring strategy should include data collection on health outcomes and process indicators. Table 3 provides a brief overview of the indicators to be considered.

In a pilot screening program, it is advisable to compare the overall and the LC mortality rates of the screened population with the non-screened population in the same geographical area. Additionally, an economic evaluation of the screening project should be conducted using a decision-tree model to compare the cost-effectiveness of screening and non-screening in the Portuguese population, assuming high-quality patient-level data. The main outcome measures should be QALY and Disability-adjusted life-years (DALY) assessed for 5, 10, and lifelong years. Costs should be calculated from both the provider and societal perspectives.

Before the implementation of the screening in each centre, the designated interveners should be identified and trained for their respective tasks, including smoking cessation brief intervention. This training is essential to enhance the reproducibility and quality of the screening program.

The results of the pilot programs should guide the implementation of LCS at the national level, and any necessary adaptations of the proposed protocol should be made based on acquired knowledge.

Transversal approach – Smoking cessation intervention

Smoking cessation is the most cost-effective measure for reducing LC mortality7,49 and is associated with better therapeutic responses and fewer complications from chemotherapy, radiotherapy, and surgery.50

Around 40–60 % of individuals still smoke at enrolment, and many of them are highly nicotine-dependent,51 while ex-smokers undergoing LCS face a high risk of relapse.50,52 LCS programs offer a unique opportunity to promote motivation to quit, support quitting attempts, and prevent relapse toward sustained abstinence among high-risk smokers and ex-smokers.50,53 Pairing LCS with smoking cessation should be the standard of care in a high-quality screening program.50,54 as it can favour the balance between screening benefits and harm,55,56 promote participants' adherence to screening,60 and enhance its cost-effectiveness.56 Furthermore, smoking cessation interventions must be made available and encouraged at any time during screening programmes.

Tobacco and nicotine use are classified as chronic relapsing disorders that require a chronic disease approach involving diagnosis, evaluation, and repeated treatment until sustained abstinence is achieved. Therefore, it is crucial to provide training to healthcare providers (HCPs) to ensure a systematic approach to smoking cessation.57 Considering tobacco cessation guidelines, expert panel recommendations, and recent systematic reviews, subsequent strategies should incorporate LCS cessation interventions.50–53,55–60

• i)

  All smokers and former smokers participating in the LCS should be strongly encouraged to quit or remain smoke-free at each visit, irrespective of their motivation to quit or screening results. It is essential to systematically record the patterns of tobacco/nicotine use and cessation advice.

• ii)

  The LCS provider team should be trained to deliver brief evidence-based tobacco cessation advice (5 As/5 Rs model) and systematically emphasize the benefits of quitting. Advice should be tailored to age, sex, tobacco/nicotine use patterns, and specific clinical situations.

• iii)

  For smokers unwilling to quit, motivational behavioural strategies, such as the 5Rs model, should be implemented during each visit to foster behavioural change.

• iv)

  Smokers ready to quit should receive assistance or be referred to evidence-based cessation programmes. This can be done by the primary care team or other HCPs involved in LCS or by referral to external cessation programs, such as quit lines or intensive smoking cessation services.

• v)

  Providing self-help leaflets or materials as a unique cessation strategy has limited efficacy in promoting abstinence.

• vi)

  The most effective intervention, particularly for long-term and highly dependent smokers, involves intensive multicomponent treatment. This should encompass motivational strategies, high-intensity behaviour therapy with multiple counselling sessions, and pharmacologic treatment.

• vii)

  The most effective pharmacotherapies are a combination of nicotine replacement therapy, varenicline or cytisine.

• viii)

  Affordability of pharmacotherapy is mandatory to enhance treatment adherence and effectiveness.

• ix)

  Treatment should include advice on exposure to second-hand smoke.

• x)

  Regular follow-up to boost motivation and prevent relapse should be conducted systematically, and retreatment should be incorporated as needed.

This task force strongly recommends that LCS combined with evidence-based smoking cessation should be the standard care in a high-quality screening program.