Tobacco smoking is the most relevant cause of avoidable death in all high-income countries,
including the European Union and Italy. Smoking increases the risk of dying from emphysema by
10 times, doubles that of having a stroke, and increases two to four times that of being
affected by a heart attack. In addition, the carcinogenic substances contained in tobacco
smoke are responsible for about 90% of lung cancers, but also for most cancers of the oral
cavity, larynx and bladder. Therefore, the main causes of death attributable to tobacco smoke
are cancers, cardiovascular and respiratory diseases. Lung cancer is a serious and
far-reaching health problem with reduced survival after 5 years. Seventy per cent of lung
cancers are at an advanced clinical stage and difficult to treat when the first symptoms
occur, and a certain diagnosis is made. Lung cancer mainly affects people over the age of 50,
with a peak incidence around 70-75 years. Over a third of deaths attributed to smoking are
between 35 and 69 years of age. For long time it was not possible to have a certain diagnosis
by diagnostic tests. Only at the end of the '90s, it became clear that computed tomography
allows lung cancer to be detected at an early stage (stage I), before symptoms occur.
Large-scale randomized clinical trials (RCTs) have shown that early detection of lung cancer
by CT can reduce lung cancer mortality between 20% and 39%, according to the duration of the
intervention. In particular, LDCT screening has been shown to significantly reduce lung
cancer mortality by 8-26% for men and 26-61% in women. International lung cancer screening
guidelines, currently adopted in the United States, recommend repeating LDCT at annual
intervals. However, annual chest LDCT screening has heavy economic impact and can induce
radiation-related damage.
Recent studies have shown that the first LDCT screening exam provides information on
individual risk thus allowing the personalization of the screening interval. In particular,
there are indications that screening interval can be extended safely for low-risk
individuals. For example, several studies show that individuals with a negative baseline exam
have a substantially lower risk than those with a positive baseline exam. A randomized
prospective assessment of risk-based screening intervals therefore has the potential to
improve efficiency and reduce the economic-health impact of lung cancer screening. In fact, a
personalized screening protocol has a less serious economic impact, both at the instrumental
level and in terms of the commitment of the radiological staff.
In this context, the RISP network aims to promote a nationwide early diagnosis program with
LDCT that reduces mortality from lung cancer, and at the same time, brings benefit in primary
prevention of smoking-related diseases, such as chronic obstructive pulmonary diseases (COPD)
and other cardiovascular diseases. RISP will start lung screening in a gradual and controlled
way, through a network of reference centers with multidisciplinary clinical competence that
provide adequate coverage of the territory, and meanwhile a level of quality fitting to the
standards currently achieved in the screening of other cancers (breast, cervix, colon). A
systematic screening program will also increase the percentage of lung cancer patients
eligible for early-stage surgical resection from the current 25% (without screening) to
50-60%.
At baseline- each volunteer will undergo:
a baseline questionnaire (e.g. socio-demographic, smoking habits, etc) with anti-smoking
counseling program that includes cytisine-based anti-smoking therapy.
blood sampling for the assessment of the inflammatory and metabolic profile (i.e.
bio-markers) (optional)
evaluation of respiratory function and measurement of carbon monoxide (CO)
chest LDCT without contrast
anthropometric evaluation (e.g. weight, height, BMI, etc)
Follow-up- each randomized volunteer will undergo:
Imaging will be performed by volumetric acquisition with a computed tomography scanner
equipped with advanced technology hardware and software, including an AI-based second reading
that will be validated by a radiologists panel.
All data will be entered into a password-protected database. The protection of the identity
of the subjects will be guaranteed by assigning unique participation numbers specific to the
study. In a separate database, accessible only by the principal investigator or assigned team
members, the unique identification number can be linked to participants' names and addresses
for the purposes of local and central administrative processes such as scheduling scans,
sending invitation letters, sending screening results and questionnaires for topics, and
collecting follow-up information. All volunteer samples and paper/electronic files will be
destroyed 15 years after completion of the study.
Participants are assured that no personal data will be published in articles, reports or
other study documentation.
Randomization will be carried out using real-time automated statistical software: eligible
subjects will be randomly assigned to one of the two intervention arms (A, B) with a 1:1
ratio.