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Lung cancer screening: the cost of inaction July 2021 This report was developed for the Lung Ambition Alliance by The Health Policy Partnership and endorsed by the International Association for the Study of Lung Cancer. It was initiated and funded by AstraZeneca, a founding partner of the Lung Ambition Alliance.
Lung cancer screening: the cost of inaction 2 Table of contents Executive summary 3 1 Introduction 7 2 Lung cancer: a public health priority 9 3 Earlier detection: the key to reducing the burden 12 of lung cancer 4 LDCT screening for lung cancer: the next big opportunity 18 in cancer detection 5 An investment in health system sustainability 21 6 Ensuring successful implementation of lung cancer 24 screening at scale 7 Conclusions 32 References 33 Appendix 1. Synthesis of published cost-effectiveness 40 studies on LDCT screening
Lung cancer screening: the cost of inaction 3 Executive summary Lung cancer is the leading cause of cancer lung cancer deaths by sex, with mortality deaths worldwide, accounting for one in rates mostly rising among women in five cancer deaths.1 Smoking is the major many countries.8 With all these factors cause of lung cancer, but lung cancer is combined, the number of people with lung not just a smokers’ disease. Global rates cancer is likely to remain significant for of smoking have been gradually declining decades to come. in men, but have remained stable, or decreased at a slower rate, in women.2 Governments around the world have Former smokers, however, remain at high committed to reducing the burden risk of lung cancer up to 25 years after of cancer, but few countries are on quitting.3 In addition, the prevalence of target to meet their goals. Lung cancer lung cancer in never-smokers is gradually accounts for the greatest economic and rising: in the UK and US, around 20% of public health burden of all cancers.9 lung cancers occur in people who have It is responsible for nearly a quarter of never smoked, and this figure is about productivity losses due to premature 53% in some Asian countries.4-7 There is mortality from cancer in Europe.10 Targeted also a global shift in the distribution of efforts on lung cancer must therefore
Lung cancer screening: the cost of inaction 4 Lung cancer accounts for the reduction in the number of deaths from lung cancer. This will have a substantial greatest economic and public health impact on cancer mortality more generally burden of all cancers. and, in turn, will dramatically decrease the economic toll of cancer on our societies. Earlier detection through screening may transform lung cancer from a be an integral part of all national cancer fatal to a treatable condition, with control plans if countries wish to achieve considerable impact on quality of life. their goals and reduce the toll of cancer The most effective means of achieving on their societies. this shift is through targeted screening using low‑dose computed tomography Early detection that allows people (LDCT).18 19 Evidence from large-scale rapid access to high-quality diagnosis clinical trials has shown that targeted LDCT and care offers the best opportunity screening can reduce lung cancer deaths in to reduce the number of deaths due high risk individuals by nearly a quarter.18 19 to lung cancer. Prognosis for lung Given that approximately 1.8 million lives cancer is poor compared with most are currently lost to lung cancer every other cancers,11-13 largely due to a high year,1 this would have a considerable public proportion of cases being detected health, economic and societal impact. at an advanced stage when treatment options are limited.14 Around 20% of In light of this evidence, it is time for people with lung cancer are diagnosed at national governments to consider stage I, when their likelihood of surviving large‑scale implementation of targeted 5 years is between 68–92%, compared lung cancer screening. Lung cancer with more than 40% of people being screening should be considered the next detected at stage IV, when their likelihood big opportunity in cancer screening: of surviving 5 years is under 10%.15-17 experts suggest it compares favourably The proportion of people detected at with other cancer screening programmes an advanced stage varies considerably in terms of cost-effectiveness and by country. Shifting detection to earlier potential benefits,20 and fewer people stages could thus result in a considerable need to be screened for lung cancer to prevent one death compared to breast or colorectal cancer screening.19 21 22 What’s more, a decade of implementation research around the world has pointed to Lung cancer screening should be factors that can help ensure successful, cost‑effective implementation at scale. considered the next big opportunity Of highest importance is the need in cancer screening to secure attendance from people at
Lung cancer screening: the cost of inaction 5 Figure a. The impact of lung cancer screening extends beyond lung cancer Reduced health inequalities in lung cancer (in terms of risk of late presentation, access to appropriate treatment and care, survival) Complement to Targeted lung cancer screening and broader Reduced loss of smoking cessation early detection productivity and fewer policies, contributing to premature deaths due to creating a tobacco free Coupled with rapid access lung cancer generation to expert diagnosis and multidisciplinary care Early detection of other non-communicable diseases (e.g. chronic obstructive pulmonary disease, cardiovascular disease) Enhanced sustainability Contribution to of healthcare systems through reduced mortality from lower costs of care non‑communicable diseases greatest risk of lung cancer, to optimise The benefits of investing in the early the balance of benefits and harms from detection of lung cancer extend beyond screening, and to integrate targeted lung cancer (Figure a). Screening screening programmes into high-quality presents an opportunity to detect other multidisciplinary care pathways, with early non-communicable diseases, such as diagnosis and effective treatment options cardiovascular disease and chronic available for all. obstructive pulmonary disease, at an early stage in high-risk individuals.23-25 It can also
Lung cancer screening: the cost of inaction 6 The need to invest in early detection and the backlog of cases the pandemic has created will undoubtedly exacerbate has never been more urgent the risk of late presentation for months to come.29-34 In England, for example, delays in diagnosis due to COVID-19 are expected to result in an 11.2% increase of stage IV diagnoses of lung cancer,35 and similarly help reduce health inequalities: people of worrying trends are emerging in other lower socioeconomic status are at highest countries.29 36 risk of lung cancer, of presenting late with symptoms, and of poor survival as Time is everything for people with lung a result.26-28 cancer. As systems rebuild following the pandemic, the need to invest in early Investing in early detection of lung detection has never been more urgent. cancer is also an investment in the future Failing to do so condemns lung cancer sustainability of our health systems and patients to poor survival and diminished post-pandemic recovery. The COVID-19 quality of life, and increases the long-term pandemic has had a dramatic impact on the strain on overstretched, under-resourced entire lung cancer care pathway – including health systems. initial presentation, diagnosis and access to treatment – and there is growing evidence Leadership as we emerge from the that it is undoing some of the progress in pandemic means acting early – the time lung cancer survival achieved in recent to act is now. The cost of not doing so is years.29 Across many countries, screening too great, not just for lung cancer patients, and urgent referrals have declined sharply, but for society as a whole.
Lung cancer screening: the cost of inaction 7 1 Introduction Lung cancer is the leading cause of cancer is the main cause of lung cancer. In most deaths worldwide. More than 2.2 million countries, smoking rates have declined people were diagnosed with lung cancer in among men but remained stable or 2020i, making it the second most commonly decreased at a slower rate among diagnosed cancer worldwide after breast women.2 However, a former heavy smoker cancer.1 Approximately one in five cancer remains at three times greater risk of deaths globally is due to lung cancer,37 and developing lung cancer than a person the five-year survival rate was just 10–20% in who has never smoked, and this risk most countries between 2010–2014.11 remains for up to 25 years after quitting smoking.3 In addition, lung cancer is not Despite falling smoking rates, the just a smokers’ disease and its frequency prevalence of lung cancer is expected among never-smokers is rising globally.5 to remain high for many years. Smoking In the UK and US, around 20% of lung i In this report we have used the most recent data available (2020). While it is possible that this number is underestimated due to under-reporting of cases during the COVID-19 pandemic, figures for 2020 are as expected based on current epidemiological trends, and comparable to data from earlier years.
Lung cancer screening: the cost of inaction 1 Introduction 8 cancers occur in people who have never that targeted screening of former and smoked, and this rate is 53% in some Asian current smokers by low-dose computed countries.4-7 There is also a global shift tomography (LDCT) can significantly reduce in the distribution of lung cancer deaths deaths from lung cancer.18 19 Given that by sex, with mortality rates mostly rising lung cancer currently kills approximately among women in many countries.8 With all 1.8 million people worldwide every year,1 these factors combined, lung cancer will this impact would be considerable. But the remain an important public health problem COVID-19 pandemic has halted translation for decades to come. of clinical trial evidence to real-world implementation of screening programmes The link with smoking has caused in many countries. The pandemic has also widespread stigma towards people with caused significant disruption to diagnosis lung cancer. Such stigma is felt equally and care of people with lung cancer, by people who do or have smoked and making the need to reduce the burden those who have not.38 Many studies have of this condition on our societies much shown that the emotional burden caused more urgent. by a lung cancer diagnosis is considered to be significantly higher than for other As we emerge from the COVID-19 cancers, and stigma is a big part of this.38-42 pandemic, we are faced with a unique Lung cancer has also traditionally received opportunity: to find the most feasible less attention and funding than other approach to reducing mortality from lung common cancers, despite its overwhelming cancer. Investment in early detection, with economic and societal impact.43 screening at its core, must be part of that effort if we are to reduce the devastating Many governments have set targets to costs of lung cancer on people, economies improve survival from cancer over the next and health systems. This report explores 20 years.44 45 As lung cancer is the biggest not just why this is something that should cancer killer, strategies to reduce lung be done, but the immense cost to society cancer mortality must be part of efforts to of not doing so. achieve those targets.37 The most effective way to do this is through early detection, specifically screening. It is recommended that screening for lung cancer take a targeted approach, focusing on people at highest risk of lung cancer. In 2020, the publication of the Dutch–Belgian Randomised Lung Cancer Screening Trial (NELSON) confirmed the findings of the US National Lung Screening Trial (NLST) more than a decade before,
Lung cancer screening: the cost of inaction 9 2 Lung cancer: a public health priority Reducing cancer deaths is a global of countries are on track to achieving imperative target reductions in the major NCDs,46 Cancer is one of the greatest public which include cancer, and only 12 health issues of our time. Globally, countries worldwide are currently on track it is responsible for one in six deaths to achieving specific targets to reduce and a third of premature deaths from cancer mortality.37 One in five people still non‑communicable diseases (NCDs) faces a cancer diagnosis before the age of in people aged 30– 69.37 As part of their 75,37 and in 2020, 10 million people died commitment to reducing mortality from from cancer.47 NCDs,46 many countries around the world have set targets to specifically achieve Lung cancer presents a considerable 10‑year survival in three out of four of public health and economic burden cancer patients by 2030.44 45 Lung cancer is the leading cause of cancer deaths globally. One in five cancer Despite these commitments, we are a deaths is due to lung cancer, and it causes long way from effectively tackling the approximately 1.8 million deaths per year global burden of cancer. Fewer than 10% (Table 1).1
Lung cancer screening: the cost of inaction 2 Lung cancer: a public health priority 10 Table 1. The public health impact of lung cancer: key facts and figures Globally, lung cancer is responsible for: • 2.21 million new cases per year1 • 1.8 million deaths per year1 • 11.4% of all new cancer cases1 • 18% of all cancer deaths1 • 45.9 million disability-adjusted life years (2019)48 • 45.3 million years of life lost (2019)48 South North America & Region* Europe America Caribbean Africa Oceania Asia New lung cancer cases 477,534 253,537 97,601 45,988 16,975 1,315,136 per year New cases as % of total 10.9% 9.9% 6.6% 4.1% 6.7% 13.8% regional cancer cases Lung cancer deaths 384,176 159,641 86,627 41,171 12,012 1,112,517 per year Deaths as % of total 19.6% 22.8% 12.1% 5.8% 17.3% 19.2% regional cancer deaths * Continental regional data reported by the World Health Organization Global Cancer Observatory (2020) 47 Table 2. Lung cancer costs in the European Union (based on 2009 data)49 Costs of Lung cancer All cancers % of all lung cancer % of lung as % of all Costs per year (billion €) cancer costs (billion €) cancer costs cancer costs Total costs 126.2 100% 18.8 100% 15% Direct healthcare costs 51.0 40.4% 4.2 22.5% 8% Productivity losses 42.6 33.7% 9.9 52.8% 23% (early death) Productivity losses 9.4 7.5% 0.8 4.3% 9% (lost working days) Informal care 23.2 18.4% 3.8 20.3% 16% Lung cancer has the highest economic toll Existing figures date back several of all cancers. In Europe, the costs of lung years, however, and more up-to‑date cancer are higher than breast, colorectal or estimates are needed to understand prostate cancer9 and represent 15% of the the full economic toll of lung cancer on total economic costs of cancer (Table 2).49 our societies.
Lung cancer screening: the cost of inaction 2 Lung cancer: a public health priority 11 Figure 1. Lung cancer accounts for nearly a quarter of productivity losses due to premature mortality in Europe, more than any other cancer type10 Lung €17.5bn(23%) Breast €6.9bn (9%) ng Lu Ot her Colorectum €6.3bn (8%) Brain + CNS €4.2bn (6%) Pancreas €3.9bn(5%) Stomach €3.3bn(4%) Brea s t Oesophagus €2.7bn (4%) L Liver €2.4bn(3%) NH Co lo Leukaemia €2.4bn (3%) ia re m c tu NHL €1.9bn(3%) r ae ve m uk us Bra Li ch Pancreas Le Other €23.9bn(32%) hag in + Stoma s op CN Oe S CNS, central nervous system; NHL, non-Hodgkin’s lymphoma The indirect costs of lung cancer, in on people’s quality of life. In most terms of productivity losses and informal countries, it is responsible for the most care, are particularly significant. These disability-adjusted life years (DALYs) of all costs outweigh direct healthcare costs cancers.43 Symptoms like breathlessness in published studies.49 50 Lung cancer’s and fatigue, along with the need to impact on productivity is considerable:50 attend medical appointments or adapt it accounts for nearly a quarter (23%) of to treatment regimens, may lead to productivity losses due to premature social withdrawal and time off work.39 mortality from cancer in Europe, a The psychological distress, impact of higher proportion than any other cancer cancer treatment and related side effects (Figure 1).10 Many people with lung cancer substantially affect the mental health stop working and do not return, resulting and wellbeing of people living with in significant cost of early retirement to lung cancer and their loved ones.39 51 individuals, their families and the economy. The day‑to-day impact on loved ones is also significant,52 with lung cancer In addition to its high financial costs, accounting for 16% of total costs of all lung cancer also has a dramatic impact informal cancer care.49
Lung cancer screening: the cost of inaction 12 3 Earlier detection: the key to reducing the burden of lung cancer Late presentation is a significant issue common cancers.11 13 Progress in survival in lung cancer for lung cancer has paled in comparison Earlier detection is recognised as the best with that seen in some other cancers way to reduce the burden of all cancers – (Figure 2).13 54 For example, in England in but lung cancer is seldom detected early. 2018, half of lung cancers were diagnosed Symptoms such as a persistent cough, at stage IV (50%), compared to 5% of breast shortness of breath and repeated lung cancers and 25% of colorectal cancers.16 infections are often difficult for people to Although precise estimates vary by country, recognise as symptoms of lung cancer.14 trends are similar. As a result, many people present to healthcare professionals only after their Shifting detection to an earlier stage cancer has advanced to a stage where could transform lung cancer from a fatal treatment options are limited and prognosis to a treatable condition. Prognosis for is poor.14 53 lung cancer is highly dependent on the stage at which the illness is diagnosed Late presentation in lung cancer has led to (Figure 3). A person diagnosed with stage poor survival compared with some other IV lung cancer has less than 10% chance
Lung cancer screening: the cost of inaction 3 Earlier detection: the key to reducing the burden of lung cancer 13 Figure 2. Improvements in lung cancer survival have lagged-behind those seen in other common cancers (US data)12 13 54 55 5 year relative survivala 1975–1977 2008–2014 All cancers 69.2% Prostate 98.9% Breastb 91.1% Colorectal 66.2% Lung 19.9% 9–15% across Europe, generally < 20% globally a Five-year relative survival rates show the percentage of people who will be alive five years after diagnosis. This does not include people who die from other diseases. Relative survival rates account for the fact that not all people diagnosed with a certain cancer type will die of that cancer. b Women only. Data: https://seer.cancer.gov 54 of surviving five years after diagnosis; this Early detection of lung cancer would increases to between 68–92% if diagnosed have a significant economic impact at stage I.17 At stage I, patients can be Shifting detection to an earlier stage offered surgical removal (resection) with would significantly reduce the total costs a high probability of cure,56 as well as of lung cancer. The costs of treating a other curative treatments, avoiding the person with late-stage lung cancer are need for more invasive and less effective higher than for earlier-stage disease due interventions later on, with considerable to more complex pathways for clinical impact on quality of life.57 management.14 60 61 With earlier detection, more people will be able to remain active Earlier detection of lung cancer would and return to work, therefore reducing translate into significant benefits for the substantial lost productivity costs of population health. Given its prevalence, lung cancer. For example, people with a stage shift in lung cancer detection would stage IV lung cancer have been shown save countless lives lost to lung cancer to incur higher wage losses and out-of- every year and would have a dramatic pocket expenses than those diagnosed impact on the overall number of deaths at a marginally earlier stage (stage IIIB).52 from cancer (Figure 4).
Lung cancer screening: the cost of inaction 3 Earlier detection: the key to reducing the burden of lung cancer 14 Figure 3. Non-small-cell lung cancer (NSCLC)* is commonly diagnosed at an advanced stage, which is associated with poor prognosis Diagnosed cases of NSCLC 5-year survival for NSCLC patients17, b by stage (%)15, a 92 41 83 77 68 60 53 16 36 14 26 10 8 6 5 13 10 1 IA IB IIA IIB IIIA IIIB IV IA1 IA2 IA3 IB IIA IIB IIIA IIIB IIIC IVA IVB * Non-small-cell lung cancer accounts for 80–85% of lung cancer cases58 59 Estimated a from SEER validation data from the 7th edition of the International Association for the Study of Lung Cancer (IASLC) staging project. Based b on the clinical staging data from the 8th edition of the IASLC staging project. Earlier detection would also significantly as late diagnosis is thought to have reduce the impact of lung cancer on quality worsened for all cancers. The World Health of life for patients and their families. Organization reports that 55% of countries Data suggest that people with advanced experienced disruption to cancer diagnosis non-small-cell lung cancer (NSCLC) have and treatment during 2020.63 Cancer worse health-related quality of life than screening programmes were halted in people with other advanced cancer types.39 many countries and urgent cancer referrals Shifting stage of detection can thus reduce decreased significantly.30-33 This situation is the impact on people and their families, likely to lead to an increase in the number including costs linked to informal care.62 of patients presenting with cancer at later stages, when prognosis is worse.34 64 The risk of late presentation in lung A survey of 221 healthcare professionals in cancer has been exacerbated by the Italy, Germany, France, Spain and the UK COVID-19 pandemic reported a 52% decline in the number of The urgency for earlier detection has been cancer patients seen per week, and a 63% enhanced by the COVID-19 pandemic, drop in the number of patients starting
Lung cancer screening: the cost of inaction 3 Earlier detection: the key to reducing the burden of lung cancer 15 Figure 4. Lung cancer offers the greatest opportunity for early detection (England, 2018)16 100 Proportion diagnosed at stage IV (%) 80 Pancreas 60 Stomach NHL Lung 40 Oesophagus Colorectal Cervical Ovarian All other 20 Kidney Prostate Bladder Melanoma Breast 0 0 5,000 10,000 15,000 20,000 Number diagnosed at stage IV NHL, non-Hodgkin’s lymphoma The size of the circles shows the relative weight of each cancer type in terms of its contribution to the total number of cancers detected at advanced stage. Update of original figure produced by the United Kingdom Lung Cancer Coalition (UKLCC).53 Data from Public Health England, 2018.16 cancer treatment.65 At time of writing, only same period the previous year.69 In the UK, Germany has seen this situation improve.66 referrals to lung cancer specialists declined by 75% in some areas during the first Lung cancer has been hit particularly wave.68 Reduced access to CT scanners and hard by the pandemic. The delays for lung diagnostic staff have led to further missed cancer diagnoses have been significant due opportunities for early detection.29 Even for to overlapping symptoms with COVID-19 those patients diagnosed early enough for and specific pressures on respiratory surgery to be an option, limited availability healthcare services.29 67 68 In Spain, the of surgery due to competing needs of number of new lung cancer patients fell COVID-19 patients has had a significant by 21–32% during the first wave of the effect on prognosis.64 70 Data for England pandemic in 2020, compared with the suggest that a three-month delay in surgery
Lung cancer screening: the cost of inaction 3 Earlier detection: the key to reducing the burden of lung cancer 16 Targeted screening is at the core of early detection for lung cancer Given the high toll of late presentation in lung cancer, there have been considerable efforts to identify an effective screening tool in recent years. As articulated in Europe’s Beating Cancer Plan, screening, coupled with primary prevention, is the most effective way to curb the burden of cancer.72 Different approaches to screening for lung cancer have been explored, including for example chest X-ray aided by artificial intelligence (AI).73 74 In particular, LDCT screening has demonstrated statistically significant benefits in large- scale, international clinical trials.18 19 for bladder, lung, oesophageal, ovarian, It is recommended that lung cancer liver, pancreatic and stomach cancers screening follow a targeted approach and would incur 4,755 excess deaths over one be offered to those considered at highest year, escalating to 10,760 excess deaths for risk of lung cancer, who are also most a six-month delay.71 likely to benefit. Current recommendations suggest that LDCT screening be offered The pandemic has also likely reversed to current or former heavy smokers within recent progress in lung cancer survival a specific age range.42 75 76 However, there in many countries. Data from England is growing appreciation that smoking suggest that delays due to missed status is insufficient to identify all people diagnosis will lead to a 4.8–5.3% increase at high risk of lung cancer. Individual risk in lung cancer deaths, equivalent to an prediction models, which incorporate additional 1,235–1,372 deaths within five important risk factors for lung cancer – such years following diagnosis.32 In Spain, as family history of cancer or pneumonia, experts have warned that the pandemic occupational exposures (e.g. asbestos), could set back lung cancer survival by 5%, race and ethnicity77 – are recognised as resulting in an additional 1,300 deaths.69 helpful tools to identify high-risk candidates Also, as healthcare systems emerge from who might be missed by only looking at ‘crisis mode’, they face a significant backlog age and smoking status.42 78 of cases which may further delay the return to normal service levels29 34 – and this will The relative importance of smoking inevitably include more people presenting compared with other risk factors with advanced lung cancer. also varies by country. In Taiwan, for example, 53% of lung cancer deaths
Lung cancer screening: the cost of inaction 3 Earlier detection: the key to reducing the burden of lung cancer 17 Figure 5. A comprehensive approach to early detection is needed Rapid referral pathways Patients who present to their primary care physician with suspected symptoms of lung cancer are rapidly referred for specialist diagnosis and care82 83 Incidental nodule detection Lung cancer diagnosis and care pathway managed Patients with a suspicious lung nodule that by a multidisciplinary happens to be detected through chest X-ray as care team82 part of routine care (e.g. for pneumonia screening) including oncologist, are rapidly referred for specialist diagnosis radiation oncologists, and care82 83 thoracic surgeons, pulmonologist, specialist nurse Targeted screening programme Patients who meet eligibility criteria for screening are invited to undergo a low-dose computed tomography scan, and are then followed up as appropriate based on findings, and invited to return for screening within a given interval82 occur among people who have never capture people with defined risk factors smoked,7 and risk factors such as family (such as smoking status and age); however, history, exposure to cooking fumes, and individuals who do not meet these criteria exposure to environmental carcinogens are and present with possible symptoms of increasingly recognised.79 Similar patterns lung cancer also need to be referred as occur throughout East Asia, leading to quickly as possible for rapid diagnosis recommendations that non‑smokers by a multidisciplinary care team. A should be included in the target comprehensive approach to early detection population for lung cancer screening in should thus include rapid referral pathways these countries.80 81 for people who present in primary care with possible symptoms, incidental nodule In light of the evolving epidemiology of protocols for people who present with a lung lung cancer, it is important that targeted nodule while undergoing a routine X-ray screening programmes be complemented for another reason, and targeted screening by other approaches to early detection. programmes for those who meet defined Targeted screening programmes can screening eligibility criteria (Figure 5).
Lung cancer screening: the cost of inaction 18 4 LDCT screening for lung cancer: the next big opportunity in cancer detection Large-scale clinical trials have shown LDCT screening also leads to a significant that LDCT screening is effective at reduction in lung cancer mortality in reducing lung cancer mortality high‑risk patients. In the NELSON trial, The evidence demonstrating the 18.4% of 868 deaths in the screening group effectiveness of LDCT screening for lung were due to lung cancer, compared to cancer reached a turning point in 2020. 24.4% of 860 deaths in the control group.18 The publication of the NELSON trial18 This equates to a reduction in lung cancer showed that LDCT screening in current mortality in men of 24% over 10 years.18 and former heavy smokers can deliver a A mortality reduction of 33% was found significant stage shift to earlier diagnosis in women, but the number of women in lung cancer (Figure 6). In the NELSON participating in the trial was too small for trial, 59% of cases among people in the this finding to be statistically significant.18 screening arm were early-stage, compared These findings have convinced experts with 14% in the control population who around the world that the evidence for were not offered screening.18 Similar figures LDCT screening to reduce lung cancer have been found in other settings.19 84 mortality is now indisputable.84 86-88
Lung cancer screening: the cost of inaction 4 LDCT screening for lung cancer: the next big opportunity in cancer detection 19 Figure 6. Screening programmes allow detection of a much higher proportion of lung cancer cases at an early stage compared to routine care85 Diagnosed outside of a screening Stage at programme Diagnosed in a screening programme diagnosis I II III IV Adapted from Sands et al. (2021). Patient decision-making aid based on combined analysis of existing clinical trials. Any potential harms caused by LDCT positive results or subsequent unnecessary screening are likely outweighed by procedures or treatments.85 86 its benefits Screening is, by definition, offered LDCT screening for lung cancer to asymptomatic individuals, so it is is expected to meet local important to ensure the benefits of cost‑effectiveness thresholds screening outweigh any potential risks. when designed appropriately With LDCT screening, the main risks are Based on all published studies, LDCT radiation exposure from the scan and screening is expected to be a cost- misdiagnosis through a false-positive result. effective investment (Appendix 1). Cumulative evidence from randomised Published cost-effectiveness ratios compare clinical trials has shown that LDCT well with other population-based screening screening presents a negligible risk of strategies, including those in place for radiation exposure.85 If performed under colorectal, breast and cervical cancers,89 high-quality standards, LDCT screening and are likely to be within accepted does not lead to a large number of false- economic thresholds.84 LDCT screening
Lung cancer screening: the cost of inaction 4 LDCT screening for lung cancer: the next big opportunity in cancer detection 20 is also expected to be more efficient than other screening programmes, meaning Box 1. Efficiency of lung cancer screening that fewer people need to be screened compared to other cancer screening for lung cancer to prevent one death programmes compared with breast or colorectal cancer Data from different studies suggest fewer screening (Box 1). screens are required to prevent one lung cancer death compared to breast or Targeted lung cancer screening is colorectal cancer: expected to offer benefits even greater • 320 people need to be screened by than those of existing cancer screening low‑dose computed tomography to prevent programmes one death from lung cancer19 The benefits of LDCT screening are • 645–1,724 people need to be screened by likely to compare favourably to those of mammography to prevent one death from existing cancer screening programmes. breast cancer21 Globally, the impact of LDCT screening on • 864 people need to be screened by flexible lung cancer mortality is expected to be sigmoidoscopy to prevent one death from significant (Box 2). Some experts suggest colorectal cancer22 that, if the highest-risk populations can be reached, lung cancer screening could have a larger absolute impact on cancer mortality than existing cervical or breast Box 2. How many lives could lung cancer cancer screening programmes.86 This is screening save? also seen in cost-effectiveness studies of LDCT screening, where optimal scenarios A summary of current estimates: confer more benefits than any present • US: approximately 12,000 lives saved cancer screening programme.20 per year 90 • Italy: 5,000 lives saved per year 91 • Australia: 12,000 lives saved over 10 years92 • Canada: 5,000–13,000 lives saved over 20 years93 • South Korea: 14,504 lives saved (91,362 life years gained) over 20 years94 • Japan: 45,774 lives saved (290,325 life years gained) over 20 years94 • Singapore: 1,290 lives saved (8,118 life years gained) over 20 years94 • China: 471,095 lives saved (3,014,215 life years gained) over 20 years94
Lung cancer screening: the cost of inaction 21 5 An investment in health system sustainability The benefits of lung cancer screening pulmonary abnormalities.96 For example, extend beyond lung cancer age and smoking history are the strongest In addition to its impact on lung cancer predictors of lung cancer and chronic mortality, lung cancer screening presents obstructive pulmonary disease (COPD), an opportunity to detect other NCDs at therefore it is possible to identify a common an early stage. As recently stated by the target population for screening and World Health Organization, investment in detection for both conditions.25 NCD prevention and management is ‘an insurance policy to improve population Promoting its potential to detect other health and mitigate the impact of any future ‘big killers’ linked to smoking could crisis’.95 Retrospective analyses of several make lung cancer screening a more LDCT studies found a high rate of incidental attractive prevention package to high- findings of cardiovascular disease and risk individuals. Experience from existing respiratory conditions among screening lung cancer screening programmes has participants.23-25 There may therefore be shown that screening can act as a life value in LDCT screening programmes event that encourages participants to quit also focusing on early detection of other smoking and take control of their health
Lung cancer screening: the cost of inaction 5 An investment in health system sustainability 22 Evidence from clinical trials and pilot studies shows that lung cancer screening amplifies the success of smoking cessation programmes, and vice versa. Experts unanimously recommend that current smokers invited to take part in screening be offered smoking cessation advice and encouraged to quit smoking.84 99 100 Several studies have shown that a positive or indeterminate screening result in current smokers prompts them to take up smoking cessation and decreases smoking relapse rates.42 101 Combining the two approaches also increases the cost-effectiveness of lung cancer screening programmes, with a greater impact on reducing mortality.42 102 103 more generally.97 98 Particularly among former smokers, it is often seen as an Lung cancer screening may help to opportunity to adopt behavioural changes address growing socioeconomic such as increased physical activity and a inequalities in health healthy diet.24 Health equity is one of the fundamental tenets of health systems, and it has been Targeted screening complements the threatened by the COVID-19 pandemic. impact of smoking cessation policies The pandemic has amplified the need to Targeted lung cancer screening should address a decade of widening inequalities also be seen as a complement to due to socioeconomic status and smoking cessation policies, contributing ethnicity.104 Such inequalities translate to to countries’ anti-tobacco agendas. an inequitable gap in life expectancy.105 Smoking cessation programmes are the For example, in England there is almost most important preventive measure for a twofold difference in mortality rates lung cancer,2 but they are not sufficient to between people in the highest and lowest decrease the global burden of lung cancer. socioeconomic groups.104 106 And as was Targeted screening (and early detection recently articulated in Europe’s Beating more generally) is needed to protect Cancer Plan, ‘there should be no first- or people who are already at high risk of lung second-class cancer patients’.72 cancer (e.g. former smokers) and for whom prevention has no immediate impact.42
Lung cancer screening: the cost of inaction 5 An investment in health system sustainability 23 Social inequalities are highly prevalent in of late presentation, and have the poorest lung cancer. On a global scale, the largest survival.26-28 Ensuring equitable access to inequalities in cancer mortality rates are screening programmes is thus essential found in smoking- and alcohol-related to address existing health inequalities.93 cancers, including lung cancer.28 People Otherwise, disadvantaged groups will of lower socioeconomic status are at continue to experience an unjust share of higher risk of lung cancer in all European the health burden.37 105 These combined countries.28 107 They are also at greatest risk benefits are captured in Figure 7. Figure 7. The impact of lung cancer screening extends beyond lung cancer Reduced health inequalities in lung cancer (in terms of risk of late presentation, access to appropriate treatment and care, survival) Complement to Targeted lung cancer screening and broader Reduced loss of smoking cessation early detection productivity and fewer policies, contributing to premature deaths due to creating a tobacco free Coupled with rapid access lung cancer generation to expert diagnosis and multidisciplinary care Early detection of other non-communicable diseases (e.g. chronic obstructive pulmonary disease, cardiovascular disease) Enhanced sustainability Contribution to of healthcare systems through reduced mortality from lower costs of care non‑communicable diseases
Lung cancer screening: the cost of inaction 24 6 Ensuring successful implementation of lung cancer screening at scale Governments should chart out a clear suitable in China, where there is a high roadmap for implementation incidence of lung cancer in women and Given the strength of the evidence, it is non-smokers.109 In Taiwan, for example, now time for governments to evaluate lung cancer is common in non-smokers, so the feasibility of lung cancer screening lung cancer screening is being proposed programmes in their specific national for other groups at high risk of lung contexts. So far, only a few countries – cancer.110 In Europe, several pilots are including the US, Japan, South Korea, exploring the potential to combine LDCT Poland, Croatia and Australia – have screening with early detection of COPD committed to implementing nationwide or other smoking‑related conditions.111 112 lung cancer screening programmes. The European Commission-funded However, pilot projects and local feasibility implementation study 4-IN THE LUNG RUN studies are being conducted in almost is looking to identify the best way to every region of the world. Findings from individualise screening intervals based on this implementation research should be levels of risk.113 built into a clear pathway to guide decisions around the most feasible way each country Based on this considerable research, can replicate benefits from screening seen several key success factors emerge which in clinical trials, while minimising potential should be built into the development harms and ensuring the most efficient use of large-scale lung cancer screening of local resources (Figure 8).108 programmes (Figure 9). Findings from existing implementation research should guide the roll-out of lung cancer screening More than a decade of feasibility and pilot studies has provided a wealth of information, with many lessons learnt to guide implementation in different countries. For example, studies have shown that eligibility criteria used in Europe and North America may not be
Lung cancer screening: the cost of inaction 6 Ensuring successful implementation of lung cancer screening at scale 25 Figure 8. A clear roadmap should be followed to guide decisions about local implementation of lung cancer screening Evidence assessment (clinical trials) Economic Local feasibility studies/ evaluation implementation research Commitment to Securing funding programme set-up sources Organisational set-up and implementation of national programme Development of national screening protocol covering: Identification of the population eligible for screening Invitation and information Screening Referral of screen positives and reporting of screen‑negative results Diagnosis Intervention, treatment and follow-up Reporting of outcomes Monitoring and continuous programme improvement Note: Timing of economic evaluation and feasibility studies varies depending on screening governance framework in each country – as does their impact on choice of national protocol
Lung cancer screening: the cost of inaction 6 Ensuring successful implementation of lung cancer screening at scale 26 Figure 9. There are several key factors in the successful implementation of targeted lung cancer screening84 93 114 1 High-quality multidisciplinary lung cancer care pathways 2 Reliable means of identifying people at highest risk 3 Securing attendance, particularly among vulnerable groups 4 Essential role of primary care professionals 5 Lung cancer screening built into overall prevention messages 6 Clear nodule management protocols and personalised screening to minimise potential harms from screening 7 Organisational model that allows optimal access and quality of screening and efficient use of resources for staffing and physical/digital infrastructure Local cost-effectiveness will be influenced by all these factors 1. Effective screening requires the success of a screening programme high‑quality, multidisciplinary depends on high-quality care lung cancer care pathways pathways.115 Everyone with a positive Investment in lung cancer screening result should have rapid access to is best inscribed in a broader comprehensive diagnosis and care, commitment to address lung led by a multidisciplinary care team.114 cancer as a priority. In particular, Embedding screening within a broader
Lung cancer screening: the cost of inaction 6 Ensuring successful implementation of lung cancer screening at scale 27 focus on early detection, as mentioned care records. Some countries, such as previously, is also crucial. the UK, have found ways to combine data sources, often using a multistep 2. Reliable means of identifying approach where a first outreach people at highest risk of lung cancer is made by a doctor or through are needed a centralised invitation, and then The success of targeted LDCT individuals are asked to complete a screening depends on being able to structured questionnaire to determine identify the population at highest risk smoking levels.84 of lung cancer, who are most likely to benefit from screening. A first step As mentioned previously, eligibility to any screening programme is thus criteria should also be looked to ensure there is a reliable database at within the context of each of the entire population that includes country’s epidemiology – and smoking history and other relevant adjusted as needed to reduce the risk factors to determine eligibility. potential for inequities in access to However, most countries do not have screening (Box 3). such a centralised database,84 with the exception of those with unified primary 3. Securing attendance from vulnerable populations is essential to reduce socioeconomic Box 3. The importance of localised inequalities eligibility criteria: the US example Screening programmes must include targeted efforts to engage vulnerable The US recently changed its definition of ‘heavy populations, to avoid exacerbating smoker’ to improve coverage of its LDCT inequalities related to lung cancer. screening programme.76 The US Preventive Data from both trial and real-world Services Task Force found that reducing the pack-year* criterion to 20 pack-years from the settings show that people with lower 2013 recommendation of 30 pack-years would socioeconomic status and other allow for inclusion of more women and non- disadvantaged groups are less likely Hispanic Black, Hispanic, and American Indian/ to participate in cancer screening Alaska Native persons, who were previously left programmes.114 118 119 Barriers to out of screening.116 attending for screening may be physical, financial, informational, * The National Cancer Institute defines a ‘pack- year’ as a measure for the amount a person has social or cultural.41 78 120 Tailored smoked over a long period of time. It is calculated interventions may help overcome by multiplying the number of packs of cigarettes some of these barriers in vulnerable smoked per day by the number of years the person has smoked. For example, 1 pack-year is equal to groups, and may also be effective at smoking 1 pack per day for 1 year, or 2 packs per overcoming barriers to attendance in day for half a year, and so on.117 other groups (Table 3).121-124
Lung cancer screening: the cost of inaction 6 Ensuring successful implementation of lung cancer screening at scale 28 Table 3. Possible approaches to address barriers to lung cancer screening, particularly among vulnerable populations Barriers Approaches to overcome them Limited information and awareness • Insufficient awareness or misinformation about • Explaining benefits and harms of screening in an the benefits of participating in lung cancer accessible format, with language- and literacy- screening124 128 level-appropriate information42 120 • Confusion around screening results or lack • Providing patient-friendly decision aids such of familiar care providers, especially due to as information brochures, videos and links to language barriers or for people with lower electronic resources that people can refer to health literacy124 129 after an appointment97 130 131 • Difficulty accessing online information services • Social media campaigns and digitally accessible or not being registered with a healthcare information on screening to reach underserved service129 or isolated communities121 132 Physical and financial barriers to access • Distance from screening centres and provision • Linking underserved communities with larger gaps in rural areas72 133 screening centres through emerging digital • Prohibitive transport and parking costs, and health tools, to enable community access to difficulty accessing screening centres93 134 multidisciplinary teams72 97 • Difficulty of fitting appointments around work • Decentralised mobile screening in public spaces or caregiving commitments134 like supermarket car parks e.g. Manchester Lung Health Check model20 126 • Offering assisted travel to imaging units e.g. the ‘hub-and-spoke’ model93 • Community pharmacists and other allied health professionals providing information on lung cancer screening to their clients/patients135 Psychological and social barriers • Forgetting to attend a scheduled appointment • Postal, text and telephone reminders after first or little awareness of the benefits of screening120 invitation letter to attend screening137 138 • Social or cultural distrust of healthcare • Personalised letter encouraging attendance services, or other psychological factors that from family physicians138 (e.g. used for cervical may undermine motivation to engage in cancer screening in the UK)121 screening e.g. denial, fatalistic health beliefs, • Targeted awareness initiatives involving embarrassment due to stigma around lung community or faith leaders28 120 cancer 42 131 134 136 • Co-designing public information and education campaigns with vulnerable groups to ensure suitability and impact of messaging42 122
Lung cancer screening: the cost of inaction 6 Ensuring successful implementation of lung cancer screening at scale 29 One model of particular interest is to refer patients for LDCT screening.141 to offer screening in public spaces Physicians should also be encouraged in socioeconomically deprived areas. to adopt a shared decision-making This model has been developed approach to screening with their in some of the Lung Health Check patients.42 97 pilots now being rolled out across England.125-127 Pilot projects in Engagement of family physicians Manchester used mobile units near should not stop with their role in supermarkets to tackle barriers securing attendance to screening. such as parking and transport They should, where feasible costs, inconvenience and location.87 depending on the organisation of the Three quarters of attendees were health system, play an active role in from the lowest socioeconomic following-up individuals after their first quintile.127 round of screening, explaining findings and making sure people continue to 4. Engagement of primary care attend screening.97 144 professionals is essential Family physicians remain people’s 5. Lung cancer screening should most trusted source of health be built into overall health information and play a key role promotion messages in engaging people to attend for Sensitive messaging about lung screening. Misinformation about cancer screening is essential and lung cancer and screening can be should tackle stigma related to potential barriers to acceptance of both lung cancer and smoking. screening.139 140 Family physicians Addressing potential fear and can help allay people’s fears about stigma surrounding lung cancer is screening, provide balanced important.41 42 Family physicians information about risks and benefits, also need to find the most appropriate and explain the importance of early way to tackle the need for smoking detection in lung cancer. cessation. In some cultures, some physicians may be reluctant to raise Training of family physicians the topic of smoking cessation, is essential. Inconsistent levels and mentioning it in invitations of awareness around screening to attend screening may reduce guidelines and eligibility, and poor participation.140 One approach understanding of the risks and is to present the opportunity to benefits of screening, have been undergo LDCT screening as part evidenced in some countries.141-143 of a proactive wellness approach A recent survey found US healthcare to one’s health (Box 4). providers with lower knowledge of screening guidelines were less likely
Lung cancer screening: the cost of inaction 6 Ensuring successful implementation of lung cancer screening at scale 30 6. Clear nodule management protocols Box 4. Lung Health Checks in England: and personalised screening taking a wellness approach intervals can reduce harm and The Lung Health Check model adopted across improve programme efficiency England takes a wellness approach for all Any screening programme carries risks respiratory disease rather than focusing on – and minimising risks is not only an cancer. Individuals are assessed for all lung ethical imperative but also a condition conditions and offered a CT scan if eligible. for cost-effectiveness. Protocols The following approaches have been found guided by the most up-to-date to encourage uptake and overcome stigma evidence148 149 are essential to guide surrounding smoking and fear of lung cancer: healthcare professionals in determining • Invitations do not mention smoking status which nodules to refer for further or smoking cessation. diagnosis and possible treatment, • Invitations do not mention lung cancer, so as and which to simply monitor.87 93 The not to put people off taking part due to fears use of protocols reduces the number about cancer. of false‑positive cases, patient recall and the need for repeat scans and • Supportive interventions (e.g. psychosocial support) are offered as part of the investigative procedures, leading to wellness check. lower costs overall.42 87 • Awareness campaigns accompanying the Tailoring follow-up protocols to programme offer good-quality information. personal levels of risk may also • During health checks, information is improve the effectiveness and provided making it clear that lung cancer cost-effectiveness of screening. can be treated if caught early. Both annual and biennial screening programmes have been deemed potentially cost-effective in existing Messaging about lung cancer and studies.61 84 102 However, personalising smoking should be targeted to different screening intervals after baseline groups – for example by gender. screening may minimise the need for Lung cancer incidence has been rising potentially unnecessary investigations in women, as have rates of smoking in people deemed at lower risk. – but smoking is not the only factor.2 They may be particularly relevant for 145 146 Cumulative evidence from lung women, for whom nodules have been cancer screening trials also suggests shown to have a slower growth rate that LDCT screening may have a than for men.150 151 more beneficial effect in women than men, both in terms of increased early-stage diagnosis and reduced mortality.18 84 147
Lung cancer screening: the cost of inaction 6 Ensuring successful implementation of lung cancer screening at scale 31 7. The right organisational model which may help ensure high quality of and health system resourcing are screening.114 Others locate screening needed to ensure sufficient staffing programmes in community settings and infrastructure to foster outreach to vulnerable Screening is about more than just populations, linking these centres to the scan itself, and selecting the specialist multidisciplinary teams in a most appropriate organisational hub-and-spoke approach.93 Careful model is key. The logistical aspects consideration of available technical of screening – centralising invitations, and workforce capacity is also an ensuring systematic follow-up, important factor to consider. recording outcomes of screening from cancer registries – require Regardless of the organisational sophisticated information systems and model, building quality assurance careful coordination,37 all of which and professional training across need appropriate resourcing. It may be all centres performing CT scans that structures or resources devoted to is essential. This can help ensure existing cancer screening programmes CT scans are of consistent quality can be leveraged – for example, if all and that interpretation follows a cancer screening is offered by a central common approach.42 Benchmarking coordinating centre.144 CT software and AI may also help improve the reliability of The most appropriate organisational interpretation.84 These approaches model should be chosen, balancing can help to relieve potential capacity the need for outreach and quality shortages in countries where assurance. Some countries have availability of trained radiologists to chosen to centralise screening in a perform CT scans may be limited.133 152 limited number of specialist centres,
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