Unnecessary loss of life – but not from COVID-19. At a time when the coronavirus infection is already inflicting a frightening death toll on the world from a previously unknown health threat, Europe cannot afford to tolerate another unnecessary and large-scale loss of life from a disease that has long been well recognized: lung cancer. But institutional neglect is causing unnecessary loss of life, according to oncologists, pulmonologists, radiotherapists, technology developers and patient representatives from across Europe. In a European Alliance for Personalised Medicine (EAPM) round table they focused on persistent delays in promoting the lung cancer screening programmes that could save thousands of life-years, writes EAPM Executive Director Dr. Denis Horgan.
In Europe, lung cancer, the leading cause of cancer-related morbidity and mortality, causes more than 266,000 deaths each year – 21% of all cancer-related deaths. That’s not quite as high as coronavirus’s death rate in 2020, but these lung cancer deaths are not a one-off crisis that has provoked an unprecedented mobilisation to bring it under control. Lung cancer deaths are happening relentlessly year after year, and are likely to continue to do so for decades to come – unless incisive high-level decisions are taken to challenge the trend, said Dr. Horgan, introducing the round table. And as Anne-Marie Baird, president of cancer patient group LuCE, pointed out: “These are not just statistics. Each patient lost is a loss to families and friends.”
How screening can change the picture
Screening is the most obvious route to arresting this destruction of life. Screening permits the early diagnosis that is crucial in a disease that is frequently discovered too late for any effective intervention. At present, many patients are identified only when their disease is incurable: fewer than 15% will survive for five years. Screening can turn that picture round. For every 1,000 people screened, five of them who would have died from lung cancer will have their survival extended beyond ten years.
A just-published IQWiG study concludes “the assumption that screening also has a positive effect on overall mortality seems justified.” Detecting disease long before symptoms makes intervention possible with treatment that drastically improves outcomes, and leads to cure rates above 80%. “A lot of lives can be saved,” said Giulia Veronesi of the Ospedale San Raffaele in Milan. And according to Baird, early diagnosis could save up to 4 million people across the world.
The evidence is overwhelming: randomised trials estimate a significant 20% reduction in lung cancer mortality when screening is used to identify those at high risk. But the potential of screening is being largely ignored by European health authorities, and opportunities for saving life are neglected. Irish MEP Sean Kelly warned the round table that “further delay to implementation of the best form of lung cancer screening will mean more unnecessary lives lost”.
For Baird, the right form of cancer screening in a high-risk population is the best way of working towards improved European outcomes. Jens Vogel-Claussen, Vice Chair of the Institute of Diagnostic and Interventional Radiology at Hanover Medical School, insisted that it was more than high time to take action: “People are suffering, and we have the ability to stop it.”
Marie-Pierre Revel of the University of Paris Descartes Service de Radiologie at the Hôpital Cochin described the paradox that there is strong scientific evidence of the benefit of lung cancer screening, and there are now optimized screening strategies that offer dose reduction and provide few false positives – but implementation is still awaited. There are only a few European countries that operate national screening programmes. And Witold Rzyman, Chief Thoracic Surgeon in the Medical University of Gdansk, demanded: “Why is screening not yet implemented in the EU? Its merits have been apparent for ten years, and there is wide interest in it from across the medical community involved in cancer care, in biology, equipment, therapy, and surgery.”
Impediments to action
Why is lung cancer screening being neglected? There is more than one reason. But none of them is good.
The most simple but most sombre reason would seem to be the negative prejudice about lung cancer. Since this is a disease most prevalent among smokers, a vestigial sense of “these people have brought their misfortunes on themselves” still persists, often compounded by the challenges of securing engagement from hard-to-reach populations where fatalism, if not nihilism, can inhibit the search for care.
But this is an unacceptable reflex in an EU committed to equity of healthcare opportunity and to overcoming the unevenness that permits inequalities not only from country to country but also from one section of the population to another. To reverse this tendency it should be enough to reflect that disadvantaged communities – for this is where smoking remains most common – deserve additional rather than less attention, as part of a policy of redressing imbalances. Mechanisms and approaches are available and are being constantly refined in national pilots to make possible effective intervention with high-risk populations on the ground. But it still needs a shift in priorities at policy level.
Another factor is the persistent negative perception of the risk-benefit ratio of lung cancer screening. The belief remains in many quarters that its merits are insufficiently demonstrated, its processes too ponderous or too imprecise, or that it can generate too many false negative results, breeding delusions of complacency, or false positives prompting unnecessary and potentially harmful interventions. The perception is amplified by outdated views of lung cancer screening and treatment as low-tech and offering little hope of improved outcomes.
But that is manifestly inaccurate. Since the beginning of the 21st century, the opportunities for treatment of lung cancer have expanded dramatically, with the earlier dependence on histology and chemotherapy being supplanted by growing insights around tumour biology, and diagnostic technologies that allow targeted treatments. Risk-based lung cancer screening strategies now focus on at-risk patients stratified on scientifically objective criteria, with AI increasingly recruited for reinforcing quality assurance. Where lung cancer screening programmes have been implemented, annually, up to 3% of participants are diagnosed with lung cancer, 50–70% of them with stage I disease, and these patients usually undergo surgery with curative intent.
There are further refinements underway in methodology and in equipment: the ever-more precise identification of the target population that will derive the greatest benefits, improving participant recruitment and compliance, the ideal frequency of screening, integration of screening with other public health interventions – including effective smoking cessation, and demonstrations of cost-effectiveness.
Richard Booton, Clinical Senior Lecturer and Honorary Consultant Respiratory Physician at The University of Manchester and North West Lung Centre, explained how stratification obviates the need to screen unnecessarily: the right criteria relating to factors such as age, smoking history, body mass, or cancer history can bring new degrees of accuracy to screening programmes. “The efficiency of diagnostics and treatment high when there is an adequate structure,” he told the round table. Luis Seijo Maceiras, co-director of the Department of Pulmonology at the Clínica Universidad de Navarra, pointed to the improved predictive identification of risk factors and the additional precision that improvements to biomarkers will bring.
Yolande Lievens, chairman of Radiation Oncology at Ghent Faculty of Medicine and Health Sciences, expounded the major improvements in radiotherapy, with less toxic treatments and shorter and more patient-friendly regimens, widening the treatment options available to patients identified early as a result of screening. And the advances in radiology now permit screening with low-dose techniques that provide unprecedentedly high levels of image detail, eliminating the risks perceived in imaging techniques of a decade and more ago.
Cost has also been advanced as a prohibitive aspect of lung cancer screening, but studies now demonstrate that in populations with a history of smoking, the benefits even in economic terms – to say nothing of the personal value – outweigh the investment. And, as Francesco de Lorenzo, Past President of the European Cancer Patient Coalition, remarked, it is necessary to compare any costs of screening with the huge slice of healthcare budgets taken up by treatment of late-stage cancer patients whose disease was not identified early enough to prevent metastasis. Marko Jakopovic, head of the Thoracic Oncology Unit in Zagreb’s University Hospital Centre, endorsed the point vigorously, pointing to the cost of spiralling costs of new immunotherapy-based treatments.
The misperception of lung cancer and a wide lack of awareness of the evolution of lung cancer screening have conspired to produce systematic institutional neglect.
While the EU has for nearly twenty years had in place recommended screening guidelines for breast, colorectal and cervical cancers, still no EU guidelines exist for lung cancer screening. Worse, the current EU plans for updating its existing screening guidelines once again omit lung cancer. “It is surprising that the biggest cancer killer doesn’t have screening guidelines,” said Cristian Busoi, the Romanian physician who chairs the European Parliament’s internal market and consumer affairs committee, in his opening remarks to the roundtable.
The absence is all the more striking since, as Horgan pointed out, most EU countries did very little on screening for colorectal or breast cancer until after the EU recommendation emerged in 2002 – at which point, most of them initiated plans. The EU’s emerging European Beating Cancer Plan is another case in point: it highlights screening as a vital tool in colorectal, cervical and breast cancer, but on screening for lung cancer – which alone kills more than those three cancers combined – it offers only a few passing references in the draft text, and no endorsement commensurate with the impact of its implementation at scale.
This semi-official neglect of lung cancer screening is, in some ways, self-reinforcing. The lack of Europe-level involvement perpetuates national divergences of approach – ranging from mildly interested in some member states to frankly indifferent or even hostile in others. The diversity and range of approaches was amply illustrated by presentations from panellist after panellist. The diversity in turn feeds back into an absence of pressure on individual countries or authorities to take initiatives – and crucially, to fund them. With member states going their own way, there are few opportunities to scale up useful demonstrations and to harmonise best practices.
“Every country faces challenges in implementing lung cancer screening, but these would be more easily overcome by a concerted EU approach,” believes Luis Seijo Maceiras, Co-director of the Department of Pulmonology at the Clínica Universidad de Navarra. “An EU impulse would pressure Spain and overcome inertia among the health authorities.”
Revel noted that the European Society of Radiology and the European Respiratory Society favour organised pathways to adapt Europe’s health systems to earlier diagnosis of lung cancer and reduced mortality, rather than relying on unsupervised initiatives. “Now is the time to set up and conduct demonstration programmes focusing on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry,” she said. Tit Albreht, associate professor of public health at Ljubljana University’s Faculty of Medicine and a key figure in EU cancer policy development for more than a decade, agreed: “We need implementation experience,” he said in his closing speech to the round table.
The impediments to action can be resolved. There are technical answers to satisfy earlier concerns about methodologies and techniques, and there are political initiatives that can create a more conducive healthcare framework for integrating lung cancer screening.
The opportunities for treatment, particularly in populations evidently at high risk, can be amplified. Those at highest risk are most likely to benefit from lung cancer screening, less likely to participate, more likely to be of lower socioeconomic background and more likely to be current smokers, said Booton, who spelled out some of the approaches he has used to ease access in geographies where hard-to-reach subjects live.
Local engagement and appropriate health education, proximity of screening services and smart integration into an organised healthcare structure for follow-up can transform reluctance and boost recruitment, he claimed. Even modifying the terminology – to the more neutral ‘lung check’ – can diminish hesitancy, he suggested. The path would be made easier, he urged, with appropriate guidelines in place, to “provide a framework for implementation, promote early detection, reduce mortality, assist prevention, and reduce inequality and utilization of healthcare resources”.
Lievens too saw the merit of guidelines as a necessary aid to wide-scale implementation. They could, the panel agreed, mean that valuable local and national pilots would be taken account of at EU level. They would also promote collaboration between specialties and primary care, or reimbursement and financing, standardise reporting, ensure education of healthcare professionals, and even extend to access to and reinforcement of the necessary infrastructure for testing and data exchange. Albreht stressed the need for integration of screening, into systemic health promotion, early detection, diagnosis, and treatment.
There are potential opportunities in the near future to remedy some of the current deficiencies and to take advantage of what lung cancer screening can do.
Jan-Willem van de Loo of the European Commission’s Health Research department spelled out the options emerging from the Cancer Mission now in preparation, with its goal of optimising existing screening programs and developing novel approaches for screening and early detection. It has set a target of Increasing the proportion of cancer diagnosed at an early stage by 20% by 2030 – and lung cancer screening could play a central role in that effort.
The Cancer Mission – along with the EBCP and other EU initiatives, such as the EU4Health programme with its €5.1 billion budget – could provide funding for further studies that would win greater acceptance and lead to its widespread adoption at scale. Busoi expressed commitment to the fullest political support for official EU engagement in lung cancer screening, from himself, and from his group in the Parliament. And Kelly fully endorsed all measures that might lead to achieving the Cancer Mission goal.
A straightforward proposition
Over the last two decades the evidence has become overwhelming that screening can transform the fate of lung cancer victims. Disturbingly, however, EU member states still hesitate over its adoption, and it remains low on policy priorities nationally and at EU level. In consequence, funding for it, and reimbursement of screening services, remain patchy and inadequate, and it is not yet integrated satisfactorily into healthcare systems.
The proposition is straightforward. Lung cancer is currently both the most commonly diagnosed cancer (accounting for 11.6% of all cancer diagnoses) and the leading cause of cancer-related mortality (18.4% of overall cancer mortality) in both men and women worldwide. Every year, at least twice as many people die from lung cancer as from other common malignancies, including colorectal, stomach, liver and breast cancer. The majority of patients with advanced lung cancer die within 5 years of diagnosis. But patients identified with stage early disease have at least a 75% chance of survival over 5 years.
Screening is particularly important for lung cancer because most cases are discovered too late for any effective intervention: 70% are diagnosed at an advanced incurable stage, resulting in the deaths of a third of patients within three months.
In England, 35% of lung cancers are diagnosed following emergency presentation, and 90% of these 90% are stage III or IV. To substantially reduce lung cancer mortality over a longer period, early detection using low-dose screening in asymptomatic individuals can offer life and quality of life-years to individuals currently condemned to unidentified progression of disease to an incurable stage.
The tools are there to improve the situation. They are just not being used. As Sebastian Schmidt of Siemens said: “Efficacy is proven. Don’t waste more time!” Or, as Revel reflected: “Now we have all the evidence we could be blamed for doing nothing.”