Many of Europe’s achievements and commitments have been exemplary in the development of health-related science, technology, and regulation, and the European Union (EU) is on the brink of providing further stimulus both to technology development and to the role of the EU in health policy. There are great expectations of the promised EU Health Data Space, the European Health Union, the Pharmaceutical Strategy, and the Cancer Mission and EU Beating Cancer Plan. However, at a time when COVID-19 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, radiation oncologists, technology developers, and patient representatives across Europe.
The practice of lung cancer screening among policymakers has taken longer to win wide endorsement than analogous procedures for breast, colon, and prostate cancers, in which success in improving outcomes has been demonstrated for more than a decade now. However, the evidence for implementing lung cancer screening has become overwhelming, and the barriers to cutting lung cancer deaths are now at a political rather than a scientific or technical level.
As such, lung cancer screening and early diagnosis are key issues that the European Alliance for Personalised Medicine has put forward to the EU and to policymakers at the member state level for several years now. The mix of European Alliance for Personalised Medicine members provides extensive scientific, clinical, caregiving, and training expertise in personalized medicine and diagnostics across patient groups, academia, health professionals, and industry. This editorial summarizes this evolution in policy and is a call to action to policymakers in the name of the thousands of Europeans who will die prematurely and avoidably every year until lung cancer screening is implemented.
Burden of Lung Cancer in the EU
Eurostat’s latest data show that lung cancer is the third-leading cause of death in the 27 member states of the European Union (EU), exceeded only by heart disease and cardiovascular disease. Annually, it kills more than 80 in 100,000 men in Europe and more than 20 per 100,000 women —and for women that figure is rising.
This is a major problem for all EU member states, but for some, it is particularly acute: Hungary recorded the highest standardized death rate from lung cancer in 2017 (89.2 deaths per 100,000 inhabitants), followed by Croatia (68.4), Poland (67.0), and Denmark (66.8).1
Yet dramatic improvements could be achieved by identifying this disease earlier.2 Most lung cancers are still diagnosed at a late stage, when they are difficult to cure. Earlier detection has been shown to increase the chances of curative treatment, and can be achieved through effective screening. This could shift the needle on the currently somber statistics, which show that 70% of lung cancer cases are diagnosed at an advanced, incurable stage, resulting in the deaths of one third of patients within 3 months.3
The evidence for implementing lung cancer screening has become overwhelming, and the barriers to cutting lung cancer deaths are now facing political rather than scientific or technical obstacles.4
The predominant cause of the lethality of lung cancer is late presentation. A leading study shows that from 2009 to 2015, 57% of patients had distant metastases at diagnosis, only 16% had localized disease, and 5-year survival among all patients with lung cancer was 21%. In England, 35% of patients with lung cancer are diagnosed following emergency symptomatic presentation, and of these, 90% are stage III or IV.5
For many patients, late presentation precludes the option of surgery, which, —despite continuing improvements in other forms of therapy, —remains the chief demonstrated method for improving long-term survival. Focusing on improving therapy for those presenting with symptomatic disease rather than prevention and early detection is therefore not going to deliver all the desired—and attainable—improvements in outcome.
Tobacco use remains the predominant driver of lung cancer.6 But lest we forget, as many as 20% of people who die from lung cancer every year have never smoked or used any other form of tobacco, and it is deadly for them also.
Current efforts to discourage and dissuade smoking are having only a limited effect and are unlikely to be fully successful for many years. In the short term, promoting tobacco cessation among current smokers and screening high-risk ever- and former smokers will achieve a higher impact in reducing tobacco-related mortality; the effects of implementing comprehensive tobacco-control policies will be felt only over the longer term.7
Globally, Europe has the highest prevalence of tobacco use, which is particularly high among females. Taking into account a time lag of approximately 30 to 40 years between the peak of smoking prevalence and the peak of lung cancer mortality, the necessity for early detection of lung cancer is especially high in the EU population. There are millions of smokers and former smokers who are at increased risk now and who will remain so for decades.8
By facilitating early detection of lung tumors, lung cancer screening has paved the way for a more personalized treatment of lung cancer and provides fertile ground for further innovations in technology, medical imaging, and statistical techniques.9
Achievements to Date
There has been rapid progress in the quality of data acquired through screening. Two decades ago, imaging of the entire lungs in a single breath was obtained in 10-mm increments, resulting in approximately 30 images per person. Today, images are obtained in sub-millimeter–slice thickness and with very low doses of radiation, resulting in unprecedented clarity of information, with approximately 700 images per person that are viewed on high-resolution monitors. Low-dose CT screening now provides the imaging acquisition parameters, imaging interpretation, definition of positive results, and recommendations for further work-up. We have gained insight into the natural history of lung cancers, identification and management of nodule subtypes, improved understanding of nodule imaging and pathologic features, and measurement variability inherent in CT scanners.
The data accumulated over the past 20 years of low-dose CT (LDCT) screening have also led to the development of a comprehensive “health check” strategy for the lungs, heart, and other thoracic organs. Early detection of major comorbidities, including cardiovascular and chronic obstructive pulmonary disease as well as emphysema, are added benefits of lung cancer screening with LDCT.
Despite the demonstrated success of lung cancer screening and increasing evidence of its potential, adoption of screening in routine clinical practice has been limited in the EU. Less than 4% of high-risk current and former smokers are screened for lung cancer. Yet, full consensus has not been reached on resource requirements and cost-effectiveness, on insurance coverage criteria, or on the acceptable incidence of false positives. There is still no single model accepted for organization of screening—through decentralized, community-based programs; centralized centers of excellence; or hybrids.
At present, these doubts and uncertainties have not been adequately countered by organized responses sufficient to clarify outstanding issues, answer questions, reassure the public and policymakers, and inspire the large-scale implementation that could save so many lives and avert so much suffering.
Decisions on whom to screen and how often should be driven by risk-prediction tools. But here, too, there is no wide consensus and no agreement on the optimal model for the effective relationship between healthcare authorities, primary care, and provider. This is, in part, due to a lack of prospective comparative data to guide the selection of the most appropriate risk-prediction tool.
As with all healthcare discussions, cost is an inevitably important factor. As long as lung cancer screening remains limited, any associated costs remain correspondingly limited—to the satisfaction of many crucial paying agencies, whose principal concern is more often cost containment than optimization of care. In the absence of compelling evidence underscoring the cost-effectiveness of lung cancer screening, which needs to be undertaken by individual countries to assess on the basis of their own requirements, there is a reluctance to expand spending tends to triumph over simple appeals, despite the existence of positive phase III trials.
The judicious identification of cardiorespiratory disease and the use of comprehensive approaches to tobacco addiction within the context of lung cancer screening programs have the potential of providing additional benefit and are understood to further contribute to the cost-effectiveness of lung cancer screening and afford an opportunity to reinvest income from other provided services to ensure capacity, sustainability, and training.
Barriers Are Surmountable—If Actions Are Taken
The EU’s Beating Cancer Plan (BCP) offers the prospect of multiple improvements in tackling cancer, and its vision embraces admirable principles—including the merits of screening, updated technology, and enlightened guidance. It foresees “putting the most modern technologies at the service of cancer care to ensure early cancer detection.” But as long as the BCP continues to hesitate to endorse screening for lung cancer, a major opportunity will remain neglected.
The BCP acknowledges that lives are saved by early detection of cancer through screening. They speak approvingly of population-based screening programs for breast, cervical, and colorectal cancer in national cancer-control plans, and of ensuring that 90% of qualifying citizens will have access by 2025. For screening of these three cancers, they even envisage reviewing the Council Recommendation and issuing new or updated guidelines and quality-assurance schemes. But lung cancer screening enjoys no such prioritization in the BCP, with only allusions to a “possible extension” of screening to new cancers and to a consideration of “whether the evidence justifies an extension of targeted cancer screening.”
There are other aspects of the BCP linked directly or indirectly to screening which could—and should—enhance early detection and accurate diagnosis of lung cancer. The text mentions exploring “early diagnosis measures to new cancers, such as prostate, lung, and gastric cancer.” By providing more precise information on tumors, lung cancer screening has opened the way to more personalized treatment for lung cancer. It provides fertile ground for further innovations in technology, image analytics, and statistical techniques; and future image interpretation will be increasingly assisted by computer-aided diagnostics.
The EU’s parallel Mission on Cancer is expected to generate new evidence on the optimization of existing population-based cancer screening programs, develop novel approaches for screening and early detection, and provide options to extend cancer screening to new cancers. It will also help to provide new biomarkers and less invasive technologies for diagnostics. The new European Cancer Imaging Initiative will facilitate the development of new, enhanced diagnostic methods to improve quality and speed of screening programs using artificial intelligence, and it will promote innovative solutions for cancer diagnostics. A new Knowledge Center on Cancer will function as an “evidence clearinghouse” for early detection through screening. An upgraded European Cancer Information System will facilitate the assessment of cancer screening programs through improved data collection on cancer screening indicators. The analysis of interoperable electronic health records will improve understanding of disease mechanisms, leading to the development of new screening methods, diagnostic pathways, and treatments.
These are encouraging concepts, and could—if implemented—assist the refinement of early detection and diagnosis. But it would be even more promising if the recognition of improved access to biomarker testing on diagnosis and progression extended to treatment and to advancing the emergence of personalized medicine. The BCP could provide the context for a more systematic development of biomarker testing. Finally, s data on variations in testing rates could be included in the envisaged cancer inequalities registry.
What's Needed for Implementation
Europe is on the threshold of a transformation that can lead to dramatic improvements in the outcome for patients with lung cancer. Europe’s health systems need to adapt to allow patients and citizens to benefit from organized pathways for early diagnosis of lung cancer. Now is the time to convince policymakers across the EU that this is an urgent societal and political need. But to make a reality out of the huge potential, current barriers need to be removed and current uncertainties and dilemmas need to be resolved. Large-scale implementation requires that the screening program is performed according to a systematic, structured, standardized, and validated protocol and that the quality of the performance is monitored continuously.
The challenges are scientific and clinical, technical, administrative, economic—and ultimately political, because wide-scale implementation of lung cancer screening will come about only when policymakers are persuaded of its merits.
- 1. 1 in 4 deaths caused by cancer in the EU28. Eurostat Press Office. Eurostat News Release. November 25, 2014. Accessed November 20, 2020. http://ec.europa.eu/eurostat/documents/2995521/6131615/3-25112014- BP-EN/aab2c2d3-aed9-430a-a561-e188b8ef49d8
- 2. Oudkerk M, Devaraj A, Vliegenthart R, et al. European position statement on lung cancer screening. Lancet Oncol. 2017;18(12):e754-e766.
- 3. Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl 4):iv1-iv21.
- 4. De Koning H, Van der Aalst C, Ten Haaf K, Oudkerk M. Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population-based screening trial. J Thor Oncol. 2018;13(10)(suppl):S185.
- 5. De Koning HJ, Van der Aalst CM, De Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. NEJM. 2020;382(6):503-513.
- 6. Burdett S, Stewart LA, Rydzewska L. A systematic review and meta-analysis of the literature: chemotherapy and surgery versus surgery alone in non-small cell lung cancer. J Thor Oncol. 2006;1(7):611-621.
- 7. Leon ME, Peruga A, McNeill A, et al. European code against cancer: tobacco and cancer. Cancer Epidemiol. 2015;39(suppl 1):S20-S33.
- 8. Clancy L. Reducing lung cancer and other tobacco-related cancers in Europe: smoking cessation is the key. Oncologist. 2014;19(1):16-20.
- 9. Hensing T, Chawla A, Batra R, Salgia R. A personalized treatment for lung cancer: molecular pathways, targeted therapies, and genomic characterization. In: Maltsev N, Rzhetsky A, Gilliam T, eds. Systems Analysis of Human Multigene Disorders. Advances in Experimental Medicine and Biology; vol 799. Springer; 2014:85-117.