UNDERSTANDING LUNG CANCER
Lung cancer, like all cancers, occurs when the body’s own cells—specifically those that control cell growth and division or the repair of damaged DNA—mutate and multiply out of control. In more than 90 percent of lung cancer cases these genetic changes are acquired, not inherited.1 Lung cancer is first defined by the appearance of cells affected, and presents as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC):
Lung cancer is the second-most commonly diagnosed cancer in the world with 2.1 million new cases in 2018.2,7 In that same year 1.8 million people died from lung cancer—more than twice as many as any other cancer type.2 The global five-year survival rate (17.8 percent) is much lower than other leading cancers.8
The rates of lung cancer vary significantly among regions of the globe and even within them.
COSTS OF LUNG CANCER
Lung cancer imposes significant costs on patients, caregivers, and societies everywhere. These include direct costs such as provider office visits, hospitalization, surgery, radiation, and medications including chemotherapy; and indirect costs including lost worker productivity from illness and early mortality.
LUNG CANCER CAUSES AND RISK FACTORS
Research has found that environmental and lifestyle factors can expose people to carcinogens and increase the risk of developing lung cancer; the greatest risk factor being long-term tobacco smoking. For the approximately 20 percent of lung cancer patients that have never smoked or used tobacco the causes can range from genetic mutations to air pollution to lung diseases like tuberculosis.19
Cigarette smokers face five to ten times the risk of lung cancer as non-smokers, while second-hand smoke exposes non-smokers to a 20 percent increased risk.3,20 Smoking contributes to 80 percent of lung cancer deaths in women and 90 percent in men.21 The causal link between smoking and cancer was established more than 50 years ago, and numerous public health campaigns have drawn attention to it since.22 While these have helped bring the rates of cigarette smoking down, they may have contributed to lung cancer stigma—the belief that a person caused their own cancer.23 Studies and surveys have associated lung cancer stigma with delays in medical help- seeking behavior.24 Considering lung cancer’s high mortality and costs, delaying diagnosis and treatment can be detrimental.
Ten to fifteen percent of people who get lung cancer have never smoked tobacco.25 The leading environmental cause of lung cancer is radon, an odorless, colorless gas that can contaminate indoor air.26 Estimates suggest that radon causes between 3 to 14 percent of all lung cancers in a country, depending on the national average radon level and smoking prevalence.26
GENETIC AND OTHER FACTORS
Studies show that people with a family history of lung cancer have two to four times the risk of lung cancer versus those without, even after controlling for smoking and other factors.3 Research is ongoing into the specific chromosomes that may make someone more susceptible to lung cancer. People with other lung diseases including COPD, asthma, and tuberculosis also face a significantly increased risk.19
EXPOSURE TO MULTIPLE CARCINOGENS CREATES COMBINED EFFECTS
Exposure to multiple risk factors can increase lung cancer risk even further:
PREVENTION, SCREENING, AND TREATMENT
There’s no sure way to prevent lung cancer, but environmental and lifestyle choices reduce risks.27
The cancer death rate rose during most of the 20th century: however, declines in smoking, as well as improvements in early detection and treatment, have resulted in a continuous decline in the cancer death rate since its peak in the U.S. of 215.1 deaths per 100,000 population in 1991. The overall drop of 29 percent as of 2017 (152.4 per 100,000) translates into an estimated 2.9 million fewer cancer deaths than if rates had remained at their peak.28
Each lung cancer case is as unique as the patient afflicted, and treatment journeys will vary. Some pathways include the following:
These pathways are changing fast. Until recently, the standard of care for metastatic NSCLC was four to six cycles of chemotherapy, and to offer second-line therapy upon tumor progression.32 While platinum chemotherapy remains an important agent for treating advanced lung cancer, there are new options that can be explored for front-line treatment.
Precision medicine focuses on disease mechanisms and developing treatments to target them.33 Currently in NSCLC there are at least ten known and testable biomarkers. Biomarkers are identified through additional screening of biopsy tissue with specialized tests, known as companion diagnostics. Additionally, more than half of lung adenocarcinoma cases (the most common subtype of NSCLC) have an identifiable molecular driver. While biomarkers continue to be researched, five have approved drug therapies: epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS, BRAF, and neurotrophic tyrosine receptor kinase (NTRK).6,34
For patients with lung cancer where the tumor’s genetic driver can be attacked, these drugs can slow cancer’s progression and potentially extend lives—providing invaluable benefits for patients and families.
The immune system is a complex network of organs, cells and molecules that protects the body from:39
Currently approved cancer-targeting immunotherapies target cellular checkpoints39:
Recent studies in patients with advanced NSCLC show prolonged survival with immunotherapy versus chemotherapy.40 One study found a fivefold advantage in 5-year survival rates while a second study showed a benefit in overall and progression-free survival with immunotherapy at five years. The 5-year overall survival was 13.4 percent compared to 2.6 percent. While current immunotherapies do not work for every patient, the science is advancing with greater numbers of lung cancer patients eligible for checkpoint inhibitor therapy.41
- U.S. National Institutes of Health (NIH). Genetics Home Reference: Lung Cancer. ghr.nlm.nih.gov/condition/lung-cancer.
- World Health Organization (WHO). Cancer fact sheet. www.who.int/news-room/fact-sheets/detail/cancer.
- Schwartz AG and Cote ML. Epidemiology of Lung Cancer (2016). Lung Cancer and Personalized Medicine: Current Knowledge and Therapies. Edited by Ahmad A and Gadgeel S. Springer International Publishing.
- American Cancer Society. Lung Cancer Survival Rates. www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html.
- CancerCare. Types and Staging of Lung Cancer. www.lungcancer.org/find_information/publications/163-lung_cancer_101/268-types_and_staging.
- Pfizer. Lung Cancer: What’s a Biomarker? (2017). www.pfizer.com/news/featured_stories/featured_ stories_detail/lung_cancer_what_s_a_biomarker.
- WHO. Skin Cancers. www.who.int/uv/faq/skincancer/en/index1.html.
- Wong MCS et al. Incidence and mortality of lung cancer: global trends and association with socioeconomic status. (2017). Scientific Reports. 7, Article number: 14300.
- The Cancer Atlas. Lung Cancer. canceratlas.cancer.org/the-burden/lung-cancer/.
- Wood R, Taylor-Stokes G. Cost burden associated with advanced non-small cell lung cancer in Europe and influence of disease stage. BMC Cancer. 2019;19(1):214. Published 2019 Mar 8. doi:10.1186/s12885- 019-5428.
- Andreas S et al. Economic burden of resected (stage IB-IIIA) non-small cell lung cancer in France, Germany and the United Kingdom: A retrospective observational study (LuCaBIS) (2018). Lung Cancer. 124, 298–309.
- Zarogoulidou V et al. Estimating the direct and indirect costs of lung cancer: a prospective analysis in a Greek University Pulmonary Department (2015). J Thorac Dis. 7(Suppl 1), S12–S19. doi:10.3978/j. issn.2072-1439.2015.01.57.
- NIH National Cancer Institute. Financial Burden of Cancer Care. progressreport.cancer.gov/after/economic_burden.
- Tompa E et al. The economic burden of lung cancer and mesothelioma due to occupational and para- occupational asbestos exposure (2017). Occup Environ Med. 74(11):816-22.
- de Barros Reis C et al. Factors associated with non-small cell lung cancer treatment costs in a Brazilian public hospital (2018). BMC Health Serv Res. 18, 124.
- Kuwabara K et al. Differences in Practice Patterns and Costs between Small Cell and Non-Small Cell Lung Cancer Patients in Japan (2009). Tohoku J Exp Med. Volume 217, Issue 1, Pages 29-35.
- Fan et al. Economic Costs of Lung Cancer in China. (2018). Int J Oncol Res. 1:007 Vol 1 issue 2.
- Tachfouti N et al. First data on direct costs of lung cancer management in Morocco (2012). Asian Pac J Cancer Prev. 13(4):1547-51.
- NIH. Genetics Home Reference: Lung Cancer. ghr.nlm.nih.gov/condition/lung-cancer#genes and www.cancer.org/latest-news/why-lung-cancer-strikes-nonsmokers.html.
- Tobacco pipe and cigar smoking are also associated with a higher risk of lung cancer, while more research is needed to establish a link between hookah smoking, vaping, and other methods of inhalation.
- American Lung Association. Lung Cancer Fact Sheet (2019). www.lung.org/lung-health-and-diseases/lung-disease-lookup/lung-cancer/resource-library/lung-cancer-fact-sheet.html.
- American Lung Association. Addressing the Stigma of Lung Cancer. (2014).
- Riley KE et al. Decreasing Smoking but Increasing Stigma? Anti-tobacco Campaigns, Public Health, and Cancer Care (2017). AMA J Ethics. 19(5), 475–485. doi:10.1001/journalofethics.2017.19.5.msoc1-1705.
- Carter-Harris L. Lung cancer stigma as a barrier to medical help-seeking behavior: Practice implications (2015). J Am Assoc Nurse Pract. 27(5), 240–245. doi:10.1002/2327-6924.12227.
- Defined as having smoked fewer than 100 cigarettes lifetime.
- WHO. Radon and Health fact sheet. www.who.int/news-room/fact-sheets/detail/radon-and-health.
- MayoClinic: Lung Cancer Symptoms and Causes. www.mayoclinic.org/diseases-conditions/lung-cancer/ symptoms-causes/syc-20374620.
- American Cancer Society. Cancer Facts & Figures 2020. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts- and-figures-2020.pdf.
- Shlomi D et al. Screening for lung cancer: time for large-scale screening by chest computed tomography. (2014) Eur Respir J. 44:217-238.
- Sweetman RW. Should You Be Screened for Lung Cancer? Get Healthy Stay Healthy: A Pfizer Program (2014). www.gethealthystayhealthy.com/articles/should-you-be-screened-lung-cancer.
- National Comprehensive Cancer Network (NCCN). Non-Small Cell Lung Cancer (2018). NCCN Clinical Practice Guidelines in Oncology. Ver. 1.2019 -- Dec 5 2018.
- Melosky B. Rapidly changing treatment algorithms for metastatic nonsquamous non-small-cell lung cancer (2018). Current Oncology. Vol 25, Supp 1. doi: http://dx.doi.org/10.3747/co.25.3839.
- NIH. What is precision medicine? ghr.nlm.nih.gov/primer/precisionmedicine/definition.
- American Cancer Society. Targeted Therapy for Non-Small Cell Lung Cancer. (2020). www.cancer.org/cancer/lung-cancer/treating-non-small-cell/targeted-therapies.html.
- Ettinger DS et al. Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology (2017). JNCCN. Vol 15, Issue 4. DOI: https://doi.org/10.6004/jnccn.2017.0050.
- Villalobos P and Wistuba II. Lung Cancer Biomarkers (2017). Hematol Oncol Clin North Am. February; 31(1): 13–29. doi:10.1016/j.hoc.2016.08.006.
- Hirsch F, et al. New and emerging targeted treatments in advanced non-small-cell lung cancer (2016). From Lancet vol 388, as referenced in Lung Cancer 101, Lungevity Foundation. lungevity.org/for-patients-caregivers/lung-cancer-101/diagnosing-lung-cancer/biomarker-testing.
- My Cancer Genome. 2020. www.mycancergenome.org/content/gene/pdgfra/.
- Daniels GA. Understanding the Role of Immuno-Oncology in Treating Cancer (2020). CancerCare. www. cancercare.org/publications/285-understanding_the_role_of_immuno-oncology_in_treating_cancer.
- Goodman A. The ASCO Post. Studies Report Prolonged Long-Term Survival with Immunotherapy vs Chemotherapy in Advances NSCLC. ascopost.com/issues/october-10-2019/prolonged-long-term-survival- with-immunotherapy-vs-chemo-in-advanced-nsclc.
- BMS. Five-Year Outcomes for Opdivo (nivolumab) in Combination with Yervoy (ipilimumab) Demonstrate Durable Long-Term Survival Benefits in Patients with Advanced Melanoma. (2019). https://news.bms.com/press-release/corporatefinancial-news/five-year-outcomes-opdivo-nivolumab-combination-yervoy-ipilimu.
- Siegel RL et al. American Cancer Society (ACS). Cancer statistics, 2020. CA Cancer J Clin. 2020;0:1–24. https://doi.org/10.3322/caac.21590.
- Langreth R. U.S. Cancer Death Rates Are Dropping at the Fastest Pace on Record. Bloomberg. Published Jan 8 2020. https://www.bloomberg.com/news/articles/2020-01-08/cancer-death-rate-in-u-s-shows-fastest-drop-on-new-treatments.
- National Cancer Institute. Advances in Lung Cancer Research (2019). www.cancer.gov/types/lung/research.
- Radiological Society of North America. Deep Learning Assists in Detecting Malignant Lung Cancers (2019). RSNA News. www.rsna.org/en/news/2019/November-December/Deep-Learning-For-Detecting-Lung-Cancers.
- Ventola CL. Cancer Immunotherapy, Part 3: Challenges and Future Trends (2017). P&T. August 2017. Vol. 42 No. 8.
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Lung cancer is the most prevalent and lethal cancer globally, afflicting more than 2 million people annually. In the U.S., someone is diagnosed with lung cancer every 2.3 minutes.1
Lung cancer healthcare costs exceed $10 billion per year in the U.S., the E.U., and China each.2
Cancers occur when mutations build up in genes that control cell growth and repair. While inherited genetics can be a factor, most mutations that drive lung cancer are acquired during a person’s lifetime.3
For a large portion of patients, risk factors for lung cancer can be genetic or acquired. Acquired risk factors include cigarette smoking, environmental carcinogens, such as exposure to radon, and other respiratory diseases. For others, lung cancers can develop with no known risk factors for the disease.
Research advances are leading to the development of biomarker-driven therapies aimed at genetic drivers of tumor growth and several immunotherapies aimed at a patient’s own immune system. Advances in research and development will continue to create new options for treatment.