Lung Cancer

 

Global Scenario of Lung Cancer

KRISHNA ARUNKUMAR & DR. LOPAMUDRA DAS ROY

Published 2021

@BreastCancerHub, All Rights Reserved

Abstract

Lung cancer remains the number-one cause of cancer deaths globally, increasing alarmingly every year than any other cancer. Nearly 1.6 million people worldwide and 160,000 people in the U.S. die from lung cancer every year. Incident rate and mortality vary between countries, but lung cancer is globally responsible for one in every five deaths in cancer. Although we have seen advances in treatment options in recent years, the prognosis remains very poor. The main reason for poor prognosis is that most lung cancers are detected in the late stages. In addition, socioeconomic status, income, and geographical inequality play an essential role in the disparity in managing lung cancer. Therefore, raising awareness, screening, early detection, and access to treatment and clinical trials remain essential to improve outcomes.

Introduction

Lung cancer is the second most common cancer in both men and women, which is the leading cause of cancer deaths worldwide, with an estimated 1.8 million deaths in 2021 (1,2)Fig1.a. In 2020, lung cancer caused 1:5 cancer deaths, more than breast and prostate cancer combined (1,2) Fig1.b. The highest incidence rates among men are in Europe, particularly in Eastern European countries such as Hungary, Western Asia (particularly in the former Soviet Union), and other countries in Asia such as Turkey and China. On the other hand, the highest incidence rates among women are in North America, North and Western Europe, Australia, and New Zealand (1).

Fig.1a Worldwide Cancer Incidence, 2020(1)

Fig1b

Lung Cancer Death Globally(2)

Fig1c

Primary lung cancer originates in the lungs, and there are two main types, Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)(3,4). NSCLC is the most common type of lung cancer and accounts for 85% of lung cancer (5). Based on the cell type, NSCLC is further classified as adenocarcinoma (40%), squamous (25-30%), and large cell carcinoma (10-15%) (3,4). Histological diagnosis of NSCLC should be accurate to help appropriate treatment decisions. SCLC accounts for 15% of lung cancer and is categorized by rapid growth and metastasis. Though SCLC has a high initial response to chemo and radiotherapy later becomes resistant to treatment with patients in metastatic disease. Mostly all SCLC patients have a history of tobacco use (6).

Researchers worldwide have made significant progress in understanding cancer mechanisms and preventing, diagnosing, and treating cancer. There are surgical advances, improvements in therapies, and the discovery of new drugs that specifically target the cancer cells and stimulate the immune system to fight the disease. Despite these advancements, lung cancer is seen by many as having no hope, which makes the patient and their family develop fear and anxiety. The screening guidelines and the availability of new drugs for lung cancer treatment vary significantly across countries. There is a significant need to detect and treat lung cancer at an early stage efficiently. The role of patient organizations and nonprofit organizations have become more active in recent years, and a recent survey has shown that 34.9% of people have received support by these organizations. (7). There is a lack of knowledge surrounding lung cancer among both patients and physicians regarding effective risk reduction and treatment options. This article aims to share the knowledge and learning across the global community and improve outcomes for lung cancer patients.

Methods:

This systematic literature review was conducted by reviewing all relevant literature in PubMed, web pages of cancer institutes, WHO and AACR. A depth search was performed regarding the topic of interest: global status of lung cancer, screening guidelines and treatment options, risk factors, psychological effects associated with lung cancer, and impact due to Covid-19 pandemic.  First key words were entered, and separate searches were performed for topics of interest. About 50 recent articles for each term were procured and analyzed in depth.

Results and Discussion

Smoking and lung cancer

Historically, lung cancer, which affects men, is alarmingly increasing in women and is the second leading cause of death in women after breast cancer. Both in men and women, exposure to tobacco smoke is the primary risk factor for the development of lung cancer. Compared to nonsmokers, long-term smokers have a 10-30-fold higher risk of developing cancer in their lifetime. However, lung cancer risk seems to decrease by 20-90% in individuals who stopped smoking compared to those who continue to smoke, with a life expectancy of 6 to 10 years depending on the age they quit. A study of 20,000 people who smoked ≥15 cigarettes or equivalent per day showed that a 50% reduction in smoking reduced cancer risk by 20%. (3,4, 8). Nonsmokers exposed to secondhand smoke at home or work are at higher risk of developing lung cancer. It was estimated that secondhand smoke causes more than 7,300 lung cancer deaths among U.S. nonsmokers yearly (5).

 Other risk factors include long-term exposure to radon, asbestos, arsenic in drinking water, chromium, nickel, silica, coal products, mustard gas, diesel exhaust, and air pollution (8,9). Chinese women exposed to smoke from burning charcoal seem to have similar incident rates as European women, who have a higher smoking rate than Chinese women (10). Globally, in 2019, residential radon exposure alone was estimated to have caused 84,000 deaths by lung cancer; in some countries, it is among the leading causes of lung cancer (9,11, 12). Every year 21,000 people die of lung cancer related to radon exposure. Other factors include family history, exposure to radiation like radiation therapy for other cancers such as breast.

Genetic Factors

Several genetic mutations cause lung cancer, such as KRAS, EGFR, BRAF, MEK1 (MAPK1), HER2, MET and RET, ALK and ROS1 rearrangements, and inactivation of tumor suppressor genes such as TP53(13). The genomic landscape of lung cancer is markedly distinct between never-smokers and smokers Fig (3). Higher frequency of EGFR, ALK, ROS1, ERBB2, RET, BRAF (V600E), and NTRK1 mutations in never-smokers, and the higher frequency of KRAS mutations in smokers were observed. EGFR mutations are found in both smokers and never-smokers, but the frequency is much higher in never-smokers.

The disparity in lung cancer screening in developed and developing countries: 

 Lung cancer screening targets only high-risk populations unlike screening programs for other cancers where the entire population is targeted. Early detection of high-risk lung cancer cases can reduce the chance of death by up to 20%. However, lung cancer can be harder to detect early because it is mostly asymptomatic until it is metastasized.  Recommendations regarding lung cancer screening come mainly from developed countries like the U.S. It is not routinely used in developing countries. The U.S. Preventive Services Task Force (USPSTF) recommends yearly lung cancer screening with low dose computed tomography (LDCT) for people who have a smoking history or have quit within the past 15 years and are between 50 and 80 years old (14). Low middle-income countries had the highest lung cancer incidence and mortality with 1,032,425 cases and 924,483 deaths in 2018. (15). This could be due to many factors and is likely associated with access to diagnostic tools resulting in delayed detection and barriers to adequate treatment. In developing countries, lung cancer screening is challenging; in some countries, an organized lung cancer screening is practically impossible. The burden of Pulmonary tuberculosis and other chest infections are very high in these countries and need to be considered while planning for lung cancer screening as this can lead to overdiagnosis.

Symptoms:

The most common symptom of lung cancer is persistent or worsening cough, chest pain, hemoptysis (coughing up blood) and shortness of breath (dyspnea), wheezing or hoarseness, and persistent chest infection. 

Diagnosis(4): 

Definitive diagnosis of lung cancer is based on imaging studies and histological assessment of tumour tissue samples.

History and Physical Examination:

  • Patient history (smoking status, family history of lung cancer) and clinical examination.

Imaging techniques:

  • Chest X-ray: usually the first test carried out after the clinical examination

  • Computed tomography (CT) scan of the chest: if cancer or cancer-related complications are suspected, to determine the location of the tumor and whether it has spread from the lungs.

  • Whole-body positron emission tomography (PET) or PET/CT scanning: may also be used if metastatic disease is suspected.

Biopsy: If imaging tests indicate cancer tumor biopsy is essential to

  • Confirm a diagnosis

  • Distinguish SCLC from NSCLC, and histological subtype of NSCLC

  • Collect tissue for molecular testing

  • Tissue samples may also be collected for cytological examination.

 Laboratory testing: A detailed clinical examination with laboratory testing (complete blood count, electrolytes, calcium, alkaline phosphatase, lactate dehydrogenase, liver function, creatinine and albumin) can predict the likelihood of metastases, particularly in patients with NSCLC.

Molecular Testing: Molecular testing has become a critical part of the diagnostic workup for NSCLC now that there are targeted therapies available that work in specific subtypes.

  • Molecular testing should be undertaken in all patients with any amount of adenocarcinoma histology

  • Tumor specimens should be tested for:

  • Specific EGFR gene mutations

  • V600E mutation in the BRAF gene

  • ALK and ROS1 gene rearrangement.

  • PD-L1: with emergence of checkpoint inhibitors as treatment option for advanced NSCLC, testing for the presence of PD-L1 has also become a recommended part of the diagnosis.

Staging and Treatment

Depending on the type and stage of lung cancer, it may be treated with surgery, chemotherapy or other medications, radiation therapy, local treatments such as laser therapy, or a combination of treatments (16, 17).

Stage la - lb

Tumor localized in lung

Surgical resection

Stage lla - llb

Tumor spread to local lymph nodes

Surgical resection

Stage llla

Tumor spread to regional lymph nodes in trachea, chest above diaphragm

Chemotherapy followed by radiation or surgery

Stage lllb

Tumor spread to contralateral lymph nodes

Combination of Chemotherapy and Radiation

Stage IV

Tumor metastasis to organs outside chest

Chemotherapy and or palliative care

Disparities in Lung cancer

Social inequalities have contributed to health disparities, including for those facing lung cancer. Several factors like race, economic status, education contribute to disparities in the treatment of lung cancer. Recent studies have shown that minorities in the US who are diagnosed with lung cancer face worse outcomes than white Americans because they are less likely to be diagnosed early, less likely to receive surgical treatment, and more likely to not receive any treatment (18). In addition, about half of the 30 million uninsured Americans are people of color, impacting their health outcomes (19).

Psychological Impact

Lung cancer is very complex and can significantly impact life expectancy, creating a vast amount of stress. Most lung cancer patients and the family felt loneliness, anxiety, fear, anger, frustration, and hopelessness. Studies have shown that patients feel guilt more in lung cancer than other cancer because of the stigma associated with smoking (7)

Covid-19 pandemic 

The covid-19 pandemic has an impact on the screening, diagnosis, and treatment of lung cancer patients. During the pandemic, reduced access to a diagnostic tool and less availability of staff delays the lung cancer diagnosis. In addition, many patients undergoing chemotherapy were put on hold as these patients receiving chemotherapy are susceptible to covid-19 infection A study has estimated that Covid 19 will lead to a 4.8 -5.3% increase in lung cancer deaths over the next five years (20).

Conclusions

Early detection of lung cancer is considered a key driver for longer-term survival. However, unlike other cancers, lung cancer screening is recommended for only those with a long history of smoking and between ages 50-80. In addition, racial disparities in lung cancer screening and treatment worldwide result in poor health outcomes. Furthermore, Covid 19 pandemic had a significant impact on lung cancer patient care. Hence there is a significant need to detect and more effectively treat lung cancer at its earliest state and develop targeted therapies for early and advanced-stage non-small cell lung cancer, accounting for 80-85% of all lung cancers today. Hence, several factors are required to improve the lives of lung cancer patients, like implementing effective screening programs, sharing the correct information at the right time with people with lung cancer and their caregivers, and ensuring equitable and timely access to treatments for all lung cancer patients.  

References

  1. Hyuna Sung, et al., Cancer J. Clin (2021) Global Cancer Statistics 202o. GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

  2. Rebecca L. Siegel MPH etal., Cancer Statistics, 2021, A Cancer  Journal for Clinicians 2021:;71:7-33

  3. Midthun, D.E. (2019). Overview of the risk factors, pathology, and clinical manifestations of lung cancer. https://www.uptodate.com/contents/clinical-manifestations-of-lung-cancer.

  4. European Society for Medical Oncology (ESMO). (2019). Non-small-cell lung cancer: a guide for patients. https://www.esmo.org/content/download/7252/143219/file/en-non-small-cell-lung-cancer-guide-for-patients.pdf

  5. Herbst, R.S., Morgensztern, D., et al. (2018). Nature. 553(7689): 446-54.

  6. Fruh, M., De Ruysscher, D., et al. (2013). Annals of Oncology.

  7. Lung Cancer Europe. 5th LuCE Report on Lung Cancer: Psychological and social impact of lung cancer. 2020.

  8. Mannino, D.M. (2019). Cigarette smoking and other possible risk factors for lung cancer.

  9. European Society for Medical Oncology (ESMO). (2019).

  10. Bray, F., Ferlay, J., et al. (2018). CA: A Cancer Journal for Clinicians. 68(6): 394-424. 

  11. Herbst, R.S., Morgensztern, D., et al. (2018). Nature. 553(7689): 446-54.

  12. https://www.who.int/news/item/04-02-2021-more-countries-act-against-exposure-to-radon-and-associated-cancer-risks.

  13. S.E.D.C. Jorge etal., Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data. Braz J Med Biol Res 47(11) 2014.

  14. National Comprehensive Cancer Network (NCCN). (2019). Lung cancer screening. Version 1.2020. 

  15. Eduardo Edelman Sau et al. The challenges of implementing low-dose computed tomography for lung cancer screening in low- and middle-income countries., nature Cancer (2020)

  16. Thomas, K.W. and Gould, M.K. (2019). https://www.uptodate.com/contents/overview-of-the-initial-evaluation-diagnosis-and-staging-of-patients-with-suspected-lung-cancer.

  17. National Cancer Institute (NCI). (2019). Non-Small Cell Lung Cancer Treatment.

  18. Ernesto Sosa MSW, et al., Racial and socioeconomic disparities in lung cancer screening in the United States: A systematic review A Cancer Journal of Clinicians 71 (4) 2021:299-314.

  19. Matthew B. Schabath et al., Racial and Ethnic Differences in the Epidemiology of Lung Cancer and the Lung Cancer Genome. Cancer Control. 2016 Oct; 23(4): 338–346.

  20. Maringe C, Spicer J, Morris M, et al. “The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study” Lancet Oncology 21(8) 2020: 1023-34.

 
Lopamudra Das Roy