Uncontrolled growth of cells in the lungs may lead to lung cancer like bronchogenic carcinoma. Lung cancer treatment includes radiation, chemo and surgery.

Lung Cancer

Dr. Saad Ullah Siddiqui Clinic

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Saad Ullah Siddiqui

Overview

The uncontrollable growth of cells in the lungs gives rise to lung cancer. This malignant tumor mostly arises from epithelial cells in the lung tissues and can metastasize to nearby or distant organs.

In 2020, lung cancer accounted for 11.4% of all new cancer cases worldwide<a href="#accordion">[1]</a>. Although female breast cancer has overtaken it as the most commonly diagnosed cancer, lung cancer remains the leading cause of cancer death across the world. An estimated 1.8 million global deaths in 2020 were a result of this illness<a href="#accordion">[1]</a>. Furthermore, more than 50% of lung cancer deaths per year occur in low- and middle-income countries<a href="#accordion">[2]</a>.&nbsp;

&nbsp;

While both genders are affected, men have a 1 in 15 chance of developing lung cancer in their lifetime, and women have a lifetime chance of 1 in 17<a href="#">[3]</a>. In Pakistan, it is the second most common cancer in men and the third most common cancer in both genders<a href="#accordion">[4]</a>. Since Pakistan lacks a National Cancer Registry, the true incidence and mortality of lung cancer are difficult to assess.&nbsp;

Approximately two-thirds of lung cancer deaths globally are linked to smoking<a href="#accordion">[1]</a>. The rising incidence of tobacco use is expected to cause a further increase in global cases and deaths. A study by the Karachi Cancer Registry (KCR) found that almost 80% of lung cancer patients in the city have a history of smoking<a href="#accordion">[5]</a>. This is not surprising as 19% of people (15 years and above) in Pakistan consume tobacco and 72.5% of adults are exposed to passive smoking in their workplace<a href="#accordion">[6]</a>.&nbsp;

Although smoking is a major risk factor, many populations with high tobacco use have low lung cancer prevalence. According to a Japanese study, 30-40% of Asian lung cancer patients are non-smokers<a href="#accordion">[7]</a>. Nevertheless, effective tobacco control strategies can help significantly reduce the disease burden.

&nbsp;

Lung cancer can be divided into two main types: small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Approximately 84% of all lung cancers are NSCLC and 13% are SCLC<a href="#accordion">[3]</a>.&nbsp;

&nbsp;

<h5>Small Cell Lung Cancer (SCLC)&nbsp;</h5>

Previously called oat cell carcinoma, SCLC is more aggressive than non-small cell lung cancer. It can be further divided into two different types: small-cell carcinoma and combined small-cell carcinoma. Due to its rapid and aggressive growth, the cancer responds well to chemotherapy. However, it often recurs in patients. Most cases of SCLC originate in the primary and secondary bronchi and are associated with cigarette smoking. Moreover, this cancer type is frequently associated with paraneoplastic syndromes.&nbsp;

&nbsp;

<h5>Non-Small Cell Lung Cancer (NSCLC)&nbsp;</h5>

This is the most common type of lung cancer. It usually grows at a slower rate than SCLC and spreads more slowly to other parts of the body. Moreover, it mostly remains asymptomatic and is often diagnosed at an advanced stage. The three main subtypes are: 
&nbsp;

<ul>
	<li>Adenocarcinoma - This subtype grows from the mucus-secreting glands of the lungs and is commonly found in the outer parts of the lungs. It is more common in women and younger people. Although adenocarcinoma mainly occurs in smokers, it is also the most common type seen in non-smokers. Adenocarcinoma in situ (AIS) is a rare subset of this lung cancer subtype and begins in the alveoli. It&rsquo;s not aggressive and has a better prognosis than other types of lung cancer.</li>
	<li>Squamous Cell Carcinoma - It begins in squamous cells present within the airways and is usually found in the center of the lung, near a bronchus. The lung cancer subtype often occurs in smokers.&nbsp;</li>
	<li>Large Cell Carcinoma - The cancer cells are large, with large nuclei and excess cytoplasm. They can occur in any part of the lungs. Moreover, it tends to grow much faster than other types of NSCLC.&nbsp;</li>
</ul>

 
Non-small cell lung cancer also has other subtypes such as adenosquamous carcinoma and sarcomatoid carcinoma. However, they are rare.&nbsp;

&nbsp;

<h5>Other Types Of Lung Cancers</h5>

Other than SCLC and NSCLC, other types of lung cancer can also occur. These include: 
&nbsp;

<ul>
	<li>Pancoast Tumors - Also called superior sulcus tumors, this cancer is rare and grows in the upper part of the lung. It is mostly a non-small cell lung cancer and can invade surrounding nerves or tissues.&nbsp;</li>
	<li>Carcinoid Tumors - This rare, slow-growing subtype mostly develops in the central airways and grows in neuroendocrine cells.&nbsp;</li>
	<li>Mesothelioma - Mesothelioma is associated with asbestos exposure and is a rare type of cancer.</li>
</ul>

 
Lymphomas, sarcomas, and adenoid cystic carcinoma of the lung can also develop. However, they are all very rare.

&nbsp;

Signs And Symptoms

Most lung cancer cases do not develop any symptoms in the early stages. Moreover, the signs and symptoms of lung cancer can resemble other diseases. Thus, making diagnosis difficult.&nbsp;

 
Common symptoms of lung Cancer include:

<ul>
	<li>Cough that worsens over time&nbsp;</li>
	<li>Coughing up blood</li>
	<li>Hoarseness</li>
	<li>Shortness of breath</li>
	<li>Chest pain that worsens on deep breaths, coughing, or laughing</li>
	<li>Recurrent respiratory infections</li>
	<li>Fatigue</li>
	<li>Loss of appetite</li>
	<li>Weight loss</li>
</ul>

&nbsp;

In advanced stages, people can develop:

<ul>
	<li>Swelling of lymph nodes in the chest or neck</li>
	<li>Headaches</li>
	<li>Dizziness or balance problems</li>
	<li>Bone pain and fractures</li>
	<li>Numbness in arms or legs</li>
	<li>Swelling of the face and the upper body</li>
	<li>Blood clots</li>
	<li>Horner&#39;s syndrome</li>
	<li>Shoulder pain</li>
</ul>

&nbsp;

Causes

Lung cancer results from cells dividing uncontrollably, resulting in tumors. Normally, the immune system attacks and kills these tumor cells. However, when the cells grow too quickly, they can form a tumor.&nbsp;

Common causes of lung cancer include: 
&nbsp;

<ul>
	<li>Smoking - According to the American Lung Association, about 90% of lung cancer cases are linked to smoking<a href="#accordion">[8]</a>. Cigarettes contain more than 70 carcinogens that can contribute to lung cancer. However, passive smoking can also lead to lung cancer in non-smokers.&nbsp;</li>
	<li>Radon Gas - It is the second most common cause of lung cancer. The colorless, odorless radioactive gas is present naturally in the soil. Radon exposure, especially when combined with cigarette smoking, can increase lung cancer risk.</li>
	<li>Asbestos - Occupational exposure to hazardous chemicals can cause lung cancer.&nbsp;</li>
	<li>Genetic Mutations - Certain gene mutations can increase one&#39;s risk of lung cancer.&nbsp;</li>
</ul>

 
Other causes include air pollution, radiation therapy to the chest, and exposure to some metals (nickel, cadmium, arsenic).

&nbsp;

Low-dose computed tomography (LDCT) scans are used to screen high-risk individuals. This can help in early diagnosis and increase survival rates for the patients. Compared to no screening, LDCT scans can cause a 24% and 33% reduction in lung cancer mortality in men and women respectively<a href="#accordion">[9]</a>.

 
The United States Preventive Services Task Force (USPSTF) recommends yearly screening in adults who meet all three criteria<a href="#accordion">[10]</a>:

<ul>
	<li>Aged 50-80 years&nbsp;</li>
	<li>Adults who currently smoke or quit smoking within the past 15 years</li>
	<li>A 20-pack/year smoking history</li>
</ul>

&nbsp;

Diagnosis

If the screening test shows unusual results, or if the doctor suspects lung cancer based on one&#39;s history, doctors may perform various tests. These include: 
&nbsp;

<ul>
	<li>Physical Exam - During a physical examination, a physician may look for swollen lymph nodes, abnormal respiratory sounds, signs of respiratory infection, breathing rate, and any mass in the abdomen.&nbsp;</li>
	<li>Imaging Tests - These include X-rays, MRI scans, CT scans, and PET scans. The various imaging tests can help rule out other lung diseases and identify lesions in the lungs.</li>
	<li>Sputum Cytology - A sample of the sputum is viewed under a microscope to look for cancer cells.</li>
	<li>Biopsy - This gives a definite diagnosis of lung cancer. Doctors can use various ways to perform a biopsy. These include bronchoscopy, mediastinoscopy, and needle biopsy. Samples of nearby lymph nodes may also be collected to check for cancer cells and stage cancer.</li>
	<li>Thoracentesis - A needle is used to remove fluid from the pleural space. The fluid is then analyzed for cancer cells.&nbsp;</li>
</ul>

&nbsp;

<h5>Stages</h5>

Staging cancers can help determine how far it has spread and help design an effective treatment regimen for patients. The TNM staging system is mostly used to stage lung cancer. It is based on the tumor&#39;s size (T), lymph node involvement (N), and the presence of metastasis (M).&nbsp;

&nbsp;

<h5>Stages Of Non-Small Cell Lung Cancer</h5>

<ul>
	<li>Occult Cancer: Cancer cells might be present in sputum, but the cancer is not seen on imaging scans<a href="#accordion">[11]</a></li>
	<li>Stage 0:&nbsp;Tumor cells are only present in the top layers of cells lining the airways</li>
	<li>Stage 1: Tumor is 4cm or less, is only present in the lung, and has not spread to any other parts of the body&nbsp;</li>
	<li>Stage 2: Tumor is 7cm or less, is present in the lung, and has spread to nearby lymph nodes</li>
	<li>Stage 3: Cancer is in the lung and has spread to the lymph nodes in the middle of the chest</li>
	<li>Stage 3A: Cancer spreads to lymph nodes present on the same side of the chest as&nbsp;the tumor</li>
	<li>Stage 3B: Cancer spreads to lymph nodes on the opposite side of the chest or to&nbsp;those above the collarbone</li>
	<li>Stage 4: Cancer has spread to both lungs and distant organs such as the brain and the bones</li>
</ul>

&nbsp;

<h5>Stages Of Small Cell Lung Cancer</h5>

SCLC has two stages, limited and extensive<a href="#accordion">[12]</a>. About 2 out of 3 people with SCLC are present in the extensive stage<a href="#accordion">[12]</a>.

<ul>
	<li>Limited Stage: Cancer may have spread to lymph nodes, but it is only present on one side of the chest. Radiation therapy is often used for treating limited-stage SCLC.</li>
	<li>Extensive Stage: In this stage, cancer has spread to the other lung, lymph nodes on the opposite side, and other parts of the body such as the bone and brain.</li>
</ul>

&nbsp;

Treatment

The treatment for lung cancer is based on the type of cancer, location, and stage of cancer, and the person&#39;s overall health.&nbsp;

&nbsp;

<h5>Chemotherapy&nbsp;</h5>

Chemotherapy helps kill cancer cells by preventing their growth and division. However, it can also damage healthy cells in the body and result in side effects such as nausea, vomiting, fatigue, hair loss, anemia, and an increased risk of infection.&nbsp;

It is often combined with radiation therapy or given alone. When given after surgery, it is called adjuvant chemotherapy. This is mostly given in stage 2 or 3 NSCLC. In most cases, the drugs are given through an IV infusion. Commonly used chemotherapeutic agents include cisplatin, carboplatin, docetaxel, and etoposide.

 
Chemotherapy is typically given in SCLC. In people with advanced NSCLC, it can help improve survival.&nbsp;

&nbsp;

<h5>Radiation therapy&nbsp;</h5>

High-energy X-rays help kill cancer cells and shrink tumors. External radiation therapy is most commonly used and sends high levels of radiation directly to the cancer site. For locally advanced lung cancers, the treatment is given before or after surgery and often combined with chemotherapy. Common side effects include fatigue, loss of appetite, and skin irritation.&nbsp;

&nbsp;

<h5>Stereotactic Body Radiotherapy</h5>

Also called radiosurgery, this treatment is used in people with SCLC who cannot undergo surgeries due to comorbidities or other factors. It can also be used for metastatic cancers that have spread to other parts of the body such as the brain. High beams of radiation are applied to cancer from various angles.

&nbsp;

<h5>Targeted Drug Therapy</h5>

This treatment targets specific genes, proteins, or environmental factors of cancer cells. They are often used for NSCLC. Options include:&nbsp;

<ul>
	<li>Epidermal growth factor receptor (EGFR) inhibitors: EGFR-positive lung cancers are responsive to this type of treatment. These drugs can help stop the growth of cancer cells. FDA-approved EGFR inhibitors include afatinib, dacomitinib, entrectinib, erlotinib, gefitinib, and osimertinib.&nbsp;</li>
	<li>Anaplastic lymphoma kinase (ALK) inhibitors: ALK proteins contribute to the growth of cells. If present in cancer cells, they can help them grow and spread. Therefore, in people with NSCLC containing ALK proteins, these drugs can stop cancer growth.&nbsp;</li>
	<li>Drugs targeting&nbsp;KRAS&nbsp;G12C mutations: KRAS G12C is one of the most common mutations present in people with NSCLC. Sotorasib is the only approved drug.</li>
	<li>Anti-angiogenesis therapy: These drugs stop the growth of new blood vessels. As a result, the cancer cells cannot spread and grow.&nbsp;</li>
</ul>

 
Other targeted drug therapies include drugs targeting&nbsp;ROS1&nbsp;fusion, drugs targeting the EGFR exon 20 insertion, drugs targeting&nbsp;NTRK&nbsp;fusion, and drugs targeting&nbsp;BRAF&nbsp;V600E mutations.

&nbsp;

<h5>Immunotherapy&nbsp;</h5>

Immunotherapy drugs boost the immune system&#39;s ability to fight cancer cells. It can be used for both SCLC and NSCLC. Drugs that block the PD-1 pathway and CTLA-4 pathway are most commonly used for treating lung cancers. Common side effects include flu-like symptoms, diarrhea, shortness of breath, skin reactions, and weight changes.&nbsp;

&nbsp;

<h5>Surgery&nbsp;</h5>

Surgical procedures are often reserved for early-stage lung cancer. Types of surgery include:

<ul>
	<li>Segmental Or Wedge Resection: A small section of the lung containing the tumor is removed along with a small margin of healthy lung tissue.</li>
	<li>Lobectomy: This is currently the most effective surgical procedure for small lung tumors and involves the removal of an entire lobe of the lung.&nbsp;</li>
	<li>Pneumonectomy: An entire lung may be removed if the tumor is close to the center of the chest.&nbsp;</li>
	<li>Sleeve Resection: A piece of the bronchus is removed, and the lung is reattached to the remaining part of the airway.&nbsp;</li>
</ul>

 
Surgeons may also remove lymph nodes during surgical procedures to check for cancer spread. In case of nodal spread or metastasis, the oncologist may also recommend chemotherapy or radiation.&nbsp;

&nbsp;

<h5>Palliative Care</h5>

Also called supportive care, palliative care aims to optimize a person&#39;s quality of life by relieving a person&#39;s symptoms and side effects of treatment.&nbsp;

<div>&nbsp;</div>

Lung cancer can be associated with several complications. These include:

<ul>
	<li>Metastasis - Lung cancer most commonly spreads to the bones, brain, adrenal glands, the opposite lung, pericardium, and the liver.</li>
	<li>Shortness Of Breath - If the cancer is big enough to block the airways, it can cause shortness of breath. Pleural effusion can also result from lung cancer, further contributing to breathing difficulty.</li>
	<li>Haemoptysis - bleeding in the airway can cause people to cough up blood.&nbsp;</li>
	<li>Lung Infections - There is a higher risk of infections such as <a href="https://merisehat.pk/disease/pneumonia">pneumonia </a>and <a href="http://merisehat.pk/disease/bronchitis-acute-and-chronic-">bronchitis</a>. This can be due to the lowered immunity from cancer itself or chemotherapeutic agents.&nbsp;</li>
	<li>Hypercalcemia - Approximately 30% of people with cancer develop hypercalcemia<a href="#accordion">[13]</a>. Elevated blood calcium levels can lead to nausea, vomiting, stomach pain, and excessive thirst.</li>
	<li>Blood Clots - People with lung cancer have a higher risk of developing blood clots in the lower legs (deep vein thrombosis). These blood clots can travel to the lungs and cause a pulmonary embolism.</li>
	<li>Neuropathy - Pancoast tumors can result in nerve pain and even lead to Horner&#39;s syndrome.</li>
	<li>Spinal Compression - Some tumors can spread to the spine and compress the area causing back pain, weakness, and difficulty walking.&nbsp;</li>
	<li>Superior Vena Cava Syndrome - Large tumors present in the upper right lung can obstruct the superior vena cava. As a result, blood flow from the upper body is blocked and results in facial swelling, breathing problems, light-headedness, and loss of consciousness.</li>
	<li>Heart Blockage - In case of tumor spread to the heart, blood vessels in the heart can get compressed. As a result, heart blockage, fluid build-up, and other heart conditions can develop.</li>
</ul>

&nbsp;

The following factors may increase a person&#39;s risk of lung cancer:

<ul>
	<li>Family history of lung cancer</li>
	<li>Smoking</li>
	<li>Passive smoking&nbsp;</li>
	<li>Exposure to radon gas, asbestos, or other carcinogens</li>
</ul>

&nbsp;

No measure can prevent lung cancer. However, the following can reduce one&#39;s risk:

<ul>
	<li>Quit&nbsp;smoking.</li>
	<li>Avoid passive smoking.&nbsp;</li>
	<li>Reduce exposure to radon by getting your home tested for radon levels.</li>
	<li>If your work exposes you to toxic chemicals such as asbestos, then take precautions to protect yourself.&nbsp;</li>
	<li>Eat&nbsp;a healthy diet.</li>
	<li>Wear a mask if you live in an area with bad air quality.</li>
</ul>

&nbsp;

At a country level, strict tobacco control strategies are implemented to reduce the risk of lung cancer in the population. The World Health Organization has introduced the MPOWER package containing 6 policy intervention strategies<a href="#accordion">[4]</a>. These include:

<ul>
	<li>Monitor tobacco use and prevention policies</li>
	<li>Protect people from tobacco smoke</li>
	<li>Offer help to quit tobacco use</li>
	<li>Warn about the dangers of tobacco</li>
	<li>Enforce bands on tobacco advertising, promotion, and sponsorship</li>
	<li>Raise taxes on tobacco</li>
</ul>

&nbsp;

Key Points

<ul>
	<li>Lung cancer is the leading cause of cancer death worldwide. More than 80% of lung cancer cases are a result of cigarette smoking. Other causes such as radon gas, asbestos, air pollution, and genetic changes can also lead to the development of lung cancer.</li>
	<li>Lung cancer can be divided into two main types, small-cell lung cancer, and non-small cell lung cancer. These can be further divided into several subtypes. Most cases present at an advanced stage as most patients do not experience any symptoms. Common symptoms of lung cancer include worsening cough, coughing up blood, chest pain, shortness of breath, fatigue, and recurrent respiratory infections.&nbsp;</li>
	<li>Low-dose CT scans help screen high-risk populations for lung cancer. A definite diagnosis is then made based on a physical exam, X-ray, MRI scans, PET scans, and lung biopsy.&nbsp;</li>
	<li>Treatment of lung cancer depends on the location of the tumor, the type of lung cancer, its stage, and the person&#39;s overall health. Chemotherapy, radiation, surgical procedures (lobectomy, wedge resection, pneumonectomy), immunotherapy, and targeted drug therapy are often employed in treating people with cancer.&nbsp;</li>
	<li>Implementation of effective tobacco control strategies can significantly reduce the disease burden of lung cancer.</li>
</ul>

&nbsp;

[1] Sung, H. et al., 2021. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. ACS Journals, 71(3), pp. 209-249.

[2] Torre, L. A., Siegel, R. L. & Jemal, A., 2015. Lung Cancer Statistics. Lung Cancer and Personalized Medicine, Volume 893, pp. 1-19.

[3] American Cancer Society, 2022. Key Statistics for Lung Cancer. [Online]

[4] Sheikh, H. S., Munawar, K., Sheikh, F. & Qamar, M. F. U., 2022. Lung Cancer in Pakistan. Journal of Thoracic Oncology, 17(5), pp. 602-607.

[5] Pervez, S. et al., 2020. Karachi Cancer Registry (KCR): Age-Standardized Incidence Rate by Age-Group and Gender in a Mega City of Pakistan. Asian Pacific Journal of Cancer Prevention, 21(11), pp. 3251-3258.

[6] Tobacco-Free Kids, 2021. The Toll of Tobacco in Pakistan. [Online]

[7] Kawaguchi, T. et al., 2010. Japanese ethnicity compared with Caucasian ethnicity and never-smoking status are independent favorable prognostic factors for overall survival in non-small cell lung cancer: a collaborative epidemiologic study of the National Hospital Organization Study. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 5(7), pp. 1001-10.

[8] American Lung Association, 2021. Lung Cancer Causes & Risk Factors. [Online]

[9] de Koning, H. J. et al., 2020. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial. The New England Journal of Medicine, 382(6), pp. 503-513.

[10] Potter, A. L., Bajaj, S. S. & Yang, C.-F. J., 2021. The 2021 USPSTF lung cancer screening guidelines: a new frontier. The Lancet Respiratory Medicine, 9(7), pp. 689-691.

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