Lung Cancer: Symptoms, Risk Factors, and Early Diagnosis

What Is Lung Cancer?

Hello, I am Dr. Emre Gecer. Lung cancer is a malignant tumor that develops from the uncontrolled proliferation of cells in lung tissue. It is the leading cause of cancer-related deaths worldwide in both men and women. Approximately 2.2 million new lung cancer cases are diagnosed and 1.8 million people die from this disease each year. In Turkey, lung cancer is the most common cancer type in men.

The main reason lung cancer is so deadly is that the vast majority of patients (more than 70%) are at an advanced stage (stage III or IV) at the time of diagnosis. While 5-year survival is 60-80% when lung cancer is caught early, it falls below 5-10% in advanced stages. Therefore, early diagnosis and screening programs are vitally important.

Types of Lung Cancer

Lung cancer is histologically divided into two main groups:

1. Non-Small Cell Lung Cancer (NSCLC) — 85%

Accounts for approximately 85% of all lung cancers. It has three main subtypes:

• Adenocarcinoma (40%): The most common subtype of lung cancer. It develops from mucus-secreting glandular cells in the periphery (outer parts) of the lung. It is the most common type in individuals who have never smoked and in women. Targetable genetic mutations such as EGFR, ALK, and ROS1 are most often found in this subtype.
• Squamous (flat) cell carcinoma (25-30%): Generally develops from the central (main) airways and has the strongest association with smoking. It may show cavitation (formation of a cavity within the tumor). Paraneoplastic hypercalcemia is more common in this type.
• Large cell carcinoma (5-10%): A poorly differentiated tumor. It can develop in any region of the lung and tends to grow rapidly.

2. Small Cell Lung Cancer (SCLC) — 15%

Accounts for 15% of all lung cancers. It originates from neuroendocrine cells and has a very strong association with smoking (more than 98% of patients are smokers). It is an extremely aggressive tumor; it grows very quickly and metastasizes early. At diagnosis, most patients already have extensive-stage disease. It initially responds very well to chemotherapy but recurrence rates are high. Paraneoplastic syndromes (SIADH — syndrome of inappropriate ADH, Lambert-Eaton syndrome, Cushing syndrome) are common in this type.

Risk Factors

Smoking: The Number One Cause

Smoking is the direct cause of 85-90% of lung cancers. Cigarette smoke contains more than 70 known carcinogens. Risk increases in direct proportion to the amount and duration of smoking. This relationship is measured in "pack-years" (packs smoked per day × years). A smoking history of 30 pack-years or more defines the high-risk group. Quitting smoking reduces risk; after 10-15 years the risk decreases significantly, but it never falls to the level of a never-smoker. Secondhand smoke exposure also increases lung cancer risk by 20-30%.

Other Risk Factors

• Radon gas: The leading cause of lung cancer in non-smokers. It is a naturally occurring radioactive gas released from the ground that accumulates in enclosed environments (basements, poorly ventilated homes) and raises lung cancer risk.
• Occupational carcinogens: Asbestos (the most important occupational carcinogen; synergistic with smoking), arsenic, chromium, nickel, beryllium, cadmium, and silica exposure
• Air pollution: Particulate matter (PM2.5) exposure increases lung cancer risk; classified as a Group 1 carcinogen by WHO
• Family history: A first-degree relative with lung cancer increases risk 1.5- to 2-fold
• Previous lung diseases: COPD, pulmonary fibrosis, tuberculosis
• Radiation exposure: Prior chest radiotherapy

Symptoms of Lung Cancer

Early-stage lung cancer usually causes no symptoms. When symptoms appear, the disease has often already reached an advanced stage. Symptoms vary by location, size, and spread of the tumor:

Pulmonary (Lung) Symptoms

• Chronic cough: The most common presenting complaint. A cough lasting longer than 2-3 weeks, changing in character, or newly developed should attract attention.
• Hemoptysis (blood-tinged sputum): Streaks of blood in sputum or spitting up fresh blood. Not every hemoptysis is lung cancer, but it must always be investigated.
• Shortness of breath: Due to tumor obstruction of the airways, pleural effusion (fluid in the lining of the lung), or atelectasis
• Chest pain: Dull, persistent pain; especially with chest wall or pleural involvement
• Recurrent lung infections: Recurrent pneumonia in the same region should raise suspicion for an obstructing tumor

Symptoms of Locally Advanced Disease

• Hoarseness (dysphonia): Due to involvement of the left recurrent laryngeal nerve
• Difficulty swallowing (dysphagia): Due to esophageal compression
• Superior vena cava (SVC) syndrome: Swelling of the face, neck, and arms, cyanosis, and headache caused by tumor compression of the superior vena cava
• Pancoast syndrome: Shoulder-arm pain, atrophy of the hand muscles, and Horner syndrome (miosis, ptosis, anhidrosis) due to tumors at the apex of the lung involving the brachial plexus and cervical sympathetic chain

Symptoms of Metastatic Disease

• Bone metastases: Bone pain, pathologic fractures
• Brain metastases: Headache, nausea-vomiting, neurologic deficits, seizures
• Liver metastases: Abdominal pain, jaundice, elevated liver enzymes
• Adrenal metastases: Usually asymptomatic

Systemic Symptoms and Paraneoplastic Syndromes

• Unintentional weight loss, loss of appetite, fatigue
• Hypercalcemia: PTHrP secretion (squamous cell type)
• SIADH: Syndrome of inappropriate ADH — hyponatremia (small cell type)
• Cushing syndrome: Ectopic ACTH production
• Digital clubbing
• Lambert-Eaton myasthenic syndrome: Proximal muscle weakness (small cell type)

Diagnosis and Staging

Imaging

• Chest X-ray: May be the first step but can miss small lesions
• Contrast-enhanced chest CT: The standard imaging modality when lung cancer is suspected. The tumor's size, location, lymph node involvement, and relationship to adjacent structures are evaluated.
• PET-CT: Assesses tumor metabolic activity and distant metastases. Critical for staging.
• Brain MRI: Routinely performed to screen for brain metastases, particularly in stage III and IV disease

Tissue Diagnosis (Biopsy)

For a definitive diagnosis, histopathologic examination (biopsy) is essential. The biopsy method is chosen based on the location of the tumor:

• Bronchoscopy: For central tumors
• CT-guided transthoracic needle biopsy: For peripheral tumors
• EBUS (endobronchial ultrasound): Sampling of mediastinal lymph nodes
• Thoracentesis: Cytologic examination when a pleural effusion is present

Molecular Testing and Biomarkers

Molecular tests that guide treatment are extremely important, especially in adenocarcinoma:

• EGFR mutation: Treatment with tyrosine kinase inhibitors (erlotinib, gefitinib, osimertinib)
• ALK translocation: Treatment with ALK inhibitors (crizotinib, alectinib, lorlatinib)
• ROS1, BRAF, MET, RET, NTRK mutations: Targeted therapy options
• PD-L1 expression: Used to predict response to immunotherapy

TNM Staging System (NSCLC)

Lung cancer is staged according to the TNM system:

• Stage I: Tumor confined to the lung, no lymph node involvement. 5-year survival 70-90%.
• Stage II: Tumor confined to the lung with ipsilateral hilar lymph node involvement. 5-year survival 50-60%.
• Stage III: Locally advanced disease; mediastinal lymph node involvement or invasion of adjacent structures. 5-year survival 15-35%.
• Stage IV: Distant metastasis (brain, bone, liver, adrenal). 5-year survival 5-10% (longer survival possible in some patients with immunotherapy).

Lung Cancer Screening

In high-risk individuals, screening with low-dose computed tomography (LDCT) has been shown to reduce lung cancer mortality by 20-24% (NLST and NELSON trials). Screening criteria:

• Aged 50-80 years
• Smoking history of 20 pack-years or more
• Currently smoking or having quit within the last 15 years

Annual screening with LDCT is recommended. Screening improves survival by increasing the rate of early-stage diagnosis.

Treatment Approaches

Treatment of NSCLC

• Stage I-II (early stage): Surgical resection (lobectomy or sublobar resection) is the primary treatment. In patients who are not surgical candidates, stereotactic body radiotherapy (SBRT) can be used as an alternative. Adjuvant chemotherapy (cisplatin-based) improves survival in stage II and high-risk stage IB.
• Stage III (locally advanced): Concurrent chemoradiotherapy is most often used. Consolidation immunotherapy with durvalumab (PACIFIC regimen) has significantly prolonged survival.
• Stage IV (metastatic): Treatment is determined by molecular profile and PD-L1 expression. Targeted therapies (in EGFR- or ALK-positive patients), immunotherapy (pembrolizumab, nivolumab, atezolizumab), and chemotherapy-immunotherapy combinations are used.

Treatment of SCLC

• Limited stage: Concurrent chemoradiotherapy (cisplatin/etoposide + thoracic RT). After complete response, prophylactic cranial irradiation (PCI) is given.
• Extensive stage: Chemotherapy (cisplatin or carboplatin + etoposide) combined with immunotherapy (atezolizumab or durvalumab) is the current standard of care.

Conclusion

Lung cancer is now a disease that can be fought more effectively thanks to early diagnosis and modern treatment approaches. Not smoking, or quitting, is the most effective form of protection. Low-dose CT screening increases the chance of early diagnosis in high-risk individuals. Advances such as molecular testing and immunotherapy have significantly prolonged survival, particularly in advanced-stage disease. If you have symptoms such as chronic cough, blood-tinged sputum, unexplained weight loss, or shortness of breath, I recommend seeing a physician without delay.

Wishing you healthy days.
Dr. Emre Gecer

References

• Murray and Nadel's Textbook of Respiratory Medicine, 7th Edition — Chapters: Lung Neoplasms
• Harrison's Principles of Internal Medicine, 22nd Edition — Chapter: Neoplasms of the Lung
• NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer, 2024
• NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer, 2024
• USPSTF Lung Cancer Screening Recommendations, 2021