Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 85% of all lung cancer cases. It comprises a heterogeneous group of epithelial lung malignancies that behave differently from small cell lung cancer (SCLC) in terms of biological characteristics, treatment approaches, and prognosis.

The major histological subtypes of NSCLC include:

• Adenocarcinoma.

• Squamous cell carcinoma.

• Large cell carcinoma.

Cigarette smoking remains the most important risk factor, although NSCLC can also occur in non-smokers, particularly adenocarcinoma. Other important risk factors include occupational exposures, environmental pollutants, and genetic susceptibility.

Early-stage disease may be asymptomatic or present with nonspecific respiratory symptoms. Many patients present with locally advanced or metastatic disease, making early diagnosis critical for improving outcomes.

Treatment depends on tumour stage, histological subtype, molecular characteristics, performance status, and comorbidities. Management may involve surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, or combinations of these modalities.

Epidemiology

Lung cancer is one of the leading causes of cancer-related mortality worldwide.

Epidemiological characteristics of NSCLC include:

• Accounts for approximately 85% of all lung cancers

• Incidence increases with age

• More common in males, although rates among females continue to rise

• Strongly associated with cigarette smoking

• Adenocarcinoma is currently the most common histological subtype globally

The burden of disease remains high because many patients present with advanced-stage disease.

Risk factors

1. Cigarette smoking

Smoking is the most important risk factor.

Risk increases with:

• Duration of smoking

• Number of cigarettes smoked

• Pack-year exposure

2. Passive smoking

Exposure to second-hand smoke increases lung cancer risk.

3. Occupational exposures

Including:

• Asbestos

• Silica

• Arsenic

• Chromium

• Nickel

• Radon

4. Environmental pollution

Risk factors include:

• Indoor biomass fuel smoke

• Air pollution

• Industrial emissions

5. Previous lung disease

Including:

• Pulmonary fibrosis.\

• Chronic obstructive pulmonary disease (COPD).\

• Previous pulmonary tuberculosis.\

6. Family history

A family history of lung cancer increases susceptibility.

7. Radiation exposure

Previous therapeutic or environmental radiation exposure may increase risk.\

Pathophysiology

NSCLC develops through progressive genetic and molecular alterations affecting bronchial and alveolar epithelial cells.

The carcinogenic process involves:

1. Chronic exposure to carcinogens

2. DNA damage

3. Accumulation of genetic mutations

4. Dysplasia

5. Malignant transformation

6. Invasive carcinoma

Common molecular abnormalities include:

• EGFR mutations

• ALK rearrangements

• ROS1 rearrangements

• KRAS mutations

• BRAF mutations

Tumour progression occurs through:

• Local invasion of lung tissue

• Lymphatic spread

• Hematogenous dissemination

Common metastatic sites include:

• Brain

• Bone

• Liver

• Adrenal glands

Clinical presentation

Clinical manifestations vary according to:

• Tumour location

• Extent of disease

• Presence of metastases

• Associated complications

Patients may present with respiratory symptoms, constitutional symptoms, or manifestations of metastatic disease.

Symptoms

Respiratory symptoms

• Persistent cough

• Chronic chest symptoms in a smoker

• Haemoptysis

• Shortness of breath

• Wheezing

• Chest pain

Constitutional symptoms

• Unexplained weight loss

• Fatigue

• Loss of appetite

• General weakness

Symptoms due to local tumour effects

• Hoarseness of voice

• Dysphagia

• Persistent cough in patients exposed to asbestos

• Recurrent respiratory infections

Symptoms due to superior vena cava obstruction (SVCO)

• Facial swelling

• Neck vein distension

• Upper limb swelling

• Headache

• Dyspnoea

Symptoms due to metastatic disease

Brain metastases

• Headache

• Seizures

• Focal neurological deficits

Bone metastases

• Bone pain

• Bone fratures

  
  

Liver metastases

• Abdominal discomfort

• Jaundice

Clinical signs

General findings

• Weight loss.

• Cachexia

• Poor performance status

• Reduced Karnofsky Performance Scale (KPS) score

Respiratory findings

• Reduced breath sounds

• Dullness to percussion

• Wheezing

• Localized crackles

• Pleural effusion

Signs of superior vena cava obstruction

• Facial oedema

• Neck vein distension

• Upper limb swelling

• Cyanosis

Signs of metastatic disease

Neurological signs

• Focal neurological deficits

• Altered mental status

Skeletal signs

• Localized bone tenderness

• Pathological fractures

Hepatic signs

• Hepatomegaly

• Jaundice

Differential diagnosis

Differential diagnoses include:

• Small cell lung cancer

• Pulmonary tuberculosis

• Chronic obstructive pulmonary disease

• Pneumonia

• Lung abscess

• Bronchiectasis

• Pulmonary fibrosis

• Metastatic lung tumours

• Benign pulmonary nodules

Diagnostic criteria

NSCLC should be suspected in patients presenting with:

• Persistent respiratory symptoms, especially smokers

• Chronic cough

• Haemoptysis

• Unexplained weight loss

• Superior vena cava obstruction syndrome

• Persistent chest symptoms despite treatment

Diagnosis is confirmed by:

• Imaging findings suggestive of lung malignancy

• Histopathological confirmation from biopsy or cytology

Investigations

Laboratory investigations

Full blood count (FBC)

Used to assess:

• Anaemia

• Infection

• Baseline treatment status

Liver function tests (LFTs)

Assess:

• Baseline hepatic function

• Hepatic metastases

Renal function tests

Includes:

• Urea

• Creatinine

Important before contrast imaging and chemotherapy.

Imaging investigations

Chest X-ray (PA and lateral views)

May demonstrate:

• Lung mass

• Collapse

• Pleural effusion

• Mediastinal widening

CT scan of thorax and abdomen

Essential for:

• Tumour characterization

• Local staging

• Assessment of lymph node involvement

• Detection of metastases

Abdominal ultrasound

Useful for:

• Assessment of liver metastases

• Evaluation of abdominal organs

Endoscopic investigations

Bronchoscopy

Allows:

• Direct visualization of endobronchial lesions

• Tissue biopsy

• Bronchial washings and brushings

Cytological investigations

Sputum cytology

May identify malignant cells in central tumours.

Bronchial aspirate cytology

Useful when tissue biopsy is difficult.

Histopathological examination

Biopsy provides:

• Confirmation of NSCLC

• Histological subtype

• Information required for treatment planning

Staging

NSCLC is staged using the TNM staging system.

T – Primary tumour

Assessment includes:

• Tumour size

• Local invasion

• Involvement of adjacent structures

N – Regional lymph nodes

Assessment of:

• Hilar nodes

• Mediastinal nodes

• Supraclavicular nodes

M – Distant metastases

Assessment of spread to:

• Brain

• Bone

• Liver

• Adrenal glands

• Other distant organs

Management

Management should be individualized according to:

• TNM stage

• Histological subtype

• Performance status

• Pulmonary reserve

• Presence of metastases

Management pathway:

1. Confirm diagnosis

2. Stage disease

3. Assess surgical operability

4. Determine suitability for curative treatment

5. Administer systemic or palliative therapy as appropriate

6. Provide long-term follow-up

Non-pharmacological treatment

Surgical treatment

Surgery is the treatment of choice for:

• Stage I disease

• Selected Stage II disease

Lobectomy

Preferred procedure when feasible.

Indicated for:

• Localized tumours

• Adequate pulmonary reserve

Pneumonectomy

Indicated when:

• Complete resection cannot be achieved by lobectomy

• Central tumours involve major bronchi

Radiotherapy

Radiotherapy may be used in:

Neoadjuvant setting

Before surgery to improve resectability.

Adjuvant setting

After surgery to reduce recurrence risk in selected patients.

Definitive treatment

For patients unsuitable for surgery.

Palliative treatment

To relieve symptoms caused by:

• Bone metastases

• Brain metastases

• Spinal cord compression

• Liver metastases

• Superior vena cava obstruction syndrome

• Atelectasis

• Obstructive pneumonitis

• Fungating tumours

Recommended palliative dose

Radiotherapy – 30 Gy – 10 fractions – over 2 weeks

This regimen provides effective symptom relief in advanced disease.

Pharmacological treatment

Chemotherapy for adjuvant, unresectable, recurrent, or metastatic disease

Carboplatin and paclitaxel regimen

Carboplatin – AUC 6 – intravenous infusion over 1 hour – day 1ANDPaclitaxel – 175 mg/m² – intravenous infusion over 3 hours – day 1

Frequency:

• Every 21 days

Duration:

• 6 cycles

Indications:

• Adjuvant treatment

• Unresectable disease

• Recurrent disease

• Metastatic disease

Management according to underlying cause

Stage I disease

Management:

• Surgical resection (lobectomy preferred)

• Surveillance after surgery.\

Stage II disease

Management:

• Surgical resection

• Consider adjuvant chemotherapy

• Follow-up imaging

Locally advanced disease

Management:

• Multidisciplinary assessment

• Chemotherapy

• Radiotherapy

• Surgery in selected patients

Unresectable disease

Management:

• Systemic chemotherapy

• Radiotherapy

• Supportive care

Metastatic disease

Management:

• Palliative chemotherapy

• Palliative radiotherapy

• Symptom control

• Palliative care services

Superior vena cava obstruction syndrome

Management:

• Urgent assessment

• Radiotherapy

• Chemotherapy where appropriate

• Supportive management

Referral

All patients with suspected or confirmed NSCLC should be referred to specialized oncology and thoracic surgery centres.

Urgent referral indications

• Haemoptysis

• Superior vena cava obstruction syndrome

• Suspected spinal cord compression

• Respiratory distress

• Rapidly progressive symptoms

• Suspected metastatic disease

Complications

Disease-related complications

• Superior vena cava obstruction

• Massive haemoptysis

• Pleural effusion

• Atelectasis

• Obstructive pneumonitis

• Respiratory failure

• Brain metastases

• Bone metastases

• Spinal cord compression

Treatment-related complications

Surgery

• Bleeding

• Pneumonia

• Respiratory failure

Chemotherapy

• Myelosuppression

• Peripheral neuropathy

• Nausea and vomiting

• Fatigue

Radiotherapy

• Radiation pneumonitis

• Oesophagitis

• Pulmonary fibrosis

Prognosis

Prognosis depends on:

• TNM stage

• Performance status

• Histological subtype

• Completeness of tumour resection

• Response to treatment

Patients with Stage I disease treated surgically have the best outcomes. Advanced metastatic disease is associated with significantly lower survival rates.

Prevention

Preventive measures include:

Tobacco control

• Smoking cessation

• Avoidance of second-hand smoke

• Smoking prevention programmes

Occupational protection

Reduce exposure to:

• Asbestos

• Silica

• Industrial carcinogens

Environmental protection

• Reduction of indoor smoke exposure

• Reduction of air pollution exposure

Early detection

High-risk individuals should undergo appropriate screening according to national and institutional recommendations.