Definition

Lung Cancer Definition

• Description
  • Uncontrolled growth of abnormal lung cells forming tumors.
  • Main cause: Long-term exposure to carcinogens, especially tobacco smoke.

• Classification
  • Broadly categorized into:
    • Non-Small Cell Lung Cancer (NSCLC): Includes subtypes like adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.
    • Small Cell Lung Cancer (SCLC): Less common but more aggressive.

• Metastasis
  • Can spread to other body parts, leading to advanced disease and a poorer prognosis.

Types of Lung Cancer

• Prevalence
  • About 95% of primary lung tumors are bronchial carcinomas.
  • Primary tumors can originate from various sites.

• Metastases
  • Common but often asymptomatic.

• Primary Bronchial Cancer Categories
  • Small Cell Lung Cancers (SCLCs):
    • 15-20% of cases.
    • Highly malignant, often inoperable at presentation, poor prognosis.
  • Non-Small Cell Lung Cancers (NSCLCs):
    • 80-85% of cases.
    • Include subtypes like squamous cell carcinoma, adenocarcinoma, large cell carcinoma, carcinoid tumors, and bronchoalveolar cell tumors.

Aetiology

Causes and Risk Factors for Lung Cancer

• Primary Cause: Exposure to carcinogens is the main cause.
• Leading Cause: Tobacco smoke, especially from cigarette smoking.
• Other Risk Factors:
  • Secondhand Smoke Exposure.
  • Occupational Exposure to Carcinogens (asbestos, radon, arsenic, industrial chemicals).
  • Air Pollution.
  • Genetic Predisposition.
  • Family History.
  • Genetic Mutations (e.g., EGFR) – particularly in non-smokers.
  • Previous radiation therapy

Risk Factors

Primary Risk Factors for Lung Cancer

• Leading Risk Factor: Tobacco Smoking.
• Other Risk Factors:
  • Secondhand Smoke Exposure.
  • Occupational Exposure to Carcinogens (asbestos, radon, arsenic, industrial chemicals).
  • Air Pollution.
  • Family History.
  • Personal History of Lung Disease (e.g., COPD).
  • Genetic Mutations (e.g., EGFR mutations).
  • Radiation therapy

Lung Cancer Risk Factors Breakdown

• Smoking: Increases risk by a factor of 10.
• Other Risk Factors: Asbestos (5x risk increase), arsenic, radon, nickel, chromate, aromatic hydrocarbon, cryptogenic fibrosing alveolitis.
• Not Related: Coal Dust.
• Synergistic Effect: Smoking and asbestos exposure result in a 50 times increased risk.

Pathophysiology

Lung Cancer Pathophysiology

• Development: Genetic mutations disrupt normal growth in lung cells.
• Carcinogens: Tobacco smoke carcinogens damage lung cell DNA.
• Genetic Abnormalities: Accumulated genetic abnormalities promote uncontrolled cell growth.
• Tumor Formation: Uncontrolled growth leads to tumor formation.
• Variation: Pathophysiology varies by lung cancer type and subtype.
• Mechanisms: Common mechanisms include oncogene activation, tumor suppressor gene inactivation, angiogenesis, immune system evasion, and metastasis.

Bronchial Cancer Pathophysiology

• Development: DNA mutations cause uncontrollable division of lung cells.
• Tumor Formation: Mutations lead to lung tissue tumor formation.
• Invasion: Tumor can invade nearby tissues.
• Metastasis: May spread to lymph nodes, liver, bones, or brain.
• Variation: Pathophysiology varies by lung cancer type and stage.

Differential Diagnosis

Differential Diagnosis of Lung Cancer:

• Coin Lesion Causes:
  • Secondary malignancy.
  • Arteriovenous malformation.
  • Pulmonary hamartoma (rare, benign tumor with calcification on CT).
  • Bronchial adenoma (slow-growing, 90% carcinoid tumors, 10% cylindromas).
  • Abscesses.
  • Granuloma (e.g., tuberculosis).
  • Encysted effusion (fluid, blood, pus).
  • Cyst.
  • Foreign body.
  • Skin tumor (e.g., seborrheic wart).

Differential Diagnosis for Bronchial Cancer:

• Pneumonia.
• Bronchitis.
• Tuberculosis.
• Other lung tumors or masses.

Epidemiology

Epidemiology of Lung Cancer in the UK

• Prevalence
  • Lung cancer ranks as the UK’s third most common cancer, comprising 13% of new cancer cases (2016-2018).
• Age and Incidence
  • Highest incidence observed in those aged 85 to 89 (2016-2018).
  • Over 44% of new cases occur in individuals aged 75 and older (2016-2018).
• Trends
  • Lung cancer incidence rates have decreased by about 9% since the early 1990s in the UK.
  • In females, rates increased by approximately 32%, while in males, they decreased by about 34% (2016-2018).
• Projections
  • Anticipated 7% decrease in lung cancer incidence rates in the UK from 2014 to 2035, reaching 88 cases per 100,000 people by 2035.
• Specific Location
  • Most common site for lung cancers in the UK: upper lobe of the bronchus or lung (2016-2018).
• Socioeconomic Impact
  • Lung cancer incidence rates significantly higher in the most deprived quintiles compared to the least deprived quintiles (2013-2017).
• Ethnicity
  • Lower incidence rates in Asian, Black, and mixed/multiple ethnicity groups compared to the White ethnic group in England (2013-2017).

Statistics and Preventable Factors for Lung Cancer in the UK

• Lifetime Risk
  • 1 in 13 males and 1 in 15 females in the UK will be diagnosed with lung cancer during their lifetime.
• Preventable Cases
  • 79% of lung cancer cases in the UK are preventable.
• Smoking Impact
  • Smoking accounts for 72% of lung cancer cases in the UK.
• Other Factors
  • 5% attributed to ionising radiation.
  • 13% associated with workplace exposures.
  • 8% linked to air pollution.

Lung cancer is a significant health concern in the UK, particularly affecting older individuals and strongly associated with smoking. Reducing smoking rates and early detection efforts are essential to mitigate its impact.

Clinical Presentation

Lung Cancer Presentation

Symptoms vary based on type, stage, and location of tumor:

• Common symptoms:
  • Persistent cough
  • Coughing up blood (hemoptysis)
  • Shortness of breath
  • Chest pain
  • Hoarseness
  • Weight loss
  • Fatigue
  • Recurrent respiratory infections
  • Wheezing

• Other symptoms and manifestations:
  • Bone pain
  • Neurological symptoms
  • Jaundice
  • Fever
  • Finger clubbing
  • Superior vena cava obstruction
  • Dysphagia
  • Headache
  • Nausea and vomiting
  • Recurrent or slowly resolving pneumonia
  • Anorexia
  • Hypertrophic pulmonary osteoarthropathy
  • Supraclavicular or axillary lymphadenopathy

• Paraneoplastic phenomena:
  • Hypercalcemia
  • Cushing syndrome
  • SIADH secretion
  • Neurologic syndromes (e.g., Lambert-Eaton myasthenic syndrome, cerebellar ataxia, autonomic neuropathy)

Diagnosis of Lung Cancer

• Most patients diagnosed at late stages.
• Manifestations due to:
  • Intrathoracic effects (cough, haemoptysis, chest pain, dyspnoea, hoarseness, pleural disease, Pancoast syndrome)
  • Extrathoracic metastasis (liver, bone, brain, adrenal glands)
  • Paraneoplastic phenomena (hypercalcemia, Cushing syndrome, SIADH, neurologic syndromes)
• Key risk factor: Cigarette smoking (90% of cases).

Bronchial Cancer Presentation

• Symptoms and signs may vary, including:
  • Persistent cough
  • Hemoptysis
  • Shortness of breath
  • Chest pain
  • Hoarseness
  • Weight loss
  • Fatigue
  • Recurrent respiratory infections
  • Wheezing

• Advanced stages may lead to additional symptoms:
  • Bone pain
  • Neurological symptoms
  • Jaundice

Note: Lung cancer can be asymptomatic in early stages, leading to delayed diagnosis.

Investigations

Investigations for Lung Cancer:

• Laboratory Investigations:
  • Full blood count
  • Urea and Electrolytes
  • Calcium
  • Alkaline phosphatase
  • ALT, AST, and bilirubin
  • Creatinine
• Radiological Investigations:
  • CT scanning of the chest, lower neck, and upper abdomen with IV contrast
    • To assess the extent of the primary tumor and potential spread
• Biopsy:
  • Diagnosis of NSCLC is based on cytologic or histopathologic evaluation of specimens
  • Tissue sampling methods include bronchoscopy, biopsy, or surgical procedures
• Staging (NSCLC):
  • Tumour, Node, Metastasis (TNM) staging system used
  • Multidisciplinary team meeting for staging and care planning
• Staging (SCLC):
  • Staged as limited or extensive stage
    • Limited stage confined to ipsilateral hemithorax
    • Extensive stage includes metastatic disease and malignant effusions
• Additional Investigations:
  • Positron emission tomography (PET) scan
  • Magnetic resonance imaging (MRI)
  • Staging procedures to assess disease extent and metastases

Investigations for Bronchial Cancer:

• Imaging Tests:
  • Chest X-ray
  • CT scan
  • PET scan
• Biopsy and Pathological Examination:
  • Tissue samples obtained through:
    • Bronchoscopy
    • Needle biopsy
    • Surgical procedures
• Other Tests May Include:
  • Blood tests
  • Pulmonary function tests
  • Genetic testing

Referral Criteria for Lung Cancer (UK):

• Refer using a suspected cancer pathway referral (within two weeks) if the patient:
  • Has chest X-ray findings suggesting lung cancer
  • Is aged 40 and over with unexplained hemoptysis
• Consider urgent chest X-ray (within two weeks) for individuals aged 40 and over with:
  • Two or more unexplained symptoms (e.g., cough, fatigue, shortness of breath, chest pain, weight loss, appetite loss)
  • A history of smoking and one or more unexplained symptoms
• Consider urgent chest X-ray (within two weeks) for individuals aged 40 and over with certain clinical features (e.g., persistent chest infection, finger clubbing, lymphadenopathy, chest signs).
• Further staging and diagnostic procedures may follow based on initial findings and clinical evaluation.

Note: Early diagnosis and staging are crucial for effective lung cancer management.

Management

Management of Lung Cancer

• Factors Affecting Management:
  • Type and stage of the disease
  • Patient’s overall health
  • Individual preferences
• Treatment Options:
  • Surgery: Removes tumor and affected tissue
  • Radiation therapy: Uses high-energy beams to kill cancer cells
  • Chemotherapy: Uses anti-cancer drugs to destroy cancer cells throughout the body
  • Targeted therapy: Targets specific cancer cells
  • Immunotherapy: Enhances the immune system’s response against cancer cells
• Palliative Care:
  • Crucial for managing symptoms and improving quality of life
  • Provides supportive care for advanced-stage disease
• Multidisciplinary Approach:
  • Teams of specialists collaborate to develop personalized treatment plans
• Clinical Trials:
  • Available for eligible patients
  • Provide access to new treatment options and advance understanding

Management (Prescribing) – NSCLC

• Late-Stage Disease (Stage III or IV):
  • Goal: Reverse, delay, or prevent symptoms due to local or metastatic tumor
  • Treatment based on histological subtype, molecular genotype, and PD-L1 status
  • Agents: Chemotherapeutic agents, Tyrosine Kinase Inhibitors (TKI)

Management (Non-Prescribing) – NSCLC

• Early-Stage (I-II) NSCLC:
  • Surgery with curative intent
  • Lobectomy preferred over wedge resection
  • Lymph node sampling recommended
• SCLC:
  • Surgery is rarely performed

Lung Cancer Referral (2015 NICE Guidelines)

• Refer for lung cancer if:
  • Chest x-ray suggests lung cancer
  • Age 40+ with unexplained haemoptysis
• Offer urgent chest x-ray (within 2 weeks) for age 40+ with 2+ unexplained symptoms or smoking history:
  • Cough, fatigue, shortness of breath, chest pain, weight loss, appetite loss
• Consider urgent chest x-ray for age 40+ with specific symptoms or signs

Staging and Management of Non-Small-Cell Lung Cancer

• Staging (TNM7 Classification):
  • Tumour (T), Regional lymph nodes (N), Metastatic involvement (M)
• Stage Groupings (IA, IB, IIA, IIB, IIIA, IIIB, IV)
• Management:
  • Smoking cessation for eligible patients
  • Global risk assessment tool (e.g., Thoracoscore)
  • Lung function tests
  • Cardiovascular risk assessment
• Surgery:
  • Lobectomy (open or thoracoscopic)
  • Lymph node sampling
  • Chest wall involvement considerations
• Surgery or Radiotherapy for Non-Lobectomy Candidates
• Combination Treatment for NSCLC:
  • Chemoradiotherapy for stage II or III NSCLC
  • Postoperative chemotherapy
  • Treatment for Pancoast tumors
  • Multimodality therapy for operable stage IIIA-N2 NSCLC
• Systemic Anti-Cancer Therapy (SACT):
  • Various options including targeted therapies and immunotherapies

Management of Small-Cell Lung Cancer

• Staging:
  • Serum tests and CT scans
  • Limited-stage vs. extensive-stage disease
• First-Line Treatment for Limited-Stage Disease SCLC:
  • Chemotherapy, radiotherapy, prophylactic cranial irradiation
• First-Line Treatment for Extensive-Stage Disease SCLC:
  • Platinum-based chemotherapy, thoracic radiotherapy, prophylactic cranial irradiation
• Second-Line Treatment for Relapsed SCLC:
  • Limited evidence for second-line chemotherapy
• Radiotherapy for Palliation:
  • For local symptom relief

Additional Treatments and Therapies

• Specific drugs and therapies recommended for various lung cancer types and stages

Supportive and Palliative Care

• Management of various symptoms and complications in lung cancer patients

Smoking Cessation

• Emphasized as a critical component of lung cancer management for smokers to improve outcomes.

Prognosis

Prognosis of Lung Cancer

• Influential Factors:
  • Disease stage at diagnosis.
  • Cancer type and subtype.
  • Patient’s overall health.
  • Response to treatment.

• General Outlook:
  • Poor prognosis, especially in advanced stages.
  • Early detection and treatment improve outcomes.
  • Five-year survival rates:
    • Around 60% for localized disease.
    • Less than 10% for metastatic cases.
  • Individual prognosis varies.
  • Advancements in targeted therapy and immunotherapy offer promise.
  • Regular follow-up care and support are vital for monitoring and symptom management.

Prognosis in England (2013-2017)

• One-year survival: 40.6%.
• Five-year survival: 16.2%.
• Ten-year survival prediction: 9.5%.
• Higher survival rates for females and those under 40.
• Limited improvement in UK lung cancer survival over 40 years.
• Early-stage diagnosis significantly improves survival.

Lung Cancer Prevention

• Over 80% of lung cancer deaths linked to tobacco use.
• Primary prevention reduces cancer burden.
• Reducing risk factors like radiation, workplace exposure, air pollution is crucial.
• No UK screening program; US uses LDCT screening for high-risk patients.
• US recommends annual LDCT screening for 55-80-year-olds with a smoking history.

Prognosis of Bronchial Cancer

• Depends on diagnosis stage, cancer type, patient health, and treatment response.
• Small cell lung cancer prognosis generally worse than non-small cell lung cancer.
• Early detection and treatment lead to better outcomes.
• Advanced or metastatic lung cancer prognosis less favorable.

Complications

Lung Cancer Complications

• Metastasis: Brain, liver, bones, adrenal glands.
• Respiratory Complications: Pneumonia, atelectasis, pleural effusion.
• Tumor Location: Airway obstruction, pneumonia, collapsed lung, pleural effusion, superior vena cava syndrome.
• Cachexia: Severe weight loss, muscle wasting.
• Paraneoplastic Syndromes: Symptoms from cancer-produced substances.
• Treatment Side Effects: Chemotherapy-related nausea, hair loss, immunosuppression.
• Palliative Care: Managing complications for better quality of life.

Complications

• Local Complications:
  • Nerve-related issues.
  • Cardiovascular problems.
  • Rib erosion.
• Metastatic Complications:
  • Brain: Confusion, neurological deficits.
  • Bone: Pain, hypercalcemia.
  • Liver: Hepatomegaly.
  • Adrenal: Addison’s disease.
• Non-Metastatic Complications:
  • Endocrine: Hormone-related syndromes.
  • Neuromuscular: Nerve-related conditions.
  • Skeletal: Joint and bone issues.
  • Renal: Kidney problems.
  • Collagen/Vascular: Immune and vascular conditions.
  • Cutaneous: Skin-related syndromes.
  • Haematological: Blood-related complications.

References

• 1. https://www.uptodate.com/contents/overview-of-the-initial-evaluation-diagnosis-and-staging-of-patients-with-suspected-lung-cancer
  2. https://www.uptodate.com/contents/overview-of-the-risk-factors-pathology-and-clinical-manifestations-of-lung-cancer
  3. https://www.uptodate.com/contents/overview-of-the-initial-treatment-and-prognosis-of-lung-cancer
  4. https://bestpractice.bmj.com/topics/en-gb/1081
  5. https://bestpractice.bmj.com/topics/en-gb/1082
  6. https://www.nice.org.uk/guidance/ng122/resources/lung-cancer-diagnosis-and-management-pdf-66141655525573