Medicine – Lung Cancer

Lung cancer is one of the most important causes of cancer-related morbidity and mortality. Most cases are strongly associated with tobacco smoking, although occupational exposures, environmental carcinogens, and pre-existing lung disease also contribute. Lung cancers are broadly divided into non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) because their biological behaviour, staging, treatment, and prognosis differ substantially.

1. Causes and Risk Factors

Cigarette Smoking

Cigarette smoking is the major preventable cause of lung cancer and accounts for the large majority of cases. Risk increases with the duration and intensity of smoking exposure and decreases progressively after smoking cessation.

Older sources sometimes quote smoking as causing approximately 95% of cases, but modern estimates are generally lower and vary by population, sex, and tumour subtype.

Occupational Exposure

Several occupational carcinogens increase the risk of lung cancer. An important example is asbestos exposure, particularly in construction, shipbuilding, insulation work, and other historically exposed industries.

Smoking and asbestos exposure have a synergistic effect, producing a substantially greater risk of lung cancer when both are present.

Environmental Exposure

Environmental factors include passive tobacco smoke and air pollution. Other important environmental or occupational carcinogens include radon, silica, arsenic, chromium, nickel, and diesel exhaust.

Pulmonary Fibrosis

Lung cancer occurs more frequently in patients with certain forms of pulmonary fibrosis, including idiopathic pulmonary fibrosis.

Chronic epithelial injury, inflammation, and abnormal tissue repair are thought to contribute to malignant transformation.

2. Histological Types

Lung cancers are divided into two major categories:

Non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC).

The percentages in older notes have changed considerably over time. In particular, adenocarcinoma is now the most common histological subtype of lung cancer in many populations, rather than squamous cell carcinoma.

Non-Small-Cell Lung Cancer

NSCLC accounts for approximately 85% of lung cancers and includes adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma.

Adenocarcinoma

Adenocarcinoma is now the most common form of lung cancer.

It frequently develops peripherally within the lung and is also the most common major histological subtype encountered in people who have never smoked, although smoking remains an important risk factor.

Modern classification incorporates several adenocarcinoma growth patterns; the older term bronchoalveolar carcinoma has largely been replaced by more specific pathological categories such as adenocarcinoma in situ and lepidic-predominant adenocarcinoma.

Squamous Cell Carcinoma

Squamous cell carcinoma is strongly associated with cigarette smoking and classically arises in the central or proximal airways.

These tumours may undergo central necrosis and cavitation. Squamous carcinoma is also particularly associated with secretion of parathyroid hormone-related peptide (PTHrP), producing paraneoplastic hypercalcaemia.

Large-Cell Carcinoma

Large-cell carcinoma is a poorly differentiated form of NSCLC diagnosed when the tumour lacks the characteristic features of adenocarcinoma, squamous carcinoma, or another defined subtype.

It can occur in either central or peripheral regions of the lung and tends to behave aggressively.

3. Small-Cell Lung Cancer

Small-cell lung cancer accounts for roughly 10–15% of lung cancers and has an exceptionally strong association with cigarette smoking.

It commonly arises centrally, close to the major bronchi, and is characterised by rapid growth, early lymphatic involvement, and early distant metastasis.

Because SCLC is usually already systemic by diagnosis, surgery has only a very limited role. Treatment generally relies on systemic therapy with or without radiotherapy, depending on disease extent and patient factors.

Respiratory Symptoms

4. Cough

A new persistent cough is one of the commonest presentations of lung cancer.

A change in the character or severity of a pre-existing chronic smoker’s cough can also be significant and warrants investigation.

5. Breathlessness

Dyspnoea may result from bronchial obstruction, collapse of part of the lung, pleural effusion, pneumonia distal to an obstructing tumour, lymphatic spread, or extensive tumour burden.

6. Haemoptysis

Haemoptysis is an important warning symptom.

The amount of blood can range from minor streaking of sputum to substantial bleeding. Persistent or unexplained haemoptysis requires investigation, particularly in an older patient or someone with significant smoking exposure.

7. Chest Pain

Chest pain can result from involvement of the pleura, chest wall, ribs, or mediastinal structures.

Persistent or severe pain may indicate locally advanced disease.

Local Complications

8. Pleural Effusion

Lung cancer can produce a pleural effusion through direct pleural involvement, lymphatic obstruction, or other mechanisms.

A malignant pleural effusion generally indicates advanced disease and has major implications for staging and treatment.

9. Superior Vena Cava Obstruction

A centrally located tumour or enlarged mediastinal lymph nodes may compress the superior vena cava (SVC).

Patients may develop facial and neck swelling, distended neck and chest-wall veins, upper-limb swelling, headache, and breathlessness.

SVC obstruction is particularly associated with centrally located thoracic malignancies, including small-cell lung cancer.

10. Recurrent Laryngeal Nerve Palsy

Involvement of the recurrent laryngeal nerve, particularly the left recurrent laryngeal nerve as it passes through the thorax, can produce vocal cord paralysis.

The characteristic clinical presentation is persistent hoarseness.

11. Phrenic Nerve Palsy

Tumour invasion or compression of the phrenic nerve can paralyse the ipsilateral diaphragm.

A chest radiograph may therefore demonstrate an elevated hemidiaphragm.

12. Pericardial Involvement

Direct or metastatic involvement of the pericardium can cause pericarditis or pericardial effusion.

Large malignant pericardial effusions can impair cardiac filling and potentially produce cardiac tamponade.

13. Dysphagia

Dysphagia may develop when a mediastinal tumour or enlarged lymph nodes compress or invade the oesophagus.

This generally suggests significant local or mediastinal disease.

Paraneoplastic and Non-Metastatic Manifestations

Lung cancers can produce systemic manifestations without direct metastatic spread. These paraneoplastic syndromes are particularly characteristic of certain histological subtypes.

14. SIADH

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is classically associated with small-cell lung cancer.

Excess ADH causes water retention and dilutional hyponatraemia, which may produce confusion, lethargy, seizures, or other neurological manifestations when severe.

15. Ectopic ACTH Production

Small-cell lung cancer can also produce ectopic adrenocorticotropic hormone (ACTH).

This results in Cushing syndrome, potentially causing hypertension, hyperglycaemia, hypokalaemia, muscle weakness, and metabolic alkalosis.

16. Hypercalcaemia

Squamous cell carcinoma is classically associated with hypercalcaemia through secretion of parathyroid hormone-related peptide (PTHrP).

Hypercalcaemia may also result from bone metastases, although this is a metastatic rather than a true paraneoplastic mechanism.

Patients may develop thirst, polyuria, constipation, confusion, weakness, and cardiac rhythm abnormalities.

17. Gynaecomastia

Rare lung cancers can secrete hormones such as human chorionic gonadotropin (hCG), potentially producing gynaecomastia.

Older texts particularly associate this with large-cell carcinoma, although it is an uncommon manifestation.

18. Clubbing

Finger clubbing is particularly associated with non-small-cell lung cancer.

It may occur alone or as part of hypertrophic pulmonary osteoarthropathy.

19. Lambert–Eaton Myasthenic Syndrome

Lambert–Eaton myasthenic syndrome (LEMS) is a characteristic paraneoplastic neurological syndrome associated particularly with small-cell lung cancer.

Autoantibodies interfere with presynaptic voltage-gated calcium channels at the neuromuscular junction, producing proximal muscle weakness, reduced reflexes, and autonomic symptoms.

20. Hypertrophic Pulmonary Osteoarthropathy

Hypertrophic pulmonary osteoarthropathy (HPOA) is associated particularly with lung cancer, most often NSCLC.

It consists of digital clubbing, periostosis of long bones, and painful arthralgia or arthritis.

Patients may complain of painful swollen wrists, ankles, knees, or long bones.

Treatment

21. Surgery

Surgical resection can potentially cure selected patients with early-stage NSCLC.

Procedures may include segmentectomy, lobectomy, or occasionally pneumonectomy. Whether surgery is appropriate depends on TNM stage, tumour location, lymph-node involvement, cardiopulmonary reserve, and overall fitness.

Modern outcomes are substantially better than the historical figures in the supplied notes, particularly for cancers detected at an early stage.

22. Radiotherapy

Radiotherapy may be used with curative intent in selected localised disease when surgery is unsuitable, including stereotactic radiotherapy for some early-stage tumours.

It may also be combined with systemic therapy in locally advanced disease or used palliatively to relieve symptoms such as pain, haemoptysis, or obstruction.

23. Systemic Treatment

Chemotherapy remains important in both NSCLC and SCLC.

Modern NSCLC treatment has expanded considerably beyond conventional chemotherapy. Depending on tumour histology and molecular testing, patients may receive targeted therapy or immunotherapy.

Testing for actionable molecular abnormalities and immune biomarkers is therefore an important part of contemporary management of advanced NSCLC.

Suitability for Surgery

24. Small-Cell Histology

Small-cell lung cancer is generally not treated surgically because of its strong tendency to metastasise early.

Surgery may occasionally be considered in exceptionally early, carefully staged disease, but this represents a small minority of patients.

25. Advanced or Metastatic Disease

Distant metastatic disease generally excludes curative surgical resection of the primary lung tumour.

Extensive mediastinal nodal disease and invasion of unresectable vital structures may also make surgery inappropriate.

26. Malignant Pleural Effusion

A confirmed malignant pleural effusion represents metastatic pleural involvement and generally excludes conventional curative lung resection.

A bloody effusion alone, however, does not automatically prove malignant involvement and requires appropriate investigation.

27. Poor Performance Status and Pulmonary Reserve

Patients must have sufficient general fitness and cardiopulmonary reserve to tolerate lung resection.

Older rules such as an absolute FEV₁ below 1.5 L are no longer used alone to determine operability. Modern assessment uses predicted postoperative lung function, exercise capacity, comorbidities, and the planned extent of resection.

28. Tumour Location

Very central tumours close to the carina or involving major mediastinal structures can make surgical resection technically difficult.

However, the older rule that a tumour less than 1.5 cm from the carina is automatically inoperable is outdated. Modern decisions are based on formal TNM staging, resectability, and multidisciplinary assessment.

Prognosis

29. Small-Cell Lung Cancer

Small-cell lung cancer generally has a poorer prognosis because of its rapid growth and tendency to metastasise early.

Limited-stage disease has a better prognosis than extensive-stage disease, but recurrence after initial treatment remains common.

30. Non-Small-Cell Lung Cancer

The prognosis of NSCLC varies enormously according to stage.

Early localised cancers treated successfully with surgery or stereotactic radiotherapy can have relatively favourable long-term survival, whereas metastatic disease has a much poorer prognosis.

The historical figure of approximately 10% overall five-year survival is therefore outdated. Modern survival has improved because of earlier detection, better staging, improved surgery and radiotherapy, targeted therapies, and immunotherapy.

Key Clinical Pattern

Think of lung cancer in a patient—particularly one with significant smoking exposure—who develops a new or changing cough, haemoptysis, unexplained breathlessness, persistent chest pain, weight loss, or recurrent chest infection.

Remember the classic paraneoplastic associations: small-cell carcinoma → SIADH, ectopic ACTH and Lambert–Eaton syndrome; squamous cell carcinoma → PTHrP-mediated hypercalcaemia; NSCLC → clubbing and hypertrophic pulmonary osteoarthropathy.

The major distinction is between NSCLC, where surgery may be curative in appropriately selected early-stage disease, and SCLC, which usually requires systemic therapy because of its tendency for rapid growth and early metastatic spread.