Lucan · Conditions

Lung cancer

Australian guidance: Cancer Council Australia Lung Cancer Guidelines

1. Definition and epidemiology

Lung cancer is a malignant tumour arising from the respiratory epithelium of the bronchi, bronchioles, or alveoli, classified broadly into non-small cell lung cancer (NSCLC, approximately 85% of cases) and small cell lung cancer (SCLC, approximately 15%). In Australia, lung cancer is the leading cause of cancer death in both men and women, with over 13,000 new diagnoses and more than 9,000 deaths annually; the five-year survival rate remains below 20%. Indigenous Australians are approximately twice as likely to be diagnosed with and to die from lung cancer compared with non-Indigenous Australians, reflecting higher rates of tobacco smoking and reduced access to timely specialist care.

2. Pathophysiology

Tobacco carcinogens, particularly polycyclic aromatic hydrocarbons and nitrosamines, produce point mutations and chromosomal deletions in bronchial epithelial cells. Key early molecular events include inactivation of tumour suppressor genes TP53 (mutated in approximately 50% of NSCLC) and RB1, and activating mutations in KRAS (most common in adenocarcinoma) or EGFR (more prevalent in never-smokers, East Asian populations, and adenocarcinoma). Squamous cell carcinoma arises centrally from metaplastic bronchial epithelium and is closely linked to smoking; adenocarcinoma arises peripherally from type II pneumocytes and Clara cells and is the predominant subtype in never-smokers. SCLC originates from neuroendocrine Kulchitsky cells, expresses synaptophysin and chromogranin A, and is characterised by rapid doubling time, early haematogenous spread, and common paraneoplastic syndromes due to ectopic hormone production (Robbins Ch 15). EGFR, ALK, ROS1, BRAF V600E, MET exon 14 skipping, RET, and KRAS G12C represent clinically actionable driver oncogenes in NSCLC for which targeted agents are available.

3. Clinical presentation and diagnostic criteria

Most patients present with locally advanced or metastatic disease. Symptoms lasting more than three weeks that require investigation include a new or changed cough, haemoptysis, hoarseness, dyspnoea, chest or shoulder pain, unexplained weight loss, fatigue, recurrent chest infection, and finger clubbing. On examination, findings may include cervical or supraclavicular lymphadenopathy, signs of superior vena cava obstruction (facial oedema, venous distension), pleural effusion, and features of distant metastases affecting the brain, bone, liver, or skin. Paraneoplastic syndromes occur in SCLC and include syndrome of inappropriate antidiuretic hormone secretion (SIADH), ectopic ACTH production causing Cushing syndrome, Lambert-Eaton myasthenic syndrome, and hypercalcaemia from parathyroid hormone-related peptide in squamous cell carcinoma. Pancoast tumours arising at the lung apex cause shoulder and arm pain, Horner syndrome (ptosis, miosis, anhidrosis), and ipsilateral hand wasting from brachial plexus invasion (Robbins Ch 15).

4. Investigations and AU-specific cutoffs

Initial GP investigation is an urgent chest X-ray for unexplained persistent symptoms lasting more than three weeks; if the X-ray is normal and symptoms persist, repeat at six weeks. Haemoptysis, signs of superior vena cava obstruction, or strong clinical suspicion of lung cancer requires an urgent contrast CT of the chest and concurrent referral to a lung cancer multidisciplinary team (MDT) within two weeks. Staging requires CT of the chest and upper abdomen in all patients, with brain MRI or CT in selected cases; PET-CT is performed when curative treatment is being considered to detect occult nodal or distant metastatic disease. Tissue diagnosis is obtained by bronchoscopy including endobronchial ultrasound guided biopsy (EBUS), CT or ultrasound guided percutaneous biopsy, excisional biopsy, or biopsy of a metastasis. For NSCLC, molecular biomarker testing including EGFR mutation, ALK rearrangement, ROS1, BRAF, MET, RET, KRAS, and PD-L1 expression is required to guide systemic therapy selection. Sputum cytology is reserved for rare cases. The National Lung Cancer Screening Program (NLCSP), introduced in Australia in 2023, offers two-yearly low-dose CT to people aged 50 to 70 years with a smoking history of at least 30 pack-years who currently smoke or have quit within the past ten years; findings are triaged using a risk category protocol (categories 1 to 6) with categories 5 and 6 triggering urgent specialist referral.

5. Management

All newly diagnosed patients should be discussed at a lung cancer MDT before treatment begins; the optimal timeframe from first specialist appointment to completion of diagnostic tests is two weeks, and treatment should begin within six weeks of the initial specialist referral. Treatment intent is established as curative, anti-cancer therapy to extend life without cure, or symptom palliation. For early-stage operable NSCLC (stage I and II), surgical resection is the standard of care; minimally invasive lobectomy is at least as effective as open lobectomy for long-term survival with lower postoperative complication rates (Grade B recommendation). Systematic mediastinal lymph node sampling is recommended in stage I patients to rule out occult nodal disease. Postoperative adjuvant radiotherapy is not recommended after complete resection of stage I NSCLC (Grade A). Platinum-based adjuvant chemotherapy is recommended for all patients with stage IB NSCLC and is standard for stages II to IIIA resected disease. For stage I inoperable NSCLC in patients with good performance status, stereotactic ablative body radiotherapy (SABR) for peripherally situated tumours 5 cm or less is a reasonable alternative; high-dose conventionally fractionated radiotherapy to 60 Gy in 30 fractions over six weeks is an appropriate option for larger or more central tumours. Locally advanced inoperable stage III NSCLC with good performance status is managed with concurrent platinum-based chemoradiotherapy followed by consolidation durvalumab for patients with PD-L1 expression at least 1%. Stage IV NSCLC management is guided by molecular biomarker status: EGFR-mutated NSCLC receives first-line osimertinib; ALK-rearranged NSCLC receives alectinib; PD-L1 greater than 50% without a driver mutation receives single-agent pembrolizumab; other stage IV NSCLC receives platinum doublet chemotherapy combined with immunotherapy. Limited-stage SCLC is treated with concurrent platinum-etoposide chemotherapy and thoracic radiotherapy; extensive-stage SCLC receives carboplatin plus etoposide with atezolizumab or durvalumab. Early palliative care referral is appropriate for all patients with lung cancer based on need rather than prognosis.

6. Pharmacology and AU PBS notes

First-line targeted therapy for EGFR-mutated NSCLC is osimertinib (Tagrisso, AstraZeneca), a third-generation EGFR tyrosine kinase inhibitor (TKI) subsidised on the PBS for EGFR exon 19 deletion or exon 21 L858R mutation. Alectinib (Alecensa, Roche) is PBS-subsidised as first-line therapy for ALK-rearranged metastatic NSCLC. Pembrolizumab (Keytruda, MSD) is PBS-subsidised for first-line treatment of NSCLC with PD-L1 tumour proportion score at least 50% and for PD-L1 at least 1% in combination with platinum chemotherapy. Durvalumab (Imfinzi, AstraZeneca) is PBS-subsidised as consolidation therapy after concurrent chemoradiation in unresected stage III NSCLC with PD-L1 at least 1%. Platinum doublet chemotherapy backbone for NSCLC uses carboplatin (AUC 5 to 6) or cisplatin (75 mg/m2) combined with paclitaxel, pemetrexed (non-squamous), or gemcitabine (squamous). Carboplatin-based regimens are as effective as cisplatin-based regimens for stage IV inoperable NSCLC with improved tolerability. For limited-stage SCLC, optimal concurrent chemotherapy with thoracic radiotherapy uses cisplatin plus etoposide. Smoking cessation pharmacotherapy including varenicline (Champix) is recommended for all patients who currently smoke and is available on the PBS; referral to the Quitline (13 78 48) is advised with an opt-out behavioural intervention approach.

7. Complications and monitoring

Local complications include superior vena cava obstruction requiring urgent intervention, post-obstructive pneumonia, haemoptysis, and malignant pleural effusion managed by talc pleurodesis or indwelling pleural catheter. Distant complications include brain metastases (managed by stereotactic radiosurgery or whole-brain radiotherapy), spinal cord compression (urgent corticosteroids and radiotherapy or surgical decompression), bone metastases with pathological fracture risk, and hypercalcaemia of malignancy. Treatment toxicities to monitor include platinum nephrotoxicity (cisplatin), myelosuppression, EGFR TKI rash and diarrhoea, immune checkpoint inhibitor pneumonitis, hepatitis, colitis, and endocrinopathy. Post-treatment surveillance following curative-intent surgery includes history, examination, and CT imaging at regular intervals (typically three-monthly for the first two years, then annually to five years), with prompt re-entry to specialist care on development of new symptoms. Advance care planning should be initiated early for all patients, particularly those with advanced disease, to guide future management if decision-making capacity is lost.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.