Lung Cancer

Lung cancer is broadly divided into non smallcell lung cancer (NSCLC, roughly 85% of cases) and small cell lung cancer (SCLC, roughly 15% of cases).

NSCLC is further subdivided into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. SCLC is biologically distinct, characterized by rapid growth, early metastasis, and strong association with smoking.

Smoking remains the dominant risk factor across both major types. Adenocarcinoma occurs more frequently in never smokers than the other subtypes, and is increasingly recognized as having distinct, targetable molecular drivers in this population.

Other risk factors include occupational exposures (asbestos, radon), and a family history of lung cancer.

Early disease is frequently asymptomatic, contributing to the typically advanced stage at diagnosis in many patients. Common presenting symptoms include a persistent or changing cough, hemoptysis, dyspnea, chest pain, and unexplained weight loss.

Locally invasive disease can cause specific syndromes depending on the site of involvement.

• Horner syndrome (ptosis, miosis, and anhidrosis) from an apical Pancoast tumor invading the sympathetic chain.
• Superior vena cava obstruction (facial and upper limb swelling, distended neck and chest wall veins, sometimes with headache and visual disturbance) from mediastinal involvement.
• Hoarseness from recurrent laryngeal nerve palsy, and dysphagia from esophageal compression.

Paraneoplastic syndromes are a recognized feature, particularly with small cell lung cancer. They include the syndrome of inappropriate antidiuretic hormone secretion (causing hyponatremia) and ectopic ACTH secretion (causing Cushing syndrome).

Lambert-Eaton myasthenic syndrome causes proximal muscle weakness that improves with repeated use, in contrast to the fatigability of myasthenia gravis. Hypertrophic pulmonary osteoarthropathy (clubbing with painful periosteal new bone formation) is more associated with non small cell tumors.

Metastatic disease can present with symptoms referable to the site of spread, including bone pain, neurological symptoms from brain metastases, and hepatic dysfunction from liver metastases.

CXR is often the first investigation, though CT chest with contrast provides substantially more detail and is required for adequate staging assessment.

Tissue diagnosis is essential. It is most commonly obtained via bronchoscopy with biopsy or endobronchial ultrasound guided sampling for central lesions, or CT guided percutaneous biopsy for peripheral lesions.

Molecular and biomarker testing is now a routine and essential part of the diagnostic workup for advanced non small cell lung cancer, particularly adenocarcinoma, given the substantial impact on treatment selection.

EGFR mutation, ALK rearrangement, ROS1 rearrangement, and PD-L1 expression are among the key markers assessed. Specific targeted therapies and immunotherapy eligibility depend directly on these results.

Staging combines CT chest and abdomen, PET CT (to assess for nodal and distant metastatic disease with greater sensitivity than CT alone), and MRI brain (given the relatively high incidence of occult brain metastases, particularly with adenocarcinoma and small cell lung cancer).

Pulmonary function testing is performed where surgical resection is being considered, to assess whether the patient has sufficient respiratory reserve to tolerate lung resection.

Differentials for a pulmonary nodule or mass include benign granuloma (particularly in tuberculosis endemic settings), pulmonary hamartoma, other primary lung malignancy, and metastatic disease from another primary site.

Early stage, resectable non small cell lung cancer is treated with surgical resection (lobectomy generally preferred over more limited resection where the patient's respiratory reserve allows).

Adjuvant chemotherapy is added, and increasingly adjuvant targeted therapy or immunotherapy where a relevant biomarker is present, to reduce recurrence risk in higher stage disease.

Locally advanced, unresectable non small cell lung cancer is typically treated with concurrent chemoradiotherapy. Consolidation immunotherapy (durvalumab) follows in patients without disease progression, an approach that has substantially improved outcomes in this group.

Metastatic non small cell lung cancer treatment is now heavily guided by molecular testing results.

Tumors with a targetable driver mutation, such as EGFR or ALK, are treated first-line with the corresponding targeted oral therapy (for example osimertinib for EGFR mutated disease). This is generally better tolerated and more effective than chemotherapy in this specific population.

Tumors without a targetable driver are treated with immunotherapy, either alone or combined with chemotherapy, with the specific approach guided by PD-L1 expression level.

Small cell lung cancer is staged more simply as limited stage (confined to a radiation field that can be safely treated) or extensive stage (beyond this), reflecting its typically rapid, disseminated growth pattern.

Limited stage disease is treated with concurrent chemoradiotherapy, followed by prophylactic cranial irradiation in patients responding well, given the high rate of subsequent brain metastasis.

Extensive stage disease is treated with chemotherapy combined with immunotherapy, given as first-line standard of care based on demonstrated survival benefit.

Palliative care input is valuable at any stage where symptom burden is significant. It should be introduced early alongside active oncological treatment rather than reserved only for the end of life, given evidence that early integration improves quality of life and, in some studies, survival itself.

Referral: respiratory medicine and oncology multidisciplinary team for all confirmed or strongly suspected cases; urgent two week wait or equivalent fast track pathway referral for any patient with hemoptysis or other red flag symptoms in an appropriate risk group.