Ep 185 – Lung cancer

Lung cancer is the leading cause of cancer-related death worldwide and is classified into two main types: non-small cell lung cancer (NSCLC), which accounts for most cases and the more aggressive small cell lung cancer (SCLC). Early detection is crucial for improving outcomes, but symptoms often emerge late in the disease course. In episode 126, Dr Hannah Rosa looked at the challenges of diagnosis, reviewed guidelines and latest research and discussed when to continue investigations after a normal chest X-ray. In this episode, Dr Roger Henderson gives an overview of detecting lung cancer in primary care and looks at treatment – including newer options for some late-stage cancers.

Key take-home points

• Lung cancer is the UK’s biggest cause of cancer mortality, accounting for 21% of all cancer deaths and one in seven of all new cancer cases.
• Worldwide, lung cancer is the most commonly diagnosed cancer.
• Tobacco smoking is the biggest cause of lung cancer.
• NSCLC accounts for 80–85% of cases with this group, including squamous cell cancer, adenocarcinoma and large cell cancer.
• SCLC accounts for the remainder of all lung cancers.
• Both types behave very differently in their presentation, metastatic spread, prognosis and response to treatment.
• In general, NSCLCs usually grow more slowly, spread later and often have a better prognosis, whereas SCLCs are typically rapidly growing, highly malignant tumours that spread early and are often inoperable at presentation with a poor prognosis.
• Lung cancer symptoms may present late in the disease progression and include cough or shortness of breath, chest discomfort, haemoptysis and weight loss; most patients have advanced disease at the time of presentation.
• Patients with chronic obstructive pulmonary disease are at a four-fold increased risk of lung cancer.
• Metastasis from lung cancer to bone is frequently symptomatic.
• A full blood count, chemistry screen and liver function tests, including alkaline phosphatase, should be performed in all patients.
• Every patient suspected of having lung cancer should ideally have a positron emission tomography-computed tomography (PET-CT) scan before treatment, an endobronchial ultrasound-guided trans-bronchial needle aspiration to confirm the staging and histological differentiation of the malignancy and a contrast-enhanced CT scan of the chest, liver, adrenals and lower neck.
• Treatment depends on cancer cell type, anatomical stage and performance status.
• Smoking cessation is advised, but surgery should not be postponed until the patient has stopped smoking.
• In early-stage NSCLC, surgery is the standard treatment with lobectomy or pneumonectomy being the surgery of choice.
• Radiotherapy should be offered to all patients with stage I–III NSCLC who are not suitable for surgery.
• Chemotherapy should be offered to patients with stage III or IV NSCLC and good performance status, to improve survival, disease control and quality of life.
• NSCLC may now be categorised and treated according to different molecular subtypes, such as high or low programmed death-ligand 1 (PD-L1) expression, anaplastic lymphoma kinase (ALK)-positive disease, ROS proto-oncogene 1 (ROS1)-positive disease and epidermal growth factor receptor (EGFR)-positive types.
• The prognosis of patients with NSCLC oncogenic driver gene alterations can be improved dramatically with the advent of molecularly targeted drugs.
• The treatment for SCLC depends on the disease stage; it is sensitive to chemotherapy but has a high recurrence rate.
• In stage I limited-stage SCLC, treatment is lobectomy followed by adjuvant chemotherapy and radiation therapy.
• Extensive stage SCLC is treated with platinum-based chemotherapy.
• The most significant factor in NSCLC prognosis is the tumour, node, metastasis stage at presentation. With SCLC, the extent of disease and the stage at presentation is the most important prognostic factor.

Key references

1. Cancer Research UK. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-Zero.
2. NICE. 2024. https://www.nice.org.uk/guidance/ng122.
3. NICE. 2023. https://www.nice.org.uk/guidance/NG12/.
4. Park H-Y, et al. Thorax. 2020;75(6):506-509. doi: 10.1136/thoraxjnl-2019-213732.
5. Abdel-Rahman O. Clin Lung Cancer. 2020;21(5):415-420.e2. doi: 10.1016/j.cllc.2020.04.009.
6. Darby S, et al. BMJ. 2005;330(7485):223. doi: 10.1136/bmj.38308.477650.63.
7. Dingemans A-MC, et al. Ann Oncol. 2021;32(7):839-853. doi: 10.1016/j.annonc.2021.03.207.
8. Jaiyesimi IA, et al. J Clin Oncol. 2024;42(11):e1-e22. doi: 10.1200/JCO.23.02744.
9. Hendriks LE, et al. Ann Oncol. 2023;34(4):358-376. doi: 10.1016/j.annonc.2022.12.013.
10. Jones GS, Baldwin DR. Clin Med (Lond). 2018;18(Suppl 2):s41-s46. doi: 10.7861/clinmedicine.18-2-s41.
11. NICE. 2015. https://www.nice.org.uk/guidance/TA374/chapter/1-guidance.