9th January 2024

Background

Lung cancers are usually divided into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). This distinction is particularly important for prognostication. Patients with SCLC often develop symptoms at a much later stage of disease, and treatment is usually limited to a palliative approach.

NSCLCs form the majority of lung cancers, and these are usually divided into adenocarcinomas, squamous cell carcinomas and large cell carcinomas.

In primary lung cancers, carcinomatous changes occur directly in the lung parenchyma, whilst in secondary lung cancers, there is metastatic spread to the lungs. The term lung cancer also encompasses mesothelioma, which is cancer of the pleura.

Epidemiology

Lung cancers are the second-most common type of malignancy worldwide but are the leading cause of cancer-related mortality. In the UK, there are around 48,500 cases of lung cancer annually and around 34,800 lung cancer-related deaths. The greatest risk factor for lung cancer is smoking, followed by radon exposure and (often) occupational exposure to certain chemicals and substances, including beryllium, silica, and asbestos.

Pathophysiology

The exact mechanism by which lung cancer occurs is not completely understood. Carcinogen exposure can deactivate tumour suppressor genes (such as p53) or activate oncogenes (such as c-myc), resulting in an abnormal cell cycle. Increased exposure results in increased cell dysplasia. Smoking cessation has been shown to reduce the incidence of lung cancer, with a reduction of up to 90 percent, dependent on the time and length of cessation.

The type of lung cancer depends on which cells are involved; for example, adenocarcinoma is a cancer of glandular cells which produce mucus, whereas squamous cell carcinoma affects squamous cells which line the airways.

Lung adenocarcinomas are the commonest type of lung cancer. They are often peripherally located and are highly associated with smoking. However, amongst individuals who have never smoked, it is the commonest form of lung cancer. Squamous cell carcinomas are usually centrally located, for example close to a main bronchus. They are also closely linked to smoking. Large cell carcinomas are so-called due to the large nuclei observed under microscopy. Around 80% of lung cancers are NSCLCs.

SCLCs account for around 20% of lung cancers. These cancers are more aggressive than NSCLCs. Many patients presenting with symptoms already have metastatic spread. They have the worst prognosis of all the lung cancer subtypes.

References

• Cancer Research UK, (https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer, accessed October 2022)
• Cancer Research UK, (https://www.cancerresearchuk.org/about-cancer/lung-cancer/stages-types-grades/types, accessed October 2022)
• Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2020 (https://gco.iarc.fr/today, accessed October 2022)
• Peto R. Smoking, smoking cessation, and lung cancer in the UK since 1950: Combination of national statistics with two case-control studies. BMJ. 2000;321(7257):323–9.
• Siddiqui F, Vaqar S, Siddiqui AH. Lung Cancer. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 (https://www.ncbi.nlm.nih.gov/books/NBK482357, accessed October 2022)