The diagnostic journey of lung cancer

Dr Thobile Goba-Mjwara describes the diagnostic journey of lung cancer and how new treatments and biomarker tests are leading the way to hope.

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Lung cancer is the most common cancer and leading cause of cancer-related deaths worldwide, accounting for over two million new cases from 2013 to 2019. More than two thirds of lung cancer patients are diagnosed at a late stage. Even with treatment, five-year survival rates are lowest. 

In SA, lung cancer ranks as the number one cause of cancer deaths. It’s estimated that 81% of lung cancer deaths in 2024 are caused directly by cigarette smoking.

The risk of lung cancer increases with the number of years spent smoking. Individuals who don’t smoke also have an increased relative risk of developing lung cancer if they are exposed to second-hand smoking. 

Other risk factors include family history, chronic lung diseases, and asbestos exposure.

Screening tools

Large prospective studies, including The US National Lung Screening Trial, have shown an all-cause mortality benefit when low-dose computed tomography (LDCT) was used as a screening modality in patients that are at high risk of developing lung cancer. 

The South African Thoracic Society, based on these findings, recommend annual LDCT offered to patients between ages 55 – 74 who are current or former smokers (having quit within the preceding 15 years), with a 30-pack year smoking history, with no history of lung cancer. Patients should be in general good health, fit for surgery, and willing to undergo further investigations if necessary. 

Given the high local prevalence of tuberculosis (TB) infection and post-TB lung disease, which can radiographically mimic lung cancer, a conservative threshold (nodule size ≥6 mm) should be used to determine whether the baseline LDCT screen is positive.

Diagnostic tests

A CT or PET-CT scan is required for diagnosis and staging to assess the extent and spread of lung cancer. To confirm the diagnosis and type of lung cancer, one or more of the following procedures may be done to obtain a sample for testing:

• A bronchoscopy is a common procedure to look into the airways and obtain a biopsy from the tumour in the main airway.
• A fine-needle biopsy is done when the tumour is at the edge of the lung. CT or ultrasound helps to guide the doctor to insert the needle into the suspicious area.
• If there is accumulation of fluid in the pleural space (pleural effusion), a pleural aspiration with a fine-needle is obtained then the fluid is examined for cancer cells.
• An endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used to get a biopsy for central lesions and mediastinum (area between the lungs).

Types of lung cancer

Lung cancer can be broadly classified into two main types: 

• Non-small cell lung cancer (NSCLC) 
• Small cell lung cancer (SCLC) 

These types can be further classified into several different subtypes. The stage of lung cancer indicates its size, location, and whether it has spread. 

NSCLC is commonly classified into four stages, typically numbered from Stage 1 to 4.

SCLC is most commonly categorised into two main stages:

• Limited stage – Tumour in one area on one side of the chest and can be treated by a single tolerable radiotherapy portal. Equivalent of Stages 1 to 3.
• Extensive stage – Cancer has spread to other parts of the body or contralateral lung. Equivalent of Stage 4.

Treatment

A team of healthcare professionals, called a multi-disciplinary team (MDT), work together to develop an appropriate treatment plan for each patient. Treatment options depend on the type of lung cancer and the stage of disease. Treating lung cancer in the early stages can reduce the risk of recurrence and increase the chance of cure.

• Surgery – Depending on stage and location.
• Radiotherapy – High energy X-rays used to kill cancer cells.
• Chemotherapy – Anti-cancer therapy that kills cancer cells in the blood.
• Immunotherapy – Treatment that works by helping the body’s immune system to fight cancer.
• Targeted therapies – Treatment that works by targeting molecules helping cancer cells grow.

Some patients may receive a combination of these treatments. 

For patients having surgery, additional treatments may be given before (neoadjuvant) and after (adjuvant) surgery to reduce the risk of recurrence. 

Patients may also receive additional treatment if their cancer recurs or progresses. 

Due to the fast-growing and aggressive nature of the disease, surgery is not common in SCLC. 

Biomarker testing in advanced NSCLC

More than half of patients with advanced NSCLC have tumours that harbour genetic alterations that can be targeted. Lung cancer biomarker testing, often referred to as genomic testing, looks for changes in the tumour’s DNA. 

A growing number of actionable targets, including those involving EGFR, ALK, ROS1, BRAF, MET, KRAS, NTRK, RET, HER2, and PD-L1 can be identified and if found to be positive, targeted therapy is a valuable option.

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