The purpose of this research is to analyse the current diagnostic and therapeutic pathways associated with lung cancer in the United Kingdom, and to evaluate their effectiveness. Lung cancer remains the third most common cancer in the UK and has the highest mortality rate of any cancer. Per annum, approximately 46,000 new cases are diagnosed, with around 35,000 deaths attributed to the disease. Despite advances in treatment strategies, unfortunately only 1 in 10 patients survive, post-diagnosis.
Early detection is essential, and recent improvements in diagnostic techniques aim to improve survival through earlier and more accurate identification of disease. Alongside developments in imaging and less invasive diagnostic procedures, the emergence of biomarkers has transformed the diagnosis strategy. Biomarkers now play a key role in arranging patients into specific groups, predicting therapeutic response, and ensuring more personalised treatment strategies. These new strategies help not only to increase the chance of survival, but also to greatly improve quality of life.
An overview of lung cancer
Lung cancer is a disease that originates from the epithelial cells that line the airways of the lungs. It is characterised by many factors such as uncontrolled cell division, ability to attack nearby tissue and its potential to spread to distant organs, such as the brain or liver. Lung cancer can be broken down into two types: non-small cell lung cancer(nsclc) and small cell lung cancer(sclc). Nsclc accounts for 80-85%, whereas sclc is far less common and contributes to the remaining 15-20%. Sclc is the more aggressive variant of the two and is identified by its rapid growth and early spread, making early diagnosis ever more necessary. Smoking is the primary risk factor(around 72% of all UK lung cancer cases are attributed to smoking), which exposes the tissues of the lungs to carcinogenic substances that lead to genetic mutation. Other risk factors include: asbestos, pollution and genetic history of the disease. At a molecular level, the disease develops through accumulating genetic mutations that activate what are known as oncogenes(overexpressed forms of genes that turn normal cells into cancerous ones by initiating continuous, abnormal growth patterns)e.g. EGFR, or by deactivating tumour suppressor genes,(genes which help to regulate the cell cycle, by inhibiting rapid cell division and inducing apoptosis), e.g. TP53. Patient outcome heavily relies on the stage of cancer at the time of diagnosis. Early stage tumours(stage I, stage II) can be removed surgically, however later stages usually require chemotherapy, immunotherapy and so on.
Current diagnostic pathways in the UK
The diagnostic pathway for lung cancer in the NHS is designed to be efficient and enable early detection. Patients who present worrying symptoms such as haemoptysis(coughing up blood), recurrent chest infections or unexpected weight loss are urgently referred by the NHS to see a specialist within 14 days. According to a publication by the NHS, there is an ongoing effort about further shortening diagnostic pathways, improving patient care and meeting the Faster Diagnostic Standard(FDS). The FDS ensures that patients are notified whether they have cancer within a period of 28 days post-referral. This standard therefore:
- Reduces time between the referral and diagnosis of lung cancer
- Reduces patient anxiety as they pend on the diagnosis
- It is a significant improvement compared to the current 2 week pathway, as it is more patient-centred.
The initial investigation usually involves patients taking a chest x-ray. This technique uses ionising radiation to provide a 2d image of the chest cavity. Although this process is fairly quick and non-invasive, it is not very useful in identifying early stage or small tumours. After this, a CT scan(computed tomography) is performed. CT scans involve taking multiple x-rays from several different angles, along with computer reconstruction, in order to provide detailed, 3D cross-sectional images. This allows clinicians to assess various factors, such as tumour size or whether the cancer has spread into neighbouring tissues. In some cases, specifically if the CT-scan is positive, a PET-CT scan(positron emission tomography) will be conducted. According to radiologyinfo.org, a PET-CT scan uses tiny amounts of radioactive materials known as radiotracers, which are injected into the patient. The most common radiotracer used in PET-CT scans, according to ncbi.nlm.nih.gov, is fludeoxyglucose. Cancer cells are more metabolically active compared to normal cells, therefore absorb more glucose to maintain a higher metabolic rate. This therefore makes metabolically active tumours visible on the scan. After these various scans have been taken, there needs to be histological confirmation of the tumour, which takes place through the form of biopsies. A biopsy is a medical procedure where a sample of tissue is extracted from the area containing the possible tumour, before being examined by a pathologist under a microscope. In recent news, liquid biopsy has become a ground-breaking tool in the UK. According to england.nhs.uk, the NHS will be the first health organisation globally to implement a “blood test-first” approach to diagnosing lung cancer; with this test taken by patients before standard biopsies. This initiative could benefit up to 15000 patients each year and could also save up to £11 million per year in lung cancer care, therefore more money can be devoted to research and new therapies. But how do these biopsies work compared to traditional ones? Liquid biopsies analyse circulating tumour DNA(ctDNA) which is secreted into the bloodstream by cancer cells. cancerresearchuk.org explains that these ctDNA fragments can help to identify the genetic changes that have caused the tumour’s growth, therefore medics can assess what is happening inside the tumour, before being able to start the treatment process. Moreover, liquid biopsies are minimally invasive compared to traditional methods, therefore reducing the risk of contracting infection, whilst also shortening the diagnostic pathway further. However, there are many limitations of using this process to guide cancer treatment. cancerrresearchuk.org argues that liquid biopsy tests can only identify ctDNA when they reach a certain level in the blood. All cancers are not the same, therefore they do not leave equal traces of DNA, as this depends on a multitude of factors, such as size, stage of cancer etc.. Furthermore an article by economist.com describes a liquid biopsy test manufactured by the American biotech company GRAIL. In October 2025, GRAIL announced the results from a trial they had conducted consisting of 23000 patients, aged 50 or older. The results showed that the test identified 40% of the cancers correctly, and usually in the correct part of the body. However, it missed the remaining 60% of cancers and generated many needless scares for patients. It showed a cancer signal in about 1/107 patients; about 40% of these signals were incorrect. Contradictory to this, the article also explains how the liquid biopsy test outcomes differed by the type of cancer. galleri.com claims that the proportion of true positives when diagnosing lung cancer is 74.6%, implying that the GRAIL liquid biopsy test is a useful tool for diagnosing lung cancer.
Although traditional methods remain crucial in initial cancer diagnosis, the addition of molecular and minimally invasive techniques highlights a massive shift towards faster, patient-centred care.
The role of cancer biomarkers in lung cancer diagnosis/treatment
What are cancer biomarkers
Cancer biomarkers are biological molecules, proteins, genes, that are found in the blood stream, tissues, or urine. These biomarkers signal the presence of a tumour, its malignancy(aggressiveness of the tumour) and how it will react to treatment. Biomarkers are essential, to ensure there is a fast diagnosis and more importantly that there is personalised therapy, allowing doctors to choose certain approaches that are tailored to the molecular structure of a patient’s tumour.
In lung cancer, there are already several established biomarkers, primarily used in NSCLC(non-small cell lung cancer) diagnosis. One well known example of an established biomarker is mutations in the EGFR . The EGFR(epidermal growth factor receptor) is a protein that lies on the cell surface membrane. Ligands(cell-signalling molecules) such as EGF(epidermal growth factor) are able to bind to EGFR and this triggers intracellular signalling pathways that turn on genes for cell growth. However, mutations can occur, and when this happens, the EGFR protein can cause rapid, uncontrolled cell growth, eventually leading to the formation of tumours. According to lung.org, there are many types of EGFR mutations, the two most common being EGFR exon 19 deletions and EGFR L858R point mutations. Exon 19 deletions represent around 60% of EGFR-positive cases and they involve the deletion of amino acids. They are associated with better patient outcomes compared to the second of the two mutations, as treatment options are wider, through the use of TKIs(Tyrosine kinase inhibitors), preventing rapid cell growth. Another widely recognised biomarker is PD-L1 expression. PD-L1(programmed death-ligand 1) is a protein expressed on cells that is an immunosuppressant. Medlineplus.gov describes that normally, in healthy cells, PD-L1 binds to receptors on T-lymphocytes, preventing the immune system from attacking healthy tissue, as t-lymphocytes become deactivated. However, cancerous cells in the lungs overexpress PD-L1 levels. By doing so, cancerous cells can evade detection by the immune system, allowing them to continue to grow whilst also possibly increasing the risk of acquiring infection as the immune system is suppressed. Drugs to prevent this phenomenon from occurring are widely available however, and they work by blocking the interaction between the PD-L1 ligand and the receptor on the lymphocyte.
In addition to these very useful and reliable biomarkers, there are several emerging ones currently being tested and looked into further. One such example is Tumour mutational burden(TMB). TMB is a diagnostic biomarker that is broadly defined as the average number of mutations per megabase(unit of length for nucleic acids, equal to 1 million nucleotides) in the tumour exome(protein-coding portion of a cancer cell). Tumours with a higher mutational burden produce more abnormal proteins, because a different gene is coded for, producing a different protein. As a result of this, patients with high TMB may benefit from immunotherapy such as the use of ICIs(immune checkpoint inhibitors) that block certain pathways, e.g. PD-L1 on immune cells. By inhibiting these receptor-ligand interactions, T-cells aren’t deactivated and cancer cells become unable to evade the immune system. Another area of research involves exosomal biomarkers. According to nih.com, exosomes are small extracellular vesicles, usually between 30-150 nanometers that are essential molecules for cell communication. They are released by tumour cells into the bloodstream and contain proteins, RNA and DNA fragments which represent the molecular characteristics of the tumour. nih.com also explains that exosomal biomarkers are gaining more support as they are minimally invasive. Exosomes are produced by both prokaryotic and eukaryotic cells, therefore exosomes can be used not only as biomarkers for cancer, but for other bacterial and viral illnesses.
Current strategies used to treat cancer
Treatment strategies for lung cancer depend on a variety of factors, including tumour stage and the growth pattern of the tumour. The main treatment strategies used include surgery, chemotherapy, radiotherapy and immunotherapy.
For patients diagnosed at an early stage, surgical resection is commonly used to offer the greatest chance of cure. The lung is divided into sections known as lobes. Using the known information about the tumour, surgeons can perform 1 of these 4 surgeries: lobectomy(1 lobe), bilobectomy(2 lobes), pneumonectomy(whole lung - more severe cases) or segmentectomy(a section of the lobe). According to cleavlandclinic.org surgeons typically don't open a patient's chest for most lung resections. Instead they use minimally invasive techniques such as robot-assisted surgery or video-assisted surgery. This means that surgeons can use tools to pass in between a patient’s ribs, without having to break or open them.
If surgery is not possible, radiotherapy may be used. Radiotherapy usually involves aiming high-energy ionising radiation at the tumour, aiming to damage cancer cells’ DNA. However there are several types of radiotherapy apart from external radiotherapy. These include: radiotherapy implants(small pieces of radioactive material are placed in the body near the tumour) and radiotherapy injections, capsules or drinks(radioactive material is ingested or injected into the bloodstream). Radiotherapy can therefore prevent cancer cells from dividing, therefore leading to cell death. Radiotherapy is mainly used to treat tumours which show no evidence of spread, or to relieve symptoms for patients in advanced stages.
The most well-known therapeutic strategy of lung cancer is chemotherapy. Chemotherapy comes in the form of drugs and these drugs work by targeting cancer cells directly and disrupting key processes such as DNA replication and mitosis. However, chemotherapy can also target normal, healthy cells, resulting in side effects such as nausea and fatigue as well as being more at risk of contracting infection due to immunosuppression.
The last major therapeutic strategy used by the NHS is immunotherapy. Immunotherapy is a major development in cancer therapy; it aims to enhance the body’s immune response against the disease. Common types of immunotherapeutic drugs include ICIs(immune checkpoint inhibitors) such as PD-L1 inhibitors(see above for PD-L1). Immunotherapeutic drugs are delivered intravenously(IV drip), usually every 2-4 weeks, lung.org explains that immunotherapeutic drugs have been shown to keep working for periods of time even after treatment has been halted.
Overall, although these treatments have greatly improved outcomes in many patients, there are still many significant barriers such as drug resistance and long term-toxicity which are yet to be overcome.
Conclusion
In recent years, there has been a significant development in cancer care and the NHS has greatly changed the diagnostic and therapeutic process since 2023, and the addition of the 2-week wait system which greatly improves the chance of early detection, therefore increasing the likelihood of survival. However, despite this, the disease continues to present major clinical challenges. Many patients continue to receive late diagnoses, further implying that further changes need to be made to diagnostic processes such as screening programmes and imaging techniques.
In conclusion, the combination of molecular biology, imaging techniques and new diagnostic techniques such as liquid biopsies represent a significant improvement in cancer care as compared to previously. However in order to ensure the greatest chance of survival and quality of life, research into more key biomarkers and targeted treatments will ultimately be crucial.