Lung Cancer: NSCLC, SCLC, Biomarkers & Treatment Guide

Lung cancer begins when cells lining the airways or lung tissue grow and divide abnormally, forming a tumour that can interfere with normal lung function and, over time, spread to lymph nodes or distant organs. It is broadly divided into two major categories based on how the cancer cells look under a microscope: non-small cell lung cancer (NSCLC), which accounts for roughly 80 to 85 percent of cases, and small cell lung cancer (SCLC), which makes up most of the remainder.

NSCLC itself includes several histological subtypes, the most common being adenocarcinoma, followed by squamous cell carcinoma and, less commonly, large cell carcinoma. These subtypes differ in where they typically arise in the lung, their relationship to smoking, and which molecular alterations are most likely to be found. Adenocarcinoma, in particular, is the subtype most often associated with targetable driver mutations and is also the type most commonly seen in people who have never smoked.

SCLC behaves quite differently. It tends to grow quickly, spreads early, and is strongly associated with cigarette smoking. Because it is rarely driven by a single targetable mutation, its treatment relies primarily on chemotherapy and immunotherapy rather than the targeted oral drugs used in molecularly defined NSCLC.

Both types of lung cancer can develop silently for months or years before causing noticeable symptoms, largely because the lungs have relatively few pain-sensing nerves and considerable functional reserve. This is one reason lung cancer is frequently diagnosed at a later stage, and why screening programmes for high-risk individuals have become an important public health tool.

Regardless of subtype, a confirmed lung cancer diagnosis today typically triggers a cascade of additional tests, imaging for staging, and molecular profiling of tumour tissue, all of which shape an individualised treatment plan rather than a uniform approach applied to everyone.

Being told you have lung cancer can feel overwhelming, but it is worth knowing that treatment today is far more personalised than it was even a decade ago. The specific type of lung cancer, its stage, and increasingly its molecular fingerprint, all determine which treatments are likely to work best for you rather than a single standard regimen applied to everyone.

If you have NSCLC, ask your care team whether your tumour has been tested for actionable mutations such as EGFR, ALK, or ROS1, and what your PD-L1 result showed, because these results can open the door to targeted therapies or specific immunotherapy combinations. If you have SCLC, treatment planning will focus more on the extent of disease and combining chemotherapy with immunotherapy or radiotherapy as appropriate.

In either case, it is reasonable to ask about clinical trials, supportive care options for symptoms such as breathlessness or fatigue, and how your specific test results influenced the plan being recommended to you.

Many lung cancers cause no symptoms in their earliest stages, which is a key reason the disease is often found later than clinicians would like. When symptoms do appear, the most common include a persistent or worsening cough, coughing up blood or blood-streaked mucus, chest pain that may worsen with deep breathing or coughing, and shortness of breath.

Other possible symptoms include hoarseness, recurrent respiratory infections such as bronchitis or pneumonia, unexplained weight loss, loss of appetite, and persistent fatigue. Some people notice new wheezing or a change in the character of a long-standing smoker's cough.

If the cancer has spread beyond the lungs, symptoms can reflect the site of spread, for example bone pain, headaches, or neurological changes if the disease has reached the brain. A relatively distinctive symptom pattern called Pancoast syndrome, caused by tumours at the top of the lung, can produce shoulder pain, arm weakness, and a drooping eyelid on one side.

Because these symptoms overlap with many common, less serious conditions, they are sometimes dismissed or attributed to smoking-related bronchitis for some time before being investigated. Any new or persistent respiratory symptom lasting more than a few weeks, particularly in someone with a smoking history or other risk factors, deserves prompt medical evaluation.

Lung cancer develops when genetic damage accumulates in the cells lining the airways, disrupting the normal controls on cell growth and division. Tobacco smoke is by far the most significant cause worldwide, containing dozens of chemicals capable of directly damaging DNA in lung cells; the risk rises with the number of years smoked and the intensity of smoking, and falls gradually after quitting, though it typically does not return fully to that of a never-smoker.

Not all lung cancer is smoking-related, however. A meaningful proportion of cases, particularly adenocarcinoma in women and in people of East Asian descent, occur in people who have never smoked. Many of these cancers are driven by specific inherited or acquired genetic alterations such as EGFR mutations or ALK gene rearrangements, which appear to arise independently of tobacco exposure and instead reflect spontaneous or environmentally triggered changes in specific genes that control cell growth.

At the molecular level, lung cancers are often described by their "driver" alteration, a single genetic change that provides the initial and ongoing impetus for the cancer's growth. Common drivers in NSCLC include mutations in EGFR and KRAS, and rearrangements involving ALK, ROS1, and less commonly RET or NTRK genes. Identifying these drivers has become central to modern treatment, since many can be directly targeted with specific drugs.

Small cell lung cancer has a different molecular profile, typically involving loss of function in tumour suppressor genes such as TP53 and RB1 rather than a single targetable driver, which helps explain why targeted therapy plays a much smaller role in its treatment.

Cigarette smoking remains the single largest risk factor for lung cancer, responsible for the majority of cases globally, and this includes exposure to secondhand smoke for non-smokers living or working with smokers. Other inhaled exposures also raise risk, including radon gas (a naturally occurring radioactive gas that can accumulate in homes), asbestos, certain industrial chemicals, diesel exhaust, and long-term exposure to air pollution.

Non-modifiable risk factors include increasing age, since most lung cancers are diagnosed in people over 60, and a personal or family history of lung cancer. Prior radiation therapy to the chest, for example for treatment of another cancer, can also increase risk over subsequent decades.

Certain groups face elevated risk from factors that combine environmental and biological influences; for instance, non-smoking women of East Asian ancestry have a comparatively higher likelihood of developing EGFR-mutant lung adenocarcinoma. Chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis are also associated with higher lung cancer risk, independent of smoking history.

While many of these risk factors cannot be changed, smoking cessation remains the single most impactful modifiable step a person can take to reduce their future risk, and avoiding known occupational and household exposures such as radon and asbestos can further lower risk over time.

Diagnosis usually begins when an abnormality is found on a chest X-ray or CT scan, either because of symptoms or through lung cancer screening in a high-risk individual. Because imaging alone cannot confirm cancer, a biopsy is required to obtain tissue for examination under a microscope.

Tissue can be obtained through several methods depending on the tumour's location, including bronchoscopy (passing a thin scope through the airways), a needle biopsy guided by CT scan through the chest wall, or, less commonly, a surgical biopsy. In some cases, a sample of fluid around the lung (pleural effusion) or an enlarged lymph node can also provide diagnostic material.

Once cancer is confirmed, the tissue sample is examined to determine histological subtype (for example, adenocarcinoma versus squamous cell carcinoma versus small cell) and, for NSCLC, is generally sent for molecular and PD-L1 testing. Additional imaging, such as PET-CT and sometimes brain MRI, is used to determine whether the cancer has spread beyond the lung, which is essential for staging and treatment planning.

In some cases, a procedure called mediastinoscopy or endobronchial ultrasound (EBUS) is used to sample lymph nodes in the chest to more precisely determine whether cancer has spread there, which can materially change the recommended treatment approach.

NSCLC is staged using the TNM system, which considers the size and local extent of the primary Tumour, whether cancer has spread to regional lymph Nodes, and whether there is distant Metastasis. These factors are combined into overall stages ranging from stage I (small, localised tumours) through stage II and III (progressively larger tumours and/or lymph node involvement) to stage IV (cancer that has spread to distant organs such as the liver, bone, brain, or the opposite lung).

Stage strongly influences treatment approach and prognosis. Stage I and II NSCLC are generally treated with curative intent, typically through surgery. Stage III disease is more varied, often described as "locally advanced," and may involve a combination of chemotherapy, radiotherapy, surgery, and immunotherapy depending on exactly how the disease is distributed within the chest. Stage IV disease is considered advanced or metastatic and is generally treated with systemic therapies aimed at controlling the cancer and relieving symptoms over the longest time possible.

Small cell lung cancer is traditionally staged using a simpler two-tier system: limited-stage disease, where the cancer is confined to one side of the chest and can be encompassed within a single radiation field, and extensive-stage disease, where the cancer has spread more widely, including to the other lung or distant organs. Many clinicians also apply the TNM system to SCLC alongside this simpler classification, particularly for early-stage disease being considered for surgery.

Staging is not simply a label; it is the primary factor that determines whether treatment is aimed at cure or at long-term disease control, and it shapes essentially every subsequent treatment decision.

For NSCLC, particularly non-squamous subtypes such as adenocarcinoma, molecular testing of tumour tissue is a standard part of the diagnostic work-up for anyone with advanced disease, and is increasingly used earlier as well. This testing, often performed using next-generation sequencing (NGS), looks for alterations in genes including EGFR, ALK, ROS1, KRAS, BRAF, MET, RET, HER2, and NTRK, each of which may be associated with a specific approved or investigational targeted therapy.

EGFR mutations are found in a meaningful proportion of lung adenocarcinomas, more frequently in never-smokers, women, and people of East Asian descent, and are matched with oral EGFR-targeted drugs. ALK and ROS1 rearrangements, though less common, identify patients who typically respond well to specific targeted inhibitors. KRAS mutations, historically considered difficult to target directly, now have specific targeted therapy options for one particular KRAS variant (G12C) in some patients.

Alongside molecular testing, immunohistochemistry is used to measure PD-L1 expression on tumour cells, reported as a percentage of cells staining positive. This result helps predict the likelihood of benefit from immune checkpoint inhibitor therapy, either alone or combined with chemotherapy, in tumours without a targetable driver mutation.

When tissue is limited or a repeat biopsy is difficult, a blood-based liquid biopsy test, which detects circulating tumour DNA, can supplement or in some cases substitute for tissue-based molecular testing. Liquid biopsy is also useful for monitoring for resistance mutations that can emerge after a period of successful targeted therapy.

Non-small cell lung cancer is the umbrella term for several related histological subtypes. Adenocarcinoma, the most common subtype overall, typically arises in the outer regions of the lung and is the subtype most often found in non-smokers and in association with targetable driver mutations. Squamous cell carcinoma tends to arise closer to the central airways and is more strongly linked to smoking history. Large cell carcinoma is a less common, less well-differentiated subtype diagnosed when a tumour does not show clear adenocarcinoma or squamous features.

Within NSCLC, molecular subtyping has become almost as important as histological subtyping. Tumours are increasingly described by their driver alteration, for example "EGFR-mutant NSCLC" or "ALK-rearranged NSCLC," because this designation often has a greater bearing on treatment selection than the histological subtype alone.

Small cell lung cancer is considered a distinct entity rather than a subtype of NSCLC. It arises from neuroendocrine cells in the lung, grows and divides rapidly, and has a strong tendency to spread early, often before it is detected. A related but rarer group of tumours, large cell neuroendocrine carcinoma, shares some biological features with SCLC and is sometimes treated similarly.

Rarer lung tumours include carcinoid tumours, which are typically slower growing neuroendocrine tumours, and various sarcomas or mesotheliomas that, while arising in or near the lung or chest lining, are biologically distinct from typical lung cancer and are managed differently.

Treatment for early-stage NSCLC (stage I and much of stage II) usually centres on surgical removal of the tumour, ranging from removal of a lung lobe (lobectomy) to smaller resections for appropriately selected patients. Adjuvant (after surgery) chemotherapy is often recommended for higher-risk stage II and III tumours to reduce the chance of recurrence, and for tumours with an EGFR mutation, adjuvant targeted therapy may also be used; immunotherapy is increasingly incorporated for eligible patients as well.

Locally advanced (stage III) NSCLC is more variable in its treatment, often involving a combination of chemotherapy and radiotherapy given together, sometimes followed by a period of consolidation immunotherapy, or in select cases surgery combined with chemotherapy before or after the operation.

For advanced or metastatic (stage IV) NSCLC, treatment is guided heavily by molecular and PD-L1 results. Tumours with an actionable driver mutation such as EGFR, ALK, or ROS1 are typically treated first with a matched oral targeted therapy, which can control disease for a meaningful period with generally manageable side effects. Tumours without a targetable driver are usually treated with immunotherapy, either alone or combined with chemotherapy, with the choice partly guided by PD-L1 expression level.

Small cell lung cancer treatment differs substantially. Limited-stage disease is generally treated with concurrent chemotherapy and radiotherapy, often followed by preventive brain radiotherapy in appropriate candidates to reduce the risk of brain spread. Extensive-stage SCLC is treated with chemotherapy combined with immunotherapy, aiming to control the disease for as long as possible.

Across all lung cancer types, supportive and palliative care, including symptom management for breathlessness, pain, and fatigue, is an important companion to disease-directed treatment at every stage, not only at the end of life. When a targeted therapy eventually stops working due to acquired resistance, repeat biopsy or liquid biopsy testing can sometimes identify a specific resistance mechanism that opens the door to a next-line targeted option.

Survival in lung cancer varies enormously by stage at diagnosis and, for NSCLC, by molecular subtype, so any single statistic should be interpreted with caution. Broadly, population data such as those tracked by the U.S. National Cancer Institute's SEER programme suggest a five-year relative survival for localised NSCLC (confined to the lung) in the range of roughly 60 to 65 percent, dropping to roughly 30 to 35 percent for regional disease (spread to nearby lymph nodes), and to roughly 8 to 9 percent for distant metastatic disease.

These population averages, however, do not fully capture the impact of modern targeted therapies and immunotherapy, which have measurably extended survival for many patients with specific biomarker profiles, particularly those with EGFR or ALK-driven disease treated with targeted drugs, and some patients with high PD-L1 expression treated with immunotherapy. Some patients with advanced, biomarker-matched NSCLC now live for several years with good quality of life, an outcome that would have been unusual before these therapies became available.

Small cell lung cancer generally carries a less favourable prognosis than NSCLC at a comparable stage, given its tendency to spread early and its more limited targeted treatment options, though the addition of immunotherapy to chemotherapy has modestly improved outcomes for extensive-stage disease in recent years.

It is important to remember that these figures are statistical averages drawn from large populations diagnosed in the past and cannot predict any individual person's outcome. Your own prognosis depends on many factors specific to you, including overall health, tumour biology, and response to treatment, and is best discussed directly with your oncology team.