Adenosquamous cell lung cancer stage III is a rare and complex type of lung cancer that has started to spread beyond the lungs but has not yet reached distant parts of the body, requiring a careful combination of treatments to improve outcomes for patients.
What Is Adenosquamous Cell Lung Cancer Stage III?
Adenosquamous carcinoma of the lung is a relatively rare subtype of non-small cell lung cancer (NSCLC), which means it is a cancer that grows more slowly than small cell lung cancer. This particular type is special because it contains two different kinds of cancer cells mixed together: adenocarcinoma cells and squamous cell carcinoma cells. While it shares some characteristics with both of these more common lung cancer types, it is not simply a combination of the two.[1]
When doctors say this cancer is at stage III, they mean it has begun spreading beyond the original lung to nearby structures in the chest. Stage III represents what medical professionals call “locally advanced” disease. The cancer might have reached lymph nodes in the chest, or it may have grown into nearby organs or tissues such as the chest wall, the diaphragm (the muscle that helps you breathe), or even the heart or esophagus. However, it has not yet spread to distant organs like the liver, bones, or brain.[3]
Stage III is further divided into smaller categories based on exactly where the cancer has spread. Stage IIIA generally means the cancer has spread to lymph nodes on the same side of the chest as the tumor, while stage IIIB indicates more extensive spread to lymph nodes on both sides of the chest or to other nearby structures. Each patient’s situation is unique, and doctors consider many factors including the exact size and location of tumors, which lymph nodes are affected, and the patient’s overall health when planning treatment.[3]
How Common Is This Type of Lung Cancer?
Adenosquamous carcinoma is considered a rare form of lung cancer. While non-small cell lung cancer accounts for more than 80% of all lung cancer cases, adenosquamous carcinoma makes up only a small fraction of these cases. The two more common types of NSCLC are adenocarcinoma (about 40% of cases) and squamous cell carcinoma (about 25-30% of cases).[2][1]
When we look specifically at stage III disease, it represents a significant portion of lung cancer diagnoses. Roughly one-third of all lung cancer patients are diagnosed when the disease is at stage III. This happens partly because early-stage lung cancer often causes no symptoms, so many people don’t realize they’re sick until the cancer has already begun to spread locally within the chest.[13]
Lung cancer in general is the third most common cancer in the United States and remains a leading cause of cancer-related deaths worldwide. The rarity of adenosquamous carcinoma means that less research has been conducted on this specific subtype compared to more common forms of lung cancer, which can make treatment decisions more challenging.[2]
What Causes Adenosquamous Cell Lung Cancer?
Smoking cigarettes is by far the most significant cause of adenosquamous cell lung cancer, just as it is for most types of lung cancer. When people inhale tobacco smoke over many years, the harmful chemicals damage the cells lining the airways deep inside the lungs. This damage can cause normal cells to change and become cancerous. Squamous cell carcinoma in particular is very strongly linked to smoking, and since adenosquamous carcinoma contains squamous cell components, smoking is its primary cause as well.[11]
However, smoking is not the only risk factor. Exposure to secondhand smoke, even if you’ve never smoked yourself, can also increase your risk of developing lung cancer. When you regularly breathe in smoke from other people’s cigarettes, you’re exposing your lungs to many of the same harmful substances that smokers inhale directly.
Asbestos exposure is another important cause of lung cancer, including adenosquamous carcinoma. Asbestos is a material that was commonly used in construction and manufacturing for many decades. When asbestos fibers are breathed in, they can lodge deep in the lung tissue and cause damage over time. The cancer may not appear until 10 to 50 years after the initial exposure, which means someone who worked with asbestos decades ago might only now be developing cancer.[11]
Other environmental exposures that can contribute to lung cancer risk include radon gas (a naturally occurring radioactive gas that can accumulate in homes), air pollution, and occupational exposures to certain chemicals or dusts. All of these substances are considered carcinogens, which means they are cancer-causing agents that can trigger the abnormal cell growth that leads to cancer.
Who Is at Higher Risk?
The biggest risk factor for developing adenosquamous cell lung cancer is a history of smoking. People who smoke or have smoked in the past face a much higher risk than those who have never smoked. The risk increases with the number of cigarettes smoked per day and the number of years someone has smoked. Even people who quit smoking years ago still carry an elevated risk compared to never-smokers, though their risk does decrease over time after quitting.
Age is another important risk factor. Most people diagnosed with lung cancer are 70 years old or older. The disease is uncommon in younger people, though it can occur at any age. As we get older, our cells have had more time to accumulate the damage that can lead to cancer, and our bodies may be less able to repair that damage effectively.[9]
People who have been exposed to asbestos in their work are at increased risk. This includes construction workers, shipyard workers, mechanics, plumbers, pipefitters, insulators, and others who worked in industries where asbestos was common. Veterans, especially those who served in the Navy or worked on ships, may also have been exposed to asbestos during their service.
Individuals with a family history of lung cancer may face a slightly higher risk, though this is less clearly established for adenosquamous carcinoma specifically than for some other cancer types. Living in areas with high levels of air pollution or radon exposure can also increase risk. People who have already had lung cancer once face an elevated risk of developing a second lung cancer.
What Are the Symptoms?
One of the challenges with lung cancer, including stage III adenosquamous carcinoma, is that symptoms often don’t appear until the disease has already progressed. When symptoms do occur, they can be vague and similar to many other, less serious conditions. This is one reason why lung cancer is often not detected until it has reached an advanced stage.
The most common symptom is a persistent cough that doesn’t go away or that gets worse over time. This isn’t the kind of cough that comes with a cold and disappears in a week or two, but rather one that lingers for weeks or months. Some people may cough up blood or rust-colored sputum (the mucus you cough up from your lungs), which is always a warning sign that should prompt immediate medical attention.[4]
Shortness of breath is another common symptom. Patients may notice they get winded more easily than they used to, even with activities they could previously do without trouble. They might find themselves breathing more rapidly or feeling like they can’t catch their breath. This happens because the tumor is blocking airways or because fluid builds up around the lungs.[4]
Chest pain that doesn’t go away and gets worse with deep breathing, coughing, or laughing can be a symptom of lung cancer. By stage III, when the cancer has begun spreading to nearby structures, pain may become more noticeable. Some people also experience hoarseness in their voice, repeated infections like pneumonia or bronchitis, or unexplained weight loss and loss of appetite.
As the cancer progresses, patients might feel persistently tired or weak. Wheezing or a whistling sound when breathing can occur if airways become narrowed. Some people experience bone pain or headaches if the cancer has started to spread, though in stage III, the cancer typically hasn’t reached distant sites like bones or the brain yet.
How Can This Cancer Be Prevented?
The single most effective way to prevent adenosquamous cell lung cancer is to never start smoking, or to quit if you currently smoke. Because smoking is responsible for the vast majority of lung cancer cases, avoiding tobacco use dramatically reduces your risk. If you’ve been smoking for years, quitting at any age can still provide substantial benefits. Within years of quitting, your lung cancer risk begins to decline, though it may never drop quite as low as someone who never smoked.
Avoiding secondhand smoke is also important. If you live with someone who smokes, encourage them to quit or to smoke only outside. At work or in public places, try to stay away from areas where people are smoking. Even occasional exposure to secondhand smoke can increase your cancer risk over time.
For people who have been exposed to asbestos or other occupational hazards, following workplace safety guidelines is crucial. This means wearing appropriate protective equipment, following proper handling procedures, and participating in any health monitoring programs offered by your employer. If you think you may have been exposed to asbestos in the past, let your doctor know, as they may recommend lung cancer screening.
Testing your home for radon and taking steps to reduce radon levels if they’re high can also help lower your risk. Radon is a naturally occurring gas that can seep into homes through cracks in the foundation. Simple, inexpensive test kits are available to check radon levels, and if levels are high, remediation systems can reduce them.
For people at high risk—such as current or former heavy smokers between ages 50 and 80—annual lung cancer screening with a low-dose CT scan may be recommended. While this doesn’t prevent cancer, it can detect it at an earlier, more treatable stage. Talk to your doctor about whether screening is appropriate for you.[2]
What Happens in the Body with This Disease?
Understanding what happens inside the body with adenosquamous cell lung cancer helps explain why symptoms occur and how the disease progresses. This cancer starts when cells in the lungs develop mutations, or changes in their genetic material, that cause them to grow and divide uncontrollably. Normal cells have built-in mechanisms to control their growth and to die when they become old or damaged. Cancer cells have lost these controls.
The lungs are designed to bring oxygen into the body and remove carbon dioxide. They’re made up of branching airways called bronchi and bronchioles that end in tiny air sacs called alveoli. Adenosquamous carcinoma contains two types of cancer cells: adenocarcinoma cells, which come from the glands that produce mucus in the airways or from the cells lining the alveoli, and squamous cell carcinoma cells, which come from the thin, flat cells lining the inside of the airways.[1]
As these cancer cells multiply, they form a mass or tumor. The tumor can grow large enough to block airways, which makes it harder to breathe and can trap air or mucus behind the blockage, leading to infections. The tumor can also press on nearby blood vessels, nerves, or other structures in the chest, causing pain, hoarseness, or other symptoms depending on what’s being compressed.
By stage III, the cancer has begun to spread beyond the original site in the lung. Cancer cells can break away from the main tumor and travel through the lymphatic system, a network of vessels and nodes that normally helps fight infection. The cells lodge in nearby lymph nodes, where they continue to grow. In stage III, cancer has typically spread to lymph nodes in the chest. It may also have grown directly into nearby tissues like the chest wall, diaphragm, or even the heart or major blood vessels.[3]
This local spread interferes with the normal functioning of affected organs. If the cancer grows into the chest wall, it can cause pain. If it affects the diaphragm, breathing becomes more difficult. As more and more lung tissue becomes involved, less area is available for gas exchange, which leads to shortness of breath and low oxygen levels in the blood.
The body tries to respond to the cancer, but often these responses aren’t enough to stop it. The immune system may recognize cancer cells as abnormal and try to attack them, but cancer cells have ways of evading or suppressing the immune response. Meanwhile, the growing tumor requires more and more nutrients and blood supply, sometimes diverting resources away from healthy tissues. This can contribute to weight loss, fatigue, and weakness that patients often experience.
What Treatment Options Are Available?
Treating stage III adenosquamous cell lung cancer typically requires a combination of different approaches. Because the cancer has spread locally but hasn’t yet reached distant parts of the body, aggressive treatment offers the possibility of long-term control or even cure in some cases. However, each patient’s treatment plan needs to be carefully tailored based on the exact stage of their cancer, their overall health, and other individual factors.[8]
Chemotherapy uses powerful drugs to kill cancer cells throughout the body. For stage III adenosquamous carcinoma, chemotherapy is almost always part of the treatment plan. Platinum-based chemotherapy, which combines a platinum drug like cisplatin or carboplatin with another chemotherapy drug, is the standard approach. Research has shown that platinum-based chemotherapy given after surgery for at least four cycles can significantly improve survival in stage III patients.[1]
Common chemotherapy combinations used include cisplatin with vinorelbine or etoposide, carboplatin with paclitaxel, or cisplatin with gemcitabine or docetaxel. These drugs work by interfering with cancer cells’ ability to divide and grow. They’re usually given through an IV, with treatment cycles repeated every few weeks. The exact combination chosen depends on various factors including the specific characteristics of the cancer and what side effects the patient can tolerate.[6]
Radiation therapy uses high-energy beams to kill cancer cells in a specific area. For stage III lung cancer, external radiation therapy (where the radiation comes from a machine outside the body) is commonly used. Radiation may be given alone or, more often, combined with chemotherapy in what’s called chemoradiation. When given together, the treatments can be more effective than either one alone, though they also cause more side effects.[6]
Chemoradiation is often the initial treatment for stage III patients, especially those whose cancer is not immediately suitable for surgery. The combination can shrink the tumor and kill cancer cells in lymph nodes. In some cases, if chemoradiation shrinks the tumor enough, surgery may become possible afterward.
Surgery to remove the cancer may be an option for some stage IIIA patients after chemoradiation has shrunk the tumor. The type of surgery depends on the location and extent of the cancer. A lobectomy removes the lobe of the lung containing the tumor. A pneumonectomy removes the entire lung. More extensive procedures may remove part of the chest wall or other nearby structures if the cancer has grown into them. Surgery is only offered if doctors believe they can remove all visible cancer and if the patient is healthy enough to tolerate the operation. For stage IIIB and IIIC disease, surgery typically isn’t offered because the cancer has spread too extensively.[6]
Targeted therapy may be an option for some patients whose cancer has specific genetic mutations. These are drugs that target particular abnormalities in cancer cells. For example, if testing shows the cancer has a mutation in the EGFR (epidermal growth factor receptor) gene, drugs called EGFR tyrosine kinase inhibitors such as erlotinib or gefitinib may be effective. These medications can block signals that tell cancer cells to grow and divide. However, not all adenosquamous carcinomas have targetable mutations, so testing is necessary to determine if this approach is appropriate.[1]
Immunotherapy is an emerging treatment approach that helps the body’s own immune system recognize and attack cancer cells. Immune checkpoint inhibitors are a type of immunotherapy that have shown promise in lung cancer treatment. These drugs work by blocking proteins that prevent the immune system from attacking cancer cells. While research on immunotherapy specifically for adenosquamous carcinoma is still limited, it may be a potential treatment choice for some patients.[1]
Diagnosis and Testing
Diagnosing adenosquamous cell lung cancer accurately is extremely challenging, especially before surgery. The disease often requires examination of a surgical specimen to make a definitive diagnosis because small tissue samples obtained through needle biopsies may not capture both the adenocarcinoma and squamous cell carcinoma components. This means doctors might initially diagnose either adenocarcinoma or squamous cell carcinoma based on a biopsy, only to discover it’s actually adenosquamous carcinoma after surgery when they can examine more tissue.[1]
The diagnostic process typically begins when symptoms or an abnormal finding on a chest X-ray prompts further investigation. A CT scan (computed tomography scan) provides detailed cross-sectional images of the chest and can show the size and location of tumors, whether lymph nodes appear enlarged, and if the cancer has grown into nearby structures. This imaging is crucial for determining the stage of the cancer.
A biopsy, where a sample of tissue is removed for examination under a microscope, is essential to confirm that cancer is present and to determine what type it is. This might be done through a bronchoscopy (inserting a flexible tube with a camera through the airways), a needle biopsy guided by CT imaging, or other methods depending on where the tumor is located.
Once cancer is confirmed, additional tests help determine how far it has spread. A PET scan (positron emission tomography scan) can show areas of active cancer throughout the body. This helps identify whether lymph nodes contain cancer and whether the disease has spread to distant sites. Blood tests check overall health and organ function to help determine whether the patient can tolerate aggressive treatments.
In some cases, a mediastinoscopy may be performed. This surgical procedure involves making a small incision in the neck to examine and biopsy lymph nodes in the mediastinum (the space between the lungs). This provides definitive information about lymph node involvement, which is crucial for accurate staging.
For patients whose cancers will be treated with targeted therapy, molecular testing of the tumor tissue looks for specific genetic mutations like EGFR, ALK, or other targetable changes. This testing guides treatment selection and helps predict which therapies are most likely to work.
