Adenosquamous Cell Lung Cancer Stage IV

Adenosquamous cell lung cancer stage IV is an advanced, rare form of lung cancer that has spread beyond its original location, presenting unique challenges for diagnosis and treatment. This disease combines features of two different cancer types and requires careful management to improve outcomes.

Table of contents

• What is adenosquamous carcinoma of the lung?
• Understanding stage IV disease
• Challenges in diagnosis
• Prognosis and survival
• Treatment approaches for stage IV
• Related lung cancer types

What is adenosquamous carcinoma of the lung?

Adenosquamous carcinoma of the lung (ASC) is a relatively rare subtype of non-small-cell lung cancer, which is cancer that forms in the tissues of the lung. ASC is defined as a malignancy containing components of both lung adenocarcinoma (a type of cancer that begins in cells that line the air sacs and produce mucus) and lung squamous cell carcinoma (cancer that forms in the thin, flat cells lining the inside of the lungs).^[1]

According to the World Health Organization classification, ASC must contain at least 10% of each component (adenocarcinoma and squamous cell carcinoma) to be diagnosed as this specific subtype.^[4] Although ASC has biological characteristics of both adenocarcinoma and squamous cell carcinoma, it is not simply a combination of these two components. The disease has its own unique molecular and genomic features that remain poorly understood.^[4]

ASC is uncommon, accounting for 2% to 4% of all lung cancers.^[4] As with other lung cancers, the average age at diagnosis is about 70 years, it affects more men than women, and most patients are current or former smokers.^[4]

adenosquamous carcinoma, ASC

• lungs
• bronchi
• bronchioles
• alveoli

Understanding stage IV disease

Stage IV cancer represents the most advanced stage of lung cancer. At this stage, cancer has spread to the other lung, the fluid around the lung, the fluid around the heart, or distant organs.^[2] This spread of cancer from its original location to other parts of the body is called metastasis.

Stage IV non-small cell lung cancer is further divided into stage IVA and stage IVB, with stage IVB being more widely spread throughout the body.^[16] When cancer reaches this advanced stage, it brings unique challenges and uncertainty for those diagnosed.^[16]

Despite being the most advanced stage, stage IV lung cancer is still treatable for most patients. New therapies that have become available in the past 5 to 10 years can dramatically change the outlook for patients.^[17]

Challenges in diagnosis

ASC is extremely difficult to diagnose before surgery. Given the mixed cell types that characterize ASC of the lung, the variation within the tumor often hinders and may delay proper diagnosis.^[1] Studies suggest that ASC is misdiagnosed as adenocarcinoma or squamous cell carcinoma in at least half of biopsies prior to surgical examination confirming an ASC diagnosis.^[4]

In one study looking at cases before surgery, nearly all ASC cases (98%) were either misdiagnosed or undiagnosed.^[4] What makes diagnosis even more challenging is that different types of biopsy samples (small pieces of tissue taken for examination) may yield different results. One case report described a patient eventually diagnosed with ASC who received three different results during initial testing: squamous cell carcinoma on one type of sample, adenocarcinoma on another test, and undifferentiated non-small cell lung cancer on a third sample.^[4]

While a diagnosis can be made using biopsy and examination of cells from fluid samples, a definitive diagnosis may require larger samples, such as several core biopsies or complete surgical removal of the tumor, to fully evaluate all components of the tumor.^[4] Pathology examination of surgically removed tissue is the most effective means for adequate diagnosis of ASC.^[1]

Prognosis and survival

ASC of the lung is reported to be relatively aggressive compared to typical adenocarcinoma and squamous cell carcinoma tumors. Studies indicate that ASCs at diagnosis have higher rates of spread to lymph nodes (small structures that filter substances in the body), spread quickly to other areas, and carry a generally poor outlook.^[4] Accordingly, the overall survival of patients with these tumors is relatively short compared to other non-small cell lung cancer subtypes.^[4]

In a 2022 study, 5-year survival rates after surgery for early-stage cancers were reportedly 65% for ASC compared to 69% for squamous cell carcinoma and 77% for adenocarcinoma.^[4] While the underlying biology driving ASC differs from more typical non-small cell lung cancer subtypes, understanding what to expect as treatment begins and maintaining open communication with your doctor can help manage the anxiety and emotions of a stage IV diagnosis.^[16]

Treatment approaches for stage IV

Chemotherapy

Chemotherapy (treatment using drugs that kill cancer cells) may be offered for stage IV non-small cell lung cancer if there are no genetic changes (mutations) that can be identified in the lung cancer tumors using cell and tissue studies.^[7] You need to be well enough to have chemotherapy.

The most common chemotherapy drug combination used to treat stage IV non-small cell lung cancer is cisplatin or carboplatin with gemcitabine.^[7] Other chemotherapy combinations that may be used include cisplatin or carboplatin combined with docetaxel, carboplatin and paclitaxel, or cisplatin and pemetrexed (though pemetrexed is only used for non-squamous types of non-small cell lung cancer).^[7]

For ASC specifically, platinum-based chemotherapy can significantly improve survival. The combination of drugs used for ASC is typically Taxol (paclitaxel) and Carboplatin, designed to target both types of cells present in the tumor.^[1]

Targeted therapy

Targeted therapy uses drugs that attack specific genetic changes in cancer cells. This type of treatment may be offered instead of chemotherapy for stage IV non-small cell lung cancer if there are genetic changes in the lung cancer cells.^[7] The type of targeted therapy given will depend on the type of genetic mutation that was identified using cell and tissue studies. If testing does not show genetic mutations that can be treated with targeted therapy, you will not be offered it as treatment.^[7]

It is important to know if you have EGFR mutations (changes in a gene called epidermal growth factor receptor), as they are present in about 30% of adenosquamous carcinomas.^[5] EGFR is a receptor on the surface of cells that sends signals allowing them to grow and divide. When there is a mutation in the EGFR gene, cancer cells can grow and divide more than normal.^[7]

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib and gefitinib can be effective therapeutic strategies for advanced EGFR-mutant ASC.^[1] EGFR-positive stage IV non-small cell lung cancer may be treated with erlotinib, gefitinib, or osimertinib instead of chemotherapy.^[7]

Another genetic change that can occur is called ALK rearrangement (a change in a gene called anaplastic lymphoma kinase), found in 5% of ASCs. Crizotinib is recommended if you have ALK rearrangement, though studies of crizotinib in the treatment of patients with ASC are very limited.^[5]

Immunotherapy

Immunotherapy is treatment that helps your body’s immune system fight cancer. Immune checkpoint blockade therapy may be a potential treatment choice for ASC patients.^[1] PD-L1 expression (a protein that helps cancer cells hide from the immune system) is found in 11% of the adenocarcinoma component and 28% of the squamous cell component in one study.^[5]

Other treatment considerations

Sometimes genetic changes are found in the cells during chemotherapy. If so, you may have targeted therapy when chemotherapy is finished, or your healthcare team may switch you to the targeted therapy drug alone.^[7]

Advances in the treatment of non-small cell lung cancer continue to develop. Be sure to talk to your doctor about new treatment options and always discuss potential side effects of treatment before you try it. Clinical trials (research studies testing new medications) may also be an option.^[16]

Palliative therapies, which focus on comfort, may help improve the quality of life for people with stage IV lung cancer. Palliative care focuses on relieving chest pain, addressing shortness of breath, removing blockages from airways, reducing fluid buildup in the lungs, and treating fluid buildup around the heart.^[16]

Related lung cancer types

ASC is classified as a less common type of non-small cell lung cancer.^[3] Other related lung cancer types include:

Adenocarcinoma is a type of lung cancer that begins in the cells that line the air sacs and make substances such as mucus.^[3] Non-small cell lung cancer accounts for over 80% of lung cancer cases, with adenocarcinoma being a common type.^[2]

Squamous cell carcinoma is a type of lung cancer that forms in the thin, flat cells lining the inside of the lungs, also called epidermoid carcinoma.^[3] It is typically found in the central parts of the lungs near a major airway.^[2]

Large cell carcinoma is a type of lung cancer that may begin in several types of large cells.^[3] Developing in any part of the lung, this subtype tends to grow and spread quickly, which can make it more difficult to treat.^[2]

Sarcomatoid carcinoma is another less common type of non-small cell lung cancer.^[3]