Adenosquamous Cell Lung Cancer Stage III

Stage III adenosquamous cell lung cancer is a rare and aggressive form of lung cancer that contains both adenocarcinoma and squamous cell carcinoma components. Though challenging to treat, advances in chemotherapy, targeted therapy, and immunotherapy offer hope for improving survival and quality of life.

Table of contents

• What Is Adenosquamous Cell Lung Cancer?
• Understanding Stage III
• Diagnosis Challenges
• Treatment Options
• Outlook and Survival

What Is Adenosquamous Cell Lung Cancer?

Adenosquamous carcinoma of the lung (ASC) is a relatively rare subtype of non-small-cell lung cancer (NSCLC), which is the most common type of lung cancer. ASC is defined as a cancer containing components of both lung adenocarcinoma and lung squamous cell carcinoma.^[1]

While ASC has biological characteristics of both adenocarcinoma and squamous cell carcinoma, it is not simply a mixture of these two components. Instead, it represents a distinct form of lung cancer with its own behavior and treatment considerations.^[1]

Adenosquamous carcinoma and sarcomatoid carcinoma are two less common types of NSCLC. NSCLC accounts for over 80% of all lung cancer cases.^[2]

Stage III Adenosquamous Cell Carcinoma of Lung, Stage III Adenosquamous Cell Carcinoma of the Lung, Stage III Adenosquamous Cell Lung Carcinoma, Stage III Adenosquamous Lung Carcinoma

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• Lungs
• Bronchi (airways)
• Alveoli (air sacs)
• Lymph nodes
• Mediastinum
• Pleura (lung lining)

Understanding Stage III

Stage III lung cancer signifies that the cancer has spread beyond the original lung but has not yet reached distant areas of the body. This stage is considered locally advanced, meaning the cancer has grown to involve nearby structures in the chest.^[13]

Stage III is divided into three substages (IIIA, IIIB, and IIIC) based on the size of the tumor, how many nodules are present, and which lymph nodes contain cancer. In Stage IIIA, cancer has spread to lymph nodes on the same side of the body as the primary tumor. Stage IIIB involves larger tumors or cancer in lymph nodes on both sides of the chest. Stage IIIC represents the most advanced form of Stage III disease.^[13]

The official definition includes multiple combinations of tumor size (T), lymph node involvement (N), and metastasis status (M). Stage III includes classifications from T1a through T4 tumors, N1 through N3 lymph node involvement, and M0 (no distant metastasis).^[3]

In Stage III adenosquamous lung cancer, tumors may be found in the bronchus (main airway of lungs), diaphragm (breathing muscle), esophagus, heart and heart lining, lymph nodes in either side of the chest, mediastinum (space between lungs), pleura and chest wall, or spine.^[13]

Around 30% of non-small cell lung cancer cases are diagnosed at Stage III.^[1] Roughly 20% of NSCLC patients receive their diagnosis at Stage III.^[13]

Diagnosis Challenges

Adenosquamous carcinoma of the lung is extremely difficult to diagnose before surgery. The most effective method for adequate diagnosis of ASC is examination of the surgically removed tissue specimen.^[1]

When lung cancer is suspected, doctors use various tests that examine the lungs to diagnose and stage the disease. If lung cancer is suspected, a biopsy will be performed. A biopsy is a procedure where tissue is removed and examined under a microscope to check for cancer cells.^[4]

After non-small cell lung cancer has been diagnosed, additional tests are done to find out if cancer cells have spread within the chest or to other parts of the body. This process is called staging.^[4]

Treatment Options

The treatment of Stage III adenosquamous lung cancer typically involves multiple approaches used together. The complex management of this disease requires discussion among teams of different medical specialists to determine the best treatment plan for each patient.^[8]

Chemotherapy

Platinum-based chemotherapy after surgery for at least four cycles can significantly improve survival in Stage III patients with adenosquamous carcinoma.^[1]

Chemotherapy may be given together with radiation therapy before surgery, or it may be given by itself if the patient is not well enough for combined treatment or surgery. Common chemotherapy drug combinations include cisplatin with vinorelbine or etoposide, cisplatin or carboplatin with gemcitabine, and cisplatin or carboplatin with paclitaxel.^[6]

Chemoradiation

Chemoradiation is chemotherapy and external radiation therapy given together. This treatment may be offered before surgery for Stage III non-small cell lung cancer if the patient is well enough to receive it. If chemoradiation shrinks the tumor enough to make removal possible, surgery may be offered afterward.^[6]

Chemoradiation may also be given if surgery is not planned and the patient is well enough for this treatment approach.^[6]

Surgery

Surgery may be offered after chemoradiation if the treatment successfully shrinks the tumor. The patient must be healthy enough to undergo surgery. Different types of surgical procedures may be used, including lobectomy (removing the lobe of the lung where the tumor is located), pneumonectomy (removing the whole lung), or other specialized resection procedures.^[6]

For Stage IIIB and IIIC non-small cell lung cancer, surgery typically will not be offered because it would not be helpful given where the cancer has spread. Other treatments are used instead.^[6]

Targeted Therapy

Targeted therapy may be used to treat Stage III non-small cell lung cancer. The specific type of targeted therapy depends on genetic changes (mutations) found during diagnosis.^[6]

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib and gefitinib can be effective treatment strategies for advanced adenosquamous carcinoma that has EGFR mutations. EGFR is a receptor on the surface of cells that sends signals allowing them to grow and divide. Mutations in the EGFR gene can cause cancer cells to grow and divide more rapidly.^[1]

Studies of crizotinib in the treatment of patients with adenosquamous carcinoma are very limited.^[1]

Immunotherapy

Immune checkpoint blockade therapy may be a potential treatment choice for adenosquamous carcinoma patients. This type of treatment helps the body’s immune system fight cancer cells.^[1]

Recent advancements in the field have highlighted the incorporation of immune-checkpoint inhibitors as an important development in treating Stage III NSCLC.^[8]

Outlook and Survival

Stage III lung cancer is harder to treat than earlier stages, but some patients can achieve long-term survival with aggressive treatment.^[13]

While there is currently no cure for Stage III lung cancer, treatments can help extend life and reduce symptoms. Early detection through screening may improve the overall outlook.^[18]

The outlook for a person with Stage III lung cancer depends on various factors, including the specific type of lung cancer, the person’s age, and overall health. As with all cancer stages, the stage alone can only estimate the outlook and cannot predict exactly what will happen for any individual patient.^[18]

Many questions remain under debate in the treatment of Stage III disease, including the optimal sequences of treatment between different approaches, how to select patients for surgery, the duration of treatments given around the time of surgery, and identifying which patients might benefit most from specific treatments like immunotherapy and targeted therapies.^[8]