What Is Metastatic Adenocarcinoma?

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Metastatic adenocarcinoma refers to adenocarcinomas (cancers affecting glandular tissues, such as most breast and colon cancers and some lung cancers) that have spread (metastasized) to other regions of the body.

Some of the time, these cancers are metastatic (stage 4) at the time of diagnosis, and at other times, they represent a progression or recurrence of a previous early-stage tumor.

What to Know About Metastic Adenocarcinoma - Illustration by Jessica Olah

Verywell / Jessica Olah

Since these cancers have spread beyond the original area, local treatments such as surgery are less effective and these cancers are no longer considered curable. That said, there are now a number of different treatments that can extend length and quality of life (sometimes very significantly) as well as longer-term control of the spread. So though these tumors aren't considered curable, they can be very treatable.

This article will look at the types of metastatic adenocarcinomas, the areas of the body where each type is most likely to spread, why cancer spreads, and treatment options.

What Is Metastatic Adenocarcinoma?

Adenocarcinomas are cancers that arise in glandular cells (mucus-secreting cells) such as milk ducts and the digestive tract.

Metastatic adenocarcinomas are tumors that have spread beyond the tissue in which they began. For cancers such as breast cancer and colon cancer, these are considered stage 4 tumors. With metastatic or stage 4 adenocarcinomas, the tumor may be any size, involve (or not involve) any lymph nodes but has spread or metastasized.

Adenocarcinomas may spread at any stage of the disease, although they may be more likely to metastasize if they are larger or have spread to nearby lymph nodes (at more advanced stages). Adenocarcinomas may also be more likely to spread if they are aggressive (those with high tumor grade), along with other factors.

How Adenocarcinomas Spread

Adenocarcinomas can metastasize to other regions of the body in these three ways:

  • Local extension: Unlike benign tumors that may grow and press on nearby tissue, cancerous tumors can invade nearby tissues. The root word "cancer," meaning crab, actually refers to these crablike extensions of tumors into adjacent tissues.
  • Through the bloodstream: Via the bloodstream, cancer cells can travel to any region of the body.
  • Through the lymphatic system: Some adenocarcinomas follow a fairly regular pattern of spreading, often traveling first to nearby lymph nodes.

In recent years, it's been determined that lung cancer can also metastasize by traveling through the airways in the lungs.


Adenocarcinoma can sometimes lay dormant for an extended period of time before recurring in a distant location (now metastatic adenocarcinoma). For example, early-stage breast adenocarcinomas that are estrogen receptor-positive are actually more likely to recur in a distant location after five years than in the first five years following a diagnosis. This is called late recurrence. It's not known exactly why this occurs.

Types of Metastatic Adenocarcinoma

Physicians use the term "primary cancer" to describe the original tumor. For example, a tumor that starts in lung tissue is considered a primary lung adenocarcinoma. A lung cancer that spreads to the liver would be called "lung adenocarcinoma metastatic to the liver," not liver cancer. Since the cells in the liver are lung cells, it would be treated as lung cancer, not as liver cancer.

With some cancers, such as breast and colon cancers, the majority of the tumors are adenocarcinomas. In contrast, only around 40% of lung cancers are adenocarcinomas.

Metastatic adenocarcinoma can be broken down by the organ or tissues where the cancer originated. Common primary adenocarcinomas include:

Cancers of Unknown Primary Origin

In some cases (roughly 3%–5% of metastatic cancers), metastases are discovered, but the origin of the primary tumor can't be determined. This is then referred to as a cancer of an unknown primary site.

This is because sometimes cancer cells resemble normal cells in a particular organ. With newer types of testing, cancers of unknown primary site are found less often in the past. When they occur, however, doctors are still able to treat the cancer.

Where Adenocarcinomas Spread

While most cancers have the ability to spread to nearly any area of the body (and sometimes do), each type of cancer has particular organs or tissues to which it is most likely to spread. For each type of primary adenocarcinoma, the most common sites of metastases (in addition to lymph nodes) are:

  • Breast cancer: Bones, brain, liver, and lungs
  • Lung adenocarcinoma: Pleura (lining of the lungs), brain, adrenal glands, liver, bones, and the other lung
  • Colorectal cancer: Liver, lungs, peritoneum (tissue lining the abdominal wall and covering most organs)
  • Prostate cancer: Bones, adrenal gland, liver, and lungs
  • Pancreatic cancer: Liver, blood vessels in the abdomen
  • Stomach cancer: Liver, lungs, peritoneum
  • Esophageal adenocarcinoma: Liver, brain, lungs, and bone
  • Thyroid cancer: Lungs, bone
  • Cervical adenocarcinoma: Vagina, bladder, and rectum

Uncommonly, some adenocarcinomas may spread to the skin, muscles, and other regions of the digestive tract)

Another type of metastases, leptomeningeal metastases, do not form a tumor. Instead, cancer cells circulate throughout the brain in the cerebrospinal fluid. They are most commonly associated with breast cancer and lung cancer.

What Are the Symptoms of Metastatic Adenocarcinoma?

Symptoms of metastatic adenocarcinoma may include symptoms related to the primary cancer (for example, a cough with lung cancer) or general symptoms, including:

  • Fatigue: The fatigue associated with cancer (cancer fatigue) differs from ordinary tiredness. It's not usually relieved by a good night's sleep or a cup of coffee.
  • A general sense of being unwell
  • Loss of appetite
  • Unintentional weight loss: Weight loss can occur despite no change in eating habits or exercise. Weight loss of greater than 10% of body weight over a six-month period without trying should always be investigated.

Symptoms may also be related to metastases to specific sites. These symptoms may be the first sign of metastatic adenocarcinoma, especially with cancers such as lung adenocarcinoma. Symptoms based on metastatic site include:

  • Bones: Bone metastases may cause pain, which can be very severe. Since the presence of cancer cells in bones weakens the bones, fractures may occur with minimal trauma (pathologic fracture) and are sometimes the first sign that a metastatic adenocarcinoma is present.
  • Liver: Liver metastases may cause symptoms such as nausea and vomiting, abdominal pain, jaundice (a yellowish discoloration of the skin and whites of the eyes), and itching (which can be very intense).
  • Lungs: Lung metastases may cause shortness of breath, chest pain, a persistent cough, or hemoptysis (coughing up blood).
  • Pleura: When fluid builds up in the pleural space (the area between the two membranes that line the lungs), it can result in chest pain (which is often worse with a deep breath). When a lot of fluid is present, people may become very short of breath.
  • Brain: Brain metastases may cause symptoms such as headaches, speech changes, vision loss, numbness or weakness on one side of the body, loss of balance, or the new onset of seizures.
  • Peritoneum: When cancer spreads through the abdominal cavity, it can result in a significant buildup of abdominal fluid (ascites). This can cause pain and interfere with breathing.
  • Adrenal glands: Most of the time, the spread of cancer to the adrenal glands is asymptomatic. It may, however, cause flank pain that's described as similar to being kicked in the back.

Causes of Metastatic Adenocarcinoma

The question as to why some adenocarcinomas metastasize (spread) and some do not is a critical question in oncology. At the current time, roughly 90% of cancer deaths occur because of metastases, and once these tumors have spread to distant sites, a cure is rarely possible.

Known factors that can affect whether a cancer will metastasize or not include:

  • The type of cancer as well as subtypes
  • The aggressiveness of the tumor
  • Age at diagnosis (for some tumors)
  • Treatments received

Research is currently looking at factors that might initiate the metastatic process, how a tumor manages to avoid the immune system both initially and after traveling to a new site, and the role of normal cells around a tumor (the tumor microenvironment) in establishing a new site for growth..

How Metastatic Adenocarcinoma Is Diagnosed

The diagnostic process for metastatic adenocarcinoma can vary depending on the type of the primary cancer.

A careful history of symptoms, past medical history, and family history of any medical conditions is a crucial first step in diagnosing these cancers. It's especially important to note any history of cancer in the past.

Labs and Tests

A number of lab tests are usually done if metastatic adenocarcinoma is suspected. This includes a complete blood count (CBC) and blood chemistries. Liver function tests may be elevated if there are metastases to the liver. With bone metastases, an elevated level of alkaline phosphatase may be seen. Serum calcium is important as elevated calcium levels can be caused for different reasons and should be treated if very high.

Tumor markers may be tested depending on the cancer type. This may include tests such as a prostate-specific antigen test (PSA) with prostate cancer or cancer antigen 15-3 (CA 15-3) with breast cancer.

Other tests, including histochemistry and molecular profiling (such as next-generation sequencing), may be done depending on the primary tumor type.

Imaging Studies

Imaging studies are often needed both in the diagnosis of metastatic adenocarcinoma and to stage the disease. Scans might include:

  • Computed tomography (CT): A CT uses multiple X-ray images of a region of the body to create a three-dimensional image. It is often the first imaging test that is done when cancer is suspected.
  • Magnetic resonance imaging (MRI): An MRI uses strong magnetic fields to create a three-dimensional image of the inside of the body. Whereas a CT scan may give a better picture when looking at bone or air, an MRI often gives a better picture of soft tissues in the body.
  • Positron-emission tomography (PET): A PET scan is currently the gold standard to determine the extent of metastasis. In this test, radioactive glucose is injected into a vein and later a CT scan is performed to see if any areas light up. Cancer cells are usually more metabolically active than normal cells and may take up more of the radioactive glucose. A PET scan can also be valuable in distinguishing cancer from benign growth. For example, both scarring from radiation and lung metastases may cause a nodule on a CT scan, but if the nodule lights up on a PET scan, it may be more suspicious for a metastasis.
  • Bone scan: With a bone scan, a radioactive tracer is injected into a vein and then a scan is done to look for uptake. A radiologist will then evaluate the scan to look for any evidence of bone metastases.

Biopsy

A biopsy (removing a sample of tissue for examination in a lab) is important both to confirm the diagnosis and to do further testing on the cancer cells. The type of biopsy will depend on the location of the primary tumor (if known) as well as metastases.

A biopsy from an area of metastasis may also be done to confirm that it is related to the primary tumor rather than a second primary cancer. For instance, one study looked at people with breast cancer who developed a lung nodule. In 64%, the new nodule was related to spread from the primary breast cancer. But in 26% of the study participants, the nodule was an unrelated new primary lung cancer.

A liquid biopsy may also be recommended for some people. This is a blood test that looks for tumor DNA that is circulating in the bloodstream, and will often detect DNA in metastatic adenocarcinoma.

Every Cancer Is Different

Another reason to evaluate tissue from a site of metastasis is that cancer cells continually evolve and develop new mutations.

An example can be seen with breast cancer. In some cases, the initial breast tumor is estrogen receptor-positive but metastasis to the lungs may be estrogen receptor-negative (and vice versa). This is referred to as discordance and may affect how a cancer is treated after it has metastasized.

How Metastatic Adenocarcinoma Is Treated

The goal when treating metastatic adenocarcinomas differs from that of early-stage tumors. With early-stage tumors, the goal is to cure the cancer, if possible. For that reason, aggressive therapy is usually used to try to eradicate the tumor and any lingering cancer cells.

With metastatic adenocarcinoma, the goal is to control the cancer with as little treatment as possible to minimize side effects and maximize quality of life. More aggressive treatment doesn't usually extend survival, but it can increase side effects.

There are exceptions to this general rule. For example, if a new therapy is expected to be approved in the near future, more aggressive therapy may be used to attempt to get to that point.

There are three primary approaches to cancer treatment, including local treatment, systemic treatments, and palliative therapy.

Local Treatment

Local treatment is designed to get rid of a tumor where it originated. This includes therapies such as surgery, radiation therapy, and ablative therapies (such as treatment to cut blood supply to the tumor).

While local treatments are most often used to treat early-stage cancers, surgery or radiation may be used to reduce the size of a tumor and control symptoms.

A relatively new approach, and one that can increase survival in some cases, is treating isolated areas of metastases or oligometastases (cancer cells that have traveled and formed new tumors). For example, isolated (or a few) brain metastases due to lung cancer or breast cancer are sometimes treated either with surgery or a specialized form of radiation (stereotactic body radiotherapy or cyber knife).

Systemic Treatments

Systemic treatments are used to treat cancer cells no matter where they are in the body. These include:

  • Chemotherapy: Chemotherapy uses cytotoxic (cell-killing) medications to get rid of tumor cells. It is most often given through a vein, though some medications can be taken orally. Since different chemotherapy medications interfere with cancer cells at different steps in the cell cycle, a combination of medications is often used to get rid of as many cells as possible.
  • Targeted therapies: Targeted therapies are medications that hone in on specific pathways involved in the growth of a cancer. Since these drugs are more "cancer specific," they tend to have fewer side effects than chemotherapy, and they have been shown to significantly increase survival for some metastatic adenocarcinoma cases. For example, stage 4 lung adenocarcinoma used to have a life expectancy of only around one year. Now, a 2019 study found that for some tumors with a particular genomic alteration (ALK positive) that were appropriately treated (and responded) to targeted therapy, the median duration of survival was recently 6.8 years.
  • Hormonal therapies: With breast cancer, roughly 70% of tumors are estrogen receptor-positive, which means that estrogen acts as a fuel to feed the cancer by binding to these receptors. Hormonal therapies such as Nolvadex (tamoxifen) and, more recently, aromatase inhibitors have reduced the risk of recurrence as well as prolonged survival for people with metastatic breast cancer. Hormonal therapies are also used for prostate cancer.
  • Immunotherapy: Immunotherapies are treatments that use the immune system or principles of the immune system to treat cancer. This category includes a broad range of treatments ranging from checkpoint inhibitors to CAR T-cell therapy to cancer vaccines and more. Checkpoint inhibitors have had dramatic results with difficult to treat cancers such as metastatic lung adenocarcinoma, with some people achieving a "durable response" with these drugs. Unfortunately, these medications do not work for everyone.
  • Clinical trials and novel treatments: In addition to these treatments, many clinical trials are in progress looking at newer drugs in these categories as well as medications such as radiopharmaceuticals (medications that are injected, migrate to the area of a cancer and release a tiny dose of radiation).

Palliative Therapy

Palliative therapy is a third category that is used to control the symptoms of cancer and cancer treatments but is not designed to address the cancer itself.

Local therapies may be used to control the symptoms of cancer. Many cancer centers now offer palliative care consultations with a team that works to maintain a person's quality of life via treatments ranging from pain control to spiritual support.

Prognosis and Coping: Living Well With Cancer

While metastatic adenocarcinoma may not be curable, it is treatable, and treatments can often both extend a patient's life expectancy and reduce the symptoms of cancer.

With treatments improving rapidly, it's hard for anyone to stay on top of all of the research. For this reason, getting a second opinion is often considered a standard of care. Many people opt for a second opinion at one of the larger National Cancer Institute–designated cancer centers. Fortunately, many of these centers now provide remote consults so people don't need to travel unless they are certain the treatment is right for them.

If you or a loved one is diagnosed with metastatic adenocarcinoma or an earlier cancer returns at a distant location, coping with an incurable disease is challenging. The importance of having a support system around you during this time can't be stressed enough.

While family and friends can be an excellent source, having the opportunity to talk with others facing a similar journey is priceless. Many online communities are now available for advanced adenocarcinomas or your healthcare team may be able to refer you to a local in-person support group.

The financial toxicity of cancer is also very real for many people. Talking with a social worker at your cancer center may help you find resources for financial support you'd otherwise overlook.

Summary

Metastatic adenocarcinoma is a cancer that originates in glandular cells (mucus-secreting cells) such as milk ducts, the digestive tract, or lungs, and has spread or metastasized beyond the tissue in which it began. Adenocarcinomas can spread at any stage of the disease or they can lay dormant for an extended period of time before recurring in a distant location.

Symptoms may include general fatigue, unexplained weight loss, or general feeling unwell, or symptoms may manifest based on where the cancer has spread. For instance, if cancer has spread to the bones, it may cause bone aches, or increased risk of fracture even from minor injuries.

If metastatic adenocarcinoma is suspected, your healthcare provider will use blood tests, imaging studies, and biopsies (tumor tissue samples) to make a diagnosis and stage the disease. While most metastatic adenocarcinomas are not considered curable, there are treatment options that can extend survival and improve quality of life. Treatment options may include chemotherapy, immunotherapy, hormone therapy, and targeted therapy, depending on the type of adenocarcinoma you are dealing with.

A Word From Verywell

If you or a loved one has been diagnosed with metastatic adenocarcinoma, you may be feeling anxious and overwhelmed. Many people associate the terms "metastatic" or "stage 4" cancer with a terminal prognosis, but while these cancers aren't usually curable, some can be controlled for a significant length of time.

Perhaps the best advice is to politely refuse to listen when friends and family members share stories of others who have faced your disease. Every tumor and each person is different, and how someone was treated even two years ago may say little about the treatment options you'll be offered today.

Staying positive (while at the same time making sure to express your feelings) can help you face the decisions to come with a bit more vigor. Surround yourself with people who lift you up. And when you hear those horror stories, try saying, "I intend to have a different outcome myself. I'd like your support in doing just that."

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