Metastasis

Metastasis - What is Metastasis?

Metastasis is a complex process that involves the spread of a tumor or cancer to distant parts of the body from its original site. However, this is a difficult process. To successfully colonize a distant area in the body a cancer cell must complete a series of steps before it becomes a clinically detectable lesion.

Steps of metastasis

The steps of metastasis include:

  • separation from the primary tumor
  • invasion through tissues around the initial lesion and penetration of their basement membranes
  • entry into the blood vessels and survival within blood - spread via blood vessels is called hematogenous spread
  • entry into lymphatics or peritoneal cavity - spread via lymph channels is called lymphatic spread
  • reaching the distant organ like lungs, liver, brain bone etc.
  • formation of a new lesion along with new blood vessels feeding the tumor - formation of new blood vessels is termed angiogenesis

All this while, the cancer cells have to avoid being killed by the body’s natural immune system.

Routes of metastasis

There are four possible routes of spread of cancer. These include:

  • spread via lymphatic channels – this is favoured by most carcinomas
  • spread via blood vessels – this is favoured by sarcomas and some carcinomas that originate in the kidneys - because of their thinner walls veins are more frequently invaded than arteries and the spread is via veins
  • spread via body cavities – the cancer cells seed onto peritoneal (covering the gut and stomach and other abdominal organs), pleural (covering the lungs), pericardial (covering the heart) or subarchnoid spaces (covering the brain) and membranes
  • transplantation of the cancer – this occurs by carriage of fragments of tumor cells via needles or surgical instruments to other parts of the body during surgery and diagnostic procedures

Why is metastasis dangerous?

Metastasis is of great importance since most of the cancer deaths are caused by spread of the primary cancer to distant sites. In most cases, cancer patients with localized tumors have a better chance at survival than those with metastatic tumors.

New evidence shows that 60% to 70% of patients have initiated the metastatic process by the time of diagnosis. In addition, even patients that have no evidence of tumor spread at diagnosis are at risk for metastatic disease and need to be treated accordingly.

Metastasis “seed and soil theory” and organs susceptible

Metastasis is one of three hallmarks of malignancy or cancer as opposed to a benign tumor. Most tumors and other neoplasms can metastasize. The degree of ability to spread, however, varies between different types of tumors. For example, basal cell carcinoma rarely spreads.
Some organs are more prone than others to metastasis of primary tumors. This was first discussed as the "seed and soil" theory by Stephen Paget over a century ago in 1889. For example, bones are the favoured site for prostate cancer, colon cancer spreads to liver, stomach cancer can metastasize to the ovaries and is then called Krukenberg tumor.

The theory states that cancer cells find survival outside their primary suites difficult. To spread they need to find a location with similar characteristics. For example, breast cancer cells need calcium ions from breast milk to proliferate. Thus they may prefer the bones as a site of spread as bones are rich in calcium. Malignant melanoma favors melanocytes and nerves and thus may spread to the brain since the neural tissue and melanocytes arise from the same cell line in the embryo.

Challenges to the “seed and soil” theory

This “seed and soil” theory was challenged by James Ewing in 1928 who suggested that metastasis occurs purely by anatomic and mechanical routes. He suggested the spread via lymphatic channels and blood vessels. He noted that cancer cells affected the regional lymph nodes near the primary tumor. This is called nodal involvement, positive nodes, or regional disease.

Primary tumors need biopsies of at least two lymph nodes near a tumor site when doing surgery to examine or remove a tumor. Localized spread to regional lymph nodes near the primary tumor is not normally counted as metastasis, although this is a sign of poor outcome.

Metastasis Treatment

Metastasis denotes distant spread of cancer from the primary organ. Treatment of any form of cancer is dependent on whether or not it has spread to distant organs. If the cancer spreads to other tissues and organs, it may decrease a patient's likelihood of survival. Cancer of the testes and thyroid however when metastasized may still be curable.

Choosing treatment

When cancer has metastasized, it may be treated with radiation therapy, surgery, chemotherapy, biological therapy, hormonal therapy or a combination of these. The choice of treatment generally depends on factors like:

  • type of primary cancer
  • size and location of the metastasis or secondary tumor
  • general health and age of the patient
  • types of treatments offered previously and their response and/or resistance in the patient
  • patient’s personal choice

Types of treatment for metastatic cancer

There are many effective treatments for metastatic cancer. These treatments fall into three main types:

  • Whole body treatment – this includes chemotherapy or anti-cancer medication that can reach all places of the body and radiation therapy
  • Local treatment for secondary tumor alone – this includes localized surgery and removal of the tumor or localized radiation therapy on the secondary tumor alone
  • Pain relief – this therapy is also called palliative therapy and is reserved for advanced cases of metastasis

Treatment of liver, lung and bone metastasis

Several treatment options are available for patients with metastases. These depend on the location of the primary cancer, the number and size of tumors, and the patient's general health.

Liver metastasis usually begins in a colon cancer in most cases. Cancers that commonly spread to the lungs include:

  • breast cancer
  • colon cancer
  • prostate cancer
  • sarcoma
  • thyroid cancer
  • stomach cancer
  • pancreatic cancer
  • kidney cancer
  • bladder cancer

Almost all types of cancer have the potential to spread to the lungs. Bones are the third most common location where cancer cells spread and metastasize. Spine and ribs along with long bones are common sites for metastasis.

Treatment includes:

Surgery to remove secondary tumors

This is given in combination with chemotherapy. Liver surgery may also be performed using laparoscopic surgery techniques. Surgery may be used to remove the affected tumor in lungs or in the bone. When spine is affected the vertebrae may undergo vertebroplasty.

Chemotherapy

Several anticancer drugs like oxaliplatin and irinotecan are used in liver metastasis. Chemotherapy may be delivered through intravenous infusion or directly to the affected region with a procedure called hepatic arterial infusion. This is called Hepatic Arterial Infusion (HAI) Chemotherapy.

Biologic Therapies

These target the cancer cells alone. They help by cutting off the cancer cells’ blood supply and kill the tumors. These are called anti-angiogenesis agents. These include bevacuzimab or Avastin. Another type of drug are the Epidermal Growth Factor Receptor (EGFR) Inhibitors. These drugs block epidermal growth factor receptor, a protein that may contribute to the progression of colorectal cancer. These include cetuximab or panitumumab. Biologic therapy is now used in combination with many chemotherapy drugs to improve the effectiveness of treatment.

Hormonal therapy

This is commonly used in endocrine cancers like breast cancer, ovarian, testicular, prostate and uterine cancers that have metastasized to other parts of the body.

Image-Guided Therapies

Those who cannot undergo surgery may need image guided therapies. Image-guided therapies use imaging techniques such as CT, ultrasound, x-ray, and MRI to guide the delivery of treatments directly to the tumor site. Image-guided therapies may be used alone along with chemotherapy. In most cases, these procedures are performed by interventional radiologists in the outpatient department or with a hospital stay.

Thermal Ablation

This therapy helps to kill the secondary tumor with heat or cold. There are currently three types of thermal ablation, including radiofrequency ablation, which uses radiowaves to heat and kill the tumor. There is also microwave ablation, which uses microwaves to heat tumor cells and cryoablation, which freezes the tumor. Radiofrequency ablation, cryoablation are commonly used in bone metastasis as well.

Radioembolization

In this a catheter is placed in the liver artery and a dye is injected to locate the tumor. Specially designed beads containing radioactive material are then inserted into the catheter. These deliver drugs to the tumor.

Radiation Therapy

This is used in some cases to control metastases that cannot be surgically removed or are too large to be treated effectively with ablation. Another method is by using stereotactic body radiation therapy that uses highly focused radiation field to deliver greater doses of radiation in fewer treatments. Stereotactic radiotherapy is used commonly in brain metastasis and lung metastasis.