Learn | Science Of CRC

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Slideshow Overview

An illustrated explanation of CRC: learn how CRC develops.

Colorectal cancer is a disease that occurs in the colon, which is the large intestine, and also occurs in the rectum, which is the connecting pathway between the colon and the anus.

Colorectal cancer typically develops from colorectal polyps, which are abnormal growths that develop silently inside the colon or rectum. Type, location, size, and the number of polyps are related to risk of developing cancer. The most common types of colorectal polyps are adenomas, serrated, and post inflammatory.

If polyps are not removed early in their development, they can become cancerous. Tumors can eventually grow through the colon wall and may spread into the surrounding tissue or to other parts of the body, resulting in metastatic colorectal cancer. The most common sites of colorectal cancer metastases are the liver, lung and bone.

Solid cancers have been shown to depend upon angiogenesis, the growth of new blood vessels from pre-existing blood vessels. A tumor that is in its early stages of development cannot grow past a few millimeters in diameter unless blood vessels supply it with oxygen and nutrients. In this way, blood vessels serve as lifelines to cancer cells.

Cells in the center of the tumor mass have to compete with their neighboring cells for access to oxygen and nutrients. When they begin to starve, they release growth factors as a “distress signal” to the surrounding tissue.

Nearby blood vessels receive these signals and begin to grow new vessels toward the source of the growth factors for as long as the signal continue. These new vessels that grow towards and into the tumor nourish the tumor tissue, delivering oxygen and essential nutrients, but are structurally abnormal. As the tumor grows larger, signaling may increase and encourage even more blood vessel growth.

As the tumor expands, it invades surrounding tissue. Cancer cells spread as metastases through the blood vessels and lymph nodes, then to distant organs in the later stages of CRC progression.

Colorectal cancer can take years to develop and rarely has any symptoms, so it is important to be consistent about getting annual screenings after the age of 50, or as determined by your doctor.

CRC Biology

Colorectal cancer (CRC) is the third most common cancer in men and women¹, usually diagnosed in people aged 50 years or older.² If colorectal cancer is not found at its earliest stages through preventative screenings, it can develop into metastatic colorectal cancer (mCRC), which is an advanced stage of disease.³ There are new treatments if you have this condition.

Understanding the Colon & the Rectum

The colon and the rectum are parts of the digestive system⁴ and make up the large intestine.⁵ The first 4 to 5 feet of the large intestine make up the colon, and the rectum is the last 7 inches.⁶ Food is digested as it travels through the small intestine and then enters the colon, which removes water and nutrients from the food and then stores the rest as waste (stool). The waste passes through the colon, into the rectum and then out of the body through the anus.⁷

The wall of the colon and rectum consists of multiple layers. Colorectal cancer starts in the innermost layer and may grow through other layers if it progresses.⁸

How Cancer Forms

Multiple factors have been shown to influence the development of cancer, including genetic, hereditary and environmental.⁹ Research demonstrates that familial history plays a role in up to 25% of patients diagnosed with colorectal cancer.^10,11 Chronic inflammatory disorders of the digestive track also increase the risk of developing CRC.¹² Colorectal cancer typically develops from a polyp, a benign (non-cancerous) tumor or tissue growth, in the inner lining of the colon or rectum. There are different kinds of polyps and some can become malignant (cancer).

You can take an active role in understanding your condition in
order to work with your doctors and manage your treatment.

References

Types of Polyps

Large Intestine Anatomy

Most colorectal cancers first develop from colorectal polyps, abnormal growths inside the colon or rectum that develop silently. Catching these polyps early through regular screenings by your doctor can prevent the development of CRC.

Polyp Shapes

Polyps are small masses of cells that can develop anywhere along the inner lining of the colon and rectum. Type, location, size, and number of polyps are related to risk of developing cancer.

There are characteristic shapes of polyps that doctors may identify as precancerous:

1. Flat polyps do not protrude from the inner lining surface, and some can even be depressed in the surface. Doctors can use special dyes to locate them.

2. Sessile polyps sit right on the surface of the mucous membrane. They are elevated but do not have a stalk.

3. Pedunculated polyps are mushroom-like tissue growths that are attached to the surface of the mucous membrane by a long, thin stalk, or peduncle.

Polyps/Lesions – Types

The most common types of colorectal polyps are ademonas, serrated, and post inﬂammatory.

Adenomatous

Adenomas are most common type of polyp (about two-thirds of the polyps found in the colon and rectum). Although most adenomas remain benign, a small percentage can develop into colorectal cancer through a process that typically takes many years.

Villous or Tubulovillous Adenoma
This type represents approximately 15% of ademonas that are found and removed with colorectal cancer screening – they have the highest likelihood of developing into colorectal cancer.

Serrated

Serrated lesions are a heterogeneous group of lesions including hyperplastic polyps. Certain types of less common serrated lesions have a significant risk of developing into cancer.

Post-Inflammatory

These polyps develop most often in people with a inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis. The presence of post-inflammatory polyps is associated with colorectal cancer.

Anyone can develop colon polyps, but you are at greater risk if you are age 50 or older and:

♦ Smoke
♦ Eat a high-fat and low-ﬁber diet
♦ Are overweight
♦ Have a personal or family history
with CRC, colon polyps or
inﬂammatory bowel diseases

Polyps form as a result of abnormal tissue growth,¹³ which is typically due to genetic alterations. The intestine has a higher tissue turnover rate than many other organs in the body, which creates greater opportunity for development of abnormal tissue and cancer cells.¹⁴

There are two general groups of genes that control the process of cells growing and dividing.¹⁵ If any of these genes mutate, it can cause cells to continue dividing and form abnormal tissue, such as polyps in the colon or rectum. Polyps are likely to become malignant if this unregulated growth continues for an extended period of time,^16,17 though colorectal cancer typically takes several years,¹⁸ or even decades,¹⁹ to develop.

Metastatic Cancer

Once cancer forms in a polyp, it gradually progresses into the wall of the colon or rectum and can then grow into blood vessels or lymph vessels. Lymph vessels are thin tubes, similar to veins, that carry fluid and debris.²⁰ They drain into nearby lymph nodes, which are small structures with immune cells that filter harmful substances and help fight infections.²¹ Cancer cells can spread to nearby lymph nodes or other parts of the body by traveling through the blood or lymph vessels.²²

The spread of the cancer to other parts of the body is called metastasis.²³ Colorectal cancer commonly spreads to the lungs,²⁴ liver²⁵ and bone.²⁶

References

Tumor Angiogenesis

Understanding Angiogenesis

Angiogenesis, the growth of new capillary blood vessels, is an important natural process in the body used for healing and reproduction. The body controls angiogenesis by producing a precise balance of growth and inhibitory factors in healthy tissues.

When this balance is disturbed, the result is either too much or too little angiogenesis. Abnormal blood vessel growth, either excessive or insufficient, is now recognized as a “common denominator” underlying many deadly and debilitating conditions, including cancer, skin diseases, age-related blindness, diabetic ulcers, cardiovascular disease, stroke, and many others. The list of diseases that have angiogenesis as an underlying mechanism grows longer every year.

Angiogenesis and Cancer

All cancers, including CRC, require the growth of new blood vessels to grow beyond a few millimeters in size. These new blood vessels supply the tumor with the oxygen and nutrients needed to grow, and act as lifelines to cancer cells.

A major advance in cancer treatment in recent years has been the development of drugs, called angiogenesis inhibitors, or antiangiogenic drugs, which are designed to target and interfere with the tumor blood supply, in essence, to ‘starve’ cancer cells. These treatments can slow or stop tumor growth. Learn more about the specific targeted treatments here.

Angiogenesis and Cancer

A tumor in its early stages of development cannot grow past a few milimeters in diameter unless it is fed by blood vessels. Angiogenesis – the growth of new blood vessels – is essential for tumor growth and spread.

Polyp to early cancer

Release
of growth
factors

Blood Vessel

1. Cells in the center of the tumor mass have to compete with their neighboring cells for access to oxygen and nutrients. When they begin to starve, they release growth factors as a “distress signal” to the surrounding tissue.

Blood vessels
sprouting

2. Nearby blood vessels receive these signals and begin to grow new vessels toward the source. As long as the signal continues, the vessels will continue to grow in its direction.

Blood vessels
feeding tumor growth

Lymph Nodes

Lungs

Bone

Liver

spread
(metastasis)

3. Vessels that grow into the tumor nourish the tumor tissue, delivering oxygen and essential nutrients. As the tumor grows larger, signaling may increase and encourage even more blood vessel growth.

4. The tumor expands and invades surrounding tissue. Cancer cells spread as metastases through the blood vessels and lymph nodes, ﬁrst locally then to distant organs in the later stages of CRC progression.

CRC Staging

Staging of cancer is the process doctors use to identify the extent and location of the cancer, including whether it has spread to other areas in the body. This information is used to plan the most effective treatments for each patient. Treatments can differ based on the stage of disease.²⁷

The most common variables considered in staging systems include the site of the primary (original) tumor, size and number of tumors, the spread of cancer into lymph nodes, how similar cancer cells are to normal cell tissue, and whether the cancer has metastasized.²⁸

Your stage will help your doctor identify the best treatment

There are ﬁve stages of colorectal cancer, ranging 0 to IV:²⁹

Stage 0

This is the earliest stage: cancer is restricted to the innermost lining of the colon and it has not yet spread. It is also called ‘Carcinoma in Situ’.

Stage I

Cancer has begun to spread, but remains in the inner lining of the colon. This stage is also sometimes called ‘Dukes A’ colorectal cancer.

Stage II

Cancer has spread to other organs near the colon or rectum, but has not reached lymph nodes. Also called ‘Dukes B’ colorectal cancer.

Stage III

Cancer has spread to lymph nodes but has not reached distant parts of the body. This is also called ‘Dukes C’ colorectal cancer.

Stage IV

Cancer has spread (metastasized) to distant parts of the body, often to the lungs or liver. This is also called ‘Dukes D’ colorectal cancer.

The stage of a cancer is designated at the time of diagnosis. It never changes, even if the cancer progresses. A cancer that spreads or reoccurs is still referred to by the stage it was given when it was first diagnosed, with information about the current extent of the cancer added to it.³⁰

Doctors gather different types of information about a cancer to determine its stage. The exact tests used for staging depend on the type of cancer.³¹

Common tests include:

Physical exams and imaging tests help to evaluate the extent of the cancer by identifying the location and size of the tumor(s) and whether the cancer has spread to the lymph nodes or to other parts of the body. Imaging tests such as MRI or CT scans, or x-rays, show pictures of the tumor.

Laboratory tests use samples of blood and other bodily fluids or tissues to gather information about the cancer.

Pathology reports provide information about the size of the tumor, the extent of the spread of the cancer into other areas of the body, the type of cancer cells and the tumor grade (how the cells differ from normal cells). Samples of the tumor help to diagnose and stage the cancer.

Surgical reports use tumor samples taken during surgery to identify the size and type of tumor, and the extent of lymph node or organ involvement.

The doctor most familiar with your situation is in the best position to assess the stage of your cancer.³²

If colon cancer is found, it is highly treatable in its early stages. If the cancer spreads into nearby lymph nodes, chemotherapy followed by surgery has been a highly successful combination treatment.

In the most difficult cases — when the cancer has metastasized to other organs, such as the liver or lungs — treatment can prolong life.³³

The doctor most familiar with your situation is in the best position to assess the stage of your cancer.

TNM Classification

TNM Classification is the most common system used to identify the stage of CRC.³⁴ It was developed by the American Joint Committee on Cancer (AJCC) and is reviewed and revised every 6 to 8 years.³⁵

The system classifies the stage of the cancer based on:³⁶

T category: the size of the original tumor and the extent to which it has grown into the inner layers of the colon or rectal tissue.

N category: whether cancer cells have spread to lymph nodes.

M category: whether the cancer has spread to other areas of the body (metastasis).

Each category’s letter is attached to a number that indicates the size of the original tumor and the extent to which the cancer has spread.³⁷ The TNM scores indicate the stage of the cancer.³⁸

Primary Tumor (T)

Not enough information to assess the primary tumor.³⁹

Presence of a primary tumor cannot be demonstrated.⁴⁰

Tis

Abnormal cells are present but are not malignant and have not spread from their original location⁴¹ or beyond the inner layer of the colon.⁴² These cells can become cancer and have the potential to ultimately spread. This condition is also known as carcinoma in situ.⁴³

Tumor has not grown beyond the inner layer.⁴⁴

Tumor has grown into the muscle layer.⁴⁵

Tumor has grown beyond the muscle layer.⁴⁶

Tumor has grown through the bowel wall and into other organs and/or other parts of the body.⁴⁷

Lymph Nodes (N)

Not enough information to assess the presence of cancer cells in lymph nodes.⁴⁸

Cancer cells have not spread to lymph nodes.⁴⁹

Cancer cells are present in 1 to 3 nearby lymph nodes.⁵⁰

Cancer cells are present in 4 or more lymph nodes.⁵¹

Metastasis (M)

Not enough information to assess whether the cancer has spread (metastasized) to other areas of the body.⁵²

Cancer cells have not spread to other areas of the body.⁵³

Cancer cells have spread to other areas of the body.⁵⁴

LINES OF THERAPY
Patients with mCRC often receive a sequence of different treatments, with one given after another. Each sequence is referred to as a “line of therapy.” If one line of therapy stops working, often a different therapy may be effective:

“First-line” mCRC therapy is the first time a patient is treated for metastatic disease.

“Second-line” therapy is used as another treatment if the cancer progresses or reoccurs during or after first line therapy.

“Third-line” therapy follows second line if that fails to produce the desired benefit.

References

Risk Factors

A risk factor is anything that affects your chance of getting a disease.⁵⁵ While the exact causes for colon cancer remain unknown,⁵⁶ research has shown that the following risk factors increase the chances of developing this cancer:

Age

More than 90 percent of people diagnosed with CRC are age 50 or older.⁵⁷ Seventy-two is the average age at diagnosis.⁵⁸

Polyps

Polyps are tumor or tissue growths (usually benign) on the inner wall of the colon or rectum. They are most typically found in groups aged 50 or older.⁵⁹

Family History

Close relatives of CRC patients have higher risk of developing the cancer.⁶⁰

Personal History

Previous CRC patients are at risk of developing the cancer again.⁶¹ Women who have had cancer of the breast, uterus (endometrium) or ovary also have a higher risk.⁶²

Genetic Mutations

About 5% to 10% of people who develop colorectal cancer have inherited gene defects (mutations) that cause the disease.⁶³

Ulcerative Colitis or Crohn’s Disease

Previous conditions that cause inflammation of the colon increase risk of developing colon cancer.⁶⁴

Poor Diet

Poor diet has shown to increase the risk of CRC.⁶⁵ Some studies suggest that nutritious diets high in calcium, folate, and fiber,⁶⁶ but low in red meat and fat, may decrease the risk of colon cancer.⁶⁷

Sedentary Lifestyle

People who are inactive are at greater risk of getting CRC. Studies have shown that daily physical activity can decrease colon cancer risk by 30-40 percent.^{68, 69}

Cigarette Smoking

A person who smokes cigarettes may be at increased risk of developing polyps and colon cancer.⁷⁰

Diabetes

Diabetes and insulin resistance may increase risk of colon cancer.⁷¹

Obesity

People considered to be of normal weight are less likely to develop and die from colorectal cancer than people who are obese.⁷²

Radiation Therapy

Previous exposure to radiation therapy that was directed at the abdomen may increase the risk of colorectal cancer.⁷³

References

Symptoms

Colorectal cancer rarely has symptoms in its early development,⁷⁷ which is when the disease is most treatable, so it is important to get screened before symptoms appear.⁷⁸

Once present, symptoms may include:⁷⁹

Change in bowel habits or the consistency in your stool
Constipation or diarrhea
Stools are narrower than usual
Bowel does not empty completely
Rectal bleeding or traces of blood in your stool
Persistent abdominal discomfort, i.e. cramps, gas, bloating
Unexpected weight loss
Fatigue or weakness
Nausea or vomiting

A number of other health conditions can cause these symptoms. Your doctor is in the best position to determine the source of your symptoms. Typically, cancer does not cause pain during early stages, so it is important to see a doctor if you experience any of these symptoms, even if you feel fine.^80,81

References

CRC Fact Sheet

1) Colorectal cancer (CRC) is the third most common cancer in men and women.

2) The colon makes up the first 4 to 5 feet of the large intestine, and the rectum is the last 7 inches.⁸²

3) Colorectal cancer typically develops from a polyp, a benign (non-cancerous) tumor or tissue growth, in the inner lining of the colon or rectum. There are different kinds of polyps and some can become malignant (cancer), which is why it is best to remove them.

4) Research demonstrates that familial history plays a role in up to 25 percent of patients diagnosed with colorectal cancer.^83,84

5) More than 90 percent of people diagnosed with CRC are age 50 or older.⁸⁵ Seventy-two is the average age at diagnosis.⁸⁶

6) Colorectal cancer rarely has symptoms in its early stages, so getting preventative screenings annually is important for catching the cancer early, when it is most treatable.

7) Cancer cells can spread to nearby lymph nodes or other parts of the body by traveling through the blood or lymph vessels.⁸⁷

8) Colorectal cancer commonly spreads to the lungs,⁸⁸ liver⁸⁹ and bone.⁹⁰

9) Colorectal cancer has five stages, depending on the location and extent of the cancer. Treatments differ by stage.

10) If colon cancer is found, it is highly treatable in its early stages. If the cancer spreads into nearby lymph nodes, chemotherapy followed by surgery has been a highly successful combination treatment.

11) In the most difficult cases — when the cancer has metastasized to other organs, such as the liver or lungs — treatment can prolong life.⁹¹

Early Diagnosis is Key!

It’s important to know that CRC can be treated and, if caught early, even cured. Preventative screenings are critical to detect CRC because it typically does not have symptoms at its early, most curable, stages.⁹²

Preventative Screenings

Anyone 50 years of age and older is at greatest risk of developing CRC⁹³ and is strongly encouraged to get annual screenings. If polyps are detected during a screening, they can be removed and CRC can be prevented.⁹⁴ If CRC has developed but is caught before it spreads beyond the inner wall of the colon or rectum, there is a strong chance of curing the disease. The danger is when cancer cells spread to the outer wall tissue and to other organs or body parts. Consistent screenings are likely to detect cancer or pre-cancer cells before this happens.

According to the Colon Cancer Alliance, 90% of deaths from colorectal cancer could be prevented if everybody aged 50 or older has regular screening tests.⁹⁵

References

Testing for CRC

Common tests and procedures that ensure an accurate diagnosis for colorectal cancer include:

Colonoscopy: This is the most common procedure, which is when a gastroenterologist examines the inner lining of the colon and rectum by inserting a colonoscope (thin, long tube with a light and camera) through the rectum.⁹⁶ Through this procedure, the doctor can find any abnormalities and can gather samples of tissue or cells for biopsy and further testing.⁹⁷

Small polyps can be removed from the colon or rectum to be analyzed for cancer. This removal is called polypectomy.⁹⁸

Barium Enema: Using x-rays and dye to visualize the colon on a film. This allows your doctor to see and evaluate the appearance of your entire colon.⁹⁹

Virtual Colonoscopy: Using multiple CT images to create a picture of the inside of your colon. This is an alternative if you are unable to undergo an actual colonoscopy.¹⁰⁰

Metastatic Colorectal Cancer – What it Means for You

If you are diagnosed with mCRC, a number of treatment options are available. Your doctor will be in the best position to identify the most effective treatment for your situation, but it is important for you to be informed of all the options in order to have a productive discussion with your doctor. Knowledge and understanding of your condition equips you to take an active role in choosing and managing your treatment.

You can start by viewing our Resources page.

References