Colorectal cancer is the third most common cancer diagnosed across both biological sexes in the United States. Experts predict that the year 2021 will see 104,270 new cases of colon cancer and 45,230 new cases of rectal cancer. The number of people diagnosed with these cancers has been in decline since the mid-80s, mostly because screening methods have been widely deployed by medical practitioners. In addition to that, the public has become aware of risk factors associated and as a consequence, a growing portion of the population are making lifestyle changes in an attempt to avoid colon cancer and other diseases.

While the trend in older adults is declining, there is an alarming rising incidence of colorectal cancer in younger adults. From the years 2012 to 2016, the number of patients younger than 50 diagnosed with this type of cancer has increased by 2% each year compared to only 1% in people aged 50 to 64.

This article will focus on understanding various aspects of colon cancer: symptoms, causes, risk factors, prevention and treatment.

Definition

Colorectal cancer is broadly defined as cancer of the colon and/or the rectum. Colon cancer and rectal cancer have many similar features, which is why they are often grouped. 

The colon and rectum are part of the large intestine (large bowel) in the digestive tract and are located in the body’s abdominal cavity. They are essentially the digestive system’s final parts, where water and salt get absorbed from the food matter that has passed through the small intestine.  

The colon is an approximately 5 feet long muscle tube with four distinct parts: the ascending colon, transverse colon, descending colon, and sigmoid colon. The rectum comes after the sigmoid colon and makes the last 6 inches of the digestive system. Waste matter (feces) is collected in the rectum before it passes through the anus.

Colorectal cancer can affect any part of the colon or the rectum. 

Symptoms

Early stages of colon cancer often do not cause any symptoms. If they do appear, they will vary depending on the size of the cancer and its location in the large bowel. Some of the most common ones include: 

• Bowel habit changes, such as constipation, narrowing of the stool, or diarrhea that lasts longer than a few days
• Bright red blood in the stool as a result of rectal bleeding
• Dark brown or black stool as a result of blood from farther up the digestive tract
• A feeling that a person needs to have a bowel movement but not feeling relieved by having one
• Abdominal (stomach) pain or cramps
• Fatigue and weakness
• Unintentional weight loss

Sometimes, colon cancer is discovered from a blood test showing a low red blood cell count. This is the result of the bleeding of the cancer into the digestive tract. The blood may turn the stool darker, but it can also appear normal. However, over time this bleeding can cause anemia or low red blood cell count. 

In some cases, individuals may not notice any colon cancer symptoms until cancer has already spread to their liver, causing an enlarged liver and jaundice (yellowing of the skin and the whites of the eyes). If cancer has spread to their lungs, they may have trouble breathing.

The symptoms listed above are not indicative only of colorectal cancer. They may be signs of hemorrhoids, an infection, or irritable bowel syndrome (IBS). Nevertheless, it is important to get properly screened just in case.

Start of Colorectal Cancer

The hallmark of the initial stages of colon cancer is polyps. Most colorectal cancers start as a growth on the inside of the colon or rectum. Some polyps may evolve into cancer over time (up to 15 years), but not all of them are precancerous. Different types of polyps have different chances of turning into cancer: 

• Adenomatous polyps (adenomas): These polyps are called a precancerous condition. They have a high tendency of becoming cancer. There are three types of adenomas based on their growth patterns: tubular, villous, and tubulovillous. 
• Sessile serrated polyps (SSP) and traditional serrated adenomas (TSA): Just like adenomas, these polyps also carry a high risk of colorectal cancer.
• Hyperplastic polyps and inflammatory polyps: This final type of polyps is common, but they are in general not precancerous. Large hyperplastic polyps (more than 1cm) might require more frequent colonoscopy screenings. 

The Spread of Colon Cancer

Colorectal cancer that forms from a polyp grows into the lining of the intestine over time. It typically starts in the mucosa layer (innermost layer) of the colon or rectum wall and spreads through the other layers.

It becomes especially dangerous when cancer cells reach blood vessels or lymph vessels. Through these channels, they can travel through the body, to nearby lymph nodes, distant lymph nodes, or other distant parts of the body. How much colorectal cancer will spread depends on how many layers of the intestine wall it has permeated and how much it has spread outside of the digestive tract. 

Types of Colon Cancer

The most common types of colorectal cancer are adenocarcinomas. They start in the mucus layer of the colon and rectum walls. There are different types of adenocarcinomas, with some having worse outlooks (prognoses) than others. 

• Carcinoid tumors – starting in the cells that release hormones in the intestine walls.
• Gastrointestinal stromal tumors (GISTs) – not as common in the colon as in other parts of the digestive tract. 
• Lymphomas – usually starting in lymph nodes, but they can also first develop in the colon, rectum, or other organs.
• Sarcomas – extremely rare in the colon and rectum. These cancers start in the muscle layer, blood vessels, or connective tissues.

Causes of Colon Cancer

There is no clear, single cause of colon cancer. However, there are a number risk factors associated with the development of this disease. 

• Aging. The majority of people diagnosed with colon cancer are over the age of 50. Recently, the number of people younger than 50 with this diagnosis has been increasing. Science is still unsure of the reasons for this.
• African-American race. African-Americans have a higher risk of colorectal cancer than people belonging to other racial groups.
• Personal history of colorectal cancer or polyps. Those who have already had polyps in the colon (even if they were noncancerous) or colon cancer have a greater risk of colon cancer in the future. 
• Family history of colon cancer. Having a blood relative who has been diagnosed with colorectal cancer also increases your risk. The risk is greater if you have more than one family member with the disease. 
• Inflammatory bowel conditions. Diseases such as Crohn’s disease and ulcerative colitis (inflammatory conditions of the colon) can increase the risk of colon cancer.
• Inherited cancer syndromes. Gene mutations passed down the family tree can significantly increase the risk of colon cancer. However, only a small percentage of these cancers are associated with genetic predisposition. The most common inherited syndromes that might cause colon cancer are Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC), and familial adenomatous polyposis (FAP).
• Radiation therapy for cancer. If you’ve already undergone radiation therapy for any type of cancer in the abdomen, it could cause the development of colon cancer. 
• Healthy diet. Even though research is mixed in this area, an increased risk of colon cancer is possible in people who eat high amounts of red meat and processed meat. Lowering your fat and calorie intake and increasing your fiber intake might help reduce this risk.
• Sedentary behavior. Limiting your daily amount of sitting or lying down and getting regular physical activity potentially reduces the risk of colon cancer. 
• Diabetes. Conditions that affect blood sugar levels, such as diabetes or insulin resistance, lead to a greater risk of colorectal cancer.
• Obesity. Obese and overweight people have a higher probability of developing colon cancer than people with a healthy weight. 
• Smoking. Quitting smoking reduces the risk of many cancers, including colon cancer.
• Alcohol. Reducing your alcohol intake lowers your risk of colorectal cancer.

Screening: Colon Cancer Prevention

Screening is the most powerful tool in early detection and prevention. It usually takes 10 to 15 years for abnormal cells and precancerous polyps in the large intestine wall to develop into cancer. Regular colon cancer screening helps to identify malignant polyps before they become cancer cells. 

People who should undergo regular colon cancer screening are individuals older than 45 and those with a strong family history of this cancer. Several types of screening tests are used, depending on the risk factors of the individual and what their doctor considers the best course of action. Screening tests for colon cancer can be divided into two primary categories: 

• Visual exams – Tests that look at the structure of the colon and rectum for any signs of abnormal areas. This can be done either via a scope (such as during colonoscopy) or with X-ray tests. 
• Stool-based tests – Compared to colonoscopy exams, these tests are less invasive and easier on a person. They are based on checking the stool for signs of cancer. Even though they are more comfortable, stool-based tests need to be performed more frequently than visual examinations. 

Standard Treatment

Colorectal cancer treatment depends on the size, location, and how far the cancer has spread. Common treatments include surgery to remove the cancer, chemotherapy, and radiation therapy. Colorectal cancer treatment is divided into two groups, local and systemic treatment. Decisions around what types of treatment to deploy depends on the extent of cancer spread, the stage of the cancer, prognosis, location, and other factors.  

Local Treatment

Local treatment targets the tumor with no or minimal effects for the rest of the body. Local treatment is useful for smaller cancers that haven’t spread (early-stage cancers), though it can be used in other situations as well.

Local treatment can include: 

• Surgery – The type and extent of colon cancer surgery depend on the stage of the cancer, its location in the colon, and the overall goal of the surgery.
• Ablation and embolization – Different ablation techniques are used to destroy small tumors (less than 1.5 inches across). Embolization is the process of reducing or blocking the blood flow to the tumor, typically used for larger tumors (about 2 inches) that cannot be treated with ablation.
• Radiation – This therapy includes using high-energy particles or rays (such as X-rays) to destroy cancer cells. 

Systemic Treatment

Systemic treatments include medication taken either by mouth or injected directly into the bloodstream. They’re called systemic because they have the potential of reaching cancer cells in the entire body, not only in a single spot. 

There are several different options for systemic treatment:

• Chemotherapy – Chemotherapy is often administered after surgical removal of colon cancer to help eliminate any cancer cells that have potentially been left behind. It can also be applied before surgery to shrink the tumor and improve the outcome of the surgery. Sometimes, chemotherapy drugs are given to patients who won’t or can’t undergo any surgery. The purpose of that is not to eliminate their cancer but ease the tumor burden and improve the patients’ quality of life. Some chemotherapy drugs that are commonly used in colon cancer treatment include:
  • Irinotecan (Camptosar)
  • 5-Fluorouracil (5-FU)
  • Capecitabine (Xeloda)
  • Trifluridine and tipiracil (Lonsurf)
  • Oxaliplatin (Eloxatin)

• Targeted therapy – Unlike chemo, which targets quickly dividing cells, regardless if they are normal or cancerous, targeted drugs specifically “target” a protein that is believed to be involved in the carcinogenesis of a tumor. For colon cancer, target drugs are those that target the 1) vascular endothelial growth factor (VEGF), a protein helps tumors form new blood vessels (a process known as angiogenesis) to get nutrients they need to grow, 2) epidermal growth factor receptor (EGFR) is a protein that helps cancer cells grow, 3) a mutant BRAF protein found in cancers and not normal cells.
  • Drugs that target VEGF are:
    • Bevacizumab (Avastin)
    • Ramucirumab (Cyramza)
    • Ziv-aflibercept (Zaltrap)
  • Drugs that target EGFR are:
    • Cetuximab (Erbitux)
    • Panitumumab (Vectibix)
  • Drugs that are BRAF inhibitors:
    • Encorafenib (Braftovi)

• Immunotherapy – The use of medicine to assist a person’s own immune system in recognizing and destroying tumor cells. Checkpoint inhibitors are an example of this. These drugs are designed to target proteins on immune cells that need to be turned on (or off) in order to kickstart an immune response. Colorectal cancer cells have the ability to affect these checkpoints to evade the patient’s immune system. Drugs that target the checkpoints restore the immune response. The drugs are commonly used to treat inoperable cancers, recurrent cancers (those that have returned after surgery), or cancers that have spread to other parts of the body (metastasized). Checkpoint inhibitors include: 
  • PD-1 inhibitors
    • Pembrolizumab (Keytruda) 
    • Nivolumab (Opdivo) 
  • CTLA-4 inhibitor
    • Ipilimumab (Yervoy) 

These colon cancer treatment options can often be used together in different combinations, such as chemoradiation therapy (a combination of radiation and chemotherapy) or surgery followed by chemotherapy. Doctors should work with their patients and discuss treatment goals and possible side effects to select the best possible treatment course. 

What’s New in Colon Cancer Treatment?

Liquid biopsy 

In standard cancer diagnosis and treatment procedures, the tumor is sampled with a needle. This process is called biopsy and it can be difficult to perform, depending on the location of the tumor. 

Liquid biopsy is an alternative to standard biopsy that is being extensively researched. In a liquid biopsy, the patient has to provide a blood, urine, spinal fluid, or pleural effusions (fluid around the lung) sample. It is easier to obtain these fluid samples than a sample of a tumor, and studies have shown that liquid biopsy can also contain cancer cells and DNA from the cancer. 

At the moment, researchers are focusing on testing colorectal cancer DNA in liquid biopsies for gene changes (mutations). They’re hoping that by pinpointing specific mutations, they will help medical professionals select the best treatment (drug) for their patients. 

Another branch of liquid biopsy research is looking into whether rising tumor DNA levels in a sample of liquid biopsy mean that the cancer is no longer responsive to certain treatment options. Liquid biopsies also have the potential of predicting a cancer’s recurrence (if the cancer comes back after treatment).