Colorectal Cancer

Colorectal cancer, also known as bowel cancer, is a serious health concern that affects thousands of people worldwide each year. This type of cancer develops in the colon (the longest part of the large intestine) or the rectum (the last several inches of the large intestine before the anus). Understanding the causes, symptoms, and risk factors associated with colorectal cancer is essential for early detection and successful treatment.

What is Colorectal Cancer?

Colorectal cancer begins when healthy cells in the lining of the colon or rectum start to change and grow uncontrollably, forming a mass called a tumour. These tumours typically start as small, noncancerous (benign) growths called polyps. Over time, some of these polyps can become cancerous if not removed during a colonoscopy. As the cancer progresses, it can grow through the layers of the colon or rectal wall and spread to nearby lymph nodes or other parts of the body, such as the liver or lungs.

There are several types of colorectal cancer which include:

• Colorectal adenocarcinoma: This is the most common type of colorectal cancer. It develops from the glandular cells that line the inside of the colon and rectum. These cells are responsible for producing mucus to lubricate the passage of stool.

• Gastrointestinal carcinoid tumours: These tumours originate from the neuroendocrine cells in the digestive tract. They are slow-growing and often develop in the appendix, small intestine, or rectum.

• Primary colorectal lymphomas: These are rare cancers that develop from the lymphoid tissue in the colon and rectum. They are more common in people with compromised immune systems, such as those with HIV/AIDS or organ transplant recipients.

• Gastrointestinal stromal tumours (GISTs): GISTs are rare tumours that develop from specialised cells in the gastrointestinal tract called interstitial cells of Cajal. They can occur anywhere in the digestive tract but are most common in the stomach and small intestine.

• Colon and rectal leiomyosarcomas: These are rare, aggressive cancers that develop from the smooth muscle cells in the colon and rectum. They tend to grow and spread quickly, making early detection and treatment crucial.

• Colon and rectal melanomas: Melanomas are cancers that typically develop in the skin, but in rare cases, they can occur in the colon or rectum. These cancers are often aggressive and have a poor prognosis.

• Colorectal squamous cell carcinoma: This is an extremely rare type of colorectal cancer that develops from the squamous cells lining the colon or rectum. Squamous cells are more commonly found in the skin and other organs but can occasionally be present in the digestive tract.

• Familial adenomatous polyposis (FAP): FAP is a rare, inherited condition characterised by the development of numerous polyps in the colon and rectum. If untreated, it carries a high risk of developing into colorectal cancer.

The early signs of colorectal cancer include:

• Changes in bowel habits, such as diarrhoea, constipation, or narrowing of the stool, that last for more than a few days

• Rectal bleeding with bright red blood or blood in the stool, which might make it look dark brown or black

• Persistent discomfort or cramping in the abdomen

• Unexplained tiredness, weakness or lack of energy

• Unintended weight loss without trying

• Feeling the need to have a bowel movement even after having one, which is not relieved by passing stools

As colorectal cancer progresses, it can cause more noticeable symptoms such as:

• Rectal bleeding: Bright red blood from the rectum is a common local symptom of colorectal cancer.

• Changes in stool consistency: Persistent diarrhoea or constipation can be signs of colorectal cancer.

• Urge to have a bowel movement: Feeling the need for a bowel movement that is not relieved by having one may indicate the presence of a tumour.

• Abdominal cramping: Persistent cramping or pain in the abdomen can be a local symptom of colorectal cancer.

• Fatigue and weakness: Feeling weak or tired without a clear reason can be a systemic symptom of colorectal cancer.

• Unintended weight loss: Losing weight without trying may be a sign that the body is fighting cancer.

• Pain: Depending on where the cancer has spread, pain can occur in various parts of the body as a systemic symptom.

The stages of colorectal cancer are used to describe the extent of the cancer in the body. The most commonly used staging system is the American Joint Committee on Cancer (AJCC) TNM system, which takes into account the size of the tumour (T), the spread to nearby lymph nodes (N), and the presence of metastasis (M). These include:

• Stage 0: This is the earliest stage of colorectal cancer, also known as carcinoma in situ. The cancer cells are only in the innermost lining of the colon or rectum and have not spread to other layers.

• Stage 1: The cancer has grown into the wall of the colon or rectum but has not spread beyond the muscular coat or into nearby lymph nodes.

• Stage 2: The cancer has spread farther into the wall of the colon or rectum but has not spread to nearby lymph nodes. There are three sub-stages:

  • 2A: The cancer has spread through the muscle layer of the colon wall to the serosa (outermost layer) of the colon wall.

  • 2B: The cancer has spread through the serosa (outermost layer) of the colon wall to the tissue that lines the organs in the abdomen (visceral peritoneum).

  • 2C: The cancer has spread through the serosa (outermost layer) of the colon wall to nearby organs.

• Stage 3: The cancer has spread to nearby lymph nodes but has not grown beyond the lymph nodes and the colon or rectum wall to other parts of the body. There are three sub-stages:

  • 3A: The cancer has spread to one to three nearby lymph nodes.

  • 3B: The cancer has spread to four or more nearby lymph nodes.

  • 3C: The cancer has spread to nearby lymph nodes and the visceral peritoneum.

• Stage 4: The cancer has spread (metastasised) to other parts of the body, such as the liver or lungs. There are two sub-stages:

  • 4A: The cancer has spread to one distant organ or set of distant lymph nodes.

  • 4B: The cancer has spread to more than one distant organ or set of distant lymph nodes, or it has spread to distant parts of the peritoneum (lining of the abdominal cavity).

Several factors can contribute to the development of colorectal cancer, including:

• Polyps: Most colorectal cancers start from polyps, which are growths on the inner lining of the colon or rectum. Removing these polyps through regular screening can prevent the development of colorectal cancer.

• Genetic factors: Family history can play a significant role in the risk of developing colorectal cancer. Inherited genetic conditions, such as Lynch syndrome and familial adenomatous polyposis (FAP), increase the likelihood of developing the disease.

• Medical conditions: Certain medical conditions, such as inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can increase the risk of colorectal cancer, especially if left untreated for an extended period.

• Lifestyle factors: A diet high in red and processed meat, physical inactivity, and smoking have all been linked to an increased risk of colorectal cancer.

Several factors can increase the risk of developing colorectal cancer:

• Having a personal or family history of colorectal cancer or polyps

• Being over 50 years old

• Having inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn's disease

• Consuming a diet high in red and processed meat and low in fibre

• Leading a sedentary lifestyle with little physical activity

• Being overweight or obese

• Smoking tobacco

• Consuming excessive amounts of alcohol

Who's at Risk?

While colorectal cancer can occur in people of all ages, certain groups are at a higher risk:

• People with a personal or family history of colorectal cancer or polyps

• Individuals over 50 years old

• Those with inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn's disease

• People who consume a diet high in red and processed meat and low in fibre

• Individuals who lead a sedentary lifestyle with little physical activity

• Those who are overweight or obese

• People who smoke tobacco

• Individuals who consume excessive amounts of alcohol

Colorectal cancer can lead to various complications, both from the tumour itself and the treatments used to manage the disease. Some of the potential complications include:

• Bleeding: Tumours in the colon or rectum can cause bleeding, leading to anaemia and severe weakness. This can sometimes be a surgical emergency.

• Obstruction: A large tumour occupying the cavity of the colon or rectum can obstruct the passage of food and stools. This is a common acute abdominal surgical condition.

• Perforation: When cancer grows through the entire thickness of the bowel wall, it can create a hole, leading to peritonitis, a life-threatening infection.

• Fistulisation: In rare cases, the tumour can create fistulas to surrounding organs, which is a serious complication.

• Anastomotic leak: After surgery, there is a risk of a leak where the surgeon joins the ends of the colon together. This serious problem may require additional surgery.

• Infection: Surgical incisions can become infected, especially in patients with diabetes, malnutrition, advanced age, or immunocompromised status.

• Bleeding: Although uncommon, bleeding is a potential complication of colon cancer surgery and may require a blood transfusion.

• Deep vein thrombosis: Cancer increases the blood's clotting ability, making deep vein thrombosis a risk, particularly during surgery.

• Respiratory infections: General anaesthesia can hamper lung function, increasing the risk of respiratory infections.

Preventing colorectal cancer involves a combination of lifestyle modifications and regular screening. Here are some key steps to reduce your risk:

• Maintain a healthy diet: Eat a diet rich in fruits, vegetables, and whole grains. Limit your consumption of red and processed meats, as they may increase the risk of colorectal cancer.

• Exercise regularly: Engage in physical activity for at least 30 minutes a day, five days a week. Regular exercise helps maintain a healthy weight and reduces the risk of colorectal cancer.

• Avoid smoking and excessive alcohol consumption: Smoking and heavy alcohol use have been associated with an increased risk of colorectal cancer. Quitting smoking and limiting alcohol intake can help lower your risk.

• Maintain a healthy weight: Being overweight or obese increases the risk of colorectal cancer. Strive to maintain a healthy body mass index (BMI) through a balanced diet and regular exercise.

• Get screened regularly: Regular screening is crucial for detecting colorectal cancer early, when it is most treatable. If you have a family history of colorectal cancer or other risk factors, your doctor may recommend earlier or more frequent screening.

• Consider genetic counselling: If you have a family history of colorectal cancer or inherited conditions like familial adenomatous polyposis (FAP) or Lynch syndrome, genetic counselling can help you understand your risk and develop an appropriate screening and prevention plan.

Diagnosing colorectal cancer involves a combination of physical examinations, imaging tests, and biopsy procedures. Some common diagnostic methods include:

• Physical examination: A doctor will perform a digital rectal exam (DRE) to check for any abnormalities in the lower rectum and may also assess the abdomen for any signs of tumours or enlarged organs.

• Faecal occult blood test (FOBT): This non-invasive test checks for hidden blood in the stool, which can be an early sign of colorectal cancer.

• Stool DNA test: This test looks for specific genetic changes in cells that are shed into the stool by colorectal cancers or precancerous polyps.

• Colonoscopy: This is the most comprehensive diagnostic method for colorectal cancer. It allows the doctor to examine the entire colon and rectum and remove any suspicious tissues for biopsy.

• Flexible sigmoidoscopy: This procedure examines the lower part of the colon and rectum. If any abnormalities are found, a full colonoscopy may be recommended.

• Biopsy: If any suspicious areas are found during a colonoscopy or sigmoidoscopy, a biopsy will be performed. The tissue sample will be analysed in a laboratory to determine if cancer is present.

• Computed tomography (CT) scan: A CT scan uses X-rays to create detailed cross-sectional images of the body. It can help determine the extent of the cancer and whether it has spread to other organs.

• Magnetic resonance imaging (MRI): An MRI uses magnetic fields and radio waves to create detailed images of the body. It is particularly useful for evaluating the rectum and assessing the extent of rectal cancer.

• Positron emission tomography (PET) scan: A PET scan uses a small amount of radioactive glucose to identify areas of active cancer growth in the body.

The management of colorectal cancer involves a multi-disciplinary approach, with treatment strategies tailored according to the stage and characteristics of the disease. The primary treatment lines include:

• Surgery: In early stages (stages 0, I, and II), surgical removal of the tumour is the mainstay of treatment. This may involve local excision or more extensive resection, depending on the size and location of the tumour.

• Chemotherapy: For stage III and IV colorectal cancer, chemotherapy is often used in combination with surgery. Neoadjuvant chemotherapy may be given before surgery to shrink the tumour, while adjuvant chemotherapy is administered after surgery to eliminate any remaining cancer cells.

• Targeted therapy: Targeted agents like bevacizumab (anti-VEGF) and anti-EGFR agents (cetuximab and panitumumab) may be added to chemotherapy based on the molecular profile of the tumour. These medications specifically target the pathways involved in tumour growth and progression.

• Immunotherapy: For patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumours, immunotherapies such as pembrolizumab, nivolumab (with or without ipilimumab), and dostarlimab have shown promising results.

• Palliative care: In advanced stages, palliative radiation therapy and chemotherapy may be used to manage symptoms and improve quality of life.

Medications for Colorectal Cancer

Colorectal cancer treatment often involves a combination of chemotherapy, targeted therapy, and sometimes immunotherapy. Commonly used medications include fluorouracil (5-FU), often in combination with leucovorin and oxaliplatin (FOLFOX regimen), and capecitabine, which is a prodrug that converts to 5-FU in the body. Targeted therapies like bevacizumab and cetuximab focus on specific pathways that promote tumour growth. In addition, novel agents such as regorafenib and trifluridine/tipiracil are used for advanced stages. The choice of medication and treatment regimen depends on the cancer's stage, genetic markers, and the patient's overall health.

It is essential to consult a doctor if you experience any symptoms suggestive of colorectal cancer, such as:

• Changes in bowel habits, including diarrhoea, constipation, or narrowing of the stool, lasting for more than a few days

• Rectal bleeding or blood in the stool

• Persistent abdominal discomfort, such as cramps, gas, or pain

• A feeling that the bowel doesn't empty completely

• Weakness or fatigue

• Unexplained weight loss

• Colorectal cancer is a prevalent malignancy that affects the colon and rectum.

• Risk factors include age, family history, inflammatory bowel disease, and lifestyle factors such as diet, obesity, and lack of physical activity.

• Symptoms may include changes in bowel habits, rectal bleeding, abdominal discomfort, weakness, and weight loss.

• Screening tests, such as colonoscopy and faecal occult blood tests, are essential for early detection and prevention.

• Management involves a multidisciplinary approach, including surgery, chemotherapy, targeted therapy, immunotherapy, and radiation therapy, depending on the stage and molecular profile of the tumour.

• Medication includes chemotherapeutic agents like 5FU, oxaliplatin, and irinotecan, as well as targeted therapies such as bevacizumab, cetuximab, and regorafenib.