Treatment of Colon Cancer

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Introduction

About colon cancer?

  • What is it?

Colon cancer, also known as bowel cancer, is a type of cancer that begins in the large intestine (colon).1 The colon makes up the final part of the digestive tract. Depending on where the cancer occurs along the intestinal tract, colon cancer is sometimes called bowel, rectal, or colorectal cancer. Colon cancer is one of the leading global cancers and is widely considered among the most life-threatening and aggressive cancers, together with lung, prostate and breast cancer.2 Several studies have shown colon and rectal cancers as the third most common type of cancer worldwide.3,4 The incidence of colon cancer is more frequent than rectal cancer; the ratio of the colon to rectum cases is 2:1 or more in both industrialised and non-industrialised countries. A 2010 study found that around 250'000 new colon cases in Europe are diagnosed yearly, accounting for 9% of total malignancies.2 Rates of colon cancer are increasing with industrialisation and urbanisation, with greater prevalence in higher-income countries like North America, Western Europe and Australia.

  • Symptoms

Colon cancer is diagnosed when a patient presents with symptoms or as a result of screening programmes. Early colon cancer generally has no symptoms. Because most of the symptoms of colon cancer are non-specific - such as changes in bowel activity, abdominal pain, weight loss, and persistent fatigue - it is imperative to check for cases through essential screening programmes. Except for patients with obstructive or perforating colon cancer, the duration of symptoms does not correlate with prognosis. The 'Critical Reviews in Oncology'2 allude to some of the most common signs and symptoms of colon cancer:

  • Intermittent abdominal pain: abdominal pain, bloating or discomfort that is always caused by eating and may be associated with weight loss with no apparent cause (unintentional weight loss) or loss of appetite
  • Nausea or vomiting occurs secondary to obstruction or perforation, where a colon tumour potentially obstructs the bowel or prevents the passage of fluid or solid waste
  • Rectal bleeding: bleeding can be acute and most commonly manifests as red blood mixed with stool Chronic blood loss with iron deficiency anaemia frequently occurs in colon cancer patients.2
  • Rectal obstruction or perforation: malignant bowel obstruction is most commonly associated with cancer of the sigmoid colon.2 In the presence of an obstruction, there may be a perforation through the tumour or the colon wall. Perforation can be acute or chronic
  • Palpable masses: a palpable mass in the lower abdomen is familiar with right colon cancer.2 A palpable mass can induce lower abdominal pain and perforation or secondary immune illnesses like fever
  • Persistent cystitis: if a tumour grows to the extent of intestinal or bladder perforation, a patient can experience the passage of gas or "air" in urine or "bubbles in the urine"- known as gross pneumaturia - or recurring urinary tract infections. The continued recurrence of cystitis despite repeated treatments could also mandate diagnostic tests 
  • Risk factors

Colon cancer commonly occurs sporadically and is inherited in only 5% of cases.5 Studies have shown that when populations move from low-risk areas (e.g. Asia, Africa) to high-risk regions (e.g. Europe, North America), the incidence of colorectal cancer increases dramatically.6

Diet is the most important exogenous factor in the literature and cohort studies on colon cancer's aetiology.7 The World Cancer Research Fund and the American Institute for Cancer Research7 concluded that an inappropriate diet and associated factors mainly cause colon cancer. The evidence suggests that consuming red meat and processed meat are causes of colon cancer. There is limited but significant evidence suggesting that foods containing iron, cheese, foods containing animal fats, and foods containing refined sugars are causes of colon cancer.7

A 2018 study concluded that physical activity is a strong risk factor for population groups with colon cancer.8 In epidemiology studies, reduced physical activity and sedentary behaviour are consistently associated with an increased risk of colon cancer. Whilst the evidence is limited, there is an association between sedentary-induced high body mass index and increased risk of colon cancer. This could suggest an added benefit of physical activity as a potential cancer prevention strategy in population groups with high-risk factors for colon cancer.

The risk of developing colon cancer increases with alcohol consumption.9,10 Substantial consumption (more than 30 grams per day of ethanol) of alcoholic drinks regularly has been shown to cause colon cancer.7

Body composition is widely associated with various health conditions, including the most aggressive forms of cancer. A greater body mass index, greater fat mass, decreased fat-free mass, increased waist circumference and greater abdominal/visceral fatness are causes of colorectal cancer.7 The metabolic consequences of excess body fat, namely high blood pressure, hypertriglyceridemia (high amounts of free fats or triglycerides in the blood), low levels of high-density lipoprotein cholesterol ("good fats"), or diabetes/hyperglycaemia, have a positive association with colon cancer incidence in extensive cohort studies.11

Other well-established non-dietary risk factors of colon cancer include tobacco smoking, chronic use of non-steroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen) and aspirin and some conditions such as select colorectal diseases, metabolic syndromes and genetic predisposition.12 Smoking is consistently positively associated with large colorectal adenomas (a benign tumours formed from the glandular structure in epithelial tissue), generally accepted as precursor lesions (minimally invasive tumours that indicate the very early stages of cancer). Thus it can be concluded that exposure to tobacco constituents is an initiating factor for colon cancer.13 Bowel diseases, such as Crohn's disease and ulcerative colitis, increase the risk of colon cancer.14 This 2007 report found that those with Crohn's disease have a 2.6 increased risk of colon cancer. Another study found a positive relationship between ulcerative colitis and colon cancer.15

  • Diagnosis

Identifying intestinal growths (adenomatous polyp) and premalignant lesions makes a candidate ideal for colorectal cancer screening. Screening aims to detect the 90% of sporadic cases of colorectal cancer which occur in people above the age of 50 years.12 The most common screening forms are a faecal occult blood test, flexible sigmoidoscopy, colonoscopy, CT colonography, and a DNA stool test.16

  • The faecal occult blood test is a test that checks the stool for blood that can only be seen with a microscope. Blood in the stool may signify polyps (benign growths), cancer or intestinal problems
  • Flexible sigmoidoscopy is a procedure to look inside the rectum and sigmoid (lower) colon for polyps, abnormalities or cancer. A sigmoidoscope is a thin, tube-like 'camera lens' inserted through the rectum into the sigmoid colon. Signs of cancer are identified through the lens. The instrument can also remove polyps or tissue samples from the colon, which are further checked for signs of cancer
  • Colonoscopy, like flexible sigmoidoscopy, is a procedure to look inside the rectum and colon for polyps, abnormalities or cancer but scans the entire colon, not just the lower portion. A colonoscope is inserted through the anus and rectum and passes into the colon, where a viewing camera scans the colon for abnormal areas
  • CT colonography, or virtual colonography, is a procedure that uses X-rays to generate a series of images of the colon. The lower abdomen is scanned using X-rays, and a computer creates detailed images that show polyps and abnormalities on the epithelial lining of the colon. It is also called CTC
  • DNA stool tests directly check for genetic indications of colon cancer in the stool. A stool sample is obtained for testing and observed under a microscope. It is checked for any genetic (i.e. DNA mutations) changes or abnormalities
  • Prevention

Colon cancer is preventable by a well-balanced diet and lifestyle intervention. A diet rich in fibre, fresh fruit and vegetables, dark green leaves, garlic, and calcium, has been shown to protect against colon cancer.7 There is also significant but limited evidence suggesting that non-starchy vegetables, fruits, folate, fish, vitamin D-rich foods, and selenium protect against colorectal cancer.7 A diet high in iron, cheese, animal fats, and refined sugar should be limited.

Sedentary individuals have a 60% to 2-fold increased risk of colon cancer17 When comparing physical inactivity to other risk factors for colon cancer, it has been estimated that 13-14% of colon cancer in the population could be attributed to physical inactivity,18 which is comparable to an estimated 12% of colon cancer cases attributed to eating a Western diet.19 Thus the importance of physical activity as a significant factor in the incidence of colon cancer should not be ignored.

Types of treatment

(Includes a brief description of each treatment type and side effects)

Depending on the Stage of malignancy, many different types of treatment can be used to treat colon cancer. After someone has been diagnosed with colon cancer, a practitioner will conduct tests to see the extent of the spread (if there is any). This is a process referred to as staging. The Stage of cancer denotes how much cancer is in the body or at a given site and helps determine how severe the cancer is and subsequent treatment options.

The first and earliest stage of colon cancer is called Stage 0, which later ranges from stages I1 to IV.4 The American Cancer Society suggests that the greater the number of the Stage, the greater the extent of the cancerous spread.20 The following stages have been illustrated in the diagram below.21

  • Stage 0: Also called Carcinoma in situ, in Stage 0, abnormal cells begin to develop in the mucosa (inner layer) of the colon wall. These cells may become cancerous and spread into the surrounding tissue
  • Stage I: Cancer has started forming in the colon wall's mucosa and has spread into the submucosa or through the submucosa to the muscular layers of the colon wall
  • Stage II: Stage II is divided into three distinct stages: IIA, IIB, and IIC. In Stage IIA, cancer has spread past the muscular layers of the colon wall. In Stage IIB, cancer has spread through the serosa. In Stage IIC, the tumour has spread beyond the serosa to surrounding organs
  • Stage III: like Stage II, Stage III has three stages: IIIA, IIIB, and IIIC. In Stage IIIA, cancer may have spread beyond the muscle layer to surrounding tissues or one to six lymph nodes. In Stage IIIB, the cancer has spread beyond the muscular layer of the colon to seven or more surrounding lymph nodes. In Stage IIIC, the tumour resides in seven or more lymph nodes or spreads to nearby organs from infected surrounding tissues
  • Stage IV: colon cancer has spread to vital organs and other parts of the body through blood and lymph nodes

Surgery for early stage colon cancer

Early-stage colon cancer refers to cancers in Stages 0 - II. Surgery is the most common treatment for Stages 0 - IV of colon cancer, making it a viable treatment option for all severities. Cancer is removed using the following techniques:21

  • Polypectomy

Also called 'local excision', this surgery is performed if the cancer is discovered in its early stages. Instead of cutting through the abdomen, a cutting tube is passed through the rectum into the colon, where a local excision is made to cut the cancer out. It has been found that polypectomy has a success rate of up to 96% for polyps with a 1cm diameter, making it a feasible and advantageous treatment option.22

  • Endoscopic mucosal resection

Endoscopic mucosal resection is a minimally invasive method of removing a polyp. An endoscope is passed through the colon to the site of infection. A metal snare passed through an endoscope is placed around the polyp, using an electric current to cut the polyp while cauterising blood flow. It is a safe and precise method for polyp removal, providing specimens for pathologic analysis.23 A 1999 study found that in those who had undergone endoscopic mucosal resection for oesophagus cancer, complete remission was achieved by 97% of patients in group A and 59% in group B.24 

  • Laparoscopic surgery

Also known as 'keyhole surgery'25 laparoscopy involves making an incision on the lower abdomen, then inflating the abdomen via a cannula. Once inflated, a laparoscope and camera are passed through the incision, which allows precise removal of polyps in the colon.

Surgery for more advanced colon cancer

More advanced cancer can refer to stages beyond Stage II. Surgical resection may be followed by chemotherapy. Surgery can involve local excision for recurrent tumours, resection, or removal of parts of other organs to which cancer may have spread. Treatment of advanced colon cancer may include the following:

  • Partial colectomy

Partial colectomy, also known as partial resection, a doctor may perform a partial colectomy to remove the cancerous site and a small amount of healthy tissue that surrounds it. It may be followed by anastomosis, which involves sewing the healthy parts of the colon together after the diseased portion has been surgically removed.26 In most cases, surrounding lymph nodes are removed near the colon and examined under a microscope for further testing. A partial colectomy is a less aggressive surgical approach, a safe and feasible option for treating colon cancer, and has a high cancer-specific survival rate (around 67.5%).27

  • Surgery to create a way for waste to leave your body

Surgery to create a way for waste to leave your body: medically referred to as resection with colostomy.26 If the healthy parts of the colon cannot be sewn together, a stoma (opening) is made on the abdomen for waste collection and removal. A bag is placed around the opening to collect waste. The colostomy bag may be required for a short time until the colon has healed or may be permanent.

  • Lymph node removal

Lymph node removal: also known as radical lymphadenectomy, is a surgical procedure to remove metastatic lymph nodes or lymph nodes likely to encounter a cancerous invasion. Studies have found a statistically significant increase in the 5-year survival rate after radical lymphadenectomy.28, 29 In cases where colon carcinoma is found between lymphatic drainage areas, lymph node removal is highly recommended.30

Chemotherapy

Chemotherapy is a cancer treatment involving drugs to inhibit the continued growth of cancer cells. This treatment either kills the cancer cells or stops them from dividing, thus multiplying.  Chemotherapy can have total body effects, impacting all of the body and cancerous cells.31 Chemotherapy drugs are administered via intravenous or oral application or direct injection into affected regions. These drugs target and kill cells that divide and proliferate, interfering with the cell's ability to replicate. During intravenous methods, chemotherapy drugs are injected into a vein or muscle. Like oral administration, the drugs enter the bloodstream and reach cancerous cells throughout the body, known as systemic chemotherapy. Regional chemotherapy involves directly administering chemotherapy drugs into the cerebrospinal fluid, organs, or body cavities on a local, more regional level. This kills the cancer cells in those affected areas. One prospective study found adjuvant chemotherapy's small but statistically significant benefit on the overall survival rate for Stage II colon cancer patients.32

Radiation therapy

Radiation therapy uses high-energy X-rays to kill active cancer cells and prevent them from replicating. Radiotherapy can be administered 'externally' or 'internally'. The most common types33 are:

  • External radiotherapy: during external therapy, a patient lies on a table, and a machine concentrates a beam of high-energy infrared radiation on the cancer site. This is commonly known as Conventional External Beam Radiotherapy. It is best to remain as still as possible throughout the treatment, which only lasts a few minutes. The machine is operated outside the treatment room, but you'll be watched through a window or camera
  • Radiotherapy implants (internal): the use of radioactive implants is known as Brachytherapy. It involves inserting temporary metal wires or tubes near the cancer site. Surgery is sometimes required to place the implant near the cancerous cells. The duration the implant is left inside the body depends on the type and the severity of your cancer. If you receive a radioactive implant, you must stay in a controlled hospital facility for a few days until the implant is removed. This is to minimise any risk to other people
  • Liquid radiotherapy (internal) involves using radiotherapy injections, drinks or capsules. After radiotherapy, you will have to stay in the hospital until radioactivity decreases, as you could pose a risk to others. It doesn't cause long-term harm to the body. You will be discharged from the hospital once the radiation has fallen to a safe level
  • Intrabeam radiotherapy (internal): is also known as Intraoperative radiotherapy. An X-ray beam is delivered in doses to the inner surface of the colon cavity via a needle attachment. Compared to external radiotherapy, intrabeam therapy can reduce overall treatment time, enhance patient convenience, and potentially leads to dose escalation34

Targeted drug therapy

Targeted therapy is a type of treatment that uses drugs or given substances to 'target' specific proteins on the cell surface of a cancerous cell, controlling its growth and replication. They cause less harm to healthy cells than systemic chemotherapy or radiation therapy. Types of targeted drug therapy include:

  • Monoclonal antibody therapy: the body naturally produces antibodies in response to immune activation. These antibodies can be lab-made to help treat specific diseases, including colon cancer. The antibodies bind to specific target proteins on the cell surface of a cancer cell which destroys it
  • Angiogenesis inhibitors: angiogenesis refers to the growth of new blood vessels, specifically the formation of new capillaries.35 This treatment inhibits the formation of new blood vessels that cancerous cells need for survival, subsequently restricting blood supply to the tumour, preventing growth and inducing apoptosis (cell death)
  • Protein kinase inhibitor therapy: this treatment involves the administration of protein inhibitor substances to block the action of enzymes called protein kinases. Protein kinases are involved in cell signalling, growth and division. By blocking these enzymes, treatment may help keep cancer cells from growing. The development of therapeutic inhibitors of protein kinases has had wide success in anti-cancer therapy, with the potential for modulating a diverse range of diseases.36 This treatment is used to treat colon cancer and is therapeutically approved for treating breast, lung and renal cancers37

Immunotherapy

Immunotherapy is a therapy involving substances to stimulate or suppress the immune system to help the body fight cancer, infection, and disease. These substances can be made by the body or made in a lab to direct, restore or heighten the body's natural response to fighting cancer. Some types of immunotherapy only target specific cells of the immune system on a regional level, whereas others affect the immune system more generally (systemically). Despite its known benefits for malignant diseases like melanoma, and renal, bladder and lung cancer, colon cancer is not susceptible to immunotherapy.38 One study found that metastatic colorectal cancer rarely showed responses to checkpoint inhibition. This drug blocks checkpoint proteins made by immune cells to keep immune cells from killing cancer cells.39

Life after treatment

For the majority of those with colon cancer, treatment can successfully remove or destroy cancer. Unfortunately for some, colon cancer may never go away completely. Regular treatment with chemotherapy, radiation therapy or surgery may be required to control cancer for as long as possible. Many side effects of treatment, namely hair loss, mouth sores, loss of appetite, nausea, vomiting and skin changes, can persist after treatment ends, but some can continue.40 Some patients with colon cancer may have long-lasting issues with chronic diarrhoea, frequent urges to use the bathroom, and an inability to hold stool.41

Speak to your practitioner if you are worried about how your side effects will affect everyday activities - they can provide information for managing side effects and caring for yourself post-treatment.

Even if there are no signs of cancer remaining, it is recommended that you have physical examinations and tests every 3 to 6 months for the first two years after treatment, then every six months for subsequent years.41 The American Cancer Society recommends regular colonoscopy, proctoscopy, blood tests, or imaging tests after treatment ends.

Previous research on the association between physical activity and colon cancer has reported a risk reduction of around 30% compared to sedentary individuals.42 Extensive literature suggests that people who regularly engage in physical activity after treatment have a lower risk of colon cancer recurrence and mortality from cancer.43 Physical activity has been shown to alleviate the side effects of treatment, improve quality of life, optimise physical functioning, and reduce fatigue.41 

Beyond the benefits of treatment, several other lifestyle factors, such as reducing alcohol consumption, quitting smoking, vitamin D supplementation, and maintaining a balanced diet, have been associated with improved outcomes after the treatment of colon cancer.44 A diet rich in fibre, plant-based sources, fresh vegetables, fruits, whole grains, poultry, and fish increases longevity post-treatment, compared to those whose diet is high in refined sugars, fats, and red or processed meats.

Summary

Colon cancer is one of the leading cancers globally and is considered among the most life-threatening of cancer types. Potential symptoms of colon cancer include blood in stool, persistent changes in bowel habits, or constant lower abdominal pain. There are many different treatment options available, with some best suited to the most minor or most severe cases of cancer. Maintaining a healthy, well-balanced diet, maintaining physical activity and quitting drinking and smoking are essential lifestyle changes. Not only are these lifestyle changes evident in preventing colon cancer, but they are imperative for reducing the risk of recurrence post-treatment.

References

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Cristina is highly motivated and an engaging life scientist, with a deep and abiding personal interest in clinical science, functional medicine, health, and medical affairs.
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