Treatment strategies for colorectal cancer

Contents

• Early diagnosis of bowel cancer is critical
• Rectal bleeding and a change in bowel habit
• Diagnosing extent of disease (staging)
• Treatment of early stage colorectal cancer
• Surgical objectives
• Types of surgery for bowel cancer
  • Laparoscopic colorectal surgery
    • Technique
    • Benefits of keyhole surgery
    • Are there any concerns about this new technique?
    • Who is suitable for keyhole surgery?
• Treatment of advanced colorectal cancer
  • Adjuvant chemotherapy
  • Adjuvant radiotherapy
  • Neo-adjuvant therapy
• Resectable liver metastases
• Resectable lung metastases
• Brain and bone metastases
• Summary

Early diagnosis of bowel cancer is critical

Bowel cancer is a major health problem in the United Kingdom. Men and women are equally affected by the disease and improved survival is dependent on the diagnosis and surgical treatment of early stage disease (no cancerousMalignant, a tumour that may invade surrounding tissues or spread to distant parts of the body. spread to the lymphA watery or milky bodily fluid containing lymphocytes, proteins and fats. Lymph accumulates outside the blood vessels in the intercellular spaces of the body tiisues and is collected by the vessels of the lymphatic system. glands or distant organs). It is now widely accepted that most bowel cancers arise from pre-cancerous polypsGrowths on the surface of a mucous membrane (a surface that secretes mucous), lining any body cavity that opens to the outside of the body., and that early detection of these polyps (screening) offers the opportunity to prevent bowel cancer developing and to treat the condition before it progresses to an advanced stage. A smaller proportion of bowel cancers are inherited and a detailed family history by the specialist is required to identify those who may be at risk of the disease. 

Rectal bleeding and a change in bowel habit

The presentation of bowel cancer may vary from no symptoms at all to worrisome complaints such as rectal bleeding, a change in bowel habit, weight loss and anaemiaA reduced level of haemoglobin, which carries oxygen in the blood. Anaemia causes tiredness, breathlessness and abnormally pale skin. (low bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. count). Sometimes an abdominalRelating to the abdomen, which is the region of the body between the chest and the pelvis. swelling arising from the colonThe large intestine. may be felt by the patient or their doctor. Diagnosis is made by visualising the entire length of large bowel with a fibre optic camera (colonoscope) to locate the site of the tumourAn abnormal swelling., and obtain tissueA group of cells with a similar structure and a specialised function. samples for confirmatory diagnosis. Sometimes it is not possible to complete the colonoscopyExamination of the colon and rectum with a colonoscope, an imaging instrument that is inserted through the anus. for technical reasons or the patient may be considered unfit for the procedure. In such circumstances, a barium enemaA barium enema is a medical procedure used to examine and diagnose problems with the colon (large intestine). X-ray pictures are taken while barium sulphate fills the colon via the rectum. or CTThe abbreviation for computed tomography, a scan that generates a series of cross-sectional x-ray images-pneumocolon / virtual colonoscopy are acceptable alternative methods of examining the large bowel. 

Diagnosing extent of disease (staging)

Once a diagnosis of bowel cancer is confirmed, your surgeon will arrange additional tests in the form of a body scan – either CT or MRIAn abbreviation for magnetic resonance imaging, a technique for imaging the body that uses electromagnetic waves and a strong magnetic field. to establish whether the disease has spread to nearby lymph glands or perhaps to more distant organs like the liver or lungs. This process is known as staging the disease and is necessary before curative surgery is contemplated. Each newly diagnosed case is discussed at a colorectal cancer multidisciplinaryRelating to a group of healthcare professionals with different areas of specialisation. meeting made up of cancer specialists who will be involved in the patients care. At this meeting, it is established whether the patient has early or advanced disease and the best evidence based treatment plan is agreed and then recommended to the patient.  

Treatment of early stage colorectal cancer

The single most effective method of treating early stage bowel cancer is radical surgical excisionThe removal of a piece of tissue or an organ from the body. (removal) of the affected bowel. The term “early stage” disease implies that the cancerous growth is confined to the bowel wall and has not spread locally or to distant organs. Sometimes but not often, isolated spread of bowel cancer to the liver or lungs may also be treatable surgically by liver and chest specialists respectively, with good long term results.

Surgical objectives

The surgical options for treating early stage disease whether by the traditional “open” surgical technique or more recently, by laparoscopic or “keyhole” approach, aims to achieve the following;

• Removal of the segment of bowel containing the cancer with clear margins (no tumour cells identifiable at the cut ends of the bowel).
• Radical excision ensuring that sufficient lymph nodesSmall, rounded organs of the immune system that are distributed along the lymphatic system that filter lymph, a fluid derived from the blood, and produce antibodies and a type of white blood cells, lymphocytes. are harvested (generally greater than 12). This is particularly important because the absence of cancerous cells in any of the lymph glands harvested, indicates early stage disease with very good prognosisAn assessment of the likely progress of a condition. and potentially curative.   

Types of surgery for bowel cancer

Laparoscopic colorectal surgery

‘Keyhole’ or laparoscopic surgery is a new effective alternative technique to traditional open surgery for the treatment of colorectal disorders including bowel cancer. This novel method of minimal access surgery has rapidly gained wide acceptance amongst bowel surgeons and nearly all colorectal conditions can be treated using this approach.

Technique

A telescopic camera and working instruments measuring between 5-10mm in width are introduced through skin incisions (port-sites) into the abdominal cavityThe part of the body that contains the stomach, intestines, liver, gallbladder and other organs. distendedSwollen due to pressure coming from the inside with air or carbon dioxide. This enables the operation to be performed using working instruments. Tissue or parts of abdominal organs such bowel can be removed by lengthening the port-site incision to about 4cm, although this may vary depending on the patient’s overall size and body shape.

Benefits of keyhole surgery

In comparison t o open surgery, the key-hole approach results in less post-operative pain and early discharge from hospital. The reduced need for painkillers means that after the operation, patients are able to move around much earlier and have a rapid return of normal bowel function. Another significant advantage of minimal access surgery is that scarring from small wounds give better cosmetic results (see Figures 1-2) and minimise problems that can arise from internal scar tissueA type of connective tissue that forms after a wound heals. formation (adhesionsAn abnormal connection between two surfaces of the body.) after open abdominal operations. 

Are there any concerns about this new technique?

There were initial concerns that the procedure took a long time (4-7 hours), failed to harvest sufficient number of lymph glands (good predictor of prognosis) from the bowel specimens, and that there was an increased risk of leaving some cancer cells along the path of the port sites (port-site cancer spread). However, clinical trials in the United States, U.K and Europe comparing the keyhole technique with traditional open surgery for bowel cancer have refuted these concerns concluding that the two techniques are equivalent. Furthermore, the trials showed that the key-hole technique provided additional benefits outlined above.   

Who is suitable for keyhole surgery?

Most patients are suitable for laparoscopic surgery but the final decision rests with the operating surgeon. Some patients may not be suitable because for a variety of medical reasons including previous multiple open abdominal operations which can be easily established during consultation with your specialist. 

Treatment of advanced colorectal cancer

Where the disease has already spread to the lymph glands or surgical clearance is incomplete or threatened, additional treatment (adjuvant) with chemotherapy / radiotherapy or a combination of the two may be required. 

In some cases when bowel cancer is locally advanced (has spread to nearby or surrounding tissue), chemotherapy with or without radiotherapy may be given before surgery (neo-adjuvant therapy) to reduce the size of the tumour and increase the chance of surgical clearance of the disease. Patients with widespread (disseminated) disease or irresectable (see below) bowel cancer unresponsive to chemotherapy or radiotherapy, are referred to the palliative A therapy that gives relief from the symptoms of a disease rather than impacting on its course. Often known as 'end of life' care. care team for supportive therapy and review.   

Adjuvant chemotherapy

Generally chemotherapy is advised when the disease has spread beyond the bowel wall. It is an attempt to treat the whole body with chemical agents that are toxic to cancerous cells wherever they might lodge. Unfortunately, these agents are also toxic to normal cells and would explain some of the side effects of treatment suffered by some but not all patients. Standard systemicAffecting the whole body. chemotherapy involves various combinations of a variety of drugs such as Oxaloplatin, Irinotecan, 5 FU and more recently monoclonal antibodyOne of a group of special proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. agents. There is good evidence of survival benefit (patients live longer) with these chemotherapy agents when compared to those with advanced disease not receiving these drugs.

Adjuvant radiotherapy

Radiotherapy may also be indicated following sub-optimal surgery particularly in a confined area like the human pelvicRelating to the pelvis. region. This form of treatment is designed to directly destroy any residual cancerous cells within the operative field. Radiotherapy may also be given combined with chemotherapy and the rationale here is that the chemotherapy agents sensitize the malignantDescribes a tumour resulting from uncontrolled cell division that can invade other tissues and may spread to distant parts of the body. cells to destruction by radiationEnergy in the form of waves or particles, including radio waves, X-rays and gamma rays.. Radiotherapy treatment may be administered as long (6 weeks) or short (1 week) course treatment and is determined during the patient’s case review at the colorectal cancer multidisciplinary team meeting.

Neo-adjuvant therapy

This term describes treatment with chemotherapy, radiotherapy or a combination of the two before surgical intervention is contemplated. There is now good evidence from clinical trials that combining the two treatments before surgery leads to shrinkage of the cancer and in some cases the cancer is known to have disappeared completely! Furthermore, reducing the size of the tumour using this approach permits surgical removal which otherwise may not have been possible because of the original size of the tumour or its location. 

Resectable liver metastases

Cancer spread to the liver maybe resectable (removable) surgically with improved patient outcome provided it meets the following criteria:

• Tumour is confined to a section of the liver that can be safely removed.
• There is no sign of the cancer elsewhere.
• Major blood vessels and bileA fluid produced by the liver, which helps the fat ingested in food to combine with the digestive juices in the gut. channels within the liver can be preserved with good function of the remaining liver tissue.

The above criteria are by no means exclusive because with recent advances in technology, liver surgeons can now combine surgery with newer treatments like radiofrequency ablation (RFA) in order to provide greater flexibility in patient selection. Using this approach 40% five year survival rates have been reported.

Resectable lung metastases

Tumour deposits involving one or both lungs can also be resected surgically with good survival rates of 30% at five years. Similar criteria are adopted as with resectable liver metastases with or without radio frequency ablation.

Brain and bone metastases

Spread of colorectal cancer cells to the brain or bone indicates that the disease is advanced and incurable. However, much can now be done for these patients to improve their quality of life. Spread of disease to the bone results in weakening of bony tissue which can easily break. By fixing the affected bone using specialist orthopaedic prosthesisAn artificial device attached to the body. will minimise pain or discomfort [see article on Image guided radiofrequency ablation (RFA) of bone metastases]. Similarly, symptoms arising from spread of tumour cells to the brain can be treated effectively with special drugs that reduce brain swelling. Unfortunately, some patients fail to respond to the above treatment and are referred to palliative care specialists whose primary function is to manage patient symptoms and ensure that they are comfortable and do not suffer any pain or discomfort.

Summary

Cure for colorectal cancer is dependent upon early detection or prevention of disease. Laparoscopic (keyhole) surgery is a new and effective alternative technique for the treatment of bowel cancer. Advancing technology has seen the emergence of newer strategies for managing advanced disease with improved patient outcome.