Bowel Cancer symptoms and treatment

The presenting features of colon cancer are often non-specific, such as weight loss and anaemia due to occult blood loss. Rectal and distal colon cancers, on the other hand, usually present with bleeding and/or altered bowel habits, symptoms that overlap with less serious, and more common conditions. A fifth of patients may present with acute bowel obstruction or peritonitis due to bowel perforation. 1,2

Endoscopy (colonoscopy or flexible sigmoidoscopy) is increasingly the investigation of choice in diagnosis rather than barium enema, and can be used to remove polyps or take tissue samples for biopsy. 3

A new form of imaging, CT colonoscopy (virtual colonoscopy), shows promise and guidance on its use has been issued. 4 Computed tomography (CT) and magnetic resonance (MR) scans are used to stage tumours and plan treatment.

The 1932 Dukes’ classification of tumours into stages A-C 5 is still used today but newer, more precise clinico/pathological staging based on TNM is being phased in. Table 7.1 shows TNM stages together with approximations to Dukes’classification. 6

Download this table (15KB)

Only 10% of patients are diagnosed as stage 0 or stage I; the remainder are distributed equally between stage II, III and IV. As the average GP in the UK will see only one new case of colorectal cancer every year and because bowel cancer symptoms can be common, non-specific and may not occur until the cancer is advanced, early diagnosis is unusual. 7 Prompt referral for all patients with suspected colorectal cancer is recommended. 3

Surgery is the main form of treatment and around 80% of patients undergo surgery. 3 Despite the removal of visible tumour, cancer may recur in up to half of rectal patients undergoing surgery, usually within 24 months. 8

To reduce recurrence rates to under 5% and thereby increase survival, a different surgical technique, total mesorectal excision (TME) is now routinely used for middle and lower third rectal cancers. 9-11

There are significant differences in patient outcome relating to the surgeon carrying out the procedure; this is directly related to variation in surgical technique. One study found that patients operated on by a general surgeon were 3.4 times more likely to develop a local recurrence than those operated on by a specialist surgeon. 12 Guidance produced by the National Institute for Health and Clinical Excellence (NICE) describing how NHS cancer services should be organised recommend that colorectal cancer patients should be treated by a multidisciplinary team that includes a specialist colorectal surgeon.

Evidence suggests that a six-month course of intravenous chemotherapy following surgery significantly reduces the chance of colon cancer recurring and improves five- year survival by 5-6%. 13 Chemotherapy should be made available to patients following surgery for Dukes’ stage C if they are well enough to tolerate it; patients with metastatic or locally inoperable primary cancer (stage D) require careful evaluation, and may be appropriate for palliative chemotherapy and/or radiotherapy. Whether to use chemotherapy in Dukes’ stage B tumours should be discussed between patients and their oncologists.

5-fluorouracil (5-FU) and folinic acid are the standard treatments with the options of adding irinotecan and oxaliplatin. 14 Irinotecan may also be given as a second-line treatment.

Evidence for the benefits of adjuvant chemotherapy for rectal cancer patients is less clear but initial results from randomised trials show significant improvement in disease free survival. 15 Combined radiotherapy and chemotherapy delivered before surgery (so-called ‘neoadjuvant therapy’) may reduce the chance of recurrence of rectal cancer and may improve the overall survival. 16

For patients with advanced disease the median survival is around six months and chemotherapy can improve median survival by three to four months. 17 It is now mandatory in the NHS for each patient’s management to be planned by multidisciplinary teams (MTD), resulting in a rising proportion of patients being referred for chemotherapy. Each MTD is to be offered training based on the Pelican centre course as part of the NHS Bowel Cancer Programme. 10,18

Several drugs, including bevacizumab (Avastin) and cetuximab (Erbitux), are being evaluated in clinical trials as single agents or in combination, for both first and second line treatment. 19

Other clinical trials are investigating the optimum dose schedules and how best to administer chemotherapy. Results from these trials may have implications for current treatment protocols and may result in changes in drugs routinely used to treat colorectal cancer.

Over the past ten years the number of treatment options for colorectal cancer has increased with many more therapeutic agents in clinical development. New targeted therapies have been designed whose action is directed against vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR). 20 These include biological therapies that are being tested in new combinations with chemotherapy for both early stage and advanced disease.

One of the greatest challenges in treating colorectal cancer is the problem of drug resistance. DNA microarray analysis is proving a powerful tool to identify markers that will help to predict the best treatment options for individual patients. 21