Colorectal cancer (CRC) is the third most common malignancy in the ‘developed’ world, after lung and breast cancer, and causes about 16,000 deaths per year in the UK and 500,000 deaths world-wide annually. It usually occurs in the 7th or 8th decade and has a similar incidence in men and women. The overall five-year survival rate from large bowel cancer is approximately 50%. Despite improvements in diagnosis, surgical technique, perioperative care and postoperative therapies, the incidence and mortality from this disease has changed little over the past 40 years. Guidelines for urgent referral of patients with suspected cancer All ages • Palpable right-sided abdominal mass• Palpable rectal (not pelvic) mass • Rectal bleeding with looser stools and/or increased frequency for 6 weeks • Iron deficiency anaemia without an obvious cause (Hb <11 g/dl in men or <10 g/dl in postmenopausal women) Over 60 years • Persistent rectal bleeding without anal symptoms (soreness, discomfort, itching, lumps, prolapse and pain) • Looser stools and/or increased frequency without rectal bleeding for 6 weeks Modified Dukes’ classification of CRC Five-year survival Stage A Tumour confined to bowel wall 83% Stage B Tumour has invaded through the wall 64% Stage C Lymph node metastases 38% Stage D* Distant metastases <5% *Stage D was not part of Dukes’ initial classification TNM staging of CRC Stage Description T0 No evidence of primary tumour Tis Carcinoma in situ T1 Tumour invades the submucosa T2 Tumour invades the muscularis propria T3 Tumour invades into the subserosa, or into the non-peritonealized pericolic or perirectal tissues T4 Tumour directly invades other structures and/or perforates the visceral peritoneum N0 No lymph nodes involved N1 Between one and three lymph nodes involved N2 More than three lymph nodes involved Mx Metastases unknown M0 No metastases M1 Histological confirmed metastases to other organ(s) Changes in CRC management Colonic stents Self-expanding metal stents have been used over the last decade to relieve obstructed large bowel tumours in patients who are unfit for surgery The left colon is more amenable for stenting but, with increasing experience, stents can be safely placed and relieve obstruction throughout the large bowel. Lesions within 5 cm of the anal verge should be avoided, as stent migration may cause pain and tenesmus. Other complications that can occur with stenting include rectal bleeding and colonic perforation. Adjuvant chemotherapy Adjuvant chemotherapy is aimed at eradicating micrometastic cancer cells before they are refractory to intervention. The benefit from this treatment is small, with around 5–10% survival improvement at 5 years (5–10 lives saved per 100 treated). For the past 40 years, 5-fluorouracil (5-FU) has been the most widely used chemotherapeutic agent for large bowel cancer. Its metabolites bind to thymidylate synthase and this inhibits synthesis of thymidine, DNA and RNA. Based on current evidence, combining 5-FU and folinic acid should be regarded as the ‘gold standard’ chemotherapy for Dukes’ C colon cancer. Role of portal vein infusion Although a meta-analysis suggested portal vein infusion might have some benefit, the results from the largest single trial (AXIS) to date showed that there was no significant advantage with this new therapy over surgery alone. Other chemotherapeutic agents New drugs (e.g. irenotecan, oxaliplatin, raltitrexed) can be useful in advanced CRC. Irenotecan, a DNA topoisomerase I inhibitor, can be used to improve survival by 2–3 months in those who fail to respond to 5-FU. Immunotherapy This has been tried in CRC by using immunostimulatory approaches, such as vaccination with autologous tumour cells ± BCG, vaccinations against tumour-associated antigens or the use of monoclonal antibodies targeted against tumour antigens, with the aim of enhancing the innate immune response against the cancer. Further study is necessary, but so far immunotherapy results have been disappointing. Gene therapy The correction of a single gene defect and the use of virus-directed enzyme prodrug treatment are two new techniques that are still in the early stages of development, but may have a role in the future. Radiotherapy Adjuvant radiotherapy Following apparent curative surgery, 3–32% (largely dependent on surgical technique) of rectal cancers recur locally in the pelvis and usually within 2 years. Over 80% of patients with tumour involvement of the radial resection margins develop pelvic recurrences. A combination of surgery and radiotherapy may allow the macroscopic disease to be adequately excised, while the microscopic malignant cells at the radial resection margins are dealt with by the radiation. Advantages of preoperative over postoperative radiotherapy :• well-oxygenated cells are being irradiated • anatomical planes are intact, making targeting easier • the small bowel is not in pelvis, therefore less risk of being irradiated • less morbidity due to smaller doses • ‘downstaging’ may allow more sphincter-saving operations • compliance and tolerance are better.