Treatment of colon and rectal cancer

Most patients (except those with advanced metastatic disease and no evidence of imminent bowel obstruction) will be advised to undergo an operation.

 

For rectal cancer there are several operations currently practised depending on the situation and staging of the tumour. For very low cancers, it is impossible to safely get below the cancer and leave enough uninvolved rectum to allow a ‘joining up‘ operation top be performed. The lower rectum and anus are therefore taken in the operative specimen and the patient comes out of the procedure with a colostomy (i.e. the bowel drains through a stoma that is brought out onto the anterior abdominal skin wall, emptying into a bag. The perineum - where the anus previously was - is sewn over). This operation is called an abdoperineal resection/excision (APR or APE).

 

In recent years, improved surgical technique has allowed surgeons to perform ‘joining up’ operations for lower rectal cancers (these are called anterior resections and the bowel above the cancer is sewn to the bowel below the resected cancer such that the patient comes out of the operation defaecating normally via the anus).

 

For higher rectal cancers, the anterior resection is the usual operation although for locally advanced tumours at any site the surgeon may find that he cannot remove the whole growth due to its local extension and fixity and he will then defunction the bowel by severing it (and sewing it over) above the obstructing tumour whilst bringing the proximal bowel end out as a colostomy (Hartmann procedure). The latter is obviously not a curative operation, unlike the rest of the operations just cited.

 

For colonic cancer, once again the operation depends on the situation of the growth but only certain operations are possible due to the vascular supply to normal colon.

 

For cancers of the caecum and ascending colon, a right hemicolectomy is performed, a transverse colectomy for those arising in the transverse colon and a left hemicolectomy for those arising in the descending and sigmoid colon. In each case the bowel is joined up end-to-end such the patient comes out of the procedure with a normal functioning bowel (although sometimes when the patient presents with an obstructing cancer the surgeon may leave in a temporary/loop colostomy above the operation site, until the previously distended bowel has settled).

 

Operative mortality associated with these operations should be low and figures of around 1% are normal, but when there are complicating factors – especially obstructing and relatively advanced cancers penetrating through the bowel wall (and most dangerous of when there is perforation of the bowel wall with spillage of bowel contents into the abdominal cavity), then the mortality rises.

 

Other complications are numerous and include those of any large abdominal operation (e.g. deep venous thrombosis pneumonia etc.) and those to do with re-establishment of bowel function.

 

The role of radiotherapy and chemotherapy, as adjuncts to surgery, has undergone many changers over the last decade.

 

For Stage B (T2) cases of rectal cancer, there is a role for pre-operative radiotherapy to the pelvis. The perceived gain of this therapy is that the x-ray therapy given prior to the operation sterilises any tumour cells at the periphery of the operative field that could shed off and metastasise around the time of operation; it is also perceived to reduce the likelihood of regrowth of tumour around the operative site after the operation. The courses of pre-operative radiotherapy are usually short, often as short as a one week course.

 

In the postoperative period, and for rectal cancer patients who have B2 or C2 disease (the stage C2 being one where the disease is both through the bowel wall and into adjacent tissues and involving the lymph nodes)- T3 cases_ and who did not receive pre-operative radiotherapy, there is a case for post operative pelvic radiotherapy – usually given on every week day over some weeks (e.g. four weeks). The patient attends daily and lies on a treatment couch whilst the beam is shone from several directions to concentrate the rays on the posterior pelvis. The side effects are those of disturbed bowel, such as nausea and perhaps some looseness of the bowel (at a time when the bowels are already fighting to re-establish normal rhythm, perhaps through a colostomy) but this is usually not severe and the course is usually well tolerated.

 

There is no routine role for post-operative radiotherapy in the therapy of colon cancer cases. It seems that the local recurrence problem encountered in rectal disease does not apply for colonic cancer and routine radiotherapy is not used.

 

The role of chemotherapy in the post-operative setting is now proven for both colon and rectal cancer. In cases of B2 and C disease, there are survival gains in those patients receiving courses of 5-fluorouracil based chemotherapy in the post-operative period and the combination of an infusional 5-fluorouracil based regime with oxaliplatin is now standard best adjunctive therapy for higher risk patinet with cancer of colon or rectum. An orally active 5-fluorouracil (pro-)drug: capecitabine may replace the %-fluorouracil in some settings. The course of chemotherapy may last four to six months, and, as fluorouracil is one of the better tolerated drugs, the chemotherapy rarely disturbs the patients much.

 

Where the patient relapses after already receiving oxaliplatin and 5-fluorouracil, it is unlikely that a further good response will occur to a re-challenge to the same drugs (unless a large amount of time has elapsed) and then alternative chemotherapy is a topic of great research interest.The drug irinotecan is the alternative chemotherapy drug of choice and its combination with a humanised monoclonal antibody directed at the (tumour cell) surface receptor protein EGFR - the drug being called Cetuximab - seems to increase the efficacy of the straight chemotherapy alone treatment. we might note that we have discussed the use of drugs targeting EGFR before (see Trastuzumab and breast cancer therapy). EGF is an oncogene that drives tumour progression and the use of an inhibitor to its 'working' protein product seems to enhance efficacy of therapy. Another analogous drug is bevaciszumab/avastin. In a comparable way to cetuximab, this agent targets vascular growth factors (so essential for any tumour to grow)and it too seems to enhance the efficacy of standard chemotherapy. Where a rectal cancer is inoperable, but without evidence of spread further afield, then some interesting chemo-radiotherapy programmes are currently under investigation and involve the delivery of synchronous 5-fluorouracil based chemotherapy and pelvic radiotherapy. Good regressions can be obtained but this approach is not recommended for operable growths.

 

Where the patient presents with metastatic disease from colorectal cancer, then after any primary operation to ensure continuity of bowel patency, then a chemotherapy programme is recommended and once again based on 5-fluorouracil/oxaliplatin - unless this has been previously delivered when irinotecan, cetuximab and bevaciszumab are sequentilally employed.

 

The treating doctor is behoven to closely monitor the therapy and that he is indeed gaining objective responses (the monitoring being by serial CT/MR scanning of the disease and blood tests e.g. CEA and CA 19-9).

 

Occasionally, the patient presents with a late and apparently single metastasis in the liver (or elsewhere) and here there may be a case for surgical resection, or if small and discrete in the liver thermo-ablation (focussed heat therapy).

 

Plowman Oncology London (e-mail: postmaster@pnplowman.demon.co.uk)