Treatment of non-localised, non-metastatic rectal cancer

The standard treatment for rectal cancer is surgical removal of the rectum and mesorectum. Is the prognosis for non-metastatic rectal cancer that extends beyond the bowel wall improved by adding radiotherapy and/or chemotherapy to surgery? To answer this question, we conducted a review of the literature using the standard Prescrire methodology. Randomised trials conducted before optimal surgery was developed showed that, compared with surgery alone, postoperative radiotherapy reduced the risk of local recurrence and possibly increased overall survival. In the only randomised trial in which the mesorectum was systematically removed, preoperative radiotherapy had no impact on overall survival but reduced the risk of local recurrence (5% at 10 years, versus 11% without radiation therapy).This result was statistically significant in patients with lymph node involvement. Radiotherapy for rectal cancer carries a risk of faecal incontinence (about 50% of patients), small bowel occlusion, and secondary cancers (about 1 in 15 patients). In patients who receive neither radiotherapy nor chemotherapy before surgery, postoperative chemotherapy based on fluorouracil or the tegafur + uracil combination increases overall survival by about 5% at 5 years, in absolute numbers, but carries a risk of serious adverse effects, including haematological and gastrointestinal disorders. Eight randomised trials suggest that the beneficial effects of post-operative chemotherapy and radiotherapy persist and are additive. However, the same is true for adverse effects. In four randomised trials, adding chemotherapy to preoperative radiotherapy roughly halved the risk of local recurrence. In three randomised trials, preoperative chemoradiotherapy appeared to be slightly more effective than postoperative chemoradiotherapy in terms of recurrence, and to carry a similar or lower risk of serious adverse effects, without improving overall survival. Preoperative chemoradiotherapy carries a risk of unnecessarily exposing between 8% and 18% of patients to adverse effects, as their tumour is found to be less extensive than initially thought. There is no firm evidence that postoperative chemotherapy is beneficial after preoperative radiotherapy. Preoperative treatments do not prevent removal of the anal sphincter. The probable benefits of adjuvant therapies in surgical patients must be weighed, on a case by case basis, against the potential risk of serious adverse effects and complications.