A short course of radiation therapy followed by high quality surgery is the most effective treatment for patients with operable rectal cancer. These are the findings of two Articles published in this week's edition of The Lancet.
The standard treatment for rectal cancer is surgery. But just removing the tumour leaves a risk of the cancer recurring in the same area—this recurrence is difficult to treat and is incurable in the majority of patients. Previous trials have shown a reduction in local recurrence with radiotherapy and chemotherapy before or after surgery. However, radiotherapy is costly and is associated with an increased likelihood of long-term complications including impaired bowel function, incontinence, and sexual dysfunction. Therefore targeting radiotherapy to patients considered at high risk of local recurrence, such as those with involvement of the circumferential resection margin*, would be ideal.
To provide further evidence, Professor Robert Steele and colleagues did the Medical Research Council (MRC) CR07 and the National Cancer Institute of Canada (NCIC) C016 trial. This study compared the selective use of chemoradiotherapy after surgery for patients who had involvement of the circumferential resection margin with the routine use of a one week course of radiotherapy before surgery, on the risk of local recurrence. In total, 1 350 patients with rectal cancer were recruited from the UK, Canada, South Africa, and New Zealand between March 1998 and August 2005. Patients were randomised to receive five daily treatments of radiotherapy followed by surgery, or surgery followed by 25 treatments of chemoradiotherapy for those at high risk of local recurrence.
Findings showed that after 3 years, 4.4% of patients in the preoperative radiotherapy group had local recurrence of the cancer compared with 10.6% of patients in the postoperative group. In addition, preoperative radiotherapy patients had a greater likelihood of disease-free survival (77.5%) than the postoperative patients (72%) at three years. However, overall survival did not significantly differ between the groups—330 patients died (157 in the preoperative radiotherapy group vs 173 in the selective postoperative chemoradiotherapy group).
Recent improvements in surgical techniques, including total mesorectal excision** have also improved patient outcomes. In a second Article, Phil Quirke from the University of Leeds, UK, and colleagues assessed the importance of circumferential resection margin and the plane of surgery (amount of tissue removed around the tumour) achieved by the surgeon on local recurrence of cancer, in 1156 patients involved in the MRC CR07 and NCIC-CTG C016 trial.
Findings showed that 128 patients (11%) had involvement of the circumferential resection margin, and the plane of surgery was classified as good (mesorectal) in 604 (52%), intermediate (intramesorectal) in 398 (34%), and poor (muscularis propria plane) in 154 (13%).
A negative circumferential resection margin and a superior plane of surgery were associated with low recurrence rates. At 3 years, 6% of patients with a negative circumferential margin had local recurrence compared with 17% of patients with a positive circumferential margin. In addition, 4% of patients in the mesorectal group had local recurrence compared with 7% of patients in the intramesorectal group, and 13% of patients in the muscularis propria plane group, at three years. However, for any plane of surgery achieved, short-course radiotherapy before surgery reduced recurrence by about half.
The authors say: "At present, only 50% of rectal cancer surgery is done in the mesorectal plane, suggesting that a further decrease in local recurrence rates might be obtained by improving the plane of surgery achieved…[This could] be achieved through education and surgical tuition".
In an accompanying Comment, Dr Robert Madoff from the University of Minnesota in Minneapolis, USA, says these findings show:"That preoperative radiation can mitigate but not eliminate the adverse effects of imperfect surgery. The best outcomes occurred when preoperative radiation was followed by optimum surgery…The next challenge is to understand which patient needs what therapy to maximise his or her chance for cure."
Professor Phil Quirke, University of Leeds, Leeds, UK. T) +44 (0)795 837 2464 (mobile) E) patpq@leeds.ac.uk
Professor Robert Steele, Ninewells Hospital, Dundee, Scotland, UK. T) +44 (0) 775 380 2144 (mobile) E) r.j.c.steele@dundee.ac.uk
Dr Robert Madoff, University of Minnesota, Minneapolis, USA. T) +1 612 625 7992 E) madoff@umn.edu
For full Articles and Comment see: http://press.thelancet.com/rectalcancer.pdf and http://press.thelancet.com/surgery.pdf
Notes to Editors:
*The presence of a tumour within 1 mm of the circumferential margin, which is associated with a high risk of local recurrence and poor survival.
** Total mesorectal excision removes the rectum and its mesentery as a single anatomical package, minimising the likelihood of an involved circumferential resection margin, a major risk factor for local recurrence and poor survival.
Journal
The Lancet