Fast track — ArticlesPreoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial
Introduction
For rectal cancer treatment, the use of total mesorectal excision (TME) instead of conventional blunt surgery has led to substantial improvements in morbidity and survival.1 Preoperative short-term radiotherapy in combination with conventional surgery improves local control and survival.2 To investigate the value of short-term radiotherapy in combination with TME, the Dutch Colorectal Cancer Group initiated the TME trial.3 For a reliable assessment of the value of preoperative radiotherapy, surgical, pathological, and radiotherapeutical techniques were standardised and controlled for quality. Early results showed a decreased risk of local recurrence for irradiated patients at 2 years (2% vs 8%, p<0·001) without a difference in overall survival.3 After a median follow-up of 6 years, the effect of radiotherapy on local recurrence persisted (6% vs 11%, p<0·001), as well as the absence of a survival benefit.4 Because of the serious consequences associated with local recurrence, guidelines in the Netherlands and several other countries recommend preoperative radiotherapy for all rectal cancer patients with the exception of those with T1 tumours. Unfortunately, preoperative radiotherapy can induce serious side-effects such as faecal incontinence, sexual dysfunction, and secondary malignancies.5, 6, 7, 8, 9, 10, 11 In the absence of a survival benefit, for some patient groups the adverse effects might outweigh the benefits of decreased local recurrence. We report the effect of short-term radiotherapy on local recurrence, distant recurrence, and overall survival from the TME trial after a median follow-up of 12 years.
Section snippets
Patients
Patients were recruited in 118 European centres and one Canadian centre. Patients were eligible if they had clinically resectable adenocarcinoma of the rectum without evidence of distant disease. Tumours had to be below the level of S1/S2 with an inferior tumour margin located 15 cm or less from the anal verge as measured during withdrawal of a flexible coloscope or a rigid rectoscope. No upper age limit was given. Central and local ethics committees gave approval for the study and included
Results
Figure 1 shows the trial profile. Between Jan 12, 1996, and Dec 31, 1999, 1861 patients from 84 Dutch, 24 Swedish, ten other European centres, and one Canadian centre were included. 56 patients were considered ineligible after randomisation. The reasons for ineligibility were reported previously.3, 4
Of the 1805 eligible patients, 62 patients did not receive the intended treatment and 85 patients were treated with postoperative adjuvant treatment against protocol guidelines. Minor violations
Discussion
After a median follow-up of 12 years, preoperative short-term radiotherapy for patients with resectable rectal cancer decreases local recurrence rates by more than 50% relative to surgery alone, with a decreased overall recurrence rate. Compared with the results after a follow-up of 6 years, the relative risk reduction remains stable at about 50%. In previous reports of this trial,3, 4 the possibility that in some cases radiotherapy might not prevent but merely postpone local recurrence could
References (35)
- et al.
Mesorectal excision for rectal cancer
Lancet
(1993) - et al.
Late side effects and quality of life after radiotherapy for rectal cancer
Int J Radiat Oncol Biol Phys
(2010) - et al.
Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision
Lancet
(1986) - et al.
Radiotherapy does not compensate for positive resection margins in rectal cancer patients: report of a multicenter randomized trial
Int J Radiat Oncol Biol Phys
(2003) - et al.
Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial
Lancet
(2009) - et al.
Pre-operative imaging of rectal cancer and its impact on surgical performance and treatment outcome
Eur J Surg Oncol
(2005) - et al.
Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs conventionally fractionated radiochemotherapy
Radiother Oncol
(2004) Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial
N Engl J Med
(1997)- et al.
Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer
N Engl J Med
(2001) - et al.
The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma
Ann Surg
(2007)