Brendan
J Moran MCh FRCSI, Consultant Colorectal Surgeon, Colorectal Research Unit, North Hampshire Hospital, Basingstoke,
Hants RG249NA, United Kingdom,
Local recurrence is common, disabling
and almost inevitably fatal complication following rectal cancer surgery. Local
recurrence rates as high as 50%, even after a “curative” resection, were not
uncommon in the 1970-80s1. Two strategies have evolved to reduce
local recurrence, namely refinement of surgical techniques, in particular Total
Mesorectal Excision (TME) and the use of adjuvant radiotherapy (RT).
TME,
popularised by Heald2, involves the complete excision of the
lymphovascular package of the rectum surrounded by an intact mesorectal fascia.
Using this technique local recurrence rates of less than 5% have been achieved3.
However, very low rectal cancers, and anterior tumours (particularly in a narrow,
inaccessible male pelvis) have a higher risk of recurrence compared to mid
rectal, upper rectal and posterior cancers. This has led most TME surgeons to
select high-risk patients for pre-operative RT4.
The
second major strategy has been the use of adjuvant RT. In Europe, this is
generally given pre-operatively, whereas in the USA, post-operative treatment
has been the standard, following the NIHCC 1990 statement5. The only
randomised trial to compare pre- and post-operative RT found that pre-operative
treatment (given in fractions of 5Gy for 5 days) was associated with fewer local
recurrences (13% versus 22%)6. This RT regime has been used in the
two Stockholm trials7,8 and the Swedish Rectal Cancer Study Group
trial9 and demonstrated a reduction in local recurrence rates from
30%, 21% and 27% to 15%, 10% and 11% respectively. The high rates of early
morbidity of RT in the earlier trials has been reduced by refinement of delivery
to a 4-field technique, with sphincter protection in those patients planned to
have a restorative surgical procedure. However, the late effects of RT are not
fully known. As a result of RT associated morbidity and the published benefits
of TME, the Stockholm surgeons adopted TME, by surgical workshop training
programmes in the early 1900s in addition to RT. A significant reduction in
local recurrence rates with TME led to a policy of selecting low risk patients
not to receive pre-operative RT. The results of this population study were
compared to the Stockholm trials10. Local recurrence was reduced by
50% and the number of abdomino-perineal was also reduced by 50% in the whole
population of 1.9 million people. In the population study 56% had preoperative
radiotherapy and there appeared to be additional benefits when patients had both
RT and TME.
The
Dutch Colorectal Cancer Group has endeavoured to answer this question in a
randomised trial in patients with resectable rectal cancer11. All
participating surgeons were trained in the technique of TME. Patients were
randomised to pre-operative RT (5 x 5Gy) or no RT and all patients
underwent major surgical excision (anterior resection of the rectum,
abdomino-perineal excision, or Hartmann’s procedure) with TME. A total of 1861
patients were included in the study, of which 1759 were eligible for analysis.
The rate of local recurrence at two years was 2.4% in the RT plus surgery group
and 8.2% in the surgery alone group (p<0.001). The report concluded
“short-term pre-operative radiotherapy reduces the risk of local recurrence in
patients with (operable) rectal cancer who undergo a standardised TME”. The
size and statistical power of this study suggests that radiotherapy is not an
option but a requisite for resectable rectal cancer.
A
detailed analysis of the data11 suggests that a measure of caution
and refection is called for. The study was designed to only include resectable
rectal cancers, but 23% (408 of 1759) had tumour-involved margins and/or tumour
spillage. The nature of pre-operative radiological assessment of patients in the
study was not detailed, and must be considered to be less than optimal. It is
likely that with modern MR imaging, some of these patients would have been
deemed locally advanced and excluded from the trial, with a reduction in local
recurrence in both arms of the study.
Local
recurrence rates at two years are the principal data supporting RT, however the
authors detail the follow-up for patients without local recurrence as a median
of 24.9 (range 1.1 to 56) months, and admit that only 54% of patients had 2 year
follow-up. Such short follow-up biases in favour of RT as RT delays presentation
with local recurrence. In Stockholm, after 2 years follow-up, local recurrence
without RT was evident in 80% of those destined to recur, but when pre-operative
RT was used 64% (Stockholm I)7 and 72% (Stockholm II)8 of
recurrences had presented by 2 years.
Whilst
local recurrence is important there are other equally important endpoints. Local
recurrence identified in patients with distant metastases often requires no
intervention, as death often intervenes before local recurrence becomes
symptomatic. Overall survival at 2 years in this study was about 82% for each
group, with no difference in the survival curves until nearly 4 years when those
in the surgery alone group seemed to fair better. This is hard to understand, as
overall recurrence (local and distant) was greater in the surgery-only group.
One possible explanation could be late RT related morbidity. Although the late
effects of high dose RT are not known, RT in this study was associated with
early morbidity, including a greater operative blood loss and more perineal
wound complications in patients who had an abdomino-perineal excision (26%
versus 18%; p=0.05)11. Acute toxicity from RT occurred in up to 19%,
and lumbosacral plexopathy in 10% of patients, with some experiencing chronic
pain12.
A
major change of practice to the universal use of RT in rectal cancer management
cannot be justified on the immature data of the Dutch trial11,12, as
the adverse effects of RT in all patients, and the benefits with regard to
prevention of symptomatic local recurrence and survival in truly resectable
patients are not yet known. An important documented factor has been omitted, in
that the local recurrence in Holland prior to the widespread use of TME was over
30% compared to approximately 5% in the current report. As subgroup analysis of
2-year rates of local recurrence failed to show a significant benefit for RT in
Stage I and IV disease and cancers with a distal margin more than 10cm from the
anal verge, the current report11, already being hailed as a landmark,
is likely to be mis-interpreted. The conclusion of this important study should
say that TME dramatically reduces local recurrence and selective use of
short-course pre-operative RT, in addition to TME, reduces local recurrence in
patients with a threatened margin. Surgical precision, sometimes with adjunctive
pre-operative RT, optimises outcomes in rectal cancer surgery.
References
1.Pahlman L, Glimelius B. Local recurrences after surgical treatment of
rectal carcinoma. Acta Chir Scand 1984; 150: 331-335.
3.Heald RJ, Moran BJ, Ryall RD, Sexton R, Marfarlane JK. Rectal cancer: The
Basingstoke experience of total mesorectal excision, 1978-1997. Ann Surg 1998;
133: 894-899.
4.Edwards DP, Mortensen NJM. Is radiotherapy for rectal cancer indicated if
surgery is optimised? Eur J Surg Oncol 2001; 27: 442-445.
5.NIH consensus conference. Adjuvant therapy for patients with colon and
rectal cancer. JAMA 1990; 264: 1444-50.
6.Pahlman L,
Glimelius B, Graffman S. Pre- versus postoperative radiotherapy in rectal
carcinoma: an interim report from a randomized multicentre trial.Brit J Surg 1985; 72: 961-6.
7.Preoperative
short-term radiation therapy in operable rectal carcinoma. A prospective
randomized trial. Stockholm Rectal Cancer Study Group.Cancer1990; 66: 49-55.
8.Randomized study
on preoperative radiotherapy in rectal carcinoma. Stockholm Colorectal Cancer
Study Group. Ann Surg Oncol 1996; 3: 423-30.
9.Improved survival
with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal
Cancer Trial. N Engl J Med 1997; 336: 980-7.
10.Lehander Martling
A, Holm T, Rutqvist L-E, Moran BJ, Heald RJ, Cedermark B. Effect of a surgical
training programme on outcome of rectal cancer in the County of Stockholm.
Lancet 2000; 256: 93-96.
11.Kapiteijn E,
Marijnen CAM, Nagtegaal ID et al. Preoperative radiotherapy combined with total
mesorectal excision for resectable rectal cancer. N Engl J Med 2001; 345:
638-646.
12.Kapiteijn E, Klein Kranenbarg E, Steup WH et al. Total mesorectal
excision (TME) with or without preoperative radiotherapy in the treatment of
primary rectal cancer. Eur J Surg 1999; 165: 410-420.
