Rune Sjödahl, Sweden
Preoperative or postoperative adjuvant treatment?
There has been much debate on the timing of the adjuvant treatment with regard to the surgical resection. Postoperative radiotherapy can be selective, based on operative
findings and the pathological report. However, that advantage is gradually being less important as preoperative imaging of the tumour growth and its spread is steadily
improving. A documented disadvantage of the postoperative radiotherapy is that it may be delayed because of postoperative complications. This was noted in the recent
Adjuvant X-ray Infusion Study (AXIS) trial in Britain. Among the patients allocated to preoperative radiotherapy 96% received the planned treatment but only 56% of those
randomised to postoperative radiotherapy could obtain that (1). To attain the same effect on microscopic tumour disease about 15-20 Gy higher radiation doses are required
than when radiation is given before surgery. Accordingly, postoperative radiotherapy with its higher doses has more complications than preoperative radiotherapy,
particularly of the small bowel in case of APER, and of the "neorectum" in case of a low pelvic anastomosis (2).
Randomised radiotherapy trials
The Swedish rectal cancer trial (SRCT) included 1,168 patients during 1987-90 (3). They were randomised between surgery alone, and surgery immediately after a
short-term regimen of high-dose fractionated preoperative radiation, i.e. 25 Gy during five days. The local recurrence rate for all resected patients, including also
those without microscopic radicality, was reduced from 27% to 11%, and the overall 5-year survival increased from 48% to 58%. SRCT was the first randomised study that
could demonstrate a statistically significant increase in survival. The Stockholm II trial included 557 patients during 1987-1993 and was partly reported within the SRCT.
Also this study showed a statistically significant improvement in survival (4).
One criticism against SRCT and the other radiotherapy trials is that they do not reflect the modern surgery of rectal cancer, including perimesorectal clearance and
total excision of the mesorectum, possibly with the exception of high rectal cancer. Local recurrence rates of 23%-46% (average 29%) for surgery alone in trials testing
adjuvant treatment indicate not optimal surgical technique and should be compared with 5%-10% now being reported from various centres (5-9). Obviously different
standards of surgery must be avoided as control arm.
Thus there is need for an evaluation of the effect of short term preoperative radiotherapy together with optimal surgery. There are, however, some data in uncontrolled
series on total mesorectal excision (TME) and radiation.
Recently a study was published where a curative abdominal procedure for rectal cancer was performed in 381 patients in 1995-1996. The total number of patients was 447,
i.e. 85% were operated with an intention to cure. Total mesorectal excision was done in 318 patients but due to various reasons not in 63 patients. Preoperative
radiotherapy was given to 196 patients in the TME group and after a follow up of 2-4 years only 3 patients had developed a local recurrence (1.5%). Out of 122 patients
who did not receive radiotherapy local recurrence was diagnosed in 11 patients (9.0%) (8). This gives support to the opinion that preoperative radiation can reduce the
rate of local recurrence also when optimal surgical technique is used.
Functional morbidity of radiation
At follow up with a questionnaire in 171 patients at least five years after the Swedish Rectal Cancer Trial the bowel frequency was twice as high in the radiated as in
the surgery alone group. Incontinence for loose stools, urgency, and disordered evacuation were more common after radiation. The radiated patients reported in 30% that
their social life was restricted by the bowel dysfunction while only 10% of those in the surgery alone arm had the same experience. During 1987-1990 the anal canal with
its surrounding sphincters was radiated as well as the rectal remnant.
Personal view
Preoperative rather than postoperative radiation should be preferred as it is more dose effective and has less adverse effects. The radiation field is focused on the
tissue at risk for microscopic cancer disease and the dose should be adequate. Preoperative radiotherapy can decrease the rate of local recurrence with at least 50%.
Improved imaging techniques will identify patients with stage I (Dukes´A) lesions as well as those with distant metastases already before surgery so they can be excluded
from radiation. Postoperative radiation is less effective, has more adverse effects, and has less compliance. Low rectal tumours have a high risk for local recurrence
and preoperative radiation should be offered all patients (except the oldest) who will have an abdominoperineal resection.
Recent reports of local recurrence rates after surgery alone of 5%-10% mean that in patients undergoing optimal surgery a reduction of 50% of the local recurrence rate
implies that the absolute number of patients who will benefit from radiation is decreased. As there is a risk for overtreatment it is mandatory to obtain more knowledge
about long-term adverse effects in order to diminish them and make radiation treatment as safe as possible. There is still no general agreement about some crucial
questions, for instance whether radiation shall be given to everybody with local disease, or only to risk groups, or not at all if surgery alone has a local recurrence
rate of 5%-10% .
References
1. James R. Perioperative radiotherapy (RT) and intraportal 5-fluorouracil (5-FU:PVI) in the adjuvant treatment of colorectal cancer. Adjucant X-ray Infusion Study (AXIS) trial. Dis Colon Rectum 1999, 42, A63.
2. Påhlman L, Glimelius B. Pre- and postoperative radiotherapy in rectal and rectosigmoid carcinoma: report from a randomized multicenter trial. Ann Surg 1990, 211, 187-195.
3. Swedish Rectal Cancer Trial. Local recurrence rate in a randomized multicentre trial of preoperative radiotherapy compared with operation alone in resectable rectal carcinoma. Eur J Surg 1996, 162, 397-402.
4. Stockholm Rectal Cancer Study Group (II). Randomized study on preoperative radiotherapy in rectal carcinoma. Ann Surg Oncol 1996, 3, 423-430.
5. Mac-Farlane JK, Ryall RDH, Heald RJ. Mesorectal excision for rectal cancer. Lancet 1993,341, 457-460.
6. Arbman G, Nilsson E, Hallböök O, Sjödahl R. Local recurrence following total mesorectal excision for rectal cancer. Br J Surg 1996, 83, 375-379.
7. Dahlberg M, Glimelius B, Påhlman L. Changing strategy for rectal cancer is associated with improved outcome. Br J Surg 1999, 86, 379-384.
8. Lehander-Martling A, Holm T, Rutqvist L, Moran B, Heald R, Cedermark B. Effect of a surgical training programme on outcome of rectal cancer in the county of Stockholm. Lancet 2000, 356, 93-96.
9. Carlsen E, Schlichtling E. Guldvog I, Johnson E, Heald RJ. Effect of the introduction of total mesorectal excision for the treatment of rectal cancer. Br J Surg 1998, 85, 526-529.
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