Correspondence
Radiotherapy for Rectal Cancer
N Engl J Med 1997; 337:346-348July 31, 1997
- Article
To the Editor:
In the Swedish Rectal Cancer Trial (April 3 issue)1 more than 100 surgeons at 70 hospitals operated on 1168 patients in three years — fewer than 17 patients per hospital in three years, or fewer than 6 patients per hospital per year. With more than 100 surgeons participating, each on average performed fewer than four operations per year.
In this trial, the local-recurrence rate for Dukes' stage A cancers (4 percent after radiotherapy plus surgery and 12 percent after surgery alone) is unacceptably high and reflects less-than-adequate surgical techniques.
As noted in the discussion, it is possible to obtain “very low rates of local recurrence and good survival without radiotherapy.” From 1980 to 1991, 666 patients with rectal cancer underwent surgery with curative intent at the Cleveland Clinic (unpublished data). Large bulky tumors were present in 18.2 percent of patients, who were selectively given preoperative radiotherapy. Two surgeons performed more than 60 percent of the operations. The mean and median follow-up times were 69.1 months and 64 months, respectively. The Kaplan–Meier estimates of rates of local recurrence and distant metastasis at five years were 10 and 20 percent, respectively. With respect to the stage of the tumor, the Kaplan–Meier estimates of the rates of local recurrence at five years for stage I, II, and III tumors were 1.6, 9.8, and 18.5 percent, respectively. Disease-free survival at five years was 71.6 percent. The survival rates for patients with stage I, II, and III tumors were 92, 75.8, and 50.3 percent, respectively. A Cox proportional-hazards model showed that the tumor–node–metastasis stage and the distance of the tumor from the anal verge were the only significant and independent factors in the prediction of local recurrence. The Kaplan–Meier estimates of local-recurrence rates at five years for tumors 0 to 9 cm from the anal verge and those 10 to 15 cm from the anal verge were 12.9 and 4.7 percent, respectively (P<0.001).
Not all patients benefit from preoperative radiotherapy. With appropriate surgical techniques, stage I tumors at any level should not require radiotherapy. Tumors of any stage that are more than 10 cm from the anal margin have not been shown to benefit from radiotherapy. Any study performed to assess the efficacy of adjunctive radiotherapy must take into account variables that include the stage of the tumor, its distance from the anal verge, and the experience of the surgeon.
1 ReferencesIan C. Lavery, M.D.
Victor W. Fazio, M.D.
Francisco Lopez-Kostner, M.D.
Cleveland Clinic Foundation, Cleveland, OH 441951
Swedish Rectal Cancer Trial
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To the Editor:
The authors of the Swedish Rectal Cancer Trial did not address the very important issue of sphincter preservation. They did not state how many patients had abdominoperineal resection and how many had sphincter preservation. For patients in whom sphincter-preserving surgery is appropriate, a short course of preoperative radiotherapy now appears to be the treatment of choice, unless a subgroup analysis showed that complications were particularly high in this subgroup after preoperative radiotherapy. For patients in whom sphincter-preserving surgery is not appropriate, on the other hand, a short course of preoperative radiotherapy may eliminate an opportunity for down-staging of the tumor by a more protracted course of preoperative radiotherapy (with or without chemotherapy), followed by sphincter-preserving surgery.
Bhadrasain Vikram, M.D.
Montefiore Medical Center, Bronx, NY 10467To the Editor:
We would like to compliment the Swedish Rectal Cancer Trial investigators on their prospective, randomized, controlled trial. In his editorial in the April 3 issue, Minsky1 compliments the investigators on the philosophy underlying the trial but observes that preoperative combination therapy with conventional radiation doses and techniques has far greater potential.
We believe there is an alternative interpretation of the data. Preoperative radiotherapy with conventional doses of radiation (between 40 and 50 Gy) and an interval to allow for down-staging of the tumor before surgery has been demonstrated to reduce local recurrences of potentially operable, locally advanced tumors2 but has failed to show a survival advantage. The Swedish Rectal Cancer Trial group focused on operable rectal tumors, using a short course of preoperative high-dose radiotherapy to improve the outcome rather than affect operability. This is the first trial to demonstrate a survival advantage of radiotherapy in the treatment of rectal cancer rather than solely a reduction in local recurrences, and as the main difference from previous trials is the use of accelerated fractionation, this is likely to be the important factor. Use of a multiple-field technique averted the increased mortality associated with the anterior–posterior irradiation technique, and the demonstrated survival advantage is equivalent to that associated with conventional postoperative radiochemotherapy.3
3 ReferencesAlexander G. Heriot, F.R.C.S.
Paul Cornes, F.R.C.R.
John P. Glees, F.R.C.R.
Davinder Kumar, F.R.C.S.
St. George's Hospital, London SW17 0QT, United Kingdom1
Minsky BD . Adjuvant therapy for rectal cancer -- a good first step. N Engl J Med 1997;336:1016-1017
Full Text | Web of Science | Medline2
Medical Research Council Rectal Cancer Working Party
CrossRef | Web of Science | Medline3
Krook JE ,Moertel CG ,Gunderson LL , et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991;324:709-715
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Author/Editor Response
The authors reply:
To the Editor: We agree with Lavery and colleagues that the rate of local recurrence for Dukes' stage A tumors in our study is unacceptably high. The figure reflects the standard surgery that was used at most centers. Today, most of us consider this surgery suboptimal, but the rates of local recurrence in this trial are similar to those in all the other randomized trials.1 There were, however, participating centers in Sweden with rates of local recurrence in the surgery-alone group that were as low as those at the Cleveland Clinic. Surgical skill is not only a matter of numbers but also a matter of education.2 Since the closure of the trial, several workshops in rectal-cancer surgery have been organized, and patients are now referred to one or a very few surgeons at each hospital in Sweden. Ongoing nationwide registration will tell us whether these efforts improve the results.
It is also our belief that with optimized surgery, high lesions in a favorable stage (Dukes' stage A), provided that they can be reliably identified before surgery, probably do not require radiotherapy. However, data from the trial showed the same recurrence rate and relative reduction with radiotherapy irrespective of the distance of the tumor from the anus.
With regard to Dr. Vikram's comment, the data on immediate adverse effects have been published.3 There was no increase in anastomotic leakage or other complications among the patients who underwent surgery with sphincter preservation. The only adverse effect was an increased risk of a perineal wound infection among the patients in the radiotherapy-plus-surgery group who underwent surgery with an abdominoperineal excision. The rationale of achieving down-staging, and thus performing more sphincter-saving procedures, by using prolonged preoperative radiotherapy or chemoradiotherapy in patients with low rectal tumors was also pointed out by Minsky in his editorial. This was not an aim of our trial. Although the approach is theoretically attractive, we are hesitant to use it. The surgical procedure may appear easier because the tumor bulk is smaller, but can the bowel be resected at a higher level without increasing the risks associated with a radical procedure? The most commonly used preoperative dose (about 50 Gy in five weeks) kills only subclinical tumor cells (five fractions of 5 Gy each in one week may be as effective). Ongoing trials in Europe and the United States can answer this question. With higher doses, the goal may be reached without an increased risk of local recurrence, but the risk of late effects on bowel function may be unacceptably high.4
4 ReferencesLars Påhlman, M.D., Ph.D.
Bengt Glimelius, M.D., Ph.D.
University of Uppsala, S-751 85 Uppsala, Swedenfor the Swedish Rectal Cancer Trial Group
1
Pahlman L ,Glimelius B . The value of adjuvant radio(chemo)therapy for rectal cancer. Eur J Cancer 1995;31:1347-1350
CrossRef | Web of Science2
Påhlman L. Surgery for rectal cancer: the relationship between treatment volume and results. In: Söreide O, Norstein J, eds. Rectal cancer surgery. Berlin, Germany: Springer, 1997:364-70.
3
Swedish Rectal Cancer Trial
CrossRef | Web of Science | Medline4
Graf W ,Ekstrom K ,Glimelius B ,Pahlman L . A pilot study of factors influencing bowel function after colorectal anastomosis. Dis Colon Rectum 1996;39:744-749
CrossRef | Web of Science | Medline
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