Correspondence
Radiotherapy for Rectal Cancer
N Engl J Med 2002; 346:137-138January 10, 2002
- Article
To the Editor:
Kapiteijn et al. (Aug. 30 issue)1 reported that short-term preoperative radiotherapy reduces the risk of local recurrence in patients with rectal cancer who undergo standardized total mesorectal excision. There was no survival advantage. Similarly, a study that compared postoperative radiotherapy and chemotherapy with chemotherapy alone found a decreased risk of local recurrence and no survival advantage.2
If radiotherapy results in minimal or no survival advantage, then the real question is whether it improves the quality of life. Kapiteijn et al. mention the long-term effects of preoperative radiotherapy on bowel function only briefly, by referring to one study that found “more incontinence” with preoperative radiotherapy.3 That study, in which there was a minimum of five years of follow-up, found that the median frequency of bowel movements was 20 per week in the group of patients who underwent irradiation before surgery and 10 per week in the surgery-only group (P<0.001). Incontinence of loose stool was more common in the group that underwent irradiation than in the surgery-only group (50 percent vs. 24 percent), as were “toilet dependence” (30 percent vs. 6 percent), the need to wear a pad (49 percent vs. 22 percent), impairment of social life due to bowel dysfunction (30 percent vs. 10 percent), and urgency and emptying difficulties (P<0.05 for all comparisons). Another study found the adverse effects of postoperative radiotherapy to be even more marked.4
Patients should be informed of the advantages and disadvantages of adjuvant therapy. Patients with resectable cancer that does not have clinical or pathological features associated with a particularly high risk of local recurrence may, reasonably, decline radiotherapy.
4 ReferencesAlan P. Meagher, F.R.A.C.S.
St. Vincent's Hospital, Darlinghurst, NSW 2010, Australia
alanpmeagher@yahoo.com 1
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
Full Text | Web of Science | Medline2
Wolmark N ,Wieand HS ,Hyams DM , et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 2000;92:388-396
CrossRef | Web of Science | Medline3
Dahlberg M ,Glimelius B ,Graf W ,Pahlman L . Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study. Dis Colon Rectum 1998;41:543-551
CrossRef | Web of Science | Medline4
Kollmorgen CF ,Meagher AP ,Wolff BG ,Pemberton JH ,Martenson JA ,Illstrup DM . The long-term effect of adjuvant postoperative chemoradiotherapy for rectal carcinoma on bowel function. Ann Surg 1994;220:676-682
CrossRef | Web of Science | Medline
To the Editor:
In an editorial accompanying the article by Kapiteijn et al., Nelson and Sargent1 suggest that the findings of the National Surgical Adjuvant Breast and Bowel Project trial of postoperative chemotherapy with or without radiotherapy (protocol R-02) justify reducing the use of radiotherapy in patients with rectal cancer because radiotherapy provided no additional benefit.2 In that trial, postoperative chemoradiotherapy was deferred to permit recovery from surgery. A 10-week cycle of fluorouracil-based chemotherapy was then administered, followed by a period of post-chemotherapy recovery. According to this schedule, the start of radiotherapy was delayed for up to 21 weeks after surgery. Populations of rectal-cancer cells can grow rapidly during treatment3; the tumor-cell doubling time is four to five days. Radiotherapy prolonged by 12 days loses its effectiveness in improving local control by 1.7 percent per day.
We believe that the design of the National Surgical Adjuvant Breast and Bowel Project trial, with its delays, nullified any possibility that radiotherapy might have substantial benefit. It provides insufficient evidence that postoperative radiotherapy can be reduced safely in patients with rectal cancer. In contrast, the successful Gastrointestinal Tumor Study Group trial GI-7175 did not defer chemoradiotherapy or radiotherapy for more than 60 days after surgery.4 Postoperative delay of effective adjuvant therapy may explain why short-course preoperative radiotherapy is such an effective treatment.
4 ReferencesPaul G.S. Cornes, F.R.C.R.
Mehdi Shahidi, F.R.C.R.
Royal Marsden Hospital, Surrey SM2 5PT, United Kingdom
paul_cornes@altavista.co. uk 1
Nelson H ,Sargent DJ . Refining multimodal therapy for rectal cancer. N Engl J Med 2001;345:690-692
Full Text | Web of Science | Medline2
Wolmark N ,Wieand HS ,Hyams DM , et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 2000;92:388-396
CrossRef | Web of Science | Medline3
Suwinski R ,Taylor JMG ,Withers HR . Rapid growth of microscopic rectal cancer as a determinant of response to preoperative radiation therapy. Int J Radiat Oncol Biol Phys 1998;42:943-951
CrossRef | Web of Science | Medline4
Thomas PRM ,Lindblad AS . Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Radiother Oncol 1988;13:245-252
CrossRef | Web of Science | Medline
To the Editor:
The Dutch Colorectal Cancer Group advocates computed tomography (CT) or magnetic resonance imaging (MRI) as the optimal staging method for selecting the patients with rectal cancer who will benefit most from preoperative radiotherapy. However, most clinical trials have convincingly demonstrated the superiority of endoscopic ultrasonography for this purpose. The accuracy of endoscopic ultrasonography in the tumor staging of rectal carcinoma ranges from 80 to 95 percent, whereas CT has 65 to 75 percent accuracy and MRI 75 to 85 percent accuracy.1-5 No single technique permits confident determination of mesorectal lymph-node involvement5; endoscopic ultrasonography has a demonstrated accuracy of approximately 70 to 75 percent for this purpose, whereas that of CT is 55 to 65 percent and that of MRI is 60 to 65 percent.1-4 However, with the incorporation of fine-needle aspiration into equipment for endoscopic ultrasonography, this technique may allow improved accuracy of nodal staging.
5 ReferencesGavin C. Harewood, M.D.
Maurits J. Wiersema, M.D.
Mayo Clinic, Rochester, MN 55905
harewood.gavin@mayo. edu 1
Hawes RH . Endoscopic ultrasound. Gastrointest Endosc Clin N Am 2000;10:161-74, viii
Medline2
Kwok H ,Bissett IP ,Hill GL . Preoperative staging of rectal cancer. Int J Colorectal Dis 2000;15:9-20
CrossRef | Web of Science | Medline3
Adams DR ,Blatchford GJ ,Lin KM ,Ternent CA ,Thorson AG ,Christensen MA . Use of preoperative ultrasound staging for treatment of rectal cancer. Dis Colon Rectum 1999;42:159-166
CrossRef | Web of Science | Medline4
Heriot AG ,Grundy A ,Kumar D . Preoperative staging of rectal carcinoma. Br J Surg 1999;86:17-28
CrossRef | Web of Science | Medline5
Hodgman CG ,MacCarty RL ,Wolff BG , et al. Preoperative staging of rectal carcinoma by computed tomography and 0.15T magnetic resonance imaging: preliminary report. Dis Colon Rectum 1986;29:446-450
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Meagher suggests that the lack of a survival advantage among the patients with rectal cancer who underwent preoperative radiotherapy is an important finding of our study. We emphasize that the median follow-up in our study was 24.9 months, a period that is sufficient for reporting the results of the primary end point of the trial (the rate of local recurrence) but not long enough to evaluate a survival benefit. The side effects described in the study1 cited by Meagher were probably due to anal-sphincter irradiation. In our trial, we did not irradiate the anal sphincter in patients who underwent a low anterior resection. The analysis of our quality-of-life study has not been completed.
We support the suggestion offered by Cornes and Shahidi that the short overall treatment, consisting of five fractions of 5 Gy, might explain our good results. We agree with their comment and recommend short-term preoperative radiotherapy for resectable rectal cancer.
We wish to emphasize that reduction in the risk of local recurrence is the primary reason for short-term preoperative radiotherapy. We do not recommend a regimen of five fractions of 5 Gy for patients with locally advanced tumors, since down-staging is a prerequisite for the subsequent treatment of these tumors. We advocate preoperative MRI or CT scanning to identify such patients, since these techniques can identify the mesorectal fascia and predict circumferential margin involvement.
1 ReferencesCorrie A.M. Marijnen, M.D.
Ellen Kapiteijn, M.D.
Cornelius J.H. van de Velde, M.D., Ph.D.
Leiden University Medical Center, 2300 RC Leiden, the Netherlands
marijnen@lumc.nl 1
Dahlberg M ,Glimelius B ,Graf W ,Pahlman L . Preoperative radiation affects functional results after surgery for rectal cancer. Dis Colon Rectum 1998;41:543-551
CrossRef | Web of Science | Medline
Author/Editor Response
The editorialists reply:
To the Editor: We agree with Cornes and Shahidi that the results of the National Surgical Adjuvant Breast and Bowel Project trial (protocol R-02), though provocative, are not definitive. Although a regimen of postoperative radiotherapy and chemotherapy was more effective than postoperative chemotherapy alone in reducing the rate of local recurrence (8 percent vs. 13 percent, respectively), it was not more effective than chemotherapy alone in increasing disease-free or overall survival.1 We believe that each treatment method and combination of methods must be critically reappraised as new options become available, including new surgical advances, such as total mesorectal excision; new radiosensitizing agents; and promising new chemotherapy agents, such as irinotecan2 and oxaliplatin.3
3 ReferencesHeidi Nelson, M.D.
Daniel J. Sargent, Ph.D.
Mayo Clinic, Rochester, MN 55905
nelsonh@mayo.edu 1
Wolmark N ,Wieand HS ,Hyams DM , et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 2000;92:388-396
CrossRef | Web of Science | Medline2
Saltz LB ,Cox JV ,Blanke C , et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2000;343:905-914
Full Text | Web of Science | Medline3
de Gramont A ,Figer A ,Seymour M , et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938-2947
Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
M. Berho, M. Oviedo, E. Stone, C. Chen, J. Nogueras, E. Weiss, D. Sands, S. Wexner. (2009) The correlation between tumour regression grade and lymph node status after chemoradiation in rectal cancer. Colorectal Disease 11:3, 254-258
CrossRef2
N. Sengul, S. D. Wexner, S. Woodhouse, S. Arrigain, M. Xu, J. A. Larach, B. K. Ahn, E. G. Weiss, J. J. Nogueras, M. Berho. (2006) Effects of radiotherapy on different histopathological types of rectal carcinoma. Colorectal Disease 8:4, 283-288
CrossRef3
Maurits J Wiersema, Gavin C Harewood. (2002) Endoscopic ultrasound for rectal cancer. Gastroenterology Clinics of North America 31:4, 1093-1105
CrossRef4
Alan P. Meagher, Robyn L. Ward. (2002) Current evidence does not support routine adjuvant radiotherapy for rectal cancer. ANZ Journal of Surgery 72:11, 835-840
CrossRef
