Correspondence
Chemoradiotherapy for Rectal Cancer
N Engl J Med 2005; 352:509-511February 3, 2005
- Article
To the Editor:
In the study reported by Sauer et al. (Oct. 21 issue),1 18 percent of the patients in the postoperative-chemoradiotherapy group were found to have stage I disease, and about 10 percent were found intraoperatively to have distant metastases or other complications. Because of the randomized assignment to treatment, it is reasonable to assume that there were similar percentages of patients with stage I and stage IV disease — patients who were not likely to derive any benefit from chemoradiotherapy — in the preoperative group. The authors' suggestion that preoperative chemoradiotherapy may be the preferred treatment would subject such patients to unnecessary toxic effects. With use of the postoperative approach, treatment can be limited to patients with pathological stage II or III disease, without compromising overall or disease-free survival. At this time, we do not have the tools to predict with any degree of confidence which specific patients will have a reduction in the risk of local recurrence if they receive preoperative chemoradiotherapy. However, patients with stage I or intraoperatively detected stage IV rectal cancer can be spared unnecessary toxic effects.
1 ReferencesSumit Gaur, M.D.
Caritas St. Elizabeth's Medical Center, Boston, MA 02135
sumitgaurmd@hotmail.com Vani Shukla, M.D.
Salem Hospital, Salem, MA 019701
Sauer R ,Becker H ,Hohenberger W , et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731-1740
Full Text | Web of Science | Medline
To the Editor:
The trial reported by Sauer et al. confirms the effectiveness of preoperative chemoradiotherapy both in down-staging the disease and in reducing local recurrences. However, as in previous randomized, controlled trials, patients with distant metastases were not included. There is a widespread policy not to irradiate patients with stage IV disease, regardless of the fact that a substantial group of them, especially those with resectable disease, are treated with the aim to cure. Recently, long-term survival outcomes for these patients have become so high1,2 that efforts to reduce the local-recurrence rate can no longer be neglected.
2 ReferencesAlexander Julianov, M.D.
Thracian University Hospital, 6000 Stara Zagora, Bulgaria1
Kanemitsu Y ,Kato T ,Hirai T ,Yasui K . Preoperative probability model for predicting overall survival after resection of pulmonary metastases from colorectal cancer. Br J Surg 2004;91:112-120
CrossRef | Web of Science | Medline2
Abdalla EK ,Vauthey JN ,Ellis LM , et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 2004;239:818-827
CrossRef | Web of Science | Medline
To the Editor:
According to Table 2 of the article by Sauer et al., 92 percent and 89 percent of the patients assigned to preoperative chemoradiotherapy received full doses of radiotherapy and chemotherapy, respectively, as compared with 54 percent and 50 percent of the patients assigned to postoperative chemoradiotherapy. We agree with the authors that preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, significantly reduced the rates of acute and long-term toxic effects and increased the rate of sphincter-preserving surgery. However, we think that the improved rate of local control achieved with the preoperative approach could have resulted from the higher percentage of patients in that group who received full doses of radiotherapy and chemotherapy and thus may not constitute clear evidence that the preoperative strategy reduces local failure. This observation could be extended to other end points examined, considering that the authors found no statistically significant difference in the incidence of distant recurrences or in the rates of disease-free and overall survival between the two groups.
Gianluigi Ferretti, M.D.
Emilio Bria, M.D.
Regina Elena Cancer Institute, 00144 Rome, Italy
gia.fer@flashnet. it Mario Mandalà, M.D.
Treviglio Hospital, 24047 Treviglio, ItalyTo the Editor:
Sauer et al. conclude that preoperative chemoradiotherapy increases the rate of sphincter preservation. However, the trial was not designed to address this issue. The benefit with respect to sphincter preservation was found only in the subgroup of patients in whom abdominoperineal resection was deemed necessary. There was no stratification according to this factor. The analysis of sphincter preservation was performed not according to the intention-to-treat principle but according to the actual treatment given. More patients in the postoperative-treatment group than in the preoperative-treatment group requested a change in their assigned treatment (19 patients vs. 9 patients, P=0.05). This difference may explain, at least in part, the imbalance in the numbers of patients who underwent abdominoperineal resection (116 in the preoperative-treatment group and 78 in the postoperative-treatment group). The authors do not mention two randomized trials designed to investigate whether shrinkage of tumors after preoperative radiotherapy, with or without chemotherapy, increases the rate of anterior resection1,2; in both, the difference in the rate of sphincter preservation was statistically nonsignificant.
2 ReferencesKrzysztof Bujko, M.D.
Marek P. Nowacki, M.D.
Lucyna Kepka, M.D.
Maria Sklodowska-Curie Memorial Cancer Center, 02-781 Warsaw, Poland
bujko@coi.waw. pl 1
Francois Y ,Nemoz CJ ,Baulieux J , et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol 1999;17:2396-2396
Web of Science | Medline2
Bujko K ,Nowacki MP ,Nasierowska-Guttmejer A , 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;72:15-24
CrossRef | Web of Science | Medline
To the Editor:
The study reported by Sauer et al. is commendable in that it confirms the theoretical advantages of adding preoperative chemotherapy to preoperative radiotherapy for the treatment of rectal cancer. However, in 75 patients in the trial, the distance of the tumor from the anal verge was unknown (Table 1 of the article). The reason for this lack of data is unclear, especially since the enrollment criteria specifically include this measurement. In addition, in about one fourth of the patients, the tumor stage was unknown; in about 7 percent, the nodal status was unknown. Patients who had tumors within 16 cm from the anal verge were eligible; these tumors might have included sigmoid and rectosigmoid tumors. The use of radiotherapy and total mesorectal excision for all patients with high rectal and rectosigmoid tumors is controversial.1,2
2 ReferencesGopalakrishnan Unnikrishnan, M.S.
Puneet Dhar, M.S., M.Ch.
S. Sudhindran, M.S., F.R.C.S.
Amrita Institute of Medical Sciences, Kochi 682026, India
gisdoctors@aimshospital.org 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
Heald RJ ,Moran BJ ,Ryall RD ,Sexton R ,MacFarlane JK . Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997. Arch Surg 1998;133:894-899
CrossRef | Web of Science | Medline
Author/Editor Response
We agree with Drs. Gaur and Shukla that accurate clinical staging is needed to avoid unnecessary treatment in patients who may not benefit from radiotherapy. Traditionally, patients with stage I disease and patients with distant metastases have been considered ineligible for postoperative radiotherapy. The Swedish Rectal Cancer Trial,1 however, demonstrated that preoperative radiotherapy significantly improved local control even in patients with stage I rectal cancer. Preoperative radiotherapy may also be beneficial for patients with early-stage tumors within the lower part of the rectum when sphincter-preserving surgery is attempted. Likewise, for those with stage IV disease, survival times have been dramatically increased in recent years through the use of more effective chemotherapy. Thus, as Dr. Julianov points out, sustained local control has become important in this group of patients too. Moreover, because of postoperative complications, increased toxicity, and reduced compliance, full-dose radiotherapy often cannot be used after pelvic surgery. This is another pragmatic reason to prefer preoperative chemoradiotherapy, and this advantage may indeed have contributed to our finding of a reduced rate of local failure in the preoperative-treatment group, as Dr. Ferretti and colleagues note. It is our conclusion that rather than advocate more toxic and less effective postoperative treatment for one group of patients (those with stage II or III disease) in order to avoid possible overtreatment for a minority of others, every effort should be made to combine the advantages of the preoperative approach with improvements in imaging techniques to select patients accurately for treatment alternatives.
A controversy with preoperative therapy is whether the degree of down-staging is adequate to enhanced sphincter preservation. The studies mentioned by Dr. Bujko and colleagues showed significantly improved down-staging effects when preoperative chemoradiotherapy was compared with short-course radiotherapy or when the interval between radiotherapy and surgery was prolonged, yet no differences in sphincter preservation were achieved. The surgeon's willingness to modify the operation in cases with tumor shrinkage is of pivotal importance in this respect.
Dr. Unnikrishnan and colleagues challenge the use of radiotherapy for cancers in the upper third of the rectum. In Germany, the standard surgical procedure for these tumors is partial mesorectal excision. In a subgroup analysis in our study, the risk of local relapse did not differ between patients with tumors in the upper part of the rectum and those with tumors in the middle part. Thus, we suggest that radiotherapy not be omitted from treatment given to the former group of patients.
1 ReferencesRolf Sauer, M.D.
Claus Rödel, M.D.
University of Erlangen, 91054 Erlangen, Germany
sekretariat@strahlen.imed. uni-erlangen. de 1
Swedish Rectal Cancer Trial
Full Text | Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
Sarah Popek, Vassiliki Liana Tsikitis, Lisa Hazard, Alfred M. Cohen. (2011) Preoperative Radiation Therapy for Upper Rectal CancerT3,T4/Nx: Selectivity Essential. Clinical Colorectal Cancer
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Roel Hompes, Chris Cunningham. (2011) Colorectal cancer: management. Medicine 39:5, 254-258
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David Cunningham, Wendy Atkin, Heinz-Josef Lenz, Henry T Lynch, Bruce Minsky, Bernard Nordlinger, Naureen Starling. (2010) Colorectal cancer. The Lancet 375:9719, 1030-1047
CrossRef4
Koen C.M.J. Peeters, Corrie A.M. Marijnen, Iris D. Nagtegaal, Elma Klein Kranenbarg, Hein Putter, Theo Wiggers, Harm Rutten, Lars Pahlman, Bengt Glimelius, Jan Willem Leer, Cornelis J.H. van de Velde. (2007) The TME Trial After a Median Follow-up of 6 Years. Annals of Surgery 246:5, 693-701
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