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ARTICLES: Brian M. Wolpin, Jeffrey A. Meyerhardt, Harvey J. Mamon, and Robert J. Mayer Adjuvant Treatment of Colorectal Cancer CA Cancer J Clin 2007; 57: 168-185 [Abstract] [Full text] [PDF]

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Authors’ response to the comments of Ferretti et al.

Brian M. Wolpin, MD, Robert J. Mayer, MD   (6 July 2007)

Chemoradiotherapy for rectal cancer

Gianluigi Ferretti MD, PhD, Alessandra Felici MD and Francesco Cognetti MD   (6 July 2007)

Authors’ response to the comments of Ferretti et al. 6 July 2007
Brian M. Wolpin, MD, Instructor in Medicine Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, Boston, MA, Robert J. Mayer, MD Send letter to journal: Re: Authors’ response to the comments of Ferretti et al. Brian_Wolpin{at}dfci.harvard.edu Brian M. Wolpin, MD, et al.	As Ferretti and colleagues correctly point out, significantly more patients in the preoperative chemoradiotherapy arm received full doses of radiotherapy (92% versus 54%) and chemotherapy (89% versus 50%) when compared to patients in the postoperative chemoradiotherapy arm. Although the precise contribution of these differences to the improvement in local recurrence is not known, they do highlight the difficulties encountered when administering chemoradiotherapy in the postoperative setting, even in the context of a well-performed clinical trial. If the ability to administer full-dose adjunctive therapy is increased in the preoperative approach and the administration of full-dose adjunctive therapy improves local control, then the use of preoperative chemoradiation should benefit patients. As Ferretti et al. correctly note, the increase in sphincter-preserving surgery in the preoperative versus postoperative chemoradiotherapy arms was only among those patients with more distal tumors felt to require abdominoperineal resection (APR) with permanent colostomy. Patients with more proximal tumors are able to undergo low anterior resection without permanent colostomy, regardless of when adjunctive therapy is administered, and would not be expected to benefit from neoadjuvant therapy, in terms of the likelihood of sphincter preservation. Although patients were not stratified according to the need for APR, they were classified prospectively and prior to randomization. In addition, stratification on this variable can be difficult due to the subjectivity inherent in surgeons’ decisions regarding resectability. Therefore, the study by Sauer and colleagues suggests that down-staging of tumors with preoperative chemoradiation in patients with distal cancers may allow for more sphincter-sparing surgeries, although this remains to be definitively proven.
Chemoradiotherapy for rectal cancer 6 July 2007
Gianluigi Ferretti MD, PhD, Division of Medical Oncology A Regina Elena Cancer Institute, Rome, Italy, Alessandra Felici MD and Francesco Cognetti MD Send letter to journal: Re: Chemoradiotherapy for rectal cancer gia.fer{at}flashnet.it Gianluigi Ferretti MD, PhD, et al.	Commenting on the study by Sauer et al. (1), Wolpin et al. (2) affirm that this study demonstrated that preoperative chemoradiation therapy lowered the rates of local recurrence and doubled the rate of sphincter-sparing operations. As previously stated (3), we think that the improved rate of local control achieved with the preoperative approach could have resulted from the higher percentage (about 90%) of patients who received full doses of radiotherapy and chemotherapy compared with the percentage (about 50%) of patients assigned to postoperative chemoradiotherapy. The pragmatic reason to prefer preoperative chemoradiotherapy does not constitute a clear evidence that the preoperative strategy reduces local failure. Similarly, the incidence of distant recurrences or the rates of disease-free and overall survival in the postoperative chemoradiotherapy group could be influenced by complications, reduced compliance, and increased toxicity due to radiotherapy delivered after pelvic surgery. Concerning sphincter preservation, in the trial by Sauer et al. (1) there was no stratification according to this factor (4). The benefit of sphincter preservation was found only in the subgroup of patients in whom abdominoperineal resection was considered necessary. References 1. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351(17):1731-1740. 2. Wolpin BM, Meyerhardt JA, Mamon HJ, Mayer RJ. Adjuvant treatment of colorectal cancer. CA Cancer J Clin 2007;57(3):168-185. 3. Ferretti G, Bria E, Mandala M. Chemoradiotherapy for rectal cancer. N Engl J Med 2005;352(5):509-511. 4. Bujko K, Nowacki MP, Kepka L. Chemoradiotherapy for rectal cancer. N Engl J Med 2005;352(5):509-511.