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Invited Critique
February 16, 2009

Improvement of Survival With Response to Neoadjuvant Radiation Therapy for Rectal Cancer—Invited Critique

Arch Surg. 2009;144(2):134-135. doi:10.1001/archsurg.2008.550

Preoperative combined modality therapy (CMT) including radiation (50.40 Gy) and fluorouracil-based chemotherapy followed by radical resection is the preferred treatment paradigm for locally advanced (T3-T4 and/or N1-N2) rectal cancer in the United States.1 Castaldo et al report data from a large cohort of patients with rectal cancer from the SEER registry that corroborate the finding, previously noted in single- and multi-institution reports,2,3 that complete or near-complete pathologic responders to CMT have significantly improved OS and DSS compared with poor responders. Evidence suggests that decreased distant failure in complete responders may be largely responsible for this phenomenon.2,3 Taken together, these studies strongly suggest that primary tumor response to CMT may be a reliable surrogate for systemic control and long-term outcome. One must avoid the temptation, however, to interpret these data as license to be less aggressive in treating complete or near-complete responders. For instance, Castaldo and colleagues suggest that postoperative chemotherapy may be unnecessary in patients with disease downstaged to stage 0 or I given their similar outcome to patients presenting with stage I disease undergoing surgery only. However, it is likely that most of the patients with pre-CMT stage II and III disease in their study received 4 to 6 cycles of postoperative chemotherapy. Given the increased likelihood of harboring occult micrometastatic disease in these high-risk patients, postoperative chemotherapy may have been central to their excellent outcome. Likewise, limiting surgery to local excision or avoiding surgery entirely in complete responders,4 analogous to anal squamous cell carcinoma, is appealing and ultimately feasible but is currently limited by our inability to preoperatively identify complete pathologic responders based on the surgeon's assessment5 or with available imaging modalities. In addition, even in complete regression of the primary lesion, nodal disease may persist in 7% to 10% of patients with ypT0 disease.2,6 For now, radical resection and postoperative chemotherapy should remain mandatory components of therapy.

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