Prognostic Markers of Local Relapse in Rectal Cancer: Are We Any Further Forward?

Rectal cancer is a major health problem affecting more than 100,000 patients in the United States and Europe each year. 1 Although it is a highly treatable and often curable disease when localized to the bowel, the prognosis for locally advanced disease varies, with local recurrence rates ranging from 4% to 40%; local recurrenceoftenisthecauseofseveremorbidityandpoormortalityin this disease. 2 Therefore, clinical approaches to prevent early recurrence are one of the major goals in the treatment of rectal cancer. The treatment for patients with clinically resectable, locally invasive rectal cancer has begun to evolve away from more radical surgical approaches such as abdominoperitoneal resection toward attempts at preservation of the anal sphincter and maintenance of anorectal function. 3 In the postoperative setting, there is clear evidence that adjuvant fluorouracil (FU) -based chemotherapy combined with radiotherapy significantly improves disease-free survival and overall survival in patients with rectal cancer. 4 More recently, several groups clearly have shown the benefit in reducing local recurrence rates and toxicity using neoadjuvant preoperative chemotherapy/radiotherapy combinations as opposed to adjuvant treatment. 5,6 Onesuchstudy,theGermanCAO/ARO/AIO-94rectalcancer group trial, randomly assigned 823 patients with T3/4 and/or node-positive rectal cancer to receive preoperative versus postoperative combined-modality therapy consisting of FU on weeks 1 and 5 and 50.4 Gy of concurrent radiation therapy. 4 There was a significant improvement in local recurrence rates (6% in the preoperative group v 13% in the postoperative group) as well as improvements in acute and long-term toxicity. Moreover, in the preoperative group, 39% of the patients initially requiring an abdominoperitoneal resection were able to undergo a sphinctersparing operation, whereas in the postoperatively treated group only 19% were eligible for a sphincter-sparing procedure. Although there was no difference in overall survival between the two groups, the preoperative combined-modality approach significantlyimprovedthechancesofsphincterpreservationandalsoled