Preoperative chemoradiation now represents the standard adjuvant care for patients with clinical stage II or III rectal cancer. The 5-year results of the German Chirurgische Arbeitsgemeinschaft Onkologie/Arbeitsgemeinschaft Radioonkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO) 94 trial of preoperative vs. postoperative chemoradiation, using modern chemoradiation and total mesorectal surgical technique, clearly demonstrate marked improvements in treatment compliance, toxicity, tumor downstaging, sphincter-preservation rates for patients with low-lying tumors, and pelvic recurrence rates in favor of preoperative therapy. Moreover, recent randomized trials emphasize the importance of concurrent systemic therapy with this preoperative radiation strategy, as the addition of chemotherapy is associated with significant improvements in tumor downstaging, pathologic response, and local control over that achieved with radiation alone. Ongoing randomized phase II and III investigations incorporating novel systemic and biologic agents may refine our current preoperative chemoradiation and adjuvant therapy strategies. Such intensified treatment approaches will likely lead to future trials of risk-stratified management utilizing clinical, pathologic, and molecular factors, as well as to the further use of highly conformal radiation delivery techniques, such as intensity modulated radiation therapy
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