Potential benefits of integration of therapies with chemoradiation in rectal cancer

Improved pelvic control with reduced toxicity and enhanced sphincter preservation has been demonstrated with neoadjuvant chemoradiation compared with postoperative adjuvant chemoradiation in patients with stage II and III rectal cancer. However, analyses from many trials of adjuvant chemoradiation indicate that patients with T3 node-positive and T4 tumors are at high risk of pelvic recurrence even with use of chemoradiation. This limitation could be addressed with treatment intensification strategies, such as increasing the radiotherapy dose using altered fractionation, or incorporation of novel cytotoxic and targeted chemotherapeutic agents. In addition, preliminary evidence suggests that selected patients with clinically staged T2 or T3 node-negative tumors may be candidates for trials evaluating organ-preserving strategies after chemoradiation, thus eliminating the morbidity of radical surgery. These efforts could be enhanced with the availability of more effective chemoradiation regimens. This paper will discuss incorporation of molecular targeted therapy with chemoradiation regimens in the context of current standards, limitations, and new concepts in the combined modality therapy of locally advanced rectal cancer.