How Can We Improve the Tumor Response to Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer?

Preoperative chemoradiotherapy (pCRT) followed by total mesorectal excision is the accepted standard treatment for patients with locally advanced rectal cancer. The purpose of pCRT is to prevent the spread of viable tumor cells within the local area during surgical procedures. Additionally, pCRT can facilitate the resection of locally advanced tumors that are otherwise challenging to remove, thereby enabling a radical resection. Although a pathologic complete response is observed in fewer than 20% of patients, the reasons for the variability in tumor response to pCRT are not fully understood. Several techniques have been researched with the aim of improving the tumor response to pCRT. These techniques include intensifying or combining chemotherapy, either simultaneously or sequentially, increasing radiation dose, modifying radiation mode or schedule, adjusting the interval between radiation and surgery, and incorporating multiple agents to increase the efficacy of pCRT. This review discusses various strategies that may improve tumor response outcomes following pCRT.