[The advances of total neoadjuvant therapy for locally advanced rectal cancer]

The multimodality treatment has significantly increased local control of locally advanced rectal cancer, with a superior oncologic efficacy and reduced local recurrence rate from 35% to less than 10%, and the proportion of patients receiving "watch and wait" strategy or delaying surgery increased as well. However, distant relapse is still the leading cause of cancer-related death without improved long-term survival outcomes. To improve treatment compliance and overall survival benefits, a novel strategy that delivered upfront chemotherapy prior to surgery, which is termed total neoadjuvant therapy (TNT), has been proposed. TNT has two major patterns, including induction and consolidation therapy; the former treatment pattern requires systemic chemotherapy before neoadjuvant chemoradiotherapy, while consolidation therapy refers to additional cycles of chemotherapy between neoadjuvant chemoradiotherapy and surgery. As a radiosensitizer, upfront chemotherapy not only reduces gross tumor volume, but targets occult micro-metastatic disease at an early stage. Several clinical trials have also reported that TNT achieves better local control of disease with a promising treatment compliance. And organ preservation rate is supposed to increase with an improved pathologic or clinical complete response rate. Besides, there existed no established consensus regarding to specific patterns and chemotherapy regimens and doses, which results in remarkable differences among studies. In conclusion, the exact oncologic efficacy and survival benefits of total neoadjuvant therapy still need clinical trials to confirm.