Current status of locally advanced rectal cancer therapy and future prospects.

Rectal cancer treatment has been evolving ever since the beginning of the 20th century. Surgery was originally the only available method regardless of the extent of tumor invasion or nodal involvement status. Total mesorectal excision was established as the standard procedure in the early 1990 s. Advances in the utilization of radiation for rectal cancer led to the addition of radiotherapy (RT) combined with chemotherapy to the postoperative treatment algorithm. The promising results of the Swedish short-course preoperative RT set the basis for a number of large randomized trials investigating the efficacy of neoadjuvant RT or chemoradiotherapy (CRT) for advanced rectal cancer. Both short-course RT and long-course preoperative CRT compared favorably to adjuvant treatment and became the standard of choice for patients with extramural invasion or lymph node involvement. Recently, the focus of clinical research has been shifted towards total neoadjuvant therapy (TNT), delivering the whole course of RT and chemotherapy before surgery, and showing good tolerance and encouraging efficacy. Although targeted therapies haven't displayed a benefit in the neoadjuvant setting, preliminary evidence suggests impressive efficacy of immunotherapy in rectal carcinomas with mismatch-repair deficiency. In this review, we provide an in-depth critical overview of all significant randomized trials that have shaped the current treatment guidelines for locally advanced rectal cancer and discuss future trends for the treatment of this common malignancy.