The Landmark Series: Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

The management of locally advanced rectal cancer (LARC) has seen much development over recent decades. Neoadjuvant radiotherapy combined with high-quality total mesorectal excision saw improvements in locoregional control. With the advent of several key trials, neoadjuvant therapy for LARC has seen a shift toward total neoadjuvant therapy, with corresponding improvements in tumor response and survival outcomes. The collective pool of evidence has allowed for increasingly personalized treatment of LARC, with organ-preservation now an option for many. The aims of the review are to summarize the evolution of neoadjuvant therapy for LARC, highlight key studies informing contemporary best practices, navigate the complexity of options available, and present areas of ongoing development.