Key clinical trials in rectal cancer shaping the current treatment paradigms: reference guide for radiologists

Total neoadjuvant therapy (TNT), which includes chemotherapy and radiation prior to surgical resection, has been recently accepted as the new standard of care for patients with locally advanced low and mid rectal cancers. Multiple clinical trials have evaluated this approach in the last several decades and demonstrated improvement in, local control and reduced risk of recurrence. In addition, in the course of these investigations, it has been shown that between a third and a half of patients experience a clinical complete response (cCR) after being treated with the TNT approach, leading to the development of new organ preservation protocol, now known as watch-and-wait (W&W). On this protocol, cCR patients are not referred for surgery after total neoadjuvant treatment. Instead, they remain on close surveillance and, thus, avoid potential complications associated with surgical resection. Multiple clinical trials are ongoing, investigating the long-term outcomes of these new approaches and the development of less toxic and more effective TNT regimens for LARC. Improvements in technology and rectal MRI protocols position radiologists as vital members of multidisciplinary rectal cancer management teams. Rectal MRI has become a critical tool for rectal cancer initial staging, treatment response assessment, and surveillance on W&W protocols. In this review, we summarize the findings of the pivotal clinical trials that contributed to establishing the current treatment paradigms in locally advanced rectal cancer (LARC) management, with the intention of helping radiologists play more effective roles in their multidisciplinary teams.