| Sumario: | Simple Summary: This review discusses the recent developments in the treatment of microsatellite-stable locally advanced rectal cancer (LARC), focusing on the evolving role of radiation therapy as part of total neoadjuvant therapy (TNT). It highlights the importance of incorporating both tumor- and patient-specific factors, along with a thorough discussion regarding individual patient preferences, in determining the best treatment approach. This may range from dose-escalated non-operative radiation therapy to the omission of radiation altogether in select patients. Treatment of locally advanced rectal cancer (LARC), clinical stages II–III, typically involves multimodal treatment options. Over the past decade, the role of radiation therapy as a neoadjuvant treatment for LARC has evolved and is currently a part of total neoadjuvant therapy (TNT). Some recently published studies advocate for the omission of radiation therapy entirely, while others report on a non-operative approach that emphasizes the use of higher radiation therapy doses. This review aims to evaluate the latest literature on the current role of radiation therapy in the management of LARC, with a discussion of how to best select the most appropriate treatment protocol based on individual patient and tumor characteristics, comorbidities, and personal needs and preferences.
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