Watch and wait in locally advanced rectal cancer: Evolution, current evidence, and future directions

Abstract

The treatment of locally advanced rectal cancer (LARC) has evolved significantly over the past century, driven by a deeper understanding of tumor biology, technological advancements, and multidisciplinary approaches. This article reviews the historical progression of LARC management, emphasizing the latest breakthroughs that are reshaping treatment paradigms. Key developments include the watch and wait strategy for patients achieving a complete clinical response after neoadjuvant therapy, the emergence of total neoadjuvant therapy as a standard approach, and the adoption of minimally invasive surgical techniques, such as transanal endoscopic microsurgery. Watch and wait may reduce treatment-related morbidity and help preserve anorectal function, but it requires rigorous patient selection and close long-term surveillance to ensure oncologic safety. Additionally, the role of targeted therapies and immunotherapy is gaining prominence, offering new opportunities for personalized treatment. These innovations aim to improve oncological outcomes while minimizing morbidity and preserving organ function, ultimately enhancing patients’ quality of life. Despite these advancements, challenges remain in optimizing patient selection, refining treatment strategies, and ensuring long-term safety and efficacy. A multidisciplinary approach involving surgeons, oncologists, and radiation specialists is crucial to tailoring therapies to individual patient profiles. As research continues, integrating novel therapeutic strategies will be key to further improving survival rates and reducing treatment-related morbidity in LARC patients.

Keywords: Locally advanced rectal cancer; Watch and wait; Total neoadjuvant therapy; Organ-preserving therapy; Target tailored therapy

Core Tip: The management of locally advanced rectal cancer has undergone major advancements, shifting toward more personalized and less invasive strategies. This review explores key innovations, including the watch and wait approach for clinical complete responders, the total neoadjuvant therapy paradigm, and the expansion of minimally invasive surgical techniques. Additionally, targeted therapies and immunotherapy are emerging as promising options. These advancements aim to improve survival while preserving organ function and minimizing morbidity. Future research should focus on optimizing patient selection and long-term outcomes, ensuring that novel therapeutic strategies continue to enhance cancer care.