Future direction of total neoadjuvant therapy for locally advanced rectal cancer

• Published in: Nature reviews. Gastroenterology & hepatology 2024-06, Vol.21 (6), p.444-455
• Main Authors: Kagawa, Yoshinori, Smith, J. Joshua, Fokas, Emmanouil, Watanabe, Jun, Cercek, Andrea, Greten, Florian R., Bando, Hideaki, Shi, Qian, Garcia-Aguilar, Julio, Romesser, Paul B., Horvat, Natally, Sanoff, Hanna, Hall, William, Kato, Takeshi, Rödel, Claus, Dasari, Arvind, Yoshino, Takayuki
• Format: Article
• Language: English
• Subjects: 631/67/1059/485; 631/67/1059/99; 631/67/1504/1885/1777; Artificial intelligence; Biomedicine; Cancer; Cancer therapies; Chemoradiotherapy; Chemoradiotherapy - methods; Chemotherapy; Clinical trials; Colorectal cancer; Decision making; Gastroenterology; Hepatology; Humans; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Metastasis; Neoadjuvant Therapy; Patients; Perspective; Quality of life; Radiation therapy; Rectal Neoplasms - pathology; Rectal Neoplasms - therapy; Rectum; Survival
• ISSN: 1759-5045; 1759-5053; 1759-5053
• DOI: 10.1038/s41575-024-00900-9

Despite therapeutic advancements, disease-free survival and overall survival of patients with locally advanced rectal cancer have not improved in most trials as a result of distant metastases. For treatment decision-making, both long-term oncologic outcomes and impact on quality-of-life indices should be considered (for example, bowel function). Total neoadjuvant therapy (TNT), comprised of chemotherapy and radiotherapy or chemoradiotherapy, is now a standard treatment approach in patients with features of high-risk disease to prevent local recurrence and distant metastases. In selected patients who have a clinical complete response, subsequent surgery might be avoided through non-operative management, but patients who do not respond to TNT have a poor prognosis. Refined molecular characterization might help to predict which patients would benefit from TNT and non-operative management. Specifically, integrated analysis of spatiotemporal multi-omics using artificial intelligence and machine learning is promising. Three prospective trials of TNT and non-operative management in Japan, the USA and Germany are collaborating to better understand drivers of response to TNT. Here, we address the future direction for TNT. In this article, the authors discuss the use of total neoadjuvant therapy for locally advanced rectal cancer. They highlight ongoing trials and discuss future treatment options, including the potential use of multi-omics and artificial intelligence to facilitate treatment selection and prediction of response.