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Future direction of total neoadjuvant therapy for locally advanced rectal cancer

  • Yoshinori Kagawa,
  • J. Joshua Smith,
  • Emmanouil Fokas,
  • Jun Watanabe,
  • Andrea Cercek,
  • Florian R. Greten,
  • Hideaki Bando,
  • Qian Shi,
  • Julio Garcia-Aguilar,
  • Paul B. Romesser,
  • Natally Horvat,
  • Hanna Sanoff,
  • William Hall,
  • Takeshi Kato,
  • Claus Rödel,
  • Arvind Dasari,
  • Takayuki Yoshino

摘要

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.