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Moving beyond anatomy: the future of rectal cancer management is biologically-informed, response-adapted, and patient-centered

  • Krishan R. Jethwa*
  • , J. Joshua Smith
  • , Hanna Sanoff
  • , Nina N. Sanford
  • , Martijn P.W. Intven
  • , Hyun Kim
  • , Alexandra E. Hotca-Cho
  • , Karyn A. Goodman
  • , Prajnan Das
  • , Mary Feng
  • , Theodore S. Hong
  • , Ane Appelt
  • , Cihan Gani
  • , Emmanouil Fokas
  • , Paul B. Romesser
  • , William A. Hall
  • *Corresponding author for this work

Research output: Contribution to journalLetterAcademicpeer-review

Abstract

The purpose of this correspondence is to expand upon the recent review article by Noiret et al. addressing management of locally advanced rectal cancer (LARC) and proposing anatomically guided treatment strategies. While tumor location influences surgical complexity and functional outcomes, we caution against an overly anatomy centric framework that may oversimplify treatment selection and underemphasize patient preferences and biological determinants of response. Current evidence does not support the assertion that chemotherapy followed by surgery provides superior long-term functional outcomes compared with total neoadjuvant therapy (TNT) with organ preservation (OP). Contemporary management of LARC includes multiple curative-intent strategies, each associated with distinct tradeoffs in oncologic control, toxicity, and quality of life. In particular, modern radiotherapy techniques and OP strategies have demonstrated favorable response rates, functional outcomes, and quality of life compared with radical surgery. We argue that future treatment paradigms should move beyond anatomy alone and prioritize biologic risk stratification, response adaptive treatment, and incorporation of multi-omic biomarkers. Ultimately, treatment decisions should integrate patient preferences, oncologic risk, functional outcomes, and evolving biologic understanding to optimize individualized care for patients with LARC.

Original languageEnglish
Article number101214
JournalClinical and translational radiation oncology
Volume60
Early online date18 Jun 2026
DOIs
Publication statusE-pub ahead of print - 18 Jun 2026

Keywords

  • Chemoradiation
  • Chemotherapy
  • Organ preservation
  • Radiation
  • Rectal cancer
  • Surgery

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