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Related Experiment Video

Updated: Jan 18, 2026

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Risk of Distant Metastasis After Total Neoadjuvant Therapy: Local Regrowth Versus Surgery After Total Neoadjuvant

Salih Karahan1, Metincan Erkaya, Mustafa Oruc

  • 1Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio.

Diseases of the Colon and Rectum
|September 12, 2025
PubMed
Summary

Local regrowth after total neoadjuvant therapy for rectal cancer did not increase distant metastasis risk. Salvage surgery yielded comparable outcomes to upfront surgery, emphasizing the need for high-quality procedures and surveillance.

Keywords:
Distant metastasisLocal regrowthRectal cancerTotal neoadjuvant therapyWatch and wait

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Area of Science:

  • Oncology
  • Surgical Oncology
  • Gastroenterology

Background:

  • Local regrowth occurs in up to 35% of rectal cancer patients achieving clinical complete response with nonoperative management.
  • Existing data on metastatic risk after regrowth primarily stem from conventional chemoradiotherapy cohorts, leaving the risk in total neoadjuvant therapy settings unclear.

Purpose of the Study:

  • To determine if local regrowth post-total neoadjuvant therapy (TNT) increases distant metastasis risk.
  • To evaluate if upfront surgery after TNT mitigates this risk compared to nonoperative management with salvage surgery.

Main Methods:

  • Retrospective cohort study at a single tertiary care center.
  • Included patients with locally advanced rectal cancer treated with TNT (2018-2024) who achieved clinical complete response.
  • Compared patients managed nonoperatively with local regrowth and salvage total mesorectal excision (TME) versus those undergoing upfront TME after TNT.

Main Results:

  • Seventy-four patients were analyzed (32 salvage TME, 42 upfront TME).
  • Local regrowth was not independently associated with an increased risk of distant metastasis (OR 0.99).
  • Advanced ypT3-4 stage (OR 5.8) independently predicted increased distant metastasis, while complete mesorectal excision (OR 0.08) was protective.

Conclusions:

  • In the TNT setting, local regrowth followed by salvage TME did not elevate distant metastasis rates compared to upfront TME.
  • High-quality salvage surgery and vigilant surveillance are crucial for optimal oncologic outcomes in rectal cancer patients.
  • Limitations include retrospective design, small sample size, and limited follow-up.