Locally Advanced Rectal Cancer: Total Neoadjuvant Therapy, Immunotherapy & Watch-and-Wait

Authored by Chinmay Jani, published on 2026-11-05 22:49:22.0

Stage II–III cT3–4 And/Or N+ M0 Rectal Adenocarcinoma
- Baseline Staging And Multidisciplinary Review
  
  Rectal MRI, CT staging, DRE/endoscopy, CEA, and universal MSI/MMR testing.
  - Is The Tumor dMMR/MSI-H?
    - Neoadjuvant Dostarlimab, Conventional management for immunotherapy-ineligible
      
      For eligible adults; FDA-approved October 2026 FDA-approved indication for previously untreated Stage II–III dMMR/MSI-H locally advanced rectal cancer. Use conventional management if contraindicated.
      - Restage After Neoadjuvant Therapy
        
        Perform DRE, endoscopy, rectal MRI, and systemic reassessment when indicated.
        
        Clinical Response After Restaging?
        
        Discuss Nonoperative Watch-And-Wait
        
        Offer only in an experienced program with intensive surveillance.
        
        Sustained CCR During Watch-And-Wait?
        
        Continue Intensive Watch-And-Wait Surveillance
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
        
        Multidisciplinary Review With Timed Repeat Assessment
        
        Repeat DRE, Endoscopy, And Rectal MRI
        
        Clinical Response After Repeat Assessment?
        
        Discuss Nonoperative Watch-And-Wait
        
        Offer only in an experienced program with intensive surveillance.
        
        Sustained CCR During Watch-And-Wait?
        
        Continue Intensive Watch-And-Wait Surveillance
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
    - Low Rectal Tumor Or High-Risk MRI Features?
      - Offer Total Neoadjuvant Therapy (TNT)
        
        Long-course chemoradiation followed by FOLFOX/CAPOX; short-course RT-based TNT is an alternative.
        
        Restage After Neoadjuvant Therapy
        
        Perform DRE, endoscopy, rectal MRI, and systemic reassessment when indicated.
        
        Clinical Response After Restaging?
        
        Discuss Nonoperative Watch-And-Wait
        
        Offer only in an experienced program with intensive surveillance.
        
        Sustained CCR During Watch-And-Wait?
        
        Continue Intensive Watch-And-Wait Surveillance
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
        
        Multidisciplinary Review With Timed Repeat Assessment
        
        Repeat DRE, Endoscopy, And Rectal MRI
        
        Clinical Response After Repeat Assessment?
        
        Discuss Nonoperative Watch-And-Wait
        
        Offer only in an experienced program with intensive surveillance.
        
        Sustained CCR During Watch-And-Wait?
        
        Continue Intensive Watch-And-Wait Surveillance
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
      - Favorable Upper-Rectal Tumor Suitable for Upfront Surgery?
        
        Proceed to Upfront Surgery
        
        Neoadjuvant FOLFOX With Selective Chemoradiation (PROSPECT-Eligible), or Other Risk-Appropriate Management
        
        Discuss FOLFOX with selective chemoradiation; TNT or chemoradiation per multidisciplinary review. Eligibility for the PROSPECT-style approach includes favorable mid/upper rectal anatomy, absence of high-risk MRI features, and feasibility of sphincter-preserving surgery.
        
        Restage After Neoadjuvant Therapy
        
        Perform DRE, endoscopy, rectal MRI, and systemic reassessment when indicated.
        
        Clinical Response After Restaging?
        
        Discuss Nonoperative Watch-And-Wait
        
        Offer only in an experienced program with intensive surveillance.
        
        Sustained CCR During Watch-And-Wait?
        
        Continue Intensive Watch-And-Wait Surveillance
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
        
        Multidisciplinary Review With Timed Repeat Assessment
        
        Repeat DRE, Endoscopy, And Rectal MRI
        
        Clinical Response After Repeat Assessment?
        
        Discuss Nonoperative Watch-And-Wait
        
        Offer only in an experienced program with intensive surveillance.
        
        Sustained CCR During Watch-And-Wait?
        
        Continue Intensive Watch-And-Wait Surveillance
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
        
        Multidisciplinary Reassess Incomplete Response, Progression, Or Recurrence
        
        Select Chemoradiation, Surgery, Or Other Standard Management
High-Risk MRI Features And Surveillance Requirements

Assess T4, EMVI, tumor deposits, threatened MRF or sphincter; ensure sustained surveillance.

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