P303 - A Novel Endoscopic Tumor Regression Grading (endoTRG) System for Predicting Pathologic Response Following Total Neoadjuvant Therapy in Rectal Cancer

Abstract Podium Presenter(s)

• 

  Metincan Erkaya, MD

  Clinical Research Fellow
  Cleveland Clinic Digestive Diseases & Surgery Institute
  Cleveland Clinic
  Cleveland, OH, United States

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no financial relationships with ineligible companies.

Author(s)

• JS

  Josh Sommovilla, MD

  Assistant Professor of Surgery
  Cleveland Clinic
  Cleveland, Ohio, United States

  Disclosure information not submitted.
• 

  Mustafa Oruc, 1020414 (he/him/his)

  Research Fellow
  Cleveland Clinic
  Cleveland, OH, United States

  Disclosure information not submitted.
• 

  Salih Karahan, MD

  Research Fellow
  Cleveland Clinic Department of Colorectal Surgery
  Cleveland Heights, OH, United States

  Disclosure information not submitted.
• 

  David R. Rosen, MD

  Colorectal Surgeon
  Cleveland Clinic
  Cleveland Clinic Lerner College of Medicine
  Cleveland, OH, United States

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no relevant relationships with ineligible companies.
• 

  Hermann Kessler, MD PhD (he/him/his)

  Professor
  Cleveland Clinic
  Cleveland Clinic
  Cleveland, OH, United States

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no financial relationships with ineligible companies.
• 

  Michael A. Valente, DO

  Associate Professor of Surgery
  Cleveland Clinic
  cleveland, Ohio, United States

  Disclosure information not submitted.
• 

  Scott R. Steele, MD, MBA (he/him/his)

  President, Cleveland Clinic, Main Campus Submarket and Rupert B. Turnbull M.D., Endowed Chair in Colorectal Surgery
  Cleveland Clinic
  Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
  Cleveland, OH, United States

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no financial relationships with ineligible companies.
• 

  David Liska, MD

  Associate Professor, Chair
  Department of Colorectal Surgery, Cleveland Clinic
  Cleveland Clinic, Cleveland, Ohio
  Cleveland, OH, United States

  All of the relevant financial relationships listed below have been mitigated.
  Medtronic: Consultant (Terminated, January 16, 2024)

Senior Author(s)

• 

  Emre Gorgun, MD, MBA. FACS, FASCRS. (he/him/his)

  Vice Chair, Department of Colorectal Surgery
  Cleveland Clinic
  Cleveland Cliinic
  Cleveland, Ohio, United States

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no relevant relationships with ineligible companies.

Purpose/Background: While pathologic and MRI-based tumor regression grading systems are widely utilized following neoadjuvant therapy for rectal cancer, no structured, quantitative endoscopic grading system currently exists for post-TNT response evaluation. This represents a critical gap in clinical practice, as subjective impressions without predefined criteria lead to significant variability across institutions and inconsistent documentation. We aimed to develop an Endoscopic Tumor Regression Grading (endoTRG) system to standardize post-TNT endoscopic assessment.

Methods/Interventions: This retrospective study analyzed LARC patients treated with TNT and surgical resection with complete pre- and post-TNT endoscopy (2018-2025). Two experienced colorectal surgeons independently evaluated pre- and post-TNT endoscopy captures in blinded fashion, scoring the presence of each endoscopic feature. Interobserver agreement was assessed using Cohen's kappa statistics.

We developed a point-based endoTRG scoring system incorporating mucosal healing features (whitening mucosa, telangiectasia, scarring, erythema), adverse features (ulceration, necrosis), mass regression levels, and stricture characteristics. Univariate logistic regression identified predictive features, with point values assigned proportional to their association strength with AJCC pathologic response. The system classifies patients into three tiers: endoTRG 1 (Complete), endoTRG 2 (Near-complete), or endoTRG 3 (Incomplete). The endoTRG system's ability to predict pathologic response was evaluated using diagnostic performance metrics and ROC analysis for pCR prediction.

Results/Outcomes: Seventy-six patients (mean age 58±12 years, 58% male) were eligible. The two endoscopists demonstrated excellent interobserver agreement for overall response assessment (weighted κ=0.9) with 88.2% exact agreement. Agreement was excellent for mass regression (weighted κ=0.86) and good for ulceration (κ=0.69), whitening mucosa (κ=0.68), and telangiectasia (κ=0.66). Agreement was moderate for scarring (κ=0.57), adenoma/raised lesion (κ=0.60), and necrosis (κ=0.42), and fair for stricture (κ=0.40).

Univariate analysis identified whitening mucosa as the strongest predictor of complete response (OR 47), followed by telangiectasia (OR 23), scarring (OR 16), and erythema (OR 16). Ulceration and necrosis were powerful negative predictors (OR 0.03 each). Each incremental level of mass regression (from no regression to < 50% to 50-99% to 100% regression) increased the odds of complete response 9.6-fold (all P< 0.01). The endoTRG scoring system demonstrated excellent discrimination for predicting pCR (AUC 0.85, 95% CI 0.76-0.93) with sensitivity 83.3%, specificity 76.1%, and accuracy 78.9%. The endoTRG Complete category identified patients with 69.4% pCR probability. (Table and Figure 1)

Conclusion/Discussion: The endoTRG system is the first statistically-weighted, objective scoring system for endoscopic response assessment after TNT in rectal cancer. Demonstrating excellent interobserver reliability and strong diagnostic performance, it addresses a critical gap in post-TNT evaluation, standardizes documentation, and facilitates the identification of patients suitable for organ preservation strategy.

The endoTRG system and receiver operating characteristic curve
Performance and Clinical Utility of the endoTRG Scoring System