Cleveland Clinic Colorectal Surgeons Develop a New Standardized Endoscopic Grading System for Rectal Cancer Response and Organ Preservation

A new endoscopic tumor regression grading system developed by researchers at Cleveland Clinic may help standardize how clinicians assess response to total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer, potentially improving selection for organ-preserving treatment strategies.

The research, presented at the 2026 Annual Meeting of the American Society of Colon and Rectal Surgeons, in Tampa, Florida, introduces the first statistically weighted, point-based endoscopic tumor regression grading system, known as EndoTRG (Endoscopic Tumor Regression Grading).

According to Emre Gorgun, MD, MBA, from the Department of Colorectal Surgery and Co-Director of the Endoluminal Surgery Center at Cleveland Clinic, the study addresses a longstanding gap in post-treatment rectal cancer assessment.

“The treatment of locally advanced rectal cancer has changed significantly over the last decade, and we are moving toward what we call non-operative management, or less surgery and more chemotherapy and radiation, to the point that we can accomplish organ preservation,” he notes.

A shift toward organ preservation

Historically, treatment for locally advanced rectal cancer relied heavily on surgery, often requiring proctectomy and removal of the rectum. While surgical techniques and outcomes have improved substantially, many patients continue to experience long-term functional consequences after surgery, including bowel urgency, frequency, leakage and major lifestyle disruption known as low anterior resection syndrome.

The emergence of TNT, combining chemotherapy and radiation before surgery, has increased the possibility of avoiding surgery altogether in select patients who achieve complete clinical response. “At our center, for example, we see up to 45% complete response rates, which means that out of 100 patients, 45 can achieve organ preservation,” says Dr. Gorgun.

However, accurately identifying which patients are true responders remains challenging. Current response assessment relies primarily on MRI, endoscopy and digital rectal examination. Although MRI-based tumor regression grading systems have existed for years, endoscopic assessment has largely remained subjective and variable between clinicians and institutions.

Developing the EndoTRG system

To address this need, investigators retrospectively analyzed patients with locally advanced rectal cancer who underwent TNT followed by surgical resection between 2018 and 2025. Seventy-six eligible patients with complete pre- and post-treatment endoscopic evaluation were included.

Two experienced colorectal surgeons independently reviewed blinded endoscopic images and evaluated multiple treatment-response features, including mucosal whitening, telangiectasia, scarring, erythema, ulceration, necrosis, mass regression and strictures.

The researchers then developed a three-tier EndoTRG scoring system:

• EndoTRG 1: Complete response
• EndoTRG 2: Near-complete response
• EndoTRG 3: Incomplete response

Importantly, the scoring system weighted features based on their predictive association with pathologic response. Whitening mucosa emerged as the strongest positive predictor of complete response, followed by telangiectasia, scarring and erythema. Conversely, ulceration and necrosis were strong negative predictors.

Strong predictive performance

The investigators found that the EndoTRG system demonstrated excellent interobserver reliability, with 88 % exact agreement between reviewers and a weighted kappa value of 0.9 for overall response assessment.

The system also showed strong predictive performance for pathologic complete response, achieving high sensitivity of 83%, specificity of 76% and overall accuracy of 79%.

Patients classified as EndoTRG 1 had a 69% probability of pathologic complete response, while patients classified as EndoTRG 3 had an 86% probability of partial or incomplete response.

“We found that the EndoTRG system is the first statistically weighted, point-based scoring algorithm for endoscopic response assessment following neoadjuvant therapy,” Dr. Gorgun says. “By quantitatively integrating multiple concurrent endoscopic features and weighting them based on predictive strength, this system addresses the limitations of qualitative grading and provides an objective three-tier risk stratification system and facilitates standardized patient selection for organ-preserving strategies.

“With this system, we are introducing a completely new tool into the field—one that did not previously exist,” he adds.

Potential impact on clinical practice

Dr. Gorgun believes the scoring system could ultimately help clinicians make more confident decisions regarding non-operative management and surveillance.

“In my opinion, this will help surgeons be much more precise in their evaluations,” he says. “And if this system proves to be accurate, then we can more safely monitor patients non-operatively versus operatively.”

The team’s next step is to integrate EndoTRG into routine clinical workflows and endoscopic reporting systems at Cleveland Clinic. According to Dr. Gorgun, incorporation into the institution’s endoscopic reporting platform could facilitate broader validation and standardization over time. “That would make the information readily available and would also allow us to further validate the scoring system over time,” he says.

If validated in larger prospective studies, the EndoTRG system could represent an important advancement in personalized rectal cancer care, helping clinicians better identify patients who may safely avoid surgery while maintaining favorable oncologic outcomes