EP595 - Total Neoadjuvant Therapy Versus Standard Long-Course Chemoradiation in Young Adults with Stage II–III Rectal Cancer: A National Cancer Database Analysis

Sunday, May 10, 2026

2:52 PM - 2:57 PM ET

ePoster Presenter(s)

SS

Sara Siskind, MD, PhD

Fellow
Colorectal
Weston, Florida, United States

Disclosure information not submitted.

Author(s)

Sameh H. Emile, MBBCh, MSc, MD, FACS

Project Scientist
Cleveland Clinic Florida
Cleveland Clinic Florida
Weston, FL, United States

Disclosure information not submitted.
Marylise Boutros, MD, FRCSC, FACS, FACRS (she/her/hers)

Colorectal Surgeon
Cleveland Clinic Florida
McGill University
Weston, Florida, United States

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

Senior Author(s)

Steven D. Wexner, MD, PhD (Hon)

Surgeon
Cleveland Clinic Florida
Cleveland Clinic Lerner College of Medicine at Case Western Reserve University
Weston, Florida, United States

Disclosure information not submitted.

All of the relevant financial relationships listed below have been mitigated.

Marylise Boutros, MD, FRCSC, FACS, FACRS: This individual has no relevant relationships with ineligible companies.

Purpose/Background: The incidence of rectal cancer in young adults is rising, and these patients frequently present with more aggressive tumor biology, advanced stage, and adverse histologic features compared with older populations. In the overall adult population with locally advanced rectal cancer, total neoadjuvant therapy (TNT) has been shown to improve pathologic response, treatment compliance, and disease-free survival. However, the optimal neoadjuvant regimen for young adults, is less well defined. This study compared outcomes of TNT versus standard long-course chemoradiation (CRT) in young adults with stage II-III rectal adenocarcinoma.

Methods/Interventions: Patients aged ≤50 years receiving multimodal therapy were identified using the National Cancer Database (NCDB) between 2016-2020. TNT and CRT groups were compared before and after 1:1 propensity score matching (PSM). Overall survival (OS) was evaluated using Kaplan-Meier and Cox models. Multivariable logistic regression identified predictors of pathologic complete response (pCR).

Results/Outcomes: A total of 6,647 patients met inclusion (CRT 2,340; TNT 4,307). TNT patients were more likely to have stage III disease and elevated CEA (p < 0.001). TNT was more often used in academic centers. After matching (n=769 per group), characteristics were balanced. Five-year OS was 85.8% for TNT versus 84.0% for CRT (p=0.571). TNT was not associated with improved survival in the unmatched (HR 0.94, 95% CI 0.80-1.11, p=0.489) or matched cohorts (HR 0.92, 95% CI 0.70-1.22, p=0.571). TNT showed fewer conversions to open surgery (4.6% vs. 9.5%, p=0.005) and lower 90-day mortality (0% vs. 0.5%, p=0.029). Complete response rates were similar (11.4% vs. 11.5%), though TNT had more cases of no response (52.8% vs. 46.3%, p=0.039). Surgical margins, lymph node yield, hospital stay, and readmission rates were comparable. In multivariable analysis, elevated pretreatment CEA (OR 0.19, p< 0.001) and mucinous histology (OR 0.21, p=0.032) were linked to reduced pCR. Model discrimination was good (AUC 0.744, 95% CI 0.712-0.775).

Conclusion/Discussion: Among young adults with stage II-III rectal cancer, TNT was more often used for advanced disease and in academic centers. After adjustment, TNT was associated with similar survival and surgical outcomes as standard CRT. These findings suggest TNT is safe and feasible in this population, although its survival benefit remains unproven. Further studies should clarify biologic predictors of treatment response and ensure equitable access to TNT across practice settings.