EP674 - Rectal Cancer Patients with T4 Tumors Experience Inferior Response to Total Neoadjuvant Therapy

Monday, May 12, 2025

8:27 AM – 8:32 AM PT

Location: Monitor 10, Sails Pavilion, Upper Level

ePoster Presenter(s)

ES

Emily F. Simon, MD (she/her/hers)

General Surgery Resident
University Hospitals Cleveland Medical Center, Department of Surgery
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)

Kamil Erozkan, MD

Research Fellow
University Hospitals Cleveland Medical Center, Department of Surgery, Division of Colorectal
Cleveland, OH, United States

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

Saher-Zahra Khan, MD

General Surgery Resident
University Hospitals Cleveland Medical Center
South Euclid, Ohio, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.
Kristen Westfall, MD, MPH (she/her/hers)

Colorectal Surgery Fellow
University Hospitals
Trinity Health Ann Arbor
Cleveland, OH, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.
Ronald Charles, MD (he/him/his)

Assistant Professor of Surgery
University Hospitals Cleveland Medical Center, Department of Surgery, Division of Colorectal
Cleveland, OH, United States

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

Sakti Chakrabarti, MD

Clinical Associate Professor
UH Seidman Cancer Center
Cleveland, Ohio, United States

Disclosure information not submitted.
SV

Satish E. Viswanath, PhD

Associate Professor
Case Western Reserve University
Cleveland, Ohio, United States

Disclosure information not submitted.

Senior Author(s)

ES

Emily Steinhagen, MD, FACS, FASCRS

Associate Professor of Surgery
University Hospitals Cleveland Medical Center, Department of Surgery, Division of Colorectal
Cleveland, Ohio, United States

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

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

Emily F. Simon, MD: This individual has no financial relationships with ineligible companies.

Kamil Erozkan, MD: This individual has no financial relationships with ineligible companies.

Saher-Zahra Khan, MD: This individual has no financial relationships with ineligible companies.

Kristen Westfall, MD, MPH: This individual has no financial relationships with ineligible companies.

Ronald Charles, MD: This individual has no financial relationships with ineligible companies.

Emily Steinhagen, MD, FACS, FASCRS: This individual has no financial relationships with ineligible companies.

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Purpose/Background: Total Neoadjuvant Therapy (TNT) is the standard of care for locally advanced rectal cancer. Patients who achieve a clinical complete response (CCR) – defined as absence of residual tumor on imaging or visual inspection - may be offered nonoperative management and active surveillance. Patients with clinical T4 (cT4) disease have been inconsistently included in trials evaluating TNT. This study aims to 1) compare clinical response, development of metastatic disease and mortality between patients with cT4 and cT3 rectal cancer after TNT, 2) compare rates of regrowth after achieving a CCR between patients with cT4 and cT3 disease and 3) identify factors associated with CCR in cT4 patients.

Methods/Interventions: We retrospectively reviewed patients with cT4N0-2M0 or cT3N0-2M0 rectal cancer who completed TNT at a single institution between 2019-2024. Univariate analysis compared demographics, tumor factors, treatment and outcomes between patients with cT4 and cT3 disease and between CCR and non-CCR cT4 patients. Multivariable logistic regression models predicting CCR were performed using cT and cN stage, age, race, distance from the anal verge, MMR status, CEA, and treatment course.

Results/Outcomes: 128 patients were included: 53 with cT4 and 71 with cT3 disease. Groups were similar in age, race, MMR status, sphincter involvement, CEA, and treatment regimen. More cT4 patients were male (53% vs. 35%; p=0.05) and had cN2 disease (27% vs. 10%; p=0.03). Median distance from anal verge was 7cm (cT4) versus 4.8cm (cT3; p=0.02).

Fewer cT4 patients achieved CCR compared to cT3 patients, however the difference was not significant (12 (23%) vs. 27 (38%); p=0.07). Fewer cT4 patients developed metastatic disease (15% vs. 31%; p=0.04). Patients who developed metastatic disease had a median follow up of 32 months versus 24 in those who did not (p=0.07). Mortality did not differ between cT4 and cT3 groups. On multivariable regression, cT4 patients had lower odds of achieving CCR (OR 0.24, CI .08-.72). Patients with tumors further from the anal verge (OR 1.24, CI 1.08-1.43), age 71 or older (OR 4.77, CI 1.25-18.19) and who underwent consolidation chemotherapy (OR 3.78, CI 1.07-13.39) had greater odds of CCR.

After achieving a CCR, cT4 and cT3 patients either proceeded directly to surgery (13% cT4 vs. 11% cT3) or started surveillance. In the surveillance group, 17% of cT4 and 26% of cT3 patients experienced regrowth and the remaining 67% of cT4 and 63% of cT3 patients continue to be surveyed (p=0.85). Four cT3 patients developed metastatic disease. No CCR patients died. Median follow up did not differ among patients who experienced regrowth (29 months, IQR 22-35 vs. 22 months, IQR 15.5-36; p=0.29).

Demographics, distance for the anal verge, sphincter involvement, MMR status, CEA at diagnosis and TNT treatment course did not differ between cT4 patients who achieved CCR versus those who did not. On multivariable regression, no patient or tumor factors predicted CCR amongst cT4 patients.

Conclusion/Discussion: Patients with cT4 rectal cancer are less likely than patients with cT3 disease to achieve CCR following TNT, but do not have higher rates of metastatic disease or mortality. cT4 patients have similar rates of regrowth after CCR compared to cT3 patients. Greater tumor distance from the anal verge, age 71 or older and consolidation chemotherapy were independently associated with CCR.