2006 - Integrated Multidomain Prognostic Factors for Disease-Free and Overall Survival After Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 16

POSTER

Presenter(s)

Firas Almomen, MBBS - King Saud University Medical City, Riyadh, Riyadh

A. M. Alswilem¹, K. K. Hassan², F. A. Almomen¹, B. A. Alruhaimi¹, N. Almazrou¹, A. Mohaimeed¹, S. Aljabab³, Y. M. Alayed⁴, E. Alsaeed⁴, and A. A. Alsuhaibani¹; ¹Oncology Center, King Saud University Medical City, Riyadh, Saudi Arabia, ²Kasr Al-Ainy Center of Clinical Oncology (NEMROCK), Cairo University, Cairo, Egypt, ³Radiation Oncology, College of Medicine, King Saud University, Riyadh, Saudi Arabia, ⁴Radiation Oncology Unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Purpose/Objective(s): Although prognostic factors for locally advanced rectal cancer (LARC) are well established, their integrated evaluation in patients treated with total neoadjuvant therapy (TNT) remains less well characterized. We evaluated multidomain predictors of disease-free survival (DFS) as the primary endpoint and overall survival (OS) as a secondary endpoint following TNT for LARC.

Materials/Methods: We conducted a retrospective cohort study of 125 patients with LARC treated with TNT, followed by total mesorectal excision between 2016 and 2022. Clinical, radiologic, surgical, and pathologic variables were analyzed, including performance status, pretreatment CEA, MRI high-risk features, pathologic stage, tumor deposits, resection margins, circumferential resection margin (CRM), and tumor regression. DFS and OS were estimated using Kaplan–Meier methods and compared with log-rank testing. Multivariable analysis was performed.

Results: At a median follow-up of five years, on univariate analysis, DFS showed clear multidomain risk stratification. Clinical factors significantly influencing DFS included elevated pretreatment CEA (P = .001) and poorer performance status (ECOG =2) (P < .001). Radiologic predictors showed a strong impact, with MRI-detected extramural vascular invasion (EMVI) (P = .01) and radiologic positive CRM (P < .001) associated with worse DFS. Pathologic variables were dominant determinants, including advanced pathologic T stage (pT3–4) (P < .001) and higher pathologic nodal stage (pN0 vs pN1 vs pN2) (P = .02). Additional adverse features included lymphovascular invasion (P = .02), perineural invasion (P = .01), tumor deposits (P = .04), and poor differentiation (P = .01). Favorable tumor regression (Dworak 3–4) correlated with improved DFS (P = .04). Surgical quality showed major impact, with positive resection margins (P = .01) and CRM involvement (P < .001) among the strongest predictors. On multivariable analysis, CRM involvement, nodal stage, tumor deposits, and EMVI remained independently associated with inferior DFS. On univariate analysis for the secondary endpoint of OS, worse survival was associated with elevated CEA (P = .001), ECOG =2 (P < .001), EMVI (P = .01), pathologic T stage (pT) (P < .001), pathologic N stage (pN) (P = .04), tumor deposits (P = .01), lymphovascular invasion (P = .02), perineural invasion (P = .03), positive resection margins (P = .01), and CRM involvement (P < .001). Distant metastases were the strongest determinant of OS (P < .001), with local recurrence also associated with inferior OS (P = .01).

Conclusion: DFS after TNT for LARC is driven by multidomain factors, with CRM involvement, nodal disease, tumor deposits, and EMVI emerging as key independent predictors. Similar factors were associated with OS. These findings suggest that established high-risk features retain prognostic significance in the TNT era and continue to inform postoperative management and surveillance strategies.