EP1013 - Straddling the Line: Does Tumor Position at the Peritoneal Reflection Predict Local Recurrence After TNT?

Purpose/Background: As emerging evidence supports the non-inferiority of a watch-and-wait approach in patients with complete clinical response following TNT, careful patient selection has become increasingly important to balance oncologic outcomes with organ preservation. However, limited data exist on how tumor position relative to the peritoneal reflection affects long-term outcomes. This study aims to evaluate outcomes of LARC, based on tumors located either straddling the peritoneal reflection versus those found below the reflection.

Methods/Interventions: This retrospective study included patients who completed TNT for LARC at our referral center between 2015 and 2024. Patients with no known metastasis on initial staging were included in the study. Patients were selected based on initial MRI at the time of diagnosis. Patients whose tumor was straddling or spanning the peritoneal reflection designated the 'spans' group. Those whose tumor was found entirely below the peritoneal reflection were designated the "below" group. The primary outcome was rate of local recurrence. Binary logistic regression was used to identify predictors of local recurrence.

Results/Outcomes: Among 116 patients with LARC, 49 had tumors spanning the peritoneal reflection and 67 had tumors below it. Baseline demographics were similar between groups including age, sex, BMI and comorbidities such as inflammatory bowel disease, family history of colorectal cancer and obesity. Tumors below the reflection more frequently involved the levator muscles (39% vs 12%, p=0.002). Tumors spanning the reflection were more often T4 (96% vs 49%, p< 0.001), larger in size (7.7 cm vs 5.6 cm, p< 0.001), and demonstrated higher rates of EMVI (61.2% vs 31.3%, p= 0.006). Post TNT, patients in the below group were more likely to achieve mrTRG1 or mrTRG2 response on MRI (42.6% vs 13.3%, p=0.001) and complete response by tumor board consensus (27.1% vs 0%, p< 0.001). More patients in the below group underwent a Watch and Wait protocol (31.3% vs 6.1% p=0.002). In patients who underwent surgery, there was no difference in pathologic complete or near complete response in the spans vs below groups (37.2% vs 29.6% p=0.43). In patients with local recurrence, time to diagnosis was similar between groups (414 days vs 372 days, p= 0.65). On subgroup multivariate analysis of patients who were initially treated with TNT followed by surgery, tumor location spanning the peritoneal reflection was associated with reduced risk of local recurrence (HR 0.03, 95% CI 0.002-0.47, p=0.012), while increasing tumor size (HR 1.54 per cm, 95% CI 1.10-2.16, p=0.011) independently predicted local recurrence when controlling for distance to the anal verge, tumor grade and invasion of the levator ani. Similarly, local recurrence-free survival was lower in the below group by KM curve (p=0.024). No differences were observed in rates of distant metastasis (22.4% vs 25.4%, p=0.72), overall survival (87.8% vs 85.1%, p=0.68), or disease-free survival (log rank p= 0.18).

Conclusion/Discussion: Tumors spanning the peritoneal reflection are associated with multiple high-risk features, such as larger size, and more frequent characterization as T4. Despite these differences, disease-free and overall survival were comparable, and local recurrence was lower in the group straddling the peritoneal reflection. As treatment paradigms shift to consider organ preservation, this study showcases a population of patients who may benefit from a Watch and Wait program. However, further studies are needed to evaluate the efficacy of such an approach.

Predictors of Local Recurrence
Table 1. Multivariate predictors of local recurrence accounting for distance to anal verge, tumor size by MRI, tumor grade, position relative to the peritoneal reflection and invasion of the levator ani.
Local Recurrence Free Survival Since TNT