3084 - Optimizing Eligibility for and Access to Non-Operative Management for Rectal Adenocarcinoma

K. Waeldner¹, C. J. Anker², S. Ades³, P. Cataldo⁴, and D. Devine⁵; ¹Larner College of Medicine at the University of Vermont, Burlington, VT, ²Division of Radiation Oncology, University of Vermont Medical Center, Burlington, VT, ³University of Vermont Cancer Center, Burlington, VT, ⁴University of Vermont Medical Center, Burlington, VT, ⁵University of Vermont Biostatistics Core, Burlington, VT

Purpose/Objective(s): Historically, some patients diagnosed with locally advanced rectal adenocarcinoma underwent a combination of chemoradiation (CRT), total mesorectal excision (TME), and adjuvant chemotherapy (i.e. trimodality therapy, TMT). Despite data showing over half of Stage II/III patients may be able to avoid TME after completing all planned radiation and chemotherapy with a resultant improvement in QoL, many patients continue to undergo TME. Barriers to adoption of non-operative management (NOM) include concerns for worse oncologic outcomes with NOM and NOM being provided to subsets of patients that are not expected to benefit. This study aimed to address current gaps, including: 1. Determine whether TME-free survival was worse for T4 vs. T3 patients. 2. Evaluate whether oncologic survival outcomes for NOM vs. TMT are equivalent in a real-world population. Materials/

Methods: Patients receiving either NOM or TMT involving long-course chemoradiation (LC-CRT) for T3/4NanyM0 or TanyN+M0 (MRI-staged) biopsy-proven rectal adenocarcinoma between 2015-2023 were included, generating a dataset of 86 consecutive patients. Clinical variables and patient characteristics were assessed for association with outcomes on multivariable logistic regression. TME-free survival, disease free survival (DFS) and overall survival (OS) were assessed with Kaplan-Meier analyses and Cox proportional modeling.
Results: Median follow-up for all patients was 48.8 months. Of all 86 patients, 32 (37%) were treated on a clinical trial (OPRA: 30 & PROSPECT: 2). Of the 62 NOM patients (T4: 23%; N+: 73%), 45 (73%) received LC-CRT followed by consolidation chemotherapy, 15 (24%) received induction chemotherapy followed by LC-CRT, and 2 (3%) received LC-CRT alone. Thirty (26 T3 patients and 4 T4 patients) of 62 (48%) achieved a complete clinical response (cCR). For NOM patients, the 3-year TME-free survival was 51% and 44% for T3 and T4 patients, respectively (p=0.76). There were no instances of regional nodal regrowth in the NOM group. Five-year DFS and OS for NOM vs. TMT patients was 58% vs. 67% and 73% vs. 71%, respectively, all nonsignificant.
Conclusion: Given the statistically equivalent DFS/OS when comparing NOM and TMT patients, as well as the high TME-free survival across all stages (approximately half of both T3 and T4 patients), it is reasonable to offer NOM to a patient with locoregionally advanced rectal cancer, particularly in the distal rectum where organ preservation may be impossible or difficult if TME is required. This mixed “real world”/clinical trial patient data shows the importance of increasing access to NOM as an option for rectal cancer patients broadly.