EP242 - Identification of Factors that Determine Compliance for Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Purpose/Background: Locally advanced rectal cancer (LARC) treatment has shifted from the utilization of neoadjuvant chemoradiation (NACRT) followed by total mesorectal excision and adjuvant chemotherapy to the implementation of total neoadjuvant therapy (TNT). This transition was influenced by data from multiple studies reporting suboptimal compliance rates (~40-50%) to the completion of adjuvant chemotherapy. As a result, there was a paradigm shift to TNT, consisting of NACRT with consolidation or induction chemotherapy followed by surgery or observation, based on the RAPIDO and PRODIGE-23 studies. This real-world study evaluates compliance with completion of TNT.

Methods/Interventions: Following IRB approval (#25714), a single-institution retrospective review was conducted at a tertiary care academic institution for patients with LARC treated between 2019-2024. Demographic, clinical, and treatment data were collected in REDCap. Exclusions included age < 18 years, pregnancy, or stage I or IV disease. The primary objective was to evaluate TNT compliance, defined as adherence to the specific treatment regimen instituted by the treating physicians and completing the course of therapy, both chemoradiation and chemotherapy. Secondary objectives assessed associations between compliance and demographic and clinical variables. STATA/SE was used for statistical analyses with chi-square tests or Fisher's exact tests.

Results/Outcomes: A total of 153 patients with LARC were included; 127 patients received TNT with full treatment data available for 121 patients. The TNT compliance rate was 86.7% (n = 105). Patient demographics for each treatment group are in Table 1; within the TNT group the mean age was 61.4 years (SD 13.1), 79 (62.2%) were male, 105 (82.6%) were white (Table 1).

Among TNT patients, 32 (25.2%) patients underwent induction and 95 (74.8%) underwent consolidation therapy. Most patients, 112 (88.2%), underwent long-course radiation. The most common chemotherapy regimens were 5-Fluorouracil + Oxaliplatin + Leucovorin (FOLFOX) with 99 (78.0%) patients and Capecitabine + Oxaliplatin (CapOx) with 14 (11.0%) patients. Non-compliance with chemotherapy was primarily due to toxicity (peripheral neuropathy, cytopenia) or patient preference.

Post-TNT, 54 (42.5%) patients entered watch and wait with a mean surveillance duration of 12.75 months (SD 7.9) and 70 (55.1%) underwent surgical intervention (47 (67.1%) immediately after completion of TNT and 23 (32.9%) after a period of watch and wait. Disease recurrence occurred in 25 (19.7%) patients within a mean time of 9.1 months (SD 7.1). When assessing compliance in relation to the demographic and clinical variables, there was a higher proportion of male gender and non-use of recreational drugs in the compliance group; this was statistically significant (Table 2).

Twenty-six patients did not undergo TNT for a variety of reasons including refusal, poor functional status, or a surgery first approach.

Conclusion/Discussion: This first real-world analysis demonstrates high TNT compliance with 86.7% completion rate, representing a significant improvement over the historical rate of 40-50% with NACRT/TME/AC. The significant predictors for compliance were male gender and recreational drug non-use. While TNT compliance rates were high, initial TME rates post TNT were double that of the Organ Preservation in Patients with Rectal Adenocarcinoma (OPRA) trial; i.e., a lower complete clinical response rate in our institution's TNT experience.

Patient Demographics
Patient demographics for patients in the TNT group and no TNT group. SD=standard deviation, CEA= Carcinoembryonic Antigen
Associations for Clinical Variables and TNT Compliance
Different patient demographic, treatment and clinical variables assessed between the compliant and non-compliant patients who underwent TNT. There is a statistically significant (p < 0.05) result for gender and recreational drug.