EPD101 - Impact of Total Neoadjuvant Therapy Sequence on Low Anterior Resection Mesorectal Excision Quality

Purpose/Background: Total neoadjuvant therapy (TNT) including chemotherapy and chemoradiation is the standard of care for locally advanced rectal cancer. Recent trials demonstrate that chemoradiation followed by chemotherapy improves complete clinical response and organ preservation rates. However, with chemoradiation as first treatment, there is a prolonged interval from completion of radiation to surgery (often as long as 6 months), which anecdotally increases operative difficulty due to fibrosis and altered tissue planes, and possibly the quality of the total mesorectal excision (TME). The goal of this study was to evaluate if the sequence of TNT treatments impacts low anterior resection (LAR) TME quality.

Methods/Interventions: A single institution rectal cancer database was queried to identify patients who underwent TNT followed by LAR between 2019 and 2024, and study populations were propensity matched between patients who received long-course chemoradiation followed by consolidation chemotherapy (cTNT) or induction chemotherapy followed by chemoradiation (iTNT). Patients were matched 1:1 using propensity scores (nearest neighbor, caliper 0.2) based on age, gender, ASA score, tumor location (low vs. mid/upper), and BMI (≥30 vs. < 30). Completeness of mesorectal excision was classified as complete, near-complete, or incomplete according to templated pathology reports. Complete and near-complete grades were analyzed together. Covariate balance between matched groups was assessed using standardized mean differences (SMD < 0.1 = adequate) and visually displayed with a Love plot. Fisher's exact test was used to compare rates of incomplete mesorectal excision between groups.

Results/Outcomes: The propensity-matched cohort included 37 cTNT and 37 iTNT patients. The match was successful, and baseline characteristics including age, gender, ASA score, tumor location and BMI were well balanced with low SMD values. Baseline characteristics of the matched groups are presented in Table 1. The median interval from completion of radiotherapy to surgery was significantly longer in the cTNT group (185 days, range 75-238) compared with the iTNT group (66 days, range 6-137); p < 0.001. When starting with chemoradiation and then consolidation chemotherapy, there was a lower rate of complete or near-complete TME rate (78.4% of cTNT patients and 89.2% of iTNT patients), although this was not statistically significant (p=0.345).

Conclusion/Discussion: In this small study, there was a higher rate of incomplete LAR TME rates when chemoradiation was the first treatment in TNT, albeit not statistically significant. If organ preservation is not the goal of TNT, and the patient will undergo an LAR, then consideration should be given to induction chemotherapy followed by CRT as the preferred TNT regimen, since it might result in higher complete TME rates. Larger studies need to be done to provide more robust statistical data, but validated results would lead to more individualized TNT approaches.



Description: A propensity-matched study evaluated whether the sequence of total neoadjuvant therapy (TNT) impacts low anterior resection (LAR) total mesorectal excision (TME) quality in locally advanced rectal cancer treatment. There was a higher rate of incomplete LAR TME when chemoradiation was the first TNT treatment, although this difference was not statistically significant. This study suggests that if organ preservation is not the goal and the patient will undergo LAR, induction chemotherapy followed by chemoradiation may be preferred to potentially improve TME completeness rates.

Table 1: Baseline characteristics and mesorectal excision completeness in the propensity-matched cohort of patients treated with long-course chemoradiation followed by consolidation chemotherapy (cTNT) or induction chemotherapy followed by chemoradiation (iTNT)