Comparing local excision with watch and wait for the management of rectal cancer patients responding to neoadjuvant chemoradiotherapy: Composite endpoint analysis using the win ratio.

Objective: The aim of this work was to apply the 'win ratio' to compare the outcomes of rectal-sparing approaches [watch and wait (WW) and local excision (LE)] in the management of locally advanced rectal cancer responding to neoadjuvant chemoradiotherapy.

Methods: Patients enrolled in the ReSARCh study (NCT02710812) between 2016 and 2021 were divided into two cohorts (WW vs. LE). The win ratio was calculated by dividing the number of successes (or wins) in the WW group by the number of successes in the LE group on matched pairs. Oncological outcomes (overall survival, distant and local recurrence), presence of a stoma and rectum not preserved were considered as outcomes of interest.

Results: Overall, 108 (62.1%) patients underwent LE and 66 (37.9%) WW. Patients who underwent WW were more likely to have a complete clinical response (cCR) at restaging [i.e. ycT = 0: n = 51 (80%) for WW vs. n = 45 (42%) for LE, p < 0.001]. After matching for age, sex, distance from the anal verge and T stage at restaging, i.e. ycT, 57 pairs of patients were identified. The overall win ratio considering only oncological outcomes was 0.4 (95% CI 0.02-0.94). The disadvantage of WW was mainly due to a higher rate of local recurrences. The overall win ratio considering oncological outcomes, presence of a stoma and rectum not preserved was 0.6 (95% CI 0.04-1.38), indicating a potential disadvantage for WW, but with wide confidence intervals suggesting uncertainty.

Conclusions: LE may have an advantage in terms of local recurrence rates compared with WW, potentially conferring a survival benefit. These results should be confirmed in further prospective randomized trials.