Neoadjuvant Treatment Response and Oncologic Outcomes After Pelvic Exenteration for Locally Advanced Rectal Cancer.

BACKGROUND: Lack of response to neoadjuvant chemoradiotherapy (nCRT) has been described as a surrogate of aggressive tumor biology leading to poor oncologic outcomes in locally advanced rectal cancer (LARC). However, there is a paucity of data on this association for LARC patients undergoing pelvic exenteration (PE). METHODS: The National Cancer Database was queried for adults with cT4 rectal adenocarcinoma between 2006-2021. Three groups were identified: upfront PE, nCRT with neoadjuvant rectal (NAR) score <8 followed by PE, and nCRT with NAR≥8 followed by PE. The NAR score is a validated endpoint that incorporates cT, pT, and pN to calculate treatment efficacy. RESULTS: Of 942 patients, 73% were <65 years old, 57% female, 84% white with a median follow-up of 40 (0-201) months; 5% underwent upfront PE, 82% nCRT with NAR≥8, and 13% nCRT with NAR<8. Overall, 15% had positive margins. On univariable analysis, compared to NAR<8, upfront PE and NAR≥8 were significantly associated with increased odds of a positive surgical margin. Five-year OS was 84% for NAR<8, 55% for NAR≥8, and 28% for upfront PE. After adjustment, upfront PE (HR 5.10, 95% CI 2.69-9.65) and NAR≥8 (HR 2.23, 95% CI 1.31-3.79) cohorts experienced worse overall survival (OS). CONCLUSIONS: In this US-based cohort of LARC undergoing PE, tumor regression after nCRT was strongly associated with lower rates of positive margins and better overall survival, confirming its significant relevance in the selection and management of these patients.