Neoadjuvant treatment response and oncologic outcomes after pelvic exenteration for locally advanced rectal cancer

Background A 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 patients with LARC undergoing pelvic exenteration (PE). Methods The National Cancer Database was queried for adults with cT4 rectal adenocarcinoma between 2006 and 2021. The following 3 groups were identified: upfront PE, nCRT with neoadjuvant rectal (NAR) score of <8 followed by PE, and nCRT with an NAR score of ≥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 months (0–201); 5% underwent upfront PE, 82% nCRT with an NAR score of ≥8%, and 13% nCRT with an NAR score of <8. Overall, 15% had positive margins. On univariable analysis, compared with an NAR score of <8, upfront PE and an NAR score of ≥8 were significantly associated with increased odds of a positive surgical margin. Five-year overall survival (OS) was 84% for an NAR score of <8, 55% for an NAR score of ≥8%, and 28% for upfront PE. After adjustment, upfront PE (hazard ratio [HR], 5.10; 95% CI, 2.69–9.65) and NAR score of ≥8 cohorts (HR, 2.23; 95% CI, 1.31–3.79) experienced worse OS. Conclusion In this US-based cohort of LARC undergoing PE, tumor regression after nCRT was strongly associated with lower rates of positive margins and better OS, confirming its significant relevance in the selection and management of these patients.