Anal adenocarcinomas are a rare condition which account for less than 10% of anal cancers. The present study aimed to assess the impact of neoadjuvant therapy on the clinical and pathologic outcomes and overall survival (OS) of patients with stage II-III anal adenocarcinomas after abdominoperineal resection (APR). A retrospective cohort study of patients with anal adenocarcinoma in the US National Cancer Database (NCDB) (2010-2020) was conducted. Propensity-score matching was used to compare patients who received neoadjuvant therapy (neoadjuvant therapy group) to the no-neoadjuvant group. The primary outcome was 5-year OS whereas secondary outcomes included conversion to open surgery, hospital stay, surgical margins, 30-day mortality, 90-day mortality, and 30-day readmission. A total of 742 patients (56% male) with a mean age of 63.6 ± 12.4 years were included. A total of 214 patients in the neoadjuvant group were matched with 107 in the no-neoadjuvant group. The mean OS was similar between the two groups (47.5 vs. 44.8 months, p = 0.253). Patients who received neoadjuvant therapy had a longer median time between diagnosis and surgery (151 vs. 54 days, p < 0.001), lower 90-day mortality (1.9% vs. 6.7%, p = 0.046), more pT0 tumors (15.7% vs. 0%), less pT3-4 tumors (28.4% vs. 36.4%, p = 0.001), less pN1-2 tumors (22.9% vs. 34.7%, p < 0.001), and less lymphovascular invasion (16.2% vs. 40%, p < 0.001) than the no-neoadjuvant group. Both groups had similar conversion rates, hospital stay, 30-day mortality, 30-day readmission, and positive surgical margins. Neoadjuvant therapy before APR was associated with significant downstaging of anal adenocarcinomas and lower 90-day mortality, yet similar OS to patients who were surgically treated without neoadjuvant treatment.
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