BackgroundAnal adenocarcinoma (AA) is reported to represent 5% to 10% of all anal cancer. Currently there is no evidence-based treatment of AA. We investigated clinical outcomes after treatment regimens in patients with AA and used the Surveillance, Epidemiology, and End Results (SEER) registry to examine the outcome. Patients and MethodsWe searched for patients diagnosed with histologically confirmed adenocarcinoma of the anal canal with stage I to III disease between 2010 and 2016 using SEER∗Stat software. ResultsA total of 393 patients treated from 2010 to 2016 for AA were identified. Patients were divided into 5 groups according to treatment: 68 patients (17.3%) receiving radiotherapy (RT) and chemotherapy (CTx), 16 patients (4.1%) receiving RT or CTx, 108 patients (27.5%) receiving surgery alone, 137 patients (34.8%) receiving preoperative RT or CTx with surgery, and 64 patients (16.3%) receiving postoperative RT or CTx with surgery. The 3-year cause-specific survival (CSS) rates were 63.9% in the RT and CTx group, 35.7% in the RT or CTx group, 77.7% in the surgery-alone group, 80.3% in the preoperative RT or CTx group, and 65.8% in the postoperative group (P < .001). Preoperative RT or CTx was associated with improved CSS on multivariate analysis (P = .024). The 3-year CSS rates for those who received surgery and those who did not receive surgery were 81.5% and 87.5% for stage I disease, and 74.4% and 57.3% for stage II/III disease. ConclusionPreoperative treatment with surgical resection may maximize the survival outcome. Although chemoradiotherapy alone may be sufficient for early stages of disease, patients with advanced disease should be treated with a combination of surgical resection and chemoradiotherapy. Future studies are required to determine the appropriate treatment strategies in AA.