Abstract Background: Surgical axillary staging is often debated in patients with microinvasive ductal carcinoma in situ (T1mi) due to the low occurrence of nodal metastasis. Axillary surgery (ASx) is associated with risks like seroma, wound complications, lymphedema, and sensory deficits. This study aims to assess the utility of surgical axillary staging in clinically node-negative (cN0) T1mi breast cancer patients and provide insights for optimizing high value surgical treatment and subsequent decision-making. Methods: This retrospective cohort study analyzed data from the National Cancer Database (NCDB) to investigate axillary status of patients with cT1mi breast cancer between 2012 and 2019. Patient demographics, clinical characteristics, treatment methods and pathologic findings were collected. Comparisons were made between those who did and did not undergo ASx, and of those who did, between patients who were pathologically node-positive (pN+) vs. node-negative (pN-). Results: Of 10,843 patients analyzed, 9,220 (85.0%) underwent ASx while 1,623 (15.0%) did not. Mean age of patients undergoing ASx and those who did not was 59.2±11.2 and 66.3±12.8 years, respectively (p< 0.001). On univariate analysis, other factors associated with undergoing ASx were having private insurance, fewer medical comorbidities, having a HER2+ or triple negative phenotype, higher grade, presence of lymphovascular invasion and undergoing mastectomy (all p< 0.05). Sentinel lymphadenectomy was performed in 83% of patients while axillary lymph node dissection (ALND) was performed in 17% of patients. Final pathology demonstrated an upgrade to a true invasive cancer (T1 or greater) in 29.3% of cases. Of 9,069 patients who underwent ASx with known pathologic nodal status, 8,512 (93.9%) were pN- and 557 (6.1%) were pN+. Factors independently associated with increased odds of having positive nodes were younger age (OR 1.02, 95% CI 1.01-1.03, p< 0.001), Black race (OR 1.51, 95% CI 1.12-2.10, p=0.007), lymphovascular invasion (OR 13.72, 95% CI 10.25-18.36, p< 0.001), and undergoing mastectomy (OR 1.98, 95% CI 1.57-2.51, p< 0.001). Among the pN+ patients, only 64 (0.7%) had ≥3 total positive nodes and would require ALND. On subset analysis of the 4,190 patients undergoing mastectomy, 244 (5.8%) did not undergo ASx, while 3,946 (94.2%) did, of whom 373 (9%) were pN+. Regarding adjuvant treatments in this group, more patients who underwent ASx received chemotherapy (12% v. 8%, p< 0.001), and among those who did undergo surgery those who were pN+ were much more likely to receive chemotherapy (58% v. 12%, p< 0.001). However, similar proportions of patients who did and did not undergo ASx received adjuvant radiation (5% v. 4%, p=0.65), while, as expected, among those undergoing ASx, a higher proportion who were pN+ underwent radiation (32% v. 5%, p< 0.001). Conclusion: Surgical axillary staging for T1mi breast cancer is common, but many patients are node-negative. More patients are undergoing ALND than necessary based on pathology. Nodal status influences adjuvant therapy decisions. Identifying factors linked to upgrade and higher pN+ probabilities can enable personalized surgical treatments, reducing morbidity for most patients. Citation Format: Christian Lava, Karen Li, Lauren Berger, Daisy Spoer, Lindy Rosal, Austin Williams, Monika Masanam, Ian Greenwalt, Jennifer Son, Lucy De La Cruz. Optimizing Treatment Decisions in Microinvasive Ductal Carcinoma in Situ: Evaluating the Need for Surgical Axillary Staging [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-12.