Abstract Background: Since our 2015 manuscript, nipple-sparing mastectomy (NSM) continues to be an increasingly adopted technique in breast cancer management. However, concerns regarding long-term oncologic safety still persist. This systematic review and meta-analysis provides a ten year update on oncologic safety associated with NSM, specifically overall survival (OS), disease-free survival (DFS), local recurrence (LR), and nipple-areolar complex recurrence (NACR). Methods: A systematic review of the literature was performed according to PRISMA guidelines to identify studies reporting outcomes after NSM. Studies with internal comparison arms evaluating therapeutic NSM versus skin-sparing mastectomy (SSM) and/or modified radical mastectomy (MRM) were included in a meta-analysis of OS, DFS, and LR. Studies lacking comparison arms were only included in the systematic review, wherein pooled analyses for NSM patients were conducted for OS, DFS, LR, and NACR using a random-effects model. Weighted averages and 95% confidence intervals (CI) were calculated, and studies were stratified by duration of follow-up: 3 years, 3-5 years, 5-10 years, and 10 years. Results: A total of 60 studies representing a total of 7,752 patients undergoing NSM were included. The meta-analysis included 11 studies with comparison arms. Nine studies reported OS with a significant pooled risk difference of 2.1% favoring NSM over MRM/SSM (95% CI: 0.0-4.3%, p=0.047). Seven studies reported DFS, with a nonsignificant pooled risk difference of 4.8% favoring NSM (95% CI: -0.8-10.3%, p=0.093). Eleven studies reported LR, with a nonsignificant pooled risk difference of -0.7% (95% CI: -2.1-0.8%, p=0.35). The systematic review included all 60 studies. Weighted average follow-up ranged from 25.6 to 133.4 months across groups. Among patients with 3 years follow-up (n=2,508), pooled OS and DFS were 98.6% (95% CI, 98.5-98.7) and 93.6% (93.2-93.9), respectively. Local recurrence was 2.4% (2.3-2.5), and NACR was 0.5% (0.4-0.5). For 3-5 years follow-up (n=1,454), OS was 98.7% (98.5-98.8), DFS 95.1% (94.7-95.5), LR 1.6% (1.5-1.6), and NACR 0.7% (0.6-0.7). At 5-10 years (n=3,399), OS was 93.4% (93.1-93.6), DFS 86.0% (85.8-86.2), LR 3.8% (3.8-3.9), and NACR 2.5% (2.4-2.5). In studies with 10 years follow-up (n=391), OS was 82.0% (80.9-93.2), DFS 60.7% (58.8-62.7), LR 15.1% (13.9-16.2), and NACR 1.1% (1.0-1.1). Conclusions: This study continues to support that NSM is associated with excellent overall and disease-free survival with low local recurrence rates comparable to that of SSM/MRM as well as low NAC recurrence rates among appropriately selected patients. This updated data provide additional support for the long-term safety of NSM. Citation Format: R. N. Rohrich, H. Soltani, I. A. Snee, K. L. Fan, L. De La Cruz. A Decade Later: Our Updated Systematic Review and Meta-Analysis of Overall Survival, Disease-Free Survival, Local Recurrence, and Nipple-Areolar Recurrence Following Nipple-Sparing Mastectomy abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-01-08.
Rohrich et al. (Tue,) studied this question.