Underutilization of post-operative radiation after nipple-sparing mastectomy for standard radiation indications

Abstract

BackgroundNipple areola complex-sparing surgeries, such as nipple-sparing mastectomy (NSM), are increasingly utilized for women with early-stage breast cancer. In the post-operative setting, two major indications for post-operative radiation (PORT) with/without regional nodal irradiation (RNI) are positive margins (margin+) and pathologically involved lymph nodes (pN+), though the frequency of these adverse pathologic features and the rate of indicated PORT use following NSM is unknown. We determined the frequency of margin+ and pN+ following NSM compared to nipple-sparing lumpectomy (BCS) and identified trends in appropriate PORT administration for these standard indications in the NSM setting. MethodsUsing the National Cancer Database, women diagnosed with cT1-3N0M0 invasive carcinoma between 2004-2017 who received NSM were compared to those who received BCS with nipple preservation. The frequencies of margin+ and pN+ by surgical subtype and utilization of PORT with/without RNI were assessed by cohort to determine if the type of surgery was associated with radiation delivery. Overall survival between the two cohorts was also compared. We performed univariable/multivariable logistic & Cox regression (MVA) with odds ratios to control for confounders. ResultsOf 624,075 women included, 611,907 had BCS and 12,168 had NSM. The surgical margin+ rate was significantly higher for NSM at 4.5% (n=544) than 3.7% for BCS (n=22,449) (p<0.001), and remained significant on MVA (OR 1.13 CI 1.03-1.25, p= 0.012). Utilization of PORT for margins+ was significantly lower by MVA after NSM (OR 0.07 CI 0.06-0.09, p<0.001). Similarly, pN+ rate was significantly higher for NSM at 22.5% (n=2,740) versus BCS 13.5% (n=82,288)(p<0.001), retaining significance on MVA (OR 1.12 CI 1.06-1.19, p<0.001). PORT with RNI for pN+ occurred less often for NSM on multivariable analysis (OR 0.73, CI 0.67-0.81, p<0.001). Neither high-risk subgroup had differences in overall survival on MVA. DiscussionNSM is associated with a higher rate of margin+ and pN+ versus BCS. Radiation is underutilized after NSM for these standard indications. Our results highlight the need to further refine patient selection for NSM, and the importance of communicating the higher potential for adverse pathologic features (and thus the potential need for radiation) to patients undergoing NSM.