Surgical de-escalation of implant-based breast reconstruction (IBBR) after mastectomy for breast cancer treatment or prevention: The international randomized phase III PREPEC trial (OPBC-02).

504 Background: The optimal positioning of implants following skin- (SSM) or nipple-sparing mastectomy (NSM) for breast cancer treatment or prevention is unclear. Pre-pectoral IBBR obviates the need to dissect the major pectoral muscle but provides less soft tissue coverage of the implant. The PREPEC trial hypothesized pre-pectoral IBBR would result in improved long-term quality of life (QoL) compared to sub-pectoral IBBR. Methods: OPBC-02/PREPEC (NCT04293146) was a pragmatic, international, randomized, phase III superiority trial. Women ≥18 years undergoing SSM or NSM for treatment or prevention of breast cancer were randomized (1:1) to pre-pectoral or sub-pectoral IBBR. Surgery otherwise followed standards of care. The primary endpoint was patient-reported physical well-being chest as assessed by BREAST-Q 24 mo after surgery (prespecified MID 4 points; SD 13). 372 pts provided 80% power (two-sided t-test α = 0.05). Multiple imputation was implemented for missing scores across all timepoints (day 10; 1, 6, 12, 18, 24 mo). The IBBR assignment difference at 24 mo was estimated by linear mixed modeling, adjusted for baseline score, stratification factors, pre-selected covariates, and random center effect. Loss or replacement of expander or implant for any reason within 24 mo was the primary safety endpoint. Results: From July 2020 to February 2023, 383 pts were randomized at 26 OPBC centers in 10 countries. The full analysis set comprised 380 pts (191 randomized to pre-pectoral, 189 to sub-pectoral IBBR). Surgery was unilateral in 72.9% of pts and NSM in 58.4%. The setting was therapeutic in 77.9% of pts, therapeutic and preventive in 15.5%, and preventive in 6.6%. BREAST-Q completion was 83-95% across 6 post-baseline timepoints. Pre-pectoral IBBR significantly improved physical well-being at 24 mo compared to sub-pectoral IBBR (least-square means 79.2 95%CI 75.5-82.8 vs 74.3 70.7-78.0, respectively). The mean difference of 4.8 (95%CI 1.0-8.7; p = 0.01) surpassed the predefined threshold for a clinically meaningful difference. The effect was robust in sensitivity analyses, and consistent in subgroup analyses. Loss or replacement of expander or implant for any reason within 24 mo occurred in 68 pts, 21.1% vs 14.5% after pre-pectoral and sub-pectoral IBBR, respectively. The covariate-adjusted model estimated 5.7% (95%CI -2.4% - 13.8%) more implant loss with pre-pectoral IBBR. At least one complication occurred in 54.1% vs 55.9% of pts, respectively. Early complications were more frequent after pre-pectoral IBBR (crude estimated increase range 3-5%); late complications were more frequent after sub-pectoral IBBR. Conclusions: Pre-pectoral IBBR significantly and relevantly improved long-term QoL at the cost of a higher risk of loss or replacement of expander or implant compared to sub-pectoral IBBR. Clinical trial information: NCT04293146 .