Reverse-sequence endoscopic versus conventional open nipple-sparing mastectomy with implant-based breast reconstruction: a single-center prospective cohort study (RECO study)

Background: Minimal-access nipple-sparing mastectomy (NSM), including endoscopic- or robotic-assisted NSM, is increasingly used in the treatment of patients with breast cancer. However, traditional minimal-access NSM is time-consuming, costly, and has a steep learning curve, hindering its widespread adoption. Our team pioneered the “reverse-sequence” endoscopic nipple-sparing mastectomy(R-E-NSM), which addresses the challenges identified in previous surgeries. This study aimed to compare the clinical outcomes of R-E-NSM with implant-based breast reconstruction (IBR) and conventional open nipple-sparing mastectomy(C-O-NSM) with IBR. Methods: In this prospective, single-center, non-randomized study, we consecutively recruited women aged 18 years or older who underwent NSM with IBR for breast cancer or risk reduction at the West China Hospital of Sichuan University from March 2021 to March 2024. We took the complication rate of the previous retrospective study as a reference, using PASS software, the test power was set as 0.8, α=0.05, the dropout rate was 10%, recruitment rate was 3:1, and 452 patients were planned to be recruited. Finally, we included 511 patients. Data about patients’ demographics and operative, oncological, complication details, and cosmetic outcomes were collected before and after surgery. We conducted a prespecified risk-factor analysis using mixed-effect regression to investigate the relationship between surgery type and incidence of complication. This study received approval from the Ethics Committee of Sichuan University and was registered on the China Clinical Trials Network with the trial registration number ChiCTR2100047862. All enrolled patients provided written informed consent. Findings: A total of 511 patients were enrolled in this study, including 406 (79.5%) patients who received R-E-NSM with IBR and 105 patients (20.5%) who underwent C-O-NSM with IBR. The median follow-up time was 24.33 (7.27-42.07) months in the R-E-NSM with IBR group and 27.00 (7.70-42.53) months in the C-O-NSM with IBR group, respectively. The unilateral operation time of patients in the R-E-NSM with IBR group was not longer than that in the C-O-NSM with IBR group (151.73±50.32min vs. 144.29±40.66min, P=0.17). Compared to the C-O-NSM with IBR group, the R-E-NSM with IBR group showed significantly lower rates of any complications (20.20% vs. 38.10%, P<0.001) and major complications (3.45% vs. 11.43%, P = 0.002). The Breast-Q, Ueda scale, and Harris scale in the R-E-NSM with IBR group were superior to those in the C-O-NSM with IBR group (P<0.05). The local-regional recurrence (P = 0.27) and distant metastasis (P = 0.16) were not different between the two groups. The R-E-NSM with IBR group showed significantly lower unilateral expenses (7006.79±817.65 USD vs. 7358.51±562.12 USD, P<0.001) and shorter hospital stay(3.12±2.86 days vs. 6.28±2.73 days, P<0.001) compared to the C-O-NSM with IBR group, respectively. Interpretation: This study represents the first prospective investigation with the largest cohort of patients undergoing R-E-NSM. Compared to C-O-NSM with IBR, R-E-NSM with IBR can bring the same surgery efficiency and a sufficient cost-effectiveness ratio, lower incidence of postoperative complications, better aesthetic outcomes, and the same oncologic safety, indicating a broader application potential.