Minimal-access nipple-sparing mastectomy: current evidence, limitations, and future evaluation

The growing adoption of minimal-access nipple-sparing mastectomy (MA-NSM), including endoscopic (E-NSM) and robotic (R-NSM) approaches, reflects efforts to reduce surgical morbidity and improve cosmetic outcomes in breast cancer treatment (Figures 1,2A,2B) (1,2). Conventional nipple-sparing mastectomy (C-NSM) typically utilizes periareolar or radial incisions (Figure 3A), with established reconstructive outcomes (Figure 3B). However, despite increasing clinical use, high-quality evidence demonstrating oncological non-inferiority and cost-effectiveness compared with C-NSM remains limited (3-5). In oncologic surgery, technical feasibility and patient-reported outcomes must ultimately be evaluated alongside durable cancer control.

Figure 1 Endoscopic nipple-sparing mastectomy incisions. (A) Axillary incision used for endoscopic access. (B) Periareolar or lateral extension approach for glandular dissection. Reproduced from Kang B et al., Ann Surg Treat Res 2024;106:147-54 with permission from the corresponding author.

Figure 2 Robot-assisted nipple-sparing mastectomy technique and operative setup. (A) Axillary and lateral mid-axillary incisions used for robotic access. (B) Operative setup for robot-assisted nipple-sparing mastectomy. Reproduced from Lee SB et al., Sci Rep 2025;15:12 with permission from Springer Nature.

Figure 3 Conventional nipple-sparing mastectomy and postoperative outcome. (A) Periareolar incision used in conventional nipple-sparing mastectomy. (B) Postoperative outcome following bilateral conventional nipple-sparing mastectomy with immediate acellular dermal matrix-assisted prepectoral implant-based reconstruction performed at the authors’ institution. The images were published with the patient’s consent.

What does the current study not demonstrate?

Lai et al. reported one of the largest single-centre comparative analyses of MA-NSM and C-NSM using propensity score matching (3). Among 905 nipple-sparing mastectomies, 317 were MA-NSM (245 E-NSM and 72 R-NSM). After matching, 289 MA-NSM cases were compared with 289 C-NSM cases.

While the study contributes to valuable long-term follow-up data, it was not designed to determine oncological non-inferiority. Matching was limited to six variables—age, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, nodal stage, and use of neoadjuvant chemotherapy—omitting several established prognostic factors such as tumour grade, lymphovascular invasion, margin status, Ki-67 index, and comorbidity burden. Consequently, residual confounding cannot be excluded.

Additionally, follow-up duration was significantly longer in the C-NSM cohort, increasing the probability of capturing late recurrences and breast cancer-related mortality. This imbalance complicates survival comparisons and limits the strength of causal inference.

MA-NSM non-inferiority has yet to be conclusively established

Although survival outcomes appeared broadly comparable, no formal non-inferiority design or predefined equivalence margins were employed. Without such methodology, oncological equivalence cannot be concluded.

In breast cancer surgery, non-inferiority margins are commonly defined as an absolute difference of approximately 2–5% in local recurrence rates. This limitation extends across the MA-NSM literature. Large registry-based and pooled analyses have not demonstrated clear oncological equivalence between minimally invasive and conventional approaches (4,5). The only randomized trial comparing robotic and open mastectomy was small and not powered to assess oncological non-inferiority, with primary endpoints focused on complications and quality of life rather than cancer outcomes (6).

Although Lai et al. reported lower severe complication rates in the MA-NSM cohort, pooled analyses and meta-analyses have generally demonstrated comparable short-term complication profiles between minimally invasive and conventional approaches (7,8). These findings suggest that short-term safety may be similar across techniques but remain insufficient to determine comparative oncological benefits.

Demonstration of oncological equivalence requires predefined non-inferiority margins and adequate statistical power, consistent with IDEAL surgical innovation recommendations (9).

Cost, value, and generalizability

From a broader value-based healthcare perspective, evaluation of new surgical technology should not be confined to peri-operative outcomes or patient preference alone. Value is defined as patient-relevant outcomes achieved relative to the total cost of care over the full cycle of treatment rather than procedural complexity or cosmetic appeal in isolation (10).

Economic evaluation should ideally incorporate cost-utility analysis (e.g., cost per quality-adjusted life year) rather than procedural cost alone.

Accordingly, adoption of more resource-intensive techniques such as MA-NSM requires demonstration of durable oncological safety and meaningful patient-centered benefit. Higher procedural expenditure without proven improvement in long-term cancer control, complication burden, or quality-of-life outcomes risk lowering overall healthcare value despite technical innovation.

Cost considerations apply to both endoscopic and robotic MA-NSM techniques. While robotic systems incur higher incremental expenses (approximately USD 5,000 per case), additional operative time and specialized equipment also contribute to increased costs in endoscopic approaches (11).

Translational implications and future directions

The principal translational issue is that technological adoption has outpaced oncological validation. Future research should prioritize prospective multicenter trials or registry-embedded studies incorporating predefined non-inferiority margins, adequate follow-up, standardized oncological endpoints, and patient-reported outcomes. Parallel cost-effectiveness and credentialing frameworks will also be required, particularly for robotic platforms. Until such data matures, MA-NSM is best considered a selective rather than a routine approach.

The MARRES study (12) is a prospective, multi-institutional cohort study enrolling adult women (>19 years) with breast cancer or a high genetic risk (e.g., BRCA1/2, TP53, PALB2) who undergo therapeutic or risk-reducing mastectomy with immediate reconstruction. The study systematically collects surgical, oncologic, photographic, patient-reported, and cost-effective data. Its primary endpoints are postoperative complication rates within 30 days, and the Clavien-Dindo severity grade of complications within 180 days. Secondary endpoints include 5-year recurrence-free survival and cancer incidence after risk-reducing mastectomy, patient and surgeon satisfaction with reconstruction outcomes, and economic evaluation of the surgery. Recruitment is planned to conclude in April 2025 with a target sample size of 2,000 patients.

Conclusions

Current evidence suggests that MA-NSM is technically feasible and safe in selected patients but remains insufficient to establish oncological equivalence or economic value compared with conventional surgery. Wider adoption should therefore be guided by prospective evidence rather than technical capability alone.

Based on current evidence, minimally invasive nipple-sparing mastectomy should presently be regarded as a selective approach rather than a universal standard in breast cancer surgery.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article has undergone external peer review.

Peer Review File: Available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-2025-1-84/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-2025-1-84/coif). K.M. serves as an unpaid editorial board member of Translational Breast Cancer Research from May 2025 to June 2027. K.M. reports a research grant from the Breast Cancer Charity; consulting fees from QMedical and Sebbin; honoraria from Merit Medical and QMedical Corporations; and holds stocks in HCA Healthcare, Datar Genetics, and OncoBotanica. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Kang B, Keum H, Park HY, et al. Usefulness of cordless ultrasonic cutting energy devices in endoscopic nipple-sparing mastectomy: a retrospective study. Ann Surg Treat Res 2024;106:147-54. [Crossref] [PubMed]
2. Lee SB, Kim J, Chung IY, et al. Use of the Da Vinci SP surgical system in robot-assisted nipple-sparing mastectomy: a single-center, retrospective study. Sci Rep 2025;15:12. [Crossref] [PubMed]
3. Lai HW, Su J, Abdul Rauf NH, et al. Long-term oncologic outcomes of minimal access (endoscopic or Robotic Assisted) nipple-sparing mastectomy compared with conventional approach in breast cancer - a propensity score matching analysis. Int J Surg 2025;112:9927-46. [Crossref] [PubMed]
4. Park HS, Lee J, Lai HW, et al. Surgical and Oncologic Outcomes of Robotic and Conventional Nipple-Sparing Mastectomy with Immediate Reconstruction: International Multicenter Pooled Data Analysis. Ann Surg Oncol 2022;29:6646-57. [Crossref] [PubMed]
5. Rizk M, Mokbel K. The role of robot-assisted mastectomy: promise, challenges, and evidence gaps. Gland Surg 2025;14:579-83. [Crossref] [PubMed]
6. Toesca A, Sangalli C, Maisonneuve P, et al. A Randomized Trial of Robotic Mastectomy Versus Open Surgery in Women With Breast Cancer or BrCA Mutation. Ann Surg 2022;276:11-9. [Crossref] [PubMed]
7. Filipe MD, de Bock E, Postma EL, et al. Robotic nipple-sparing mastectomy complication rate compared to traditional nipple-sparing mastectomy: a systematic review and meta-analysis. J Robot Surg 2022;16:265-72. [Crossref] [PubMed]
8. Nessa A, Shaikh S, Fuller M, et al. Postoperative complications and surgical outcomes of robotic versus conventional nipple-sparing mastectomy in breast cancer: meta-analysis. Br J Surg 2024;111:znad336. [Crossref] [PubMed]
9. McCulloch P, Altman DG, Campbell WB, et al. No surgical innovation without evaluation: the IDEAL recommendations. Lancet 2009;374:1105-12. [Crossref] [PubMed]
10. Porter ME. What is value in health care? N Engl J Med 2010;363:2477-81. [Crossref] [PubMed]
11. Lai HW, Chen ST, Mok CW, et al. Robotic versus conventional nipple sparing mastectomy and immediate gel implant breast reconstruction in the management of breast cancer- A case control comparison study with analysis of clinical outcome, medical cost, and patient-reported cosmetic results. J Plast Reconstr Aesthet Surg 2020;73:1514-25. [Crossref] [PubMed]
12. Ryu JM, Lee J, Lee J, et al. Mastectomy with Reconstruction Including Robotic Endoscopic Surgery (MARRES): a prospective cohort study of the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) and Korean Breast Cancer Study Group (KBCSG). BMC Cancer 2023;23:571. [Crossref] [PubMed]