Clinical Perspectives on Robot-assisted Nipple-sparing Mastectomy

Advances in endoscopic devices have enabled surgeons to perform surgery via small incisions or small laparoscopic or endoscopic trocars inserted in the torso. These rigid endoscopic devices are sufficient to mimic a surgeon's motion, such as grasping, releasing, cutting, and ligating tissues via small trocars. However, the use of rigid endoscopic devices in breast surgery remains a challenge, given their limited motion in a narrow working space. Therefore, only a few surgeons in East Asia, where many women have small-to-medium-sized breasts, can employ endoscopic or laparoscopic devices in breast surgery to reduce or hide incisions to obtain better cosmetic outcomes.

Robotic surgical systems, such as highly flexible robotic arms, ergonomic consoles, high-resolution three-dimensional cameras, have facilitated endoscopic or laparoscopic surgeries in various fields, including gastric, colorectal, thyroid, urologic, and thoracic surgeries. The concept of robotic surgical systems aims to advance endoscopic/laparoscopic technologies while simultaneously improving the surgeon's skills in terms of surgical outcomes. For example, robotic surgery preserves urinary functions better than conventional surgery in urologic surgery, as precise robotic instruments improve surgical movement in a narrow space [1]. Accordingly, some pioneering breast surgeons applied robotic surgical systems to nipple-sparing mastectomy, one of the most labor-intensive and complex procedures in breast surgery. Robotic surgical systems have allowed nipple-sparing mastectomy to be successfully performed via a small axillary incision. This procedure is called “robot mastectomy,” “robotic mastectomy,” “robotically-assisted mastectomy,” or “robot-assisted nipple-sparing mastectomy (RNSM).”

This review article summarizes indications, learning curves, technical issues, advantages and disadvantages, and ongoing studies of RNSM to enhance their understanding of this new procedure.

The indications for RNSM can differ according to the surgeons' and patients' preferences; however, there are general similarities in case selection [2]. Typically, no clinical signs of nipple or skin involvement by tumors and low tumor burden are common indications for RNSM. In addition, small-to-medium-sized breasts and absence or low-grade ptosis are preferred for RNSM.

Toesca et al., [3] at the European Institute of Oncology, Milan, Italy, reported the first RNSM, and the initial 3 cases were risk-reducing mastectomies in germline BRCA mutation carriers. After verifying the technical safety, the authors performed RNSM as a treatment option for patients with in situ carcinoma or invasive cancer [4]. The general indications for RNSM were as follows: tumor size less than 4 cm; clinically negative axillary lymph node; more than 1 cm distance from the nipple-areola complex (NAC); low incidence of risk factors for systemic or local perioperative complications; no comorbidities; body mass index less than 25 kg/m²; breast volume less than or equal to bra size C; no history of heavy smoking (more than 20 cigarettes/day); low and intermediate risk for anesthesia (American Society of Anesthesiologists Scale) [4]. The exclusion criteria were as follows: previous thoracic radiation therapy for any reason, inflammatory breast cancer, skin involvement, preoperative diagnosis (radiological or cytological) of NAC disease; pregnancy; psychiatric, addictive, or any disorder compromising ability to provide informed consent for study participation; uncontrolled diabetes mellitus; and high-risk for anesthesia [4]. At Gustave Roussy in Paris, France, Sarfati et al. [5] performed risk-reducing mastectomy using robotic surgical systems in carriers with high-risk genetic mutations. The indications were as follows: breast cup size A, B, or C (based on bra size) and ptosis grade B2 (Regnault ptosis scale), between ages 18 and 70 years, and Eastern Cooperative Oncology Group score 0 or 1. Patients were excluded if postoperative radiation therapy was indicated. Additionally, patients with a history of breast surgery or breast radiation therapy, heavy smokers (more than 20 cigarettes per day), and patients with uncontrolled diabetes mellitus were excluded from the study. In East Asia, indications similar to those in previous studies were reported by Park et al. [6, 7, 8] at Severance Hospital, Seoul, Korea, and Lai et al. [9] at Changhua Christian Hospital in Taiwan. Table 1 summarizes the suggested absolute and relative contraindications for RNSM.

Table 1
Contraindications for RNSM

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An expert panel discussion was held at the International Endoscopic and Robotic Breast Surgery Symposium (IERBS) 2019 to summarize current indications used by several pioneers in breast surgery using robotic surgical systems. According to the consensus meeting at IERBS 2019, the following patient groups are suitable for RNSM [10]: small-to-moderate breast size with a cup size C or less; clinical tumor size less than 5 cm (T3 and below); an adequate tumor-skin distance of ≥3 mm with no NAC involvement on preoperative imaging. Especially regarding the tumor distance from the nipple, the latest version of the National Comprehensive Cancer Network guideline for breast cancer recommends that (ideally intraoperative) nipple margin assessment should be mandatory for nipple-sparing mastectomy without any distance criteria for the tumor from the nipple [11]. This indication of nipple-sparing mastectomy could be applied to RNSM. Women with clinically node-negative disease, as well as patients with no clinical or radiological evidence of skin or nipple involvement, are suitable for RNSM. Additionally, RNSM can be employed in women indicated for risk-reducing mastectomy. In contrast, RNSM is not typically recommended in the following scenarios: ptotic breast or cup size D or larger, possible suboptimal cosmesis, poor performance status, multiple comorbidities, or clinical NAC involvement.

Surgeons might speculate that a certain number of cases is imperative to gain adequate expertise in RNSM. However, a retrospective multicenter study assessing 80 RNSM cases in South Korea [12] has demonstrated that RNSM permitted relatively short learning curves. For example, a surgeon with experience in 41 RNSM showed stabilization after the 15th RNSM, whereas another surgeon who performed 14 RNSM revealed a stable learning curve after the 9th surgery.

Based on preliminary experience in 35 patients with breast cancer who underwent RNSM at a single institution [9], the time required for mature phase procedures such as “docking,” “operation time for RNSM” and “total operation time for RNSM, and immediate prosthesis breast reconstruction (IPBR)” were 10 minutes, 100 minutes, and 240 minutes, respectively. The number of cases needed to decrease the time for “docking,” “operation time for RSNM,” and “total time for RNSM and IPBR” were 13, 13, and 12 procedures, respectively. The time needed to complete RNSM correlated with the weight of the mastectomy specimen. A comparison of learning curves for RNSM and endoscopic nipple-sparing mastectomy (ENSM) revealed that the operation time decreased from the 27th and 10th ENSM and RNSM procedures, respectively [13].

Typically, RNSM learning curves were stabilized between the 10th and 15th procedures, indicating a shorter learning duration than that required for ENSM; this might be because of the 3-dimensional optics, user-friendly system, and intuitive robotic arms.

RNSM can be categorized into 2 distinct techniques for maintaining the working space: the gas-inflated technique and the gasless technique. The gas-inflated technique by Toesca et al. [3] was introduced earlier than the gasless technique that was developed by Park et al. [7] Both techniques use a similar location on the axillary line to perform a single incision. The primary difference between the 2 techniques is the manner in which the flap is raised. In the gas-inflated technique, gas insufflation is used to separate the flap and parenchyma. In contrast, the gasless technique utilizes a self-retractor to raise the flap and maintain working space. According to a previous study that compared these 2 techniques, the gasless technique requires an incision that is approximately 1 cm longer than that required in the gas-inflated technique [14]. No other clinical or surgical factors showed statistically significant differences between the 2 techniques.

The gas-inflated technique can be classified into 2 methods based on the number of access sites (insertion site of cannulas or trocars). Some surgeons prefer to use a single access method by performing a single incision without an additional port. However, Sarfati et al. [15] employed an additional access site near the axillary or lateral incision. Furthermore, the main incision in the axillary line can be manipulated into 2 cannula insertion sites by partial suturing. An additional access site below the cephalic end of the main incision can render the working space more accessible and reduce collisions between robotic arms [15].

There are several da Vinci systems available for RNSM. Si, X, Xi, and SP systems from Intuitive Surgical (Sunnyvale, CA, USA) are popularly used in various surgical fields. The da Vinci Si, X, and Xi systems are multiport systems, whereas the da Vinci SP is a single-port system. The da Vinci SP system is the latest version and fourth-generation robotic system. It was designed for single-port access with a single 2.5 cm cannula. The da Vinci SP system allows RNSM with a smaller incision and affords a deeper reach without extracorporeal arm collision.

Table 2 summarizes the comparison of various RNSM techniques.

Table 2
Differences in techniques of RNSM of several pioneers

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Previous studies have presented various advantages of RNSM [2, 4, 16, 17, 18]. The small-sized incision hidden in the axilla remains the most important benefit for maintaining the NAC viability and reducing the rate of nipple necrosis [2, 17, 18]. In addition, other immediate postoperative surgical outcomes, including lower rates of skin necrosis and high-grade complications, reportedly improve with RNSM when compared with the conventional method [16, 17, 18]. Toesca et al. [4] investigated complications that occurred within 90 days of RNSM in 73 patients and reported complications requiring reoperation in 4.3% of patients and flap or nipple necrosis in 1.1% of patients. In 56 oncologic patients who underwent RNSM, disease-free survival was 100% during a median follow-up of 19 months [4]. Lee et al. [18] reported that RNSM resulted in a significantly lower nipple necrosis rate than conventional nipple-sparing mastectomy (CNSM) (2.4% vs. 15.2%); Houvenaeghel et al. [16] reported that grade 2–3 breast complication rates were 13% with RNSM and 17.3% following CNSM. Furthermore, the minimal counter-retraction of CO₂ insufflation for RNSM may improve blood supply when compared with manual retraction in a conventional mastectomy, which reduces skin flap injury [4, 19]. Additionally, the inconspicuous scar in the axilla is associated with superior aesthetic results and improved quality of life, as measured by patient-reported cosmetic outcomes (Fig. 1) [17, 19, 20]. Lai et al. [17] reported that patients who underwent RNSM showed higher overall satisfaction than those who underwent conventional nipple-sparing mastectomy (92% excellent and 8% good vs. 75.6% excellent and 24.4% good, p=0.046), as well as good wound/scar-related outcomes in patient-reported aesthetic results. The minimally invasive approach of robotic surgical systems can be attributed to the three-dimensional, high-resolution, and magnified optic window and sophisticated movements of instrument arms, thus enabling advanced visualization and microscale manipulation while the surgeon sits comfortably at the console and performs mastectomy [4, 5, 7, 21, 22]. For autologous breast reconstruction, the benefits of robotic surgical systems could allow microsurgeries within a confined space and at difficult angles [23]. The ergonomically comfortable and intuitive motion of robotic arms can assist surgeons in acquiring appropriate surgical skills within a relatively short period [7, 12].

Fig. 1
Pre- and postoperative images of a patient who underwent a robot-assisted nipple-sparing mastectomy and immediate autologous breast reconstruction on the left breast using the da Vinci SP system. (A) Preoperative images. (B) Postoperative images.

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Despite the various documented advantages of RNSM, a few hurdles need to be overcome to successfully apply this innovative procedure in clinical practice. First, cost-effectiveness is an important issue in RNSM [10, 24]. The high cost of RNSM when compared with conventional mastectomy and immediate reconstruction might decrease after more robotic surgical systems are available in this industry [17]. Second, the prolonged operation time, including preparation of the working space, insertion of a single-port device, docking of robotic arms, or preparation for reconstruction, compared with conventional methods, is another disadvantage to be noted [7, 12]. However, previous studies have revealed that the learning curve and total operation time can be reduced after the initial learning curve and refinements in surgical techniques [2, 17, 18]. Furthermore, a reduction in the surgical duration after achieving the requite skill may partially enhance the efficiency of using operating room and reduce the cost of RNSM [5]. Third, perioperative complications related to the robotic surgical system, such as subcutaneous emphysema, may be observed. However, most cases of subcutaneous emphysema are not associated with severe morbidity or mortality, subsiding spontaneously without necessitating any intervention [19]. Fourth, the lack of oncologic outcomes for long-term follow-up and assessment tools for measuring the experience or surgical skills need to be addressed [2, 4]. Accordingly, some researchers have initiated randomized controlled trials or prospective cohort studies to develop and initiate standardized education programs for beginners of RNSM (NCT03440398, NCT04585074, NCT03892980) [12, 21]. Finally, the absence of a tactile sense could be a limitation of robotic surgical systems. Tactile sense plays the most important role in assessing flap thickness and residual suspicious lesions on the flap during RNSM. To overcome this problem, we could estimate flap thickness with magnified and high-resolution surgical vision and transillumination of the breast skin performed by an assistant. In addition, residual suspicious lesions of the flap could be identified by manual palpation after specimen retrieval.

In a recent announcement, the USFDA recommends that robotic surgical systems should be cautiously employed to treat and prevent cancer in the United States [25]. Accordingly to this report, the use of robotic surgical systems in cancer surgery requires additional evidence, not only in terms of early postoperative outcomes but also clinical outcomes longer than 30 days postoperatively [25]. This announcement cited a study documenting inferior outcomes following minimally invasive surgery in women with cervical cancer [26]. This safety communication regarding the use of robotic surgical systems is recommended not only for breast cancer but also for other cancers. Despite the USFDA announcement, the application of robotic surgical systems in the treatment and prevention of cancer differs among countries, given the different national medical systems. Furthermore, available data favors the use of a minimally invasive approach in cancer surgery [27]. Nevertheless, to support the widespread use of robotic surgical systems in mastectomy, prospective clinical trials are needed to establish robust conclusions. Although prospective randomized surgical trials still need to overcome substantial hurdles, several prospective clinical trials assessing RNSM are ongoing and are registered at ClinicalTrials.gov (Table 3).

Table 3
Ongoing prospective studies of robot-assisted nipple-sparing mastectomy

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Indications for RNSM are similar to those for conventional nipple-sparing mastectomy; however, small- to medium-sized breasts without ptosis are the best candidates for RNSM. Short learning curves for RNSM can be achieved with robotic surgical systems possessing high-resolution vision, flexible robotic arms, and ergonomic consoles. Accordingly, RNSM can provide better cosmesis and favorable surgical outcomes. However, there is a lack of long-term and high-level evidence supporting the application of robotic surgical systems in breast surgery. Further investigations, including prospective cohort and randomized clinical trials, are necessary to reach solid conclusions regarding the use of robotic surgical systems in breast surgery.