Robotic-Assisted Nipple Sparing Mastectomy

Abstract

Minimally invasive approaches to breast surgery have evolved from endoscopic techniques to recent developments in robotic-assisted mastectomies. Initial studies on robotic-assisted nipple-sparing mastectomy (RNSM) have shown improved patient satisfaction and aesthetic outcomes with similar complication rates and oncological outcomes in selected patients. This chapter reviews techniques used and available data on complications and clinical outcomes for RNSM. Currently, RNSM is an investigational technique in the United States and should be performed in clinical trials with U.S. Food & Drug Administration approval to rigorously evaluate the safety and effectiveness of this approach.

Breast cancer is the leading cause of death from cancer worldwide and the second leading cause of death from cancer for women in the United States. ¹ Multidisciplinary care and accurate staging are essential to develop the most appropriate treatment plan and promote the best oncological and reconstructive outcomes. ² The approach to surgical resection of breast cancers has evolved significantly since the radical mastectomy was first proposed in 1894, with the goal to leave more healthy native tissue, minimize scarring, and reduce morbidity while ensuring adequate resection to minimize the risk of recurrence or metastasis. ³ With improvements in treatment and earlier detection with screening mammograms, mortality from breast cancer has improved significantly, with a 43% decline in the death rate from 1989 to 2020. As survival continues to improve for breast cancer patients, there has been greater emphasis on patient quality of life including cosmetic outcomes. ⁴

Patients with early-stage breast cancer may be candidates for either breast-conserving treatment (lumpectomy with adjuvant radiation) or total mastectomy (also called simple mastectomy) or both, which have been shown to have similar oncological safety profiles in appropriately selected patients. ^{5 6 7 8 9} These surgical options have become possible through early detection with increased awareness in patients and providers, accurate staging through improved imaging and biopsy techniques, and more options for adjuvant/neoadjuvant chemotherapy, radiation therapy, and hormone therapy. ¹ For patients who undergo total mastectomy and are interested in reconstruction, an immediate approach to reconstruction offers a superior cosmetic outcome compared with delayed reconstruction. When immediate reconstruction is planned, skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) is performed by the oncological surgeon and the breast reconstruction is performed (either in part or completely) during the same surgery.

Skin- and Nipple-Sparing Mastectomy

SSM, which removes the breast parenchyma and nipple-areolar complex but preserves the native breast skin envelope and inframammary fold, followed by immediate breast reconstruction, was initially reported in 1991. ¹⁰ SSM is associated with a superior cosmetic result compared with total mastectomy or modified radical mastectomy, in which the native breast skin is excised. ¹¹ NSM refers to the removal of the breast parenchyma with the preservation of the nipple-areolar complex (NAC) and was first described by Bishop in 1990. ¹² This technique was developed to augment the cosmetic potential of a mastectomy as many women report preservation of the NAC improves body image. ^{3 13 14} Although its early widespread endorsement lagged due to concerns about oncological safety, numerous studies have shown no significant difference in disease-free survival, overall survival, or local recurrence rates when compared with SSMs or modified radical mastectomies. ^{13 14 15 16 17}

SSM and NSM are both associated with superior cosmetic outcomes and patient satisfaction compared with traditional mastectomy techniques; however, NSM has been shown to further improve postmastectomy body image, aesthetic satisfaction, and nipple sensitivity. ^{18 19} However, there are limitations to this technique. Incisions placed around the NAC can affect the aesthetic outcome and threaten the nipple's vascular supply. The use of retractors and cautery may further compromise mastectomy flap and NAC viability. ^{9 20 21} Additionally, the size of the incisions can significantly restrict the field of view and limit the maneuverability of instruments during dissection. ^{9 20} The combination of these technical challenges results in adverse effects on the surgeon, including increased mental and physical demand, surgeon frustration, and fatigue. ^{22 23 24}

Evolution of Minimally Invasive Breast Surgery

Minimally invasive techniques have been widely adopted in most surgical fields to reduce side effects and accelerate patient recovery compared with conventional, open techniques. The application of minimally invasive approaches for breast surgery has lagged behind other specialties, although endoscopic NSM (E-NSM) was first described in 2002 and was reported to minimize skin incisions and blood loss while enhancing operative field visualization and cosmetic outcomes relative to open NSM. ^{25 26} Thereafter, the oncological safety of E-NSM was shown in numerous studies with similar rates of local recurrence, distant metastasis, and overall survival compared with open NSM, thus establishing it as a safe mastectomy alternative. ^{27 28 29 30 31} E-NSM is typically performed through two separate axillary and periareolar incisions; however, more recent techniques have focused on optimizing the approach through a single axillary incision, thus reducing the risk of NAC ischemia/necrosis. ^{28 32 33 34 35} Regardless of the technique, widespread adoption of the E-NSM has been limited by technical challenges including an inconsistent optical window around the curvature of the breast, limited mobility of rigid endoscopic instruments, and poor dissection angles. ^{34 35}

Endoscopic NSM has been safely performed and reported to result in a shorter incision length and improved patient satisfaction with the breasts compared with open NSM. ^{34 36} Tools needed for endoscopic mastectomy are readily found in laparoscopic equipment kits and have the cost-efficient advantage of reusability of endoscopic instruments. ³⁶ However, E-NSM has not been approved by the U.S. Food and Drug Administration (FDA), and therefore, more evidence is needed to support the oncological safety of this procedure in the United States. For limited-resource regions, endoscopic breast surgery may be an attractive option that is less expensive and more accessible than the newer, emerging approach using robotic surgical platforms.

Robotic-Assisted Nipple Sparing Mastectomy

As an alternative to the technical challenges of E-NSM, robotic-assisted NSM with immediate implant-based reconstruction was first proposed by Toesca et al in 2015 and has since been used by various authors around the world, with clinical trials ongoing in the United States. ^{37 38 39 40 41} While R-NSM is currently being investigated for FDA approval in the United States, most of the published experiences on the R-NSM technique have originated from surgeons in Italy, France, Taiwan, and Korea. ^{20 42 43 44}

R-NSM has been completed utilizing the da Vinci S, Si, and Xi systems (Intuitive Surgical, Sunnyvale, CA). ^{20 39 42 43 45 46 47 48} The patient is placed in the supine position with the ipsilateral arm either resting below the plane of the operating table or abducted to 90 degrees on a surgical armrest attached to the operating table. Reported techniques describe the placement of 1 to 3 incisions (3–6 cm in length depending on breast size), with the main port site placed at the lateral aspect of the breast near the anterior axillary line. ^{20 39 42 43 45 46 47} The location of this incision allows it to be easily hidden when the patient's arm is down alongside the body ( Fig. 1 ).

Fig. 1.

Illustrations of different ipsilateral upper limb positions, incision placements, and techniques used in robotic nipple sparing mastectomy (R-NSM). ( A ) Photo showing ipsilateral upper limb position: downward with hand placed on the hip (change in position might be required in different stages of the operation). ( B ) Photo showing ipsilateral upper limb position: 90 degrees out on an arm board (change in position might be required in different stages of the operation). ( C ) Photo showing ipsilateral upper limb position-above the head (change in position might be required in different stages of the operation). ( D ) Photo showing intraoperative set-up and positioning of surgeon at the console and first assistant by the patient in R-NSM using da Vinci Si system. ( E ) Photo showing intraoperative view in R-NSM using da Vinci Xi system. ( F ) Intraoperative photo showing the tunneling technique: tunnels (indicated by red arrows) created by blunt dissection of Metzenbaum scissors after tumescent solution injection. ( G ) Intraoperative photo showing subnipple biopsy with the glandular tissue and lactiferous duct removed as cleanly as possible with only the nipple areolar complex (NAC) left behind. ( H ) Intraoperative view showing peripheral dissection of breast glandular tissue: the boundary of dissection was marked with methylene blue containing xylocaine jelly. ( I ) Intraoperative view showing subpectoral muscular dissection for preparation of muscular pocket using da Vinci surgical system. ( J ) Postoperative photo of patient A with left breast cancer who had R-NSM and immediate gel implant breast reconstruction (IGBR) showing a small and well-hidden scar in the axilla region. ( K ) Postoperative photo of patient B with left breast cancer who had R-NSM and IGBR showing a small and well-hidden scar along the anterior axillary line at the NAC level. (Reprinted with permission from Lai HW, et al. Consensus statement on robotic mastectomy—expert panel from international endoscopic and robotic breast surgery symposium (IERBS) 2019. Ann Surg 2020;271(6):1005–1012.)

The robot is docked at the patient's head. Several reports describe a technique with hydrodissection in which the breast parenchyma is infiltrated with an injection of saline containing saline, lidocaine 0.05%, and epinephrine 1:1,000,000, although other techniques could be used as well. In addition to the main 3 to 6 cm incision at the lateral breast, Toesca et al described a second incision placed 8 cm caudally from the main incision that is used for camera placement. ⁴² Additional ports can be added using either separate small incisions or multiple instruments placed into a single access platform and the breast is insufflated at a pressure of 7 to 8 mm Hg ( Fig. 2 ). ^{37 49}

Fig. 2.

Intraoperative breast insufflation and robotic arm placement used in R-NSM. (Reprinted with permission from Sarfati B, et al. Robotic nipple-sparing mastectomy with immediate prosthetic breast reconstruction: Surgical technique. Plast Reconstr Surg 2018;142(3):624–627.)

Dissection of the breast parenchyma at the anterior plane is performed using either sharp dissection or monopolar cautery with forceps for traction, counter-traction, and manipulation of the mastectomy skin flap to maintain optimal exposure. After superficial dissection is complete, a subareolar biopsy may be performed for intraoperative frozen section analysis. If cancer cells are present in the subareolar area, the entire nipple-areolar complex is then removed. The peripheral portions of the gland are dissected from the mastectomy flap in all four quadrants. Posterior subglandular dissection is then performed, to separate the deep portion of the gland from the pectoralis muscle. During dissection, hemostasis is obtained using either monopolar or bipolar energy. Once dissection is complete, the robot is undocked, ports are removed, and the breast specimen is extracted through the main incision and sent for pathologic analysis. A drain is placed in the inferolateral quadrant of the breast. Breast reconstruction is then performed as with open NSM with either a tissue expander, breast implant, and/or autologous tissue flap, which is detailed in a later chapter. ^{20 39 42 43 45 46 47 48}

A consensus statement by a team of R-NSM experts was released in 2019 outlining R-NSM recommendations pertaining to six domains: indications, contraindications, technical considerations, patient counseling, outcome measures, training, and learning curve assessment. ⁵⁰ Patients eligible for R-NSM were described as those with up to 5 cm of the tumor with at least 3 mm between the tumor and the skin, without NAC involvement, up to clinical stage IIIA. ⁴⁴ R-NSM candidates should have breast size of a C cup and below with nonptotic breasts to maximize successful perfusion preservation of the NAC postoperatively. These eligibility criteria are conservative and are similar to those used for conventional, open NSM, particularly during the early experience of NSM.

Outcomes

Operative time is longer with R-NSM compared with open NSM in the initial learning phase, but decreases with experience, including with docking the robot, performing the mastectomy, assistance with direct-to-implant or tissue expander placement, and pedicled latissimus dorsi harvest ( Tables 1 & 2 ). ^{9 20 39 40 42 45 51 52 53 54} Comparison studies between R-NSM, E-NSM, and open NSM have shown that R-NSM takes longer than either E-NSM or open NSM on average; however, other studies have shown that after 10 to 12 attempts, total operative time for R-NSM was similar to open NSM. ^{38 45 55 56}

Table 1. Comparison of timing for R-NSM procedure from first to last performed over time.

		Cases	First (hour:minute)	Last (hour:minute)	Average (hour:minute)
Toesca et al	2017	29	5:00	1:30
Sarfati et al	2018	63	1:15	0:38
Lai et al	2018	2	1:22	1:27	1:24
Toesca et al	2019	94	3:50	0:47	1:22
Lai et al	2019	23	4:10	1:06	1:57
Jeon et al	2021	16	5:38	1:39	1:59

Table 2. Comparison of timing for robotic-assisted pocket creation and implant placement from first to last performed over time.

		Cases	First (hour:minute)	Last (hour:minute)	Average (hour:minute)
Toesca et al	2017	29	2:00	1:00
Ahn et al	2018	4	1:47	1:20	1:26
Toesca et al	2019	94	3:12	0:24	1:35
Lai et al	2019	23	2:06	0:40	1:15
Jeon et al	2021	16	2:20	0:59	1:21

Perioperative complications are similar for NSM, regardless of the technique used. Most studies on R-NSM reported outcomes including major complications (reoperation, implant loss, and conversion to open technique), minor complications (transient neuropathy, hematoma, seroma, thermal injury, eschar formation, mastectomy flap, or NAC necrosis), postoperative pain, and hospital length of stay. In studies comparing R-NSM to either E-NSM or open NSM, no significant differences in overall complication rates were observed. ^{38 55 56} When assessing the complication profiles for R-NSM, it is important to note that all studies included various additional reconstructive procedures (e.g., direct to implant reconstruction, tissue expander placement, latissimus dorsi harvest, and contralateral symmetrizing procedures) which can make it difficult to determine specifically whether the complication is attributed to the R-NSM procedure itself or the associated procedures.

Since R-NSM is an emerging technique with relatively short follow-up, there is a paucity of data on oncological outcomes for breast surgery patients undergoing this procedure. In addition, most published studies on R-NSM included predominantly patients at increased risk for breast cancer, such as BRCA and other pathogenic mutations, and no personal history of breast cancer with fewer patients with invasive or noninvasive breast cancer. ^{42 49 57}

Toesca et al reported clinical outcomes for R-NSM with 73 breast patients, 39 of whom had invasive breast cancer, 17 had ductal carcinoma in situ, and 17 had BRCA mutations. ⁹ Those with invasive breast cancer had a mean tumor size of 1.7 cm, the majority of which (34/39) were estrogen receptor positive. With a mean follow-up of 20 months, disease-free survival was 100% for the 56 breast cancer patients and overall survival was 98%. ⁹

R-NSM has been associated with an improvement in surgical and aesthetic outcomes, as well as increased patient-reported satisfaction measures. ^{38 39} A case-control comparison study conducted by Lai et al compared 91 E-NSM patients to 40 R-NSM patients with early-stage breast cancer (DCIS, stage I, II, or IIIA), evaluating surgical margin positivity and patient-reported cosmetic outcomes. ³⁸ While R-NSM had a lower incidence of surgical margin involvement (2.5%) than E-NSM (4.4%), the difference was not statistically significant ( p  = 0.52). R-NSM resulted in less blood loss (32 ± 29 mL vs. 79 ± 62 mL, p  < 0.01) and higher patient satisfaction rates in terms of scar appearance, scar length, and surgical wound position. The locoregional cancer recurrence rate for E-NSM was 5.5% at 45.6 ± 25.5 months and 0% for R-NSM; however, the reported follow-up duration was significantly shorter for the R-NSM group at 13.5 ± 6.8 months and, therefore, cannot be directly compared. There were no significant differences between R-NSM and E-NSM for postoperative aesthetic measures such as dressed or undressed breast appearance, symmetry of breast size, shape, or nipple areolar position, and overall satisfaction. ³⁸

The most extensive data on patient-reported outcomes after R-NSM were reported by Toesca et al in a randomized controlled trial involving 80 women with either breast cancer or BRCA mutation. ⁵⁸ Patient satisfaction, quality of life, and body image were measured using validated tools including the BREAST-Q questionnaire, the Hopwood body image scale (BIS), as well as a NAC-specific questionnaire. With a median time of 1 year from surgery to follow-up BREAST-Q, patient satisfaction with their breasts increased in the R-NSM group and decreased in the open surgery group ( p  = 0.03). Patients in the R-NSM group initially reported decreased physical well-being and sexual well-being after surgery but these scores returned to preoperative levels 1 year after surgery, whereas scores remained low and did not return to baseline in the open surgery group ( p  = 0.03). Satisfaction with breasts and psychosocial well-being increased from baseline at 1 year after R-NSM with no change in the open surgery group. Results of the BIS questionnaire showed significantly less distress with appearance and body changes in the robotic surgery group compared with the open group (BIS score 20.7 ± 9.9 vs. 13.8 ± 5.1; p  < 0.001). When patients were surveyed with NAC-specific questions, there was a significant improvement in the R-NSM group with no change in nipple sensitivity compared with preoperative levels in 26% (compared with 0% in the open group; p  = 0.0002); however, the majority of patients (68%) still reported decreased or no nipple sensation. All other parameters of the NAC-specific questionnaire, such as nipple reaction, sexual pleasure, and satisfaction with NAC position, were significantly improved in the robotic group. ⁵⁸

The pooled data from four international centers (Korea, Taiwan, Italy) comparing R-NSM to conventional open NSM were analyzed for 659 women, 609 of whom had invasive breast cancer and 50 of whom had an increased risk of developing breast cancer. ⁴³ After controlling for confounders with propensity score matching, R-NSM had a lower rate of nipple necrosis ( p  < 0.001), 30-day postoperative complications ( p  = 0.003), and Clavien–Dindo grade III complications (those requiring surgical, endoscopic, or radiologic intervention; p  < 0.001). ⁵⁹ When comparing only women with invasive breast cancer, R-NSM had lower rates of nipple necrosis ( p  = 0.003) and Clavien–Dindo grade III complications ( p  = 0.010); however, the incidence of 30-day postoperative complications was not significant ( p  = 0.21). There were no differences in disease-free survival and overall survival for women with invasive breast cancer. ⁴³ Of note, these data include those already reported separately by each group but the pooled analysis with the larger sample size confirmed that R-NSM was associated with lower postoperative complications and nipple necrosis compared with open NSM with equivalent oncological outcomes.

Few authors have specifically performed cost analysis for R-NSM to date. A multicenter nonrandomized trial originating in Taiwan performed a medical cost analysis comparing R-NSM, E-NSM, and open NSM. ⁶⁰ R-NSM was associated with a significantly higher overall cost per breast ($10,301 ± 408) than open NSM ($6,254 ± 499) and E-NSM ($7,699 ± 738; p  < 0.01), along with a lower amount covered by health insurance ( p  = 0.017). As a result, the out-of-pocket patient expense was higher for R-NSM ($7,667–$8,333) compared with open NSM ($3,667–$4,333) and E-NSM ($4,000–$5,667; p  < 0.01). Importantly, the study's estimates are based on the Taiwanese healthcare system and, therefore, may not be directly translatable to the United States or other countries. Lai additionally proposes that the lower cost and similar outcomes of E-NSM to R-NSM may make E-NSM a more prudent choice for resource-limited areas. ⁶⁰

Finally, a robotic approach to NSM may have potential benefits to surgeons and their assistants, as well as patients. NSM can be technically challenging, with suboptimal visualization through a small operative window and constant mastectomy pocket retraction for adequate exposure of the breast parenchyma. The poor ergonomics of performing NSM has been linked to increased neck and lower back pain for the operating surgeon, in addition to higher rates of mental strain and fatigue. ⁶¹ CO ₂ insufflation of the breast during R-NSM creates an inflated working space above the breast parenchyma, which improves the visualization of the dissection plane and spares the need for manual retraction by an assistant or surgeon. ³⁷ The 3D high-definition robotic camera used in R-NSM provides enhanced optics, as illumination and magnification of the operative field are projected by the camera and displayed on the console. The improved ergonomics and visualization gained by R-NSM could ameliorate some of the challenges experienced in open NSM. However, further studies are needed to directly quantify surgeon benefits.

Discussion

While the early experience with R-NSM in Europe and Asia has shown promising results, this procedure is not yet approved by the U.S. FDA and is currently being investigated as a therapeutic procedure for breast cancer patients, as well as in the prophylactic setting for patients at increased risk for breast cancer. ^{44 45 62} Although minimally invasive surgery for the treatment of various cancers has been shown to be oncologically safe in numerous studies, there has been renewed interest in this question with the recent publication of two studies in 2018 that reported shorter overall survival for patients with cervical cancer who underwent a minimally invasive radical hysterectomy. ^{53 63 64} In 2019, the FDA released a statement that the effectiveness and safety of robotic-assisted oncological surgery, including breast surgery, had not been established for the treatment and prevention of cancer. ^{44 62} The FDA announcement urged that the safety and effectiveness of robotic surgery for mastectomies in breast cancer should be carefully studied in clinical trials with FDA oversight under an investigational device exemption (IDE).

Indeed, the safety and effectiveness of the da Vinci Xi surgical system for prophylactic R-NSM are being evaluated in a prospective, multicenter clinical trial that opened in 2021 with an FDA-approved IDE for patients at increased risk to develop breast cancer (NCT03892980). In addition, the da Vinci SP surgical system will be evaluated for the safety and effectiveness of therapeutic R-NSM compared with conventional, open NSM in a randomized controlled trial which recently opened in 2023 (NCT05720039). The primary outcomes of this trial include the conversion rate to open surgery, the intraoperative and postoperative adverse event rate, and the incidence of positive surgical margins. Additional secondary outcomes include oncological endpoints (cancer recurrence, disease-free, and overall survival) and patient- and surgeon-reported outcomes. Similar clinical trials are underway in Korea, Italy, and Taiwan and the results of all these trials will be critical to carefully assess the safety and effectiveness of R-NSM, particularly for the treatment of breast cancer.

Conclusion

Robotic-assisted NSM has evolved as a potentially viable alternative to conventional or endoscopic techniques that allows several different reconstructive methods to be performed according to patient and surgeon preference. R-NSM provides superior patient-reported aesthetic outcomes with similar complication profiles, and early data have shown similar oncological efficacy, at the expense of higher overall operative time and cost. However, due to the relatively short follow-up and uncertainty about long-term oncological safety, surgeons should only perform these procedures in the United States through approved clinical trials and with adequate experience using the robotic platform.