Robotic Versus Conventional or Endoscopic Nipple Sparing Mastectomy in the Management of Breast Cancer-Prospective Study

Study Overview
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Brief Summary
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This study will prospectively evaluate the surgical outcomes of robotic nipple sparing mastectomy (NSM) compared with endoscopic assisted NSM or conventional NSM in the management of breast cancer. One-third patients would received R-NSM, another one-third received C-NSM while the other one-third would receive E-NSM.

Detailed Description
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Nipple-sparing mastectomy (NSM), which preserved the nipple areolar complex (NAC) and skin flap during mastectomy, was increasingly performed in breast cancer patients due to better cosmetic outcome, higher patient satisfaction, and maintained oncologic safety. Minimal invasive surgery had become the main stream of operations, and new surgical innovations of NSM, like endoscopic nipple sparing mastectomy (E-NSM) or robotic nipple sparing mastectomy (R-NSM), were emerging and applied in the surgical treatment of breast cancer. E-NSM, which is performed through small axillary and/or peri-areolar incisions, was reported to be associated with small inconspicuous incision and good cosmetic outcome. Conventional E-NSM was performed with two separate incisions over axilla and peri-areolar regions. E-NSM with areolar incision, just like NSM with areolar related incision (NAC ischemia/necrosis rate: range 7%-81.8%), was associated with increased NAC ischemia/necrosis (reported ranged: 9.1-19%). New technique modifications of E-NSM were emerging focusing on single axillary incision NSM, which spare the peri-areolar incision and thereby decrease the compromise of bloody supply from mastectomy skin flap, was reported to have low NAC necrosis rate (0%). However, the 2-dimensional endoscopic in-line camera produces an inconsistent optical window around the curvature of the breast skin flap, and the internal mobility was limited and the dissection angles were inadequate with traditional endoscopic rigid tips instruments through single access. Due to the limitations of endoscopy instruments and technique difficulty, neither conventional E-NSM nor single access E-NSM was widespread used in breast cancer R-NSM, which introduce da Vinci surgical platform through a small extra-mammary axillary or lateral chest wound to perform NSM, had been applied in the surgical treatment of early breast cancer or risk reducing mastectomy. R-NSM, which incorporated 3-dimensional (3D) imaging system and flexibility of robotic arm and instruments, was reported to have the potential to overcome the technique difficulty of E-NSM. The preliminary results of R-NSM from current reported series and ours were safe, and associated with good cosmetic outcome and high patients' satisfaction. However, evidence comparing R-NSM to conventional NSM (C-NSM) or E-NSM was lacking. In this study, the authors aim to investigate and analyze the clinical and aesthetic outcomes as well as the cost effectiveness of R-NSM through a prospective cohort of patients undergoing R-NSM, E-NSM or C-NSM.

Official Title
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Robotic Versus Conventional or Endoscopic Nipple Sparing Mastectomy in the Management of Breast Cancer- A Prospective Registry Case Control Study

Conditions
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Breast Cancer Female

Intervention / Treatment
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* Device: robotic assisted nipple sparing mastectomy
* Procedure: Endoscopic assisted nipple sparing mastectomy
* Procedure: Conventional nipple sparing mastectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A. Indications and selection criteria for nipple sparing mastectomy (NSM) in general and conventional nipple sparing mastectomy (C-NSM) NSM will be offered to patients who are suitable for mastectomy but keen to conserve nipple areolar complex (NAC), with or without reconstruction. Patients must not have clinical or radiological involvement of the NAC. Patients with nipple involvement proven via intra-operative frozen section analysis will receive NAC excision and hence a skin-sparing mastectomy (SSM) performed instead. B. Indications and selection criteria for robotic nipple sparing mastectomy (R-NSM) or endoscopic nipple sparing mastectomy (E-NSM) The general inclusion criteria or pre-requisite for nipple sparing mastectomy apply to R-NSM or E-NSM as well. In addition, R-NSM or E-NSM should only include early stage breast cancer (carcinoma in situ, stage I - IIIA), a tumor size less than 5 cm, no evidence of multiple lymph node metastasis, and no evidence of nipple, skin or chest wall invasion. Exclusion Criteria: - Contraindications for R-NSM, C-NSM or E-NSM include those with apparent NAC involvement, inflammatory breast cancer, breast cancer with chest wall or skin invasion, locally advanced breast cancer, breast cancer with extensive axillary lymph node metastasis (stage III B or later), and patients with severe co-morbid conditions, such as heart disease, renal failure, liver dysfunction, and poor performance status as assessed by the primary physicians Relative contraindications include women with large (breast cup size larger than E or breast mastectomy weight >600gm) or ptotic breast as the aesthetic outcomes may be suboptimal.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: prospective registry of R-NSM versus C-NSM or E-NSM in the management of breast cancer. 3 arms study for comparisons
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Robotic assisted nipple sparing mastectomy (R-NSM)<br>R-NSM, which introduce da Vinci surgical platform through a small extra-mammary axillary or lateral chest wound to perform NSM. | Device: robotic assisted nipple sparing mastectomy<br>* R-NSM, which introduce da Vinci surgical platform through a small extra-mammary axillary or lateral chest wound to perform NSM, had been applied in the surgical treatment of early breast cancer or risk reducing mastectomy. R-NSM, which incorporated 3-dimensional (3D) imaging system and flexibility of robotic arm and instruments, was reported to have the potential to overcome the technique difficulty of E-NSM.<br>|
| Active Comparator: Conventional nipple sparing mastectomy (C-NSM)<br>Nipple-sparing mastectomy (NSM), which preserved the nipple areolar complex (NAC) and skin flap during mastectomy. | Procedure: Conventional nipple sparing mastectomy<br>* Nipple-sparing mastectomy (NSM), which preserved the nipple areolar complex (NAC) and skin flap during mastectomy, was increasingly performed in breast cancer patients due to better cosmetic outcome, higher patient satisfaction, and maintained oncologic safety.<br>|
| Active Comparator: Endoscopic assisted nipple sparing mastectomy (E-NSM)<br>E-NSM, which is performed through small axillary and/or peri-areolar incisions, with endoscopic instruments to performed nipple sparing mastectomy. | Procedure: Endoscopic assisted nipple sparing mastectomy<br>* E-NSM, which is performed through small axillary and/or peri-areolar incisions, was reported to be associated with small inconspicuous incision and good cosmetic outcome. Conventional E-NSM was performed with two separate incisions over axilla and peri-areolar regions. E-NSM with areolar incision, just like NSM with areolar related incision (NAC ischemia/necrosis rate: range 7%-81.8%), was associated with increased NAC ischemia/necrosis (reported ranged: 9.1-19%). New technique modifications of E-NSM were emerging focusing on single axillary incision NSM, which spare the peri-areolar incision and thereby decrease the compromise of bloody supply from mastectomy skin flap, was reported to have low NAC necrosis rate (0%).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Operation time | Overall operation time (minute), including breast cancer operations, lymph node surgery, and breast reconstructions | immediate post operation | 
| Morbidity and complications | Delayed wound healing, degree of nipple ischemia/necrosis, seroma formation needing repeated aspiration, Blister formation, Skin flap ischemia necrosis, Hematoma formation, Implant loss will be collected and analyzed between different R-NSM, C-NSM and E-NSM groups. | within one month (30 days) post operation | 
| Nipple areolar complex ischemia/necrosis grading | To evaluate the post-operative perfusion and survival of nipple areolar complex (NAC), a grading system was used in current study. The perfusion of NAC was evaluated in 2 weeks to 3 months post operation. The survival of NAC was confirmed at post-operative 3 months. The NAC ischemia/necrosis was divided into 5 different grades, which were: No ischemia/necrosis was observed in NAC (Grade I). Transient ischemia recovered without necrosis (Grade II). Partial ischemia/necrosis, recovered without loss of nipple volume (Grade III). Partial NAC necrosis with partial volume loss of nipple (Grade IV). Total NAC necrosis with all volume loss of nipple (Grade V). NAC ischemia/necrosis was segregated into no NAC necrosis (Grade I-III) and NAC necrosis (Grade IV-V). The ischemia/necrosis of NAC between different R-NSM, C-NSM and E-NSM groups were recorded and compared. | evaluated in post operative 2 weeks to 3 months post operation | 
| Surgical margin involvement | Surgical margin involvement was defined as tumor on the ink. The postoperative adjuvant hormone therapy, chemotherapy and radiotherapy were given to patients according to current breast cancer guidelines. | post operative 2 weeks after pathologic report available | 
| Aesthetic outcome evaluation-Patient reported cosmetic outcome results | - Post-operative aesthetic results will be evaluated by comparing pre-operative and post-operative results. A self-reported questionnaire to evaluate the cosmetic outcome of breast cancer patients with mastectomy following breast reconstruction was conducted 1-3 months after the operation. This questionnaire comprises of 10 questions based on 4 itemized scales, which will be graded as 1, dis-satisfied, 2, fair, 3, satisfied, and 4, very satisfied. | 1-3 months after the operation when the wound was healed | 
| Blood loss during operations | Blood loss (ml) from skin incision to completion of operations | immediate post operation | 
| Hospital stay | Hospital stay (days) during operation period, recorded from admission to day of discharge at the breast cancer operation. | within 2 weeks of operation | 
| Resection mastectomy weight | Mean mastectomy weight (gm) of patients received different mastectomy operations | immediate post operation | 
| Reconstruction implant volume | Reconstruction implant volume (ml) | immediate post operation | 
| Pain assessments | Pain assessments will also be collected as part of the post-operative parameters. Visual analogue scale (VAS) for pain assessments will be used in this study (range from 0 to 10 points, 0 indicate no pain, 10 indicate maximal pain ever experienced). VAS for pain per day would be recorded very day and compared. | within post operation two weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost- analysis of C-NSM versus R-NSM or E-NSM | The medical cost associated with robotic versus conventional or endoscopic assisted NSM will be collected and compared. The medical cost incurred for each procedure include overall hospital cost. Information on surgery-related expenses will obtained from the finance department of the institution. In Taiwan, the operation fees of breast reconstruction and robotic breast surgery are not reimbursed by national insurance. The medical cost covered by national insurance include operations fee for breast cancer and/or axillary lymph node surgery, anesthesia, admission fee, and all other medical related expenses. The medical cost not reimbursed by national insurance, and needed to be paid for by patients include fees for breast reconstruction, robotic breast surgery, endoscopic breast surgery, instruments and prosthetic implants. Cost is expressed in New Taiwan dollars (NTDs) and in United States dollars (USDs). An exchange rate of 31 NTD/USD was used to convert NTD to USD. | post operation one month | 
| Disease free survival | any local regional recurrence, or distant metastasis was recorded as an event. Disease free survival would be compared between R-NSM, C-NSM and E-NSM groups | 5 years post operation | 
| Overall Survival | overall survival would be compared between R-NSM, C-NSM and E-NSM groups | 5 years post operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nipple sparing mastectomy, robotic nipple sparing mastectomy (R-NSM), conventional nipple sparing mastectomy (C-NSM), endoscopic assisted nipple sparing mastectomy (E-NSM), immediate breast reconstruction (IBR), immediate prothesis breast reconstruction (IPBR)