Robotic Versus Conventional or Endoscopic Nipple Sparing Mastectomy for Breast Cancer

Breast Cancer Female Clinical Trial

— RCENSM-R  

Official title:

Robotic Versus Conventional or Endoscopic Nipple Sparing Mastectomy in the Management of Breast Cancer- A Retrospective Study With Multi-center Pooled Data Analysis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04049305
• Other study ID #: CCH-IRB-190414-R
• Secondary ID: MOST 108-2314-B-
• Status: Recruiting
• Phase: N/A
• Start date: August 22, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: July 2020
• Source: Changhua Christian Hospital
• Contact: Hung-Wen Lai, MD, PhD
• Phone: +886933496822
• Email: hwlai650420[@]yahoo.com.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will retrospectively collect and evaluate the surgical outcomes of robotic nipple sparing mastectomy (R-NSM) compared with endoscopic assisted NSM (E-NSM) or conventional NSM (C-NSM) in the management of breast cancer. Multi-centers pooled data analysis would be performed for comparisons of R-NSM compared with C-NSM or E-NSM.

Description:

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 extramammary 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 literature reported series and ours were safe, and associated with good cosmetic outcome and high patients' satisfaction. However, evidence comparing R-NSM to conventional NSM (CNSM) 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 longitudinal cohort study design whereby a retrospective review will be carried out for patients undergoing R-NSM, E-NSM or C-NSM. Multi-centers pooled data analysis would be performed for comparisons of R-NSM compared with C-NSM or E-NSM.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 900
• Est. completion date: December 31, 2021
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 80 Years

Eligibility

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 - III A), 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 sub-optimal.

Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms

Intervention

Device:
• Robotic assisted nipple sparing mastectomy (R-NSM)
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.

Procedure:
• conventional nipple sparing mastectomy (C-NSM)
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.
• Endoscopic assisted nipple sparing mastectomy (E-NSM)
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%).

Locations

Country	Name	City	State
Italy	European Institute of Oncology	Milan
Korea, Republic of	Severance Hospital	Seoul
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Shin Kong Wu Ho-Su Memorial Hospital	Taipei
Taiwan	Taipei Municipal Wan Fang Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	Shuang-Ho Hospital - Taipei Medical University	Taipei county
Taiwan	Chang Gung Memorial Hospital	Taoyuan

Sponsors (3)

Lead Sponsor	Collaborator
Changhua Christian Hospital	Intuitive Surgical, Ministry of Science and Technology, Taiwan

Countries where clinical trial is conducted

Italy,  Korea, Republic of,  Taiwan, 

References & Publications (14)

Lai HW, Chen ST, Chen DR, Chen SL, Chang TW, Kuo SJ, Kuo YL, Hung CS. Current Trends in and Indications for Endoscopy-Assisted Breast Surgery for Breast Cancer: Results from a Six-Year Study Conducted by the Taiwan Endoscopic Breast Surgery Cooperative Gr — View Citation

Lai HW, Chen ST, Lin SL, Chen CJ, Lin YL, Pai SH, Chen DR, Kuo SJ. Robotic Nipple-Sparing Mastectomy and Immediate Breast Reconstruction with Gel Implant: Technique, Preliminary Results and Patient-Reported Cosmetic Outcome. Ann Surg Oncol. 2019 Jan;26(1) — View Citation

Lai HW, Huang RH, Wu YT, Chen CJ, Chen ST, Lin YJ, Chen DR, Lee CW, Wu HK, Lin HY, Kuo SJ. Clinicopathologic factors related to surgical margin involvement, reoperation, and residual cancer in primary operable breast cancer - An analysis of 2050 patients. — View Citation

Lai HW, Lin SL, Chen ST, Kuok KM, Chen SL, Lin YL, Chen DR, Kuo SJ. Single-Axillary-Incision Endoscopic-Assisted Hybrid Technique for Nipple-Sparing Mastectomy: Technique, Preliminary Results, and Patient-Reported Cosmetic Outcome from Preliminary 50 Proc — View Citation

Lai HW, Wang CC, Lai YC, Chen CJ, Lin SL, Chen ST, Lin YJ, Chen DR, Kuo SJ. The learning curve of robotic nipple sparing mastectomy for breast cancer: An analysis of consecutive 39 procedures with cumulative sum plot. Eur J Surg Oncol. 2019 Feb;45(2):125- — View Citation

Leff DR, Vashisht R, Yongue G, Keshtgar M, Yang GZ, Darzi A. Endoscopic breast surgery: where are we now and what might the future hold for video-assisted breast surgery? Breast Cancer Res Treat. 2011 Feb;125(3):607-25. doi: 10.1007/s10549-010-1258-4. Epu — View Citation

Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, Klimberg S, Chavez-MacGregor M, Freedman G, Houssami N, Johnson PL, Morrow M. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Ann Surg Oncol. 2014 Mar;21(3):704-16. doi: 10.1245/s10434-014-3481-4. Epub 2014 Feb 10. — View Citation

Park SW, Lee TJ, Kim EK, Eom JS. Managing necrosis of the nipple-areola complex in breast reconstruction after nipple-sparing mastectomy: immediate nipple-areola complex reconstruction with banked skin. Plast Reconstr Surg. 2014 Jan;133(1):73e-4e. doi: 10.1097/01.prs.0000436805.58165.d3. — View Citation

Petit JY, Veronesi U, Luini A, Orecchia R, Rey PC, Martella S, Didier F, De Lorenzi F, Rietjens M, Garusi C, Sonzogni A, Galimberti V, Leida E, Lazzari R, Giraldo A. When mastectomy becomes inevitable: the nipple-sparing approach. Breast. 2005 Dec;14(6):527-31. Epub 2005 Oct 12. — View Citation

Sakamoto N, Fukuma E, Higa K, Ozaki S, Sakamoto M, Abe S, Kurihara T, Tozaki M. Early results of an endoscopic nipple-sparing mastectomy for breast cancer. Ann Surg Oncol. 2009 Dec;16(12):3406-13. doi: 10.1245/s10434-009-0661-8. — View Citation

Sarfati B, Struk S, Leymarie N, Honart JF, Alkhashnam H, Tran de Fremicourt K, Conversano A, Rimareix F, Simon M, Michiels S, Kolb F. Robotic Prophylactic Nipple-Sparing Mastectomy with Immediate Prosthetic Breast Reconstruction: A Prospective Study. Ann — View Citation

Toesca A, Peradze N, Galimberti V, Manconi A, Intra M, Gentilini O, Sances D, Negri D, Veronesi G, Rietjens M, Zurrida S, Luini A, Veronesi U, Veronesi P. Robotic Nipple-sparing Mastectomy and Immediate Breast Reconstruction With Implant: First Report of Surgical Technique. Ann Surg. 2017 Aug;266(2):e28-e30. doi: 10.1097/SLA.0000000000001397. — View Citation

Toesca A, Peradze N, Manconi A, Galimberti V, Intra M, Colleoni M, Bonanni B, Curigliano G, Rietjens M, Viale G, Sacchini V, Veronesi P. Robotic nipple-sparing mastectomy for the treatment of breast cancer: Feasibility and safety study. Breast. 2017 Feb;3 — View Citation

Tukenmez M, Ozden BC, Agcaoglu O, Kecer M, Ozmen V, Muslumanoglu M, Igci A. Videoendoscopic single-port nipple-sparing mastectomy and immediate reconstruction. J Laparoendosc Adv Surg Tech A. 2014 Feb;24(2):77-82. doi: 10.1089/lap.2013.0172. Epub 2014 Jan 8. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Operation time	Overall operation time (minute), from skin incision to completion of operations. Compared overall operation time between R-NSM, C-NSM and E-NSM.	immediate post operation
Primary	Wound healing status	rate of Delayed wound healing between R-NSM, C-NSM and E-NSM groups.	within one month (30 days) post operation
Primary	Skin blister formation	rate of skin blister formation between R-NSM, C-NSM and E-NSM groups.	within one month (30 days) post operation
Primary	Skin flap ischemia/necrosis rate	rate of skin flap ischemia/necrosis between R-NSM, C-NSM and E-NSM groups.	within one month (30 days) post operation
Primary	Implant loss rate	rate of implant loss between R-NSM, C-NSM and E-NSM groups.	within one month (30 days) post operation
Primary	Post operation Bleeding/hematoma rate	rate of post operative bleeding/hematoma rate between R-NSM, C-NSM and E-NSM groups.	within one month (30 days) post operation
Primary	Post operation Bleeding/hematoma rate	rate of post operative bleeding/hematoma between R-NSM, C-NSM and E-NSM groups.	within one month (30 days) post operation
Primary	Seroma formation rate	rate of post operative seroma formation needing repeat aspiration between R-NSM, C-NSM and E-NSM groups.	within one month (30 days) post operation
Primary	Grade of Nipple areolar complex ischemia/necrosis	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
Primary	Rate of Surgical margin involvement in specimen pathologic examination	Rate of Surgical margin involvement in specimen during pathologic examination, and surgical margin involvement was defined as tumor on the ink.	post operative 2 weeks after pathologic report available
Primary	Aesthetic outcome evaluation-Patient reported cosmetic outcome results	- Post-operative aesthetic results will be evaluated by comparing pre-operative and post-operative results. A selfreported 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
Primary	Blood loss during operation	Blood loss (ml) during operation was compared between groups (R-NSM, C-NSM and R-NSM)	immediate post operation
Primary	Hospital stay	Hospital stay (days) of patients receiving different operations (R-NSM, C-NSM, and E-NSM)	within 2 weeks of operation
Primary	Mean mastectomy weight	Mean mastectomy weight (gm) of patients receiving different operations (R-NSM, C-NSM, and E-NSM)	immediate post operation
Primary	Reconstruction implant volume	Reconstruction implant volume (ml) of patients receiving different operations (R-NSM, C-NSM, and E-NSM)	immediate post operation
Secondary	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
Secondary	Disease free Survival	disease-free survival between R-NSM, C-NSM or E-NSM .	5 years post operation
Secondary	Overall survival	overall survival between R-NSM, C-NSM or E-NSM .	5 years post operation