Robot-assisted vs. Open Nipple-sparing Mastectomy With Immediate Breast Reconstruction

Breast Cancer Patients in Stage 0-3A in Preoperative Evaluation Clinical Trial

— ROM  

Official title:

A Prospective Multicenter Randomized Clinical Trial: Robot-assisted vs. Open Nipple-sparing Mastectomy With Immediate Breast Reconstruction (ROM) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05490433
• Other study ID #: 4-2022-0600
• Status: Recruiting
• Phase: N/A
• Start date: October 26, 2022
• Est. completion date: June 2030

Study information

• Verified date: November 2023
• Source: Yonsei University
• Contact: Hyung Seok Park, MD, PhD
• Phone: 82-10-6760-2974
• Email: imgenius[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

the purpose of the study: It provides the highest level of evidence ever studied on the use of robotic surgical systems during breast surgery for breast cancer treatment, and aims to reveal the clinical significance of successive breast reconstruction(immediate breast reconstruction, IBR) at the same time as Robot-assisted nipple-sparing mastectomy (RNSM)

Description:

- Background: Robot-assisted nipple-sparing mastectomy (RNSM) has emerged for breast cancer treatment and for risk reducing mastectomy in women who have high risk of pathogenic variants. Even though several studies have reported that RNSM is a feasible procedure, some argue that RNSM is only performed by several specialized surgeons and there is only limited data reporting about the oncologic outcomes and patient reported outcomes (PRO). Recently, the United States Food and Drug Administration and several surgeons have warned that robot breast surgery should be performed only by specialized surgeons and the benefits, risks, and alternatives of all available treatment options should be discussed with patients to make the most informed treatment decision. The Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) has been established to evaluate, standardize, and teach this cutting-edge procedure. We designed a prospective multicenter randomized clinical trial evaluating oncologic outcomes of RNSM with immediate breast reconstruction (IBR) compared to open conventional NSM (CNSM) with IBR, which is Robot vs. Open nipple-sparing Mastectomy trial (ROM trial). - Detail description: This study is a multi-organ randomized clinical trial that evaluates oncological results of RNSM compared to Conventional Nipple Sparing Mastectomy (CNSM). Retrospective studies on robot-endoscopic surgery have shown that beginners are technically feasible and reliable with a short learning curve. However, the absence of a well-organized randomized trial remains a major limitation in expanding robotic surgery in breast surgery worldwide, so in this study, we designed a prospective multi-organ randomized trial 'Robot-to-Open Nipple Preservation Mastectomy Clinical Trial' compared to CNSM for oncological results after RNSM and IBR. - Data collection: Collections of clinical pathological factors include height, weight, breast volume/weight, age, germline likely pathogenic/pathogenic mutation, affected breast, bilateral surgery, breast ptosis, Tumor size, TNM stage, histological grade, histological type, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor (HER), Ki67 levels, nipple invasion status, adjuvant/neoplastic treatment status, and postoperative complications by clavien-Dindo classification, surgical time, border invasion, postoperative drainage/period, RRM performance, reconstruction type, patient's pre-surgical recurrence status, medical cost data, and follow-up data. - Subject satisfaction assessment: After 3 to 12 months (+-30 days) of final surgery, the subject was surveyed to evaluate satisfaction with robotic surgery. Follow the BREAST-Q Korean questionnaire for evaluation. - Cost effectiveness evaluation according to surgical method (option): The cost effectiveness of robotic surgery is evaluated by surveying the subject 3 to 12 months after the final surgery (+-30 days). Follow the EQ5D Korean.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 790
• Est. completion date: June 2030
• Est. primary completion date: June 2030
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years to 70 Years

Eligibility

Inclusion Criteria:

• Adult women over the age of 19 with breast cancer scheduled for therapeutic mastectomy and who want immediate reconstruction
• Stage 0-III breast cancer at initial evaluations
• ECOG performance status of 0 or 1

Exclusion Criteria:

• Patients planned for breast-conserving surgery or who are not candidates for IBR are excluded.
• Clinical evidence for nipple or skin involvement of tumors in preoperative evaluations
• A pregnant or lactating woman
• Only tumors with lobular carcinoma in situ
• Mammary Paget's disease
• Inflammatory breast cancer
• Male breast cancer
• Stage IIIB-IV disease at initial presentation
• Women with breast Cup E or higher
• Previous history of breast cancer (metachronous breast cancer)
• Previous history of non-mammary malignant disease excluding non-melanoma skin cancer or thyroid papillary/follicular cancer
• Special type cancer (phyllodes tumor, sarcoma, and lymphoma)
• Age > 70
• ASA, grade 4 or higher
• Patients who do not have the ability to give informed consent
• Previous thoracic radiation history
• Patients who have not been tested for hepatitis before surgery (HBV, HCV) and HIV (compensation insurance policy)

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Procedure:
• robot assisted nipple sparing mastectomy(RNSM)
Patients receiving RNSM and IBR are enrolled in this group. The RNSM is performed using a robotic surgical system. The robotic surgical system includes da Vinci S, Si, X, Xi, and SP Systems. An armpit or lateral chest incision is used in this surgical procedure. A lateral chest incision is used. Posterior flow tissue collection is recommended for frozen segment biopsy during surgery. If a suspected lesion is observed on the superficial or posterior interface during surgery, a frozen section for that lesion. Biopsy is recommended. For NAC, superficial edges, and/or posterior edges in frozen intercept biopsy, If tumor invasion is identified, additional resection or postoperative radiotherapy, including skin and NAC, should be considered do. In IBR, tissue extensor insertion, prosthesis insertion, photolateral sheath, transverse abdominal rectangular sheath, or deep lower abdominal perforated vessels. The skin plate is applicable.
• Conventional nipple sparing mastectomy(CNSM)
Patients who receive CNSM and IBR are enrolled in this group. CNSM uses a robot or endoscopic surgical system Do not travel. All kinds of skin incisions can be performed in this technique. It is recommended to collect posterior mammary gland tissue for frozen segment biopsy during surgery. If a lesion suspected of tumor invasion is observed at the edge of the surface or posterior edge during surgery, a freeze-intercept biopsy is recommended for that lesion. If a frozen segment biopsy identifies invasion of tumors on NAC, superficial edges, and/or posterior edges, further resection or postoperative radiotherapy, including skin and NAC, is considered. In IBR, tissue extensor insertion, prosthesis insertion, photomultiplier sheath, transverse rectangular sheath, or deep lower abdominal perforated vessels. It includes a sheath. It is excluded if there is no IBR.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Changwon Medical Center	Changwon
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Myongji Hospital	Goyang-si
Korea, Republic of	The Catholic University of Korea, Incheon ST. Mary's Hospital	Incheon
Korea, Republic of	Kosin University Gospel Hospital	Pusan
Korea, Republic of	Chungnam National University Sejong Hospital	Sejong
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Health System, Severance Hospital	Seoul
Korea, Republic of	Yongin Severance Hospital	Yongin-si

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5-year disease-free survival rate(DFS)	Events of disease-free survival (DFS) include local outbreaks, local recurrence, remote recurrence, opposite breast cancer and all-cause mortality.; Local relapses include recurrence of the east breast or chest muscles, recurrence of the east chest wall, and recurrence of the east axillary lymph nodes, recurrence of the east subclavicular/clavicular lymph nodes, and recurrence of the east internal mammary lymph nodes.; Events of local recurrence and opposite breast cancer include intraepithelial carcinoma.; Using the stratification factor(proportional hazards models: organ and staging), find the Hazard ratio and the 95% confidence interval. If the upper limit of the confidence interval is less than the non-inferior limit, it is evaluated as non-inferior.	The DFS period is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Five-year overall survival (OS) rates	Event of OS is death with any cause. OS time is calculated using months between the operation date to the event date.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Five-year breast cancer-specific survival (BCSS) rates	Event of BCSS only includes death related to breast cancer. Death related to causes other than breast cancer is censored	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Five-year distant recurrence-free survival (DRFS) rates	Event of DRFS includes distant recurrence as the first event. Locoregional recurrence and contra-lateral breast cancer are censored.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Five-year locoregional recurrence-free survival (LRFS) rates	Event of LRFS includes local recurrence and regional recurrence as the first event. Distant recurrence and contra-lateral breast cancer are censored.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Five-year nipple recurrence (NR) rates	Event of NR only includes recurrence in the NAC as the first event. Ipsilateral in-breast or pectoralis muscle recurrence, ipsilateral chest wall recurrence, ipsilateral regional recurrence, contralateral breast cancer, and distant recurrence are censored.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Margin positive rates	Turmo involvement of NAC, superficial, posterior, or circumferential margins, which is confirmed in final permanent pathology after the definitive surgery, are considered to be margin positive. Margin positive rates will be analyzed.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Open conversion rate (RNSM arm only)	Open conversion of RNSM to CNSM during surgery in the RNSM group is analyzed. The reason of open conversion is documented.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Operation time	Total operation time including mastectomy and reconstruction time. Each operation time will be collected.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Postoperative complication rates in postoperative 30 days	Postoperative complication rates are calculated as a total number of occurences of postoperative complications per total patients in each group. Number of postoperative complications per person is also assessed. Number of postoperative complication ? grade III per person is measured. NAC necrosis rates will be analyzed.; Estimation of postoperative complications rates in 30 days With a sample size of 790 (710 excluding 10% loss of follow up), it has at least 80% power to detect various assumptions of complication rates with a non-inferiority margin of 7.5% between the open and robotic arms. The 30-day complication rate for the open arm is assumed to be between 25-50% , the corresponding maximum 30-day complication rates for the robotic arm to conclude non-inferiority are provided in table 6. These will be analyzed as secondary endpoints.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Clavien-Dindo grade of postoperative complications in postoperative 180 days	Clavien-Dindo grade of postoperative complications is evaluated. Postoperative complication ? grade III including flap or implant loss are assessed for the analysis.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Implant or graft (flap) loss rates within 1 year from surgery		secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Patient reported outcomes in postoperative 3 - 12 months from the definitive surgery (patient satisfaction)	Mastectomy Module Pre-and Postoperative Scales Satisfaction with Breasts assessed by BREAST-Q version 2.0. Higher scores reflect a better outcome.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Surgeon's satisfaction in postoperative 3 month to 1 year	Satisfaction of surgery assessed by Surgeon(s) Overall symmetry, postoperative scar, and NAC symmetry are measured using scoring system 0-10. The higher scores are, the better an outcome is.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)
Secondary	Cost-effectiveness in postoperative 3 month to 1 year	Cost-effectiveness evaluation according to the surgical method, by conducting a questionnaire survey on the subject 6 months to 1 year after the last surgery. Evaluation follows the EuroQol five-dimension scale (EQ5D) Korean version questionnaire. In all scales, higher scores reflect a better outcome.	secondary outcome is calculated from the date of surgery to the time the first event occurs, or if the event is not reported on the last follow-up date.(After 5 years of follow-up observation of subject registration)