Pre- Versus Sub-pectoral Implant-based Breast Reconstruction After Skin-sparing Mastectomy or Nipple-sparing Mastectomy OPBC-02PREPEC

Study Overview
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Brief Summary
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This trial is to investigate whether pre-pectoral Implant-Based Breast Reconstruction (IBBR) provides better Quality of Life (QoL) with respect to long-term (24 months) physical well-being (chest) compared to sub-pectoral IBBR for patients undergoing skin-sparing mastectomy or nipple-sparing mastectomy for prevention or treatment of breast cancer.

Detailed Description
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This trial is to investigate whether pre-pectoral Implant-Based Breast Reconstruction (IBBR) provides better Quality of Life (QoL) with respect to long-term (24 months) physical well-being (chest) compared to sub-pectoral IBBR for patients undergoing skin-sparing mastectomy or nipple-sparing mastectomy for prevention or treatment of breast cancer.The aim is to adhere to standard of care as much as possible to follow the pragmatic trial design to generate data that are applicable to today's practice. Therefore, surgeons are allowed to use their preferred Acellular Dermal Matrix (ADM), synthetic meshes, expanders and implants, thereby offering practitioners considerable leeway in deciding how to perform the procedure. For the same reason, both the one- and two-staged IBBR approaches are allowed when studying pre- versus sub-pectoral IBBR.

Official Title
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Pre- Versus Sub-pectoral Implant-based Breast Reconstruction After Skin-sparing Mastectomy or Nipple-sparing Mastectomy (OPBC-02/ PREPEC): A Pragmatic, Multicenter, Randomized, Superiority Trial

Conditions
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Breast Reconstruction, Implant-Based Breast Reconstruction (IBBR)

Intervention / Treatment
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* Procedure: pre-pectoral IBBR
* Procedure: sub-pectoral IBBR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent according to ICH/GCP regulations prior to any trial specific procedures Patients undergoing NSM or SSM and IBBR in the therapeutic or risk-reducing Setting Ability to complete the Quality of Life questionnaires Exclusion Criteria: No indication for IBBR according to clinical judgment of the treating surgeon Skin flaps inadequate for pre-pectoral IBBR.

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will objectively assess the results and complication of two surgical techniques and thus provide evidence to assess whether there are differences between these techniques.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: pre-pectoral IBBR<br> | Procedure: pre-pectoral IBBR<br>* The breast is reconstructed by positioning a breast implant above (pre-pectoral) the pectoralis major muscle.<br>|
| Active Comparator: sub-pectoral IBBR<br> | Procedure: sub-pectoral IBBR<br>* The breast is reconstructed by positioning a breast implant below (sub-pectoral) the pectoralis major muscle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BREAST-Q scale | compare the Quality of Life (QoL) with respect to long-term physical well-being (chest) after pre-pectoral or sub-pectoral IBBR. The BREAST-Q module specific to breast reconstruction version 2.0 consists of 13 independent scales covering health-related QoL domains and satisfaction domains. Each scale is scored to generate a numerical score on a scale from 0 (worst) to 100 (best). | within 24 months after mastectomy (screening, day 10, and months 1, 6, 12 and 24) | 
| Change in EQ-5D-5L questionnaire | The 5-level version of the EQ-5D (EQ-5D-5L) consists of the EQ-5D descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/Depression (5 answer levels each: no problems, slight problems, moderate problems, severe problems and extreme problems), resulting in a 1-digit number that expresses the level for that dimension. The digits for each dimension are combined into a 5-digit number that describes the patient's health state and is subsequently converted into a preference-based quality of life weight (utility) using an algorithm derived from population-based studies. In addition, patients are asked to rate their health on a vertical visual analogue scale (EQ VAS), where the anchors are labelled with 'The best health you can imagine' and 'The worst health you can imagine'. | within 24 months after mastectomy (screening, day 10, and months 1, 6, 12 and 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| loss of expander or implant | compare the safety of pre-pectoral and sub-pectoral IBBR, in terms of loss of expander or implant. Loss of expander or implant is defined as an unplanned surgical removal of expander/implant with or without immediate replacement. | within 24 months of undergoing mastectomy and immediate reconstruction | 
| surgical complications | compare the safety of pre-pectoral and sub-pectoral IBBR, in terms of surgical complications. The complications include: Wound dehiscence, Haematoma, Seroma, Implant/expander exposure/Extrusion, Implant/Expander rotation/malpositioning, Infection, Mastectomy skin flap necrosis, Capsular contraction, Lymphedema | within 24 months of undergoing mastectomy and immediate reconstruction | 
| thromboembolic events | compare the safety of pre-pectoral and sub-pectoral IBBR, in terms of thromboembolic events according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | within 24 months of undergoing mastectomy and immediate reconstruction | 
| patient satisfaction | compare patient satisfaction after pre-pectoral or sub-pectoral IBBR | over 24 months since mastectomy | 
| animation deformity | compare animation deformity after pre-pectoral or sub-pectoral IBBR by using pictures from before and 24 months after the mastectomy | before and 24 months after the mastectomy | 
| capsular contracture | compare capsular contracture after pre-pectoral or sub-pectoral IBBR by using pictures from before and 24 months after the mastectomy | before and 24 months after the mastectomy | 
| aesthetic results | compare aesthetic results after pre-pectoral or sub-pectoral IBBR assessed by photographs of the breast taken in a standardized way. They will be evaluated by an experienced investigator who is blinded for group assignment. The blinded outcome assessment team will be trained to enter data for the two most widely used semi-automatic software for objective aesthetic evaluation, the 'Breast Cancer Conservative Treatment cosmetic results' (BCCT.core) | before and 24 months after the mastectomy | 
| Recurrence-free survival (RFS) | RFS is defined as the time from randomization until the first documentation of any of the following events: local-regional occurrence or recurrence of invasive disease or ductal carcinoma in situ (DCIS), distant breast cancer metastasis, or death from any cause. | until 10 years after mastectomy and IBBR. | 
| aesthetic results evaluated by patients | evaluated by patients using a four point scale: excellent, good, regular, bad. | at baseline and after 24 months | 
| total number of operative procedures | assess the burden on patients by total number of operative procedures | until 24 months after mastectomy | 
| length of hospital stay (index hospitalization and overall) | length of hospital stay (index hospitalization and overall) following randomization until discharge and the cumulative number of days the patient was hospitalized | until 24 months after randomization | 
| total number of outpatient visits at the trial site and the emergency department | assess the burden on patients by total number of outpatient visits at the trial site and the emergency department | from admission for mastectomy until 24 months after randomization | 
| aesthetic results evaluated by local physicians | evaluated by local physicians using a four point scale: excellent, good, regular, bad. | at baseline and after 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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skin-sparing mastectomy (SSM), nipple-sparing mastectomy (NSM), immediate breast reconstruction, pre-pectoral breast implant, sub-pectoral breast implant