Two-stage implant-based breast reconstruction compared with immediate one-stage implant-based breast reconstruction augmented with an acellular dermal matrix: an open-label, phase 4, multicentre, randomised, controlled trial

Summary

Background

The evidence justifying the use of acellular dermal matrices (ADMs) in implant-based breast reconstruction (IBBR) is limited. We did a prospective randomised trial to compare the safety of IBBR with an ADM immediately after mastectomy with that of two-stage IBBR.

Methods

We did an open-label, randomised, controlled trial in eight hospitals in the Netherlands. Eligible women were older than 18 years with breast carcinoma or a gene mutation linked with breast cancer who intended to undergo skin-sparing mastectomy and immediate IBBR. Randomisation was done electronically, stratified per centre and in blocks of ten to achieve roughly balanced groups. Women were assigned to undergo one-stage IBBR with ADM (Strattice, LifeCell, Branchburg, NJ, USA) or two-stage IBBR. The primary endpoint was quality of life and safety was assessed by the occurrence of adverse outcomes. Analyses were done per protocol with logistic regression and generalised estimating equations. This study is registered at Nederlands Trial Register, number NTR5446.

Findings

142 women were enrolled between April 14, 2013, and May 29, 2015, of whom 59 (91 breasts) in the one-stage IBBR with ADM group and 62 (92 breasts) in the two-stage IBBR group were included in analyses. One-stage IBBR with ADM was associated with significantly higher risk per breast of surgical complications (crude odds ratio 3·81, 95% CI 2·67–5·43, p<0·001), reoperation (3·38, 2·10–5·45, p<0·001), and removal of implant, ADM, or both (8·80, 8·24–9·40, p<0·001) than two-stage IBBR. Severe (grade 3) adverse events occurred in 26 (29%) of 91 breasts in the one-stage IBBR with ADM group and in five (5%) of 92 in the two-stage IBBR group. The frequency of mild to moderate adverse events was similar in the two groups.

Interpretation

Immediate one-stage IBBR with ADM was associated with adverse events and should be considered very carefully. Understanding of selection of patients, risk factors, and surgical and postsurgical procedures needs to be improved.

Funding

Pink Ribbon, Nuts-Ohra, and LifeCell.

Introduction

Breast cancer is the most common malignant disease in women, with an incidence of 1·8 million cases worldwide per year.¹ Survival has increased in high-income countries, meaning long-term clinical care to improve the quality of life of women who survive breast cancer has become ever more important. Mastectomy is indicated in most women with breast cancer, and the loss of a breast can intensely affect a woman's quality of life. In high-income countries, breast reconstructive surgery has become an important part of breast cancer treatment.2, 3 Additionally, increasing numbers of women with genetic predisposition for breast cancer are choosing prophylactic mastectomy followed by immediate reconstruction.⁴ In many countries, immediate breast reconstruction, performed during the same session as mastectomy, is routinely offered to women without contraindications.

Several surgical techniques are available for breast reconstruction, and these fall into two main categories: implant-based breast reconstruction (IBBR) and reconstruction with autologous tissue.⁵ IBBR accounts for most breast reconstruction procedures, and may be achieved in one stage (direct-to-implant reconstruction) or two stages (temporary implantation of a tissue expander followed by definite implant reconstruction). Many surgeons prefer two-stage IBBR despite the need for an additional operation, multiple visits for tissue expansion, the associated burden on the patient (time and number of procedures), and health-care costs. Generally, the subpectoral pocket left after mastectomy is assumed to be too small to accommodate an implant, which can lead to poor coverage of the lower part of the prosthesis.⁶ The use of acellular dermal matrices (ADMs) to augment the subpectoral pocket and allow immediate implantation of a larger-volume implant or tissue expander has increased over the past decade.⁷ This change has made one-stage IBBR feasible, which could lessen the burden on patients and decrease health-care costs. The cosmetic outcome with one-stage ADM-assisted IBBR is also thought to achieve a more natural-looking breast than can be created with two-stage IBBR.8, 9, 10, 11 Although early reports of one-stage IBBR with ADM were overwhelmingly promising, there is little high-level evidence showing that the potential advantages are realised in practice. Outcomes of studies of IBBR with ADM vary widely,¹² and studies that directly compare IBBR techniques with and without the use of ADMs are scarce.

Research in context

Evidence before this study

The use of acellular dermal matrices (ADMs) in implant-based breast reconstruction (IBBR) has increased substantially over the past decade. Although early reports were overwhelmingly promising, evidence on the safety of ADMs in breast reconstructive surgery has since been ambiguous. We searched MEDLINE and Embase for papers reporting studies done to assess safety outcomes of ADM-assisted breast reconstruction, according to the the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and published before April, 2016. We used the search term (“Acellular Dermis”[Mesh] OR acellular dermis[tiab] OR acellular dermal matri*[tiab] OR acellular tissue matri*[tiab] OR collagen matri*[tiab] OR adm[tiab] OR strattice[tiab] OR alloderm[tiab] OR veritas[tiab]) AND (“Mammaplasty”[Mesh] OR mammaplast*[tiab] OR (breast[tiab] AND reconstruct*[tiab]) OR mammoplast*[tiab] OR (mamma[tiab] AND reconstruct*[tiab])). After screening, we found 99 studies that were suitable to include in a meta-analysis. Most were retrospective. Reported incidences of complications varied substantially between studies. Meta-analyses of the incidences of complications revealed that study heterogeneity was significant for almost all safety outcomes. The overall proportion of events was 18·7% (95% CI 0·159–0.219). Which factors underlie the variation in outcomes, however, was unclear. Additionally, comparison of ADM-assisted techniques with conventional breast reconstructive techniques was lacking. Prospective studies are needed to investigate whether the use of ADM is beneficial in IBBR compared with conventional breast reconstructive surgery.

Added value of this study

The Breast Reconstruction in One Stage (BRIOS) randomised study prospectively assessed conventional two-stage IBBR with the newer one-stage direct-to-implant technique with ADM.

Implications of all the available evidence

The evidence before this study did not show whether the proposed advantages of ADM in breast reconstruction were realised in practice. We found far more early postoperative complications after one-stage IBBR with ADM than after two-stage IBBR, particularly wound healing problems, such as wound dehiscence, skin necrosis, and wound infection, that led to reoperation and, often, removal of the implant. Our results suggest that use of one-stage IBBR with ADM should be considered carefully. This outcome will have direct implications for all women undergoing IBBR, and understanding of selection of patients, risk factors, and surgical and postsurgical procedures will need to be improved.

To our knowledge, the Breast Reconstruction in One Stage (BRIOS) study is the first prospective randomised study assessing clinical and patient-reported outcomes of immediate one-stage IBBR with ADM compared with those of two-stage IBBR. Due to worries about safety, just after the final patient was enrolled but before seven women had undergone surgery, the Dutch Health Care Inspectorate requested a preliminary safety analysis. The study ethics board decided to suspend surgery for these seven women and, therefore, here we report the early safety outcomes for the remaining enrolled women. The quality of life data analysis is continuing and will be published in the future.