Prepectoral breast reconstruction with and without acellular dermal matrix: a systematic review and meta-analysis

Introduction

Breast reconstruction after mastectomy is a crucial component for restoring both the physical appearance and psychological well-being of patients. Among the various techniques available, prepectoral implant placement has gained popularity due to its potential benefits, such as reduced postoperative pain, shorter recovery times, and preservation of the chest wall anatomy (1,2). Unlike traditional approaches, this technique often incorporates acellular dermal matrices (ADMs) as an adjunct designed to improve clinical and aesthetic outcomes by providing additional support to the implant and promoting tissue integration (1-3).

Breast cancer is the most common malignancy among women worldwide, with over 2.3 million new cases diagnosed annually. Of these, a significant proportion undergoes mastectomy, and implant-based breast reconstruction represents one of the most common reconstructive approaches (4,5). Data suggests that approximately 70–80% of these reconstructions involve tissue expanders (TEs) or implants, with ADM being utilized in 40–50% of cases in specific regions (6). Historically, the evolution of implant placement in breast reconstruction has been driven by the need to balance aesthetic outcomes with postoperative function and patient comfort (7). Early approaches often involved submuscular or dual-plane placement to ensure adequate implant coverage in the absence of native breast tissue. However, these techniques were associated with complications such as animation deformity and postoperative pain. More recently, the development of the prepectoral approach, enabled by advancements in ADM technology, has acquired popularity in the post-mastectomy setting, offering reduced morbidity, improved recovery, and favorable cosmetic outcomes (7). ADM is a bioengineered scaffold derived from human or animal dermis, initially developed for burn and wound care. Its integration into breast reconstruction has shown the potential to reduce capsular contracture rates (10–15% in traditional reconstructions without ADM) and improve aesthetic results. However, ADM use remains controversial due to complications such as infections (up to 15%), seroma formation (5–10%), and implant loss (up to 7%). Furthermore, its inclusion increases procedural costs by 20–40%, posing an economic challenge (2,8). Importantly, most available evidence is derived from retrospective, non-randomized cohort studies, which inherently limits the level of evidence and the strength of the conclusions that can be drawn.

Current meta-analyses on ADM use in prepectoral reconstruction reveal mixed findings. While some studies highlight its benefits (8,9) such as improved aesthetic satisfaction and reduced capsular contracture, others report increased overall complication rates. For example, a 2023 meta-analysis found that ADM was associated with improved aesthetics but a 10% increase in complications (9). Another study published in 2024 emphasized cost-related concerns, further contributing to the ongoing debate (8).

This meta-analysis aims to comprehensively evaluate the impact of ADM use in prepectoral breast reconstruction, focusing on postoperative complications, aesthetic outcomes, and associated costs. Unlike previous reviews, this study seeks to resolve conflicting findings by emphasizing objective comparisons and a patient-centered approach. Given that all included studies are retrospective and non-randomized, the findings should be interpreted with caution in light of this methodological limitation. We present this article in accordance with the MOOSE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-309/rc) (10).

Methods

The review protocol was registered in PROSPERO under ID: CRD420251005406

Selection criteria

We identified relevant studies by setting specific selection criteria. The population of interest were patients ≥18 years old who underwent mastectomy and subsequent prepectoral breast reconstruction with or without ADM. We included comparative studies utilizing a cohort with ADM while incorporating a non-ADM group as the control arm. For consistency, only biologic ADMs (human-, porcine-, or bovine-derived) were eligible. Studies that evaluated synthetic meshes or non-biologic scaffolds were excluded. One included study (11) described the intervention as “mesh”, but the material used was Braxon, a porcine-derived ADM, and was therefore considered within scope; these consisted only of observational studies to ensure result reliability. Studies not meeting these criteria were excluded. Case reports, case series, systematic reviews, conference abstracts, articles without available full text, and non-primary research articles were also excluded. No language restrictions were applied during the study selection process.

Literature search strategy and study screening

A comprehensive electronic search was performed on three databases (PubMed, SCOPUS, and COCHRANE) from inception to August 2024 and was updated in April 2025 to ensure the inclusion of the most recent studies. The search was designed by three authors of the project. Keywords and free words were used in our search strategy to search for implant pre pectoralis, ADM, and reconstruction procedure. Duplicates were removed using Zotero. Reference lists of included articles were also screened if they met our inclusion criteria. Retrieved references were assessed through title and abstract screening, and then full-text screening was performed. Three authors (L.D.C.R., A.A.C.G., and C.J.d.R.M.) evaluated each paper independently and in duplicate for inclusion, with a fourth author resolving any conflicts. Efforts were made to contact authors for missing data when necessary.

Data extraction and quality assessment

Three reviewers collected data independently and in duplicate, and organized it into four main categories: study characteristics, demographic characteristics, clinical outcomes, and aesthetic outcomes. Variables included type of study, population analyzed, demographic data [age, gender, body mass index (BMI), comorbidities]. Complications analyzed included: hematoma, necrosis, seroma, infection, reoperation, and capsular contracture, which was assessed using the Baker classification, where grades III and IV indicate significant contracture. It is important to note that the studies included in this analysis consistently used this classification for measuring capsular contracture. However, some studies defined grades III and IV slightly differently, depending on the clinical or radiological criteria used. This variability in definitions could affect the comparability of results, highlighting the need for standardization of these criteria in future studies. Rippling, dehiscence, and implant removal. The aesthetic results were evaluated through quality of life and patient satisfaction scales, in addition to objective indicators of shape and symmetry.

The methodological quality of the included studies was assessed independently by two reviewers using the Cochrane risk of bias assessment tool (ROBINS-I) (12). Any discrepancies were resolved by consensus. The quality evaluation tool was selected following the Cochrane Handbook of Systematic Reviews of Interventions 6.4 Risk-of-bias Visualization (robvis) was used to generate the risk of bias plots (13).

Publication bias and heterogeneity

We planned to assess publication bias using Egger’s test (14). However, due to the limited number of included studies and the frequent presence of zero-event outcomes, the test was not feasible. Therefore, publication bias assessment was restricted to a qualitative evaluation. Additionally, heterogeneity among the included studies was evaluated using the Higgins I² statistic (15). Values above 50% indicated high heterogeneity.

Statistical analysis

All statistical analyses were conducted using the R Studio software. For dichotomous data, event frequencies and group totals were pooled to calculate the risk ratio (RR) with 95% confidence intervals (CIs). The mean difference (MD) with 95% CI was used for continuous data. The inverse variance method was used to estimate within-study variance and weight studies accordingly in the meta-analysis. When mean values and standard deviations (SDs) were unavailable, Hozo’s method was applied to calculate them (16). Heterogeneity was assessed using the I² statistic. Variables with I²>50% were analyzed using a random-effects model; otherwise, a fixed-effect model was used. A P<0.05 was considered statistically significant.

Additionally, a meta-analysis of pooled proportions was performed to estimate overall and subgroup-specific complication rates for direct-to-implant (DTI) and TE techniques, using a random-effects model with logit transformation.

Results

Study selection and characteristics

A comprehensive analysis was conducted on a total study population of 1,455 patients, derived from nine retrospective cohort studies that met our inclusion criteria out of an initial pool of 636 studies. One additional study was identified during an updated search conducted in April 2025. The study selection process is represented in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram in Figure 1.

Figure 1 PRISMA diagram.

All nine studies compared outcomes of prepectoral breast reconstruction with and without ADM (5,6,8,11,17-21). In six studies where ADM allocation was reported at the patient level (n=1,081), 817 patients (75.6%) underwent reconstruction with ADM and 264 patients (24.4%) without ADM. In the remaining three studies (8,20,21), ADM use was reported only at the breast level (334, 121, and 115 breasts, respectively) and is therefore presented separately in Table 1.

Detailed study characteristics, including type of ADM, implant position, surgical technique, and type of implants used, are summarized in Table 1. Briefly, most studies reported prepectoral reconstruction, with human-derived ADM (AlloDerm, FlexHD, DermACELL, Cortiva) or porcine-derived ADM (Fortiva, Braxon) when specified. Surgical techniques included either two-stage reconstruction with TE placement followed by implant exchange, or DTI reconstruction, depending on flap viability. Smooth, round silicone implants were the most commonly reported, whereas some studies did not specify the definitive implant type. A detailed summary of the included studies is provided in Table 1. An overview of the baseline characteristics is shown in Table 2.

Reoperation

We performed a meta-analysis for reoperation. Three studies (8,17,18) reported outcomes related to reoperation, with a RR of 1.02 (95% CI: 0.52–1.98, P=0.91) with a null heterogeneity (I²=0%). These findings are illustrated in Figure 2.

Figure 2 Forest plot of reoperation rates in prepectoral breast reconstruction with vs. without ADM. This analysis includes three studies (8,17,18), comparing reoperation rates between ADM and non-ADM groups. A random-effects model was applied. Individual study weights and effect sizes (RRs, 95% CI) are displayed. The pooled RR was 1.02 (95% CI: 0.52–1.98, P=0.91), showing no statistically significant difference in reoperation rates between groups. ADM, acellular dermal matrix; CI, confidence interval; RR, risk ratio.

Capsular contracture

Capsular contracture was reported in four studies (5,6,8,20). The pooled analysis demonstrated no statistically significant difference between groups. RR of 0.72 (95% CI: 0.19–2.75; P=0.49), with moderate-to-high heterogeneity (I²=50.4%). While some individual studies suggested lower rates of capsular contracture with ADM use, the overall effect was not statistically significant. These findings are illustrated in Figure 3.

Figure 3 Forest plot of capsular contracture rates in prepectoral breast reconstruction with vs. without ADM. This analysis includes four studies (5,6,8,20). A random-effects model was applied. Individual study weights and RRs (95% CI) are shown. The pooled RR was 0.72 (95% CI: 0.19–2.75; P=0.49), indicating no significant difference in capsular contracture rates between ADM and non-ADM groups. ADM, acellular dermal matrix; CI, confidence interval; RR, risk ratio.

Dehiscence

Six studies provided dehiscence data (5,6,8,11,17,21). Analysis revealed no statistically significant difference between groups. RR of 0.97 (95% CI: 0.40–2.35, P=0.93). Low heterogeneity was found (I²=0%). These findings are illustrated in Figure 4.

Figure 4 Forest plot of wound dehiscence rates in prepectoral breast reconstruction with vs. without ADM. This analysis includes six studies (5,6,8,11,17,21). A random-effects model was used. Individual study weights and effect sizes (RRs, 95% CI) are displayed. The pooled RR was 0.97 (95% CI: 0.40–2.35, P=0.93), showing no statistically significant difference in wound dehiscence between groups. ADM, acellular dermal matrix; CI, confidence interval; RR, risk ratio.

Hematoma

Hematoma was described in six studies (5,6,11,17,18,21). Pooled analysis demonstrated a non-significant RR of 0.98 (95% CI: 0.29–3.28, P=0.96) with null heterogeneity. These findings are illustrated in Figure 5.

Figure 5 Forest plot of hematoma rates in prepectoral breast reconstruction with vs. without ADM. This analysis includes six studies (5,6,11,17,18,21). A random-effects model was applied. The pooled RR was 0.98 (95% CI: 0.29–3.28, P=0.96), indicating no significant difference in hematoma rates between groups. ADM, acellular dermal matrix; CI, confidence interval; RR, risk ratio.

Implant removal

Five studies provided implant removal data (5,8,11,17,20). Analysis showed a RR of 0.74 (95% CI: 0.46–1.20, P=0.16) with low heterogeneity (I²=0%). These findings are illustrated in Figure 6.

Figure 6 Forest plot of implant removal rates in prepectoral breast reconstruction with vs. without ADM. This analysis includes five studies (5,8,11,17,20). A random-effects model was used. The pooled RR was 0.74 (95% CI: 0.46–1.20, P=0.16), showing no significant difference in implant removal between groups. ADM, acellular dermal matrix; CI, confidence interval; RR, risk ratio.

Infection

Six studies reported infection (5,6,8,17,19,21). The pooled analysis showed no statistically significant difference between groups. RR of 0.73 (95% CI: 0.51–1.05; P=0.07), with low heterogeneity (I²=0%). These findings are illustrated in Figure 7.

Figure 7 Forest plot of infection rates in prepectoral breast reconstruction with vs. without ADM. This analysis includes six studies (5,6,8,17,19,21). A random-effects model was applied. The pooled RR was 0.73 (95% CI: 0.51–1.05; P=0.07), showing no significant difference in infection between groups. ADM, acellular dermal matrix; CI, confidence interval; RR, risk ratio.

Necrosis

Necrosis was reported in six studies (5,8,11,17,19,21). The pooled analysis showed no statistically significant difference between groups. RR of 1.27 (95% CI: 0.64–2.53; P=0.41), with low heterogeneity (I²=16.6%). These findings are illustrated in Figure 8.

Figure 8 Forest plot of necrosis rates in prepectoral breast reconstruction with vs. without ADM. This analysis includes six studies (5,8,11,17,19,21). A random-effects model was used. The pooled risk ratio was 1.27 (95% CI: 0.64–2.53; P=0.41), showing no significant difference in necrosis between groups. ADM, acellular dermal matrix; CI, confidence interval; RR, risk ratio.

Rippling

Three studies reported rippling outcomes (5,6,20). Pooled analysis revealed a RR of 0.54 (95% CI: 0.01–37.58, P=0.59) with high heterogeneity (I²=69.5%). These findings are illustrated in Figure 9.

Figure 9 Forest plot of rippling rates in prepectoral breast reconstruction with vs. without ADM. This analysis includes three studies (5,6,20). A random-effects model was applied. The pooled RR was of 0.54 (95% CI: 0.01–37.58, P=0.59), showing no statistically significant difference in rippling between groups. ADM, acellular dermal matrix; CI, confidence interval; RR, risk ratio.

Seroma

Eight studies reported seroma data (5,6,8,11,17-19,21). Analysis showed a RR of 0.81 (95% CI: 0.65–1.02, P=0.07) without reaching a statistically significant difference between groups. Low heterogeneity was observed. These findings are illustrated in Figure 10.

Figure 10 Forest plot of seroma rates in prepectoral breast reconstruction with vs. without ADM. This analysis includes eight studies (5,6,8,11,17-19,21). A random-effects model was applied. The pooled RR was 0.81 (95% CI: 0.65–1.02; P=0.07), indicating no significant difference in seroma rates between groups. ADM, acellular dermal matrix; CI, confidence interval; RR, risk ratio.

Subgroup analysis by technique

A supplementary meta-analysis of pooled proportions was conducted to quantify absolute complication rates. The global rates were as follows: necrosis 3.49% (95% CI: 1.13–10.3%), seroma 7.83% (95% CI: 3.2–17.91%), hematoma 0.73% (95% CI: 0.24–2.21%), and infection 2.79% (95% CI: 0.8–9.28%). Subgroup analysis stratified by reconstructive technique demonstrated a distinct complication profile. Tissue expander (TE) reconstruction was associated with higher rates of seroma (14.04% vs. 4.26%), infection (12.62% vs. 0.74%), and necrosis (5.39% vs. 2.09%) compared to DTI reconstruction. High heterogeneity was observed for necrosis (I²=91%) and seroma (I²=89%), predominantly within the TE subgroup (Figures S1-S8).

Risk of bias

Among the nine non-randomized studies included in this meta-analysis, all were assessed as having a moderate risk of bias. This was primarily due to the absence of explicit statements regarding adjustments for multiple comorbidities, the lack of multivariate analyses, and inadequate consideration of covariates and confounders, all of which could affect the validity of the results. We used the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool to evaluate the quality of the included studies. The tool evaluated each study in seven domains for potential biases. A visual summary of the overall risk of bias and domain-specific assessments is presented in Figure S9 and Figure S10, respectively.

Publication bias

Our ability to assess publication bias was limited by the rarity of complications (many zero-event studies) and the small number of studies reporting each outcome. This prevents meaningful statistical testing for small-study effects.

Discussion

This meta-analysis aimed to critically evaluate the clinical utility of ADM in prepectoral breast reconstruction, focusing on three domains: postoperative complications, aesthetic outcomes, and cost-effectiveness. The rationale stems from ongoing debate within reconstructive surgery regarding the balance between ADM’s proposed benefits, improved implant support and aesthetics, and its drawbacks, including increased cost and complications such as flap necrosis. Despite its widespread use in implant-based breast reconstruction overall, reported in 84.2% of American Society of Plastic Surgeons (ASPS) members across all reconstruction types in a 2015 survey by Ibrahim et al. (22), a consensus on the use of ADM, particularly in the prepectoral, remains lacking. Therefore, this study provides a consolidated analysis of evidence from nine retrospective cohorts involving 1,455 patients, offering critical insight into whether ADM should remain a routine component of prepectoral reconstruction or be reserved for selected cases. It is also important to acknowledge the considerable heterogeneity among the included studies, encompassing variations in patient populations, surgical techniques, and the types of ADM utilized (human, porcine, and bovine). Such heterogeneity may influence both complication rates and aesthetic outcomes, thereby limiting the generalizability of the pooled findings to all clinical settings. This variability underscores the need for cautious interpretation of the results and highlights the importance of future studies with standardized protocols to better delineate the true impact of ADM in prepectoral breast reconstruction.

Postoperative complications

Overall, our pooled analysis revealed no statistically significant differences in most postoperative complications between the ADM and non-ADM groups, including rates of reoperation, infection, seroma, hematoma, implant removal, rippling, and capsular contracture. This finding is consistent with previous studies that also failed to demonstrate significant differences in overall complication rates between reconstructions performed with and without ADM (5,6,8,11,17-21). A recent meta-analysis by Nolan et al. (9), which evaluated 515 breast reconstructions, most of which involved nipple-sparing mastectomies and TE-based techniques, demonstrated comparable complication rates between ADM and non-ADM cohorts, with no statistically significant differences in either short-term or long-term complications (P>0.05). Likewise, Cook et al. (23), in a systematic review of 22 studies encompassing 3,822 breast reconstructions, found no significant difference in overall complication or failure rates between groups. However, they noted substantial heterogeneity in results for capsular contracture, wound dehiscence, and implant rippling, suggesting limitations in generalizability. Similarly, Plotsker et al. (19) analyzed 1,225 TEs in 714 patients and observed comparable TE loss and secondary complication rates between ADM (3.8%) and non-ADM (6.7%) reconstructions. Pires et al. (17), conducted a comparative study involving 124 patients and found no significant differences in postoperative complications, unplanned reoperations, or explantation rates between ADM and no-ADM cohorts.

In our study, there was no statistically significant difference in necrosis rates between groups; however, a non-significant trend toward higher necrosis with ADM was observed, suggesting a potential safety concern. Focusing specifically on prepectoral breast reconstruction with ADM, previous studies have reported mastectomy flap necrosis as one of the most common complications, with rates ranging from 3.4% to 27.8% (8,24). In a meta-analysis of 1,425 patients (2,270 breasts) undergoing prepectoral implant-based reconstruction with ADM, Mangialardi et al. (24) reported an overall complication rate of 19%, with infection (7.9%), seroma (4.8%), flap necrosis (3.4%), and implant loss (2.8%) being the most common. Similarly, Wagner et al. (25) concluded in their systematic review that although ADM was associated with lower rates of capsular contracture (with ADM: 2.3% and without ADM: 12.4%, respectively) and global complications, it correlated with higher incidences of implant loss, infection, and flap necrosis. Bushong et al. (8) provided further evidence of this trend, reporting significantly higher rates of nipple necrosis in the ADM group (28.0%) versus the no-ADM group (10.0%) (P=0.02), with no-ADM associated with an 80% reduction in risk of nipple necrosis [odds ratio (OR) =0.20].

Multiple pathophysiological mechanisms may explain the increased necrosis risk associated with ADM use. Because ADM lacks intrinsic vascularization, its integration depends entirely on revascularization from the mastectomy flaps, which may be compromised in patients with known risk factors such as smoking, diabetes, obesity (BMI >35 kg/m²), prior breast surgery, and radiation therapy (9,17,26,27). A thin or poorly perfused flap may confer an increased risk of necrosis, infection, seroma, or other complications (9).

Bushong et al. (8) hypothesized that ADM may exert additional outward tension on mastectomy flaps and that anchoring techniques might exacerbate ischemia, especially around the nipple-areolar complex (NAC), which relies on terminal branches from multiple arterial systems and is thus particularly vulnerable. Sigalove et al. (27) systematically employed ADM in all cases of immediate prepectoral reconstruction but excluded patients with known high-risk features due to their established association with postoperative complications such as skin necrosis, wound dehiscence, seroma, and implant loss. These included poor mastectomy flap perfusion, BMI >40 kg/m², uncontrolled diabetes [hemoglobin A1c (HbA1c) >7.5%], active smoking, prior radiotherapy, and inadequate fat donor sites. Importantly, all adverse events occurred exclusively in previously irradiated breasts, reaffirming radiotherapy as a key independent predictor of morbidity, even under standardized ADM-assisted protocols and careful patient selection.

Although some studies report these comorbidities as risk factors for flap necrosis, other studies report no relation. Doyle et al. (3) analyzed 64 prepectoral reconstructions with BRAXON®Fast ADM, reporting an 18.7% overall complication rate, 10.9% infections, and 6.2% implant loss. Major infections (3.1%) and full-thickness necrosis (6.2%) were the main causes of implant failure, often linked to smoking or immunosuppression. BMI, radiotherapy, and chemotherapy showed no clear impact on complications. Similar to the findings of Jones et al. (28) in their study of 73 prepectoral single-stage implant-based reconstructions using anterior AlloDerm ADM, observed that factors such as BMI, smoking, and large mastectomy weight, did not appear to significantly influence complication rates. The success of prepectoral reconstruction depends not only on ADM use but also on proper patient selection, the surgeon’s expertise in mastectomy technique, and the intraoperative assessment of flap perfusion (4,26,29). Furthermore, emerging data suggest that the type of ADM used influences complication profiles. Pires et al. (17) concluded that bovine ADM showed higher rates of capsular contracture (6.1%), infection (9.0%), skin flap necrosis (8.3%), dehiscence (5.4%), and hematoma (6.1%) compared to human ADM and porcine ADM, reinforcing the idea that ADM composition may directly impact flap viability.

Regarding capsular contracture, our meta-analysis showed no statistically significant difference between ADM and non-ADM groups (P=0.49). Nonetheless, a non-significant trend toward lower rates was observed in the ADM group. In prepectoral breast reconstruction, this trend aligns with previously published data supporting ADM’s potential protective effect against contracture (2,8,25,30-32). Onesti et al. (31) hypothesized that ADM acts as a physical and biological barrier, disrupting the circumferential contractile activity of the periprosthetic capsule and reducing inflammatory cell migration. Such proposed mechanisms could explain the observed reduction in capsular contracture in ADM-based reconstructions.

Aesthetic outcomes in prepectoral breast reconstruction

Technical overviews suggests that ADM can enhance contour, upper-pole coverage, and soft-tissue support in the prepectoral plane, facilitating pocket control and projection, while prepectoral placement itself reduces animation deformity, pectoralis disruption, shoulder dysfunction, window-shading, and postoperative pain when flap perfusion is judiciously assessed and adjuncts (e.g., fat grafting) are used to mitigate rippling (26). In ADM-assisted cohorts, patient-reported and clinically rated cosmesis are generally favorable in carefully selected candidates. For risk-reducing, single-stage reconstructions with complete ADM coverage, Breast Evaluation And Satisfaction Tool-Quality of Life (BREAST-Q) follow-up at 1 year shows high satisfaction (satisfaction with breasts 77.2±15.6, psychosocial well-being 88.3±19.7, sexual well-being 69.8±18.5; all P<0.05) without early capsular contracture, aligning with the concept that well-perfused flaps and cohesive implants can secure early aesthetic quality (33). Prospective institutional series of immediate DTI using fenestrated (meshed) ADM and semi-smooth implants similarly report low complication rates and high aesthetic satisfaction on 0–10 patient scales [mean 9.3/10 in 72 immediate reconstructions, including irradiated cases (mean 8.5; P=0.09)], with low reoperation (6.9%), no implant loss, and minimal rippling (1.4%), suggesting safety and cosmetic reliability of prepectoral ADM when indications are respected (34). Belmonte & Campbell (35) further showed that early aesthetic ratings in meshed ADM reconstructions were comparable to other implant-based series, while regression identified BMI >30 kg/m², fat grafting, and highly cohesive anatomic implants as protective against rippling, whereas radiotherapy was a predictor of higher capsular contracture (P<0.05). Expert consensus generally supports the notion that ADM may facilitate pocket control and lower-pole definition, yet adjunctive techniques such as autologous fat grafting remain crucial to optimize upper-pole fullness and minimize rippling (26).

Parallel experiences without ADM reinforce that favorable cosmesis is achievable with meticulous patient selection and surgical technique. A 3-year single-institution review of immediate prepectoral TE placement without ADM reported complication and explant rates comparable to historical subpectoral-with-ADM benchmarks, supporting ADM-free staging when mastectomy flaps are carefully vetted clinically and with indocyanine green, and expansion is managed conservatively (36). Likewise, a multicenter DTI series after nipple-sparing mastectomy without ADM or mesh reported overall complication rates within expected ranges and good-to-excellent cosmetic ratings in 87.3% of patients, with no animation deformity, rippling in 3.8%, and capsular contracture in 15.7%, indicating that one-stage prepectoral reconstruction can deliver favorable aesthetic outcomes without adjunctive mesh in appropriately selected candidates (37). Taken together, these data suggest that ADM is not indispensable for achieving satisfactory cosmesis; rather, flap viability, radiation exposure, implant cohesivity, and adjunctive fat grafting consistently emerge as the dominant determinants of long-term aesthetic quality.

Across comparative cohorts that applied formal aesthetic assessments, there is no consistent aesthetic advantage to using ADM. In experience of the Manrique et al. (18), patient-reported outcomes (BREAST-Q) and blinded surgeon ratings with the Aesthetic Item Scale were equivalent between ADM and non-ADM groups; importantly, blinded raters could not reliably identify ADM use from standardized postoperative photographs, underscoring the clinical and aesthetic similarity of both approaches. In a Wise-pattern, DTI series, BREAST-Q satisfaction and complication profiles did not differ with or without ADM, and revision requirements were similar (21). Marquez et al. (38) likewise found no aesthetic benefit of ADM after implant exchange: BREAST-Q domains of psychosocial, breast, and sexual satisfaction were comparable, while physical well-being and satisfaction with visible rippling favored the non-ADM cohort; lipofilling was also more frequently employed in the no-ADM group, potentially mitigating contour irregularities. These findings are consistent with larger single-surgeon datasets cataloguing aesthetic limitations, where ADM use was not an independent predictor of contracture or rippling, while radiation and thin mastectomy envelopes were the primary drivers of aesthetic compromise (20). Taken together, comparative data indicate that ADM does not independently improve long-term aesthetics, as no quantitative pooling of BREAST-Q or androgen insensitivity syndrome (AIS) was conducted; outcomes are more influenced by flap thickness and perfusion, irradiation status, implant cohesivity, and the use of secondary refinements such as fat grafting Full details of comparative studies are presented in Table 3.

Cost-effectiveness of ADM in prepectoral breast reconstruction

The cost-effectiveness of ADM in prepectoral breast reconstruction remains controversial. Some studies suggest that ADM may provide long-term economic value by reducing complications and reoperations (39,40), while others emphasize its substantial financial burden with limited improvement in outcomes (18,41). Cost analyses have shown that ADM-based reconstructions are more expensive at baseline and when factoring in complications, although some decision-analytic models support acceptable cost-utility ratios. In contrast, ADM-sparing or ADM-free techniques have consistently demonstrated lower costs—up to 25% less—without increased complication rates (36,42). It is important to note that much of the economic evidence derives from U.S.-based datasets collected between 2012 and 2016, and may not fully reflect current cost structures or international healthcare systems. Therefore, these estimates should be considered time dependent. Table S1 summarizes baseline costs, complication-related costs, and potential savings reported across studies.

Reconstructive technique

Our subgroup analysis by reconstructive technique uncovered significant differences that warrant attention. The TE approach was consistently associated with higher absolute rates of seroma, infection, and necrosis compared to the DTI technique. This finding suggests that the reconstructive protocol itself is a major determinant of complication risk, independent of ADM use. The inherently longer process of TE reconstruction, involving multiple expansions and a second surgery, may prolong tissue inflammation and susceptibility to complications like seroma and infection. Furthermore, the initial placement of a potentially under-filled expander might not provide the same optimal support and tension to the mastectomy flaps as a definitive implant in DTI, potentially contributing to perfusion-related issues. This underscores that surgical decision-making must consider the trade-offs between the two-stage (TE) and single-stage (DTI) approaches, as the choice of technique significantly influences the patient’s risk profile.

Limitations and future directions

This study has several limitations. First, all included studies were observational in nature, either retrospective cohort or case-control designs, which introduces selection bias, confounding, and limits the ability to control for all relevant clinical variables. Second, there was marked heterogeneity in surgical techniques, implant types, ADM materials (human, porcine, bovine), and adjunctive procedures such as fat grafting, which precludes standardization and complicate direct comparison across studies.

Third, most aesthetic outcomes were assessed using patient-reported measures such as the BREAST-Q or AIS, with only a minority of studies incorporating third-party blinded evaluations. This may have increased the risk of reporting bias. Additionally, retrospective series often lacked standardized definitions for complications such as flap necrosis or rippling, possibly leading to underreporting. The moderate risk of bias across all included studies, particularly the absence of multivariate analyses and prospective follow-up, may further limit the reliability of specific complication rates. Moreover, the limited number of studies reporting each individual outcome restricted the ability to conduct subgroup or sensitivity analyses. Cost-effectiveness assessments were derived from heterogeneous healthcare systems with varying currencies, institutional reimbursement models, and procedural practices, thereby reducing external validity. Additionally, the majority of cost-effectiveness data are based on dated analyses (2012–2016), further limiting generalizability to present-day practice.

Although a non-significant trend toward increased flap necrosis was observed with ADM use, most included studies did not report flap necrosis outcome stratified by baseline comorbidities that are known clinical predictors of flap viability such as smoking, BMI, and radiotherapy. As a result, subgroup analysis to evaluate whether these factors modify necrosis risk was not feasible. Prospective studies or individual patient data meta-analysis are needed to clarify whether specific patient comorbidities influence the association between the ADM use and flap necrosis. Despite these limitations, this meta-analysis highlights the need for prospective, randomized controlled trials that incorporate standardized definitions for key complications, uniform aesthetic assessment methods, and consistent outcome measures. Future studies should also stratify results by ADM type, surgical technique, and patient risk profile. Such methodological rigor is essential to improve data comparability, enable reliable pooling of outcomes, and more accurately define the clinical and economic value of ADM in implant-based breast reconstruction.

Conclusions

This meta-analysis summarizes current evidence comparing prepectoral breast reconstruction with and without ADM. While ADM did not significantly reduce overall complications, a consistent trend toward lower capsular contracture was noted, suggesting possible clinical relevance in high-risk patients. Conversely, ADM may increase the risk of flap necrosis, particularly in those with comorbidities or poor perfusion. Aesthetic benefits appear more evident in third-party evaluations than in patient-reported outcomes, with comparable BREAST-Q scores between groups. ADM may improve contour and symmetry, especially when combined with fat grafting and cohesive implants, though perceived benefit varies. Cost analyses consistently show ADM’s high financial burden, with limited support for long-term cost-effectiveness, an important factor in resource-limited settings. ADM may be useful in select patients with thin flaps, prior radiation, or high aesthetic expectations, but routine use is not supported. Careful patient selection, protocol standardization, and further randomized trials are essential to clarify its role.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the MOOSE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-309/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-309/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-309/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Highton L, Johnson R, Kirwan C, et al. Prepectoral Implant-Based Breast Reconstruction. Plast Reconstr Surg Glob Open 2017;5:e1488. [Crossref] [PubMed]
2. Zingaretti N, Piana M, Battellino L, et al. Pre-pectoral Breast Reconstruction: Surgical and Patient-Reported Outcomes of Two-Stages vs Single-Stage Implant-Based Breast Reconstruction. Aesthetic Plast Surg 2024;48:1759-72. [Crossref] [PubMed]
3. Doyle B, Matthews EK, Murray K, et al. Risk factors and complications in immediate pre-pectoral breast reconstructions with BRAXON®Fast acellular dermal matrix after skin-sparing and skin-reducing mastectomies. Ann Breast Surg 2024;8:21.
4. Xie J, Wang M, Cao Y, et al. ADM-assisted prepectoral breast reconstruction is not associated with high complication rate as before: a Meta-analysis. J Plast Surg Hand Surg 2023;57:7-15. [Crossref] [PubMed]
5. Salibian AA, Bekisz JM, Kussie HC, et al. Do We Need Support in Prepectoral Breast Reconstruction? Comparing Outcomes with and without ADM. Plast Reconstr Surg Glob Open 2021;9:e3745. [Crossref] [PubMed]
6. Klinger F, Lisa A, Testori A, et al. Immediate direct-to-implant breast reconstruction: A single center comparison between different procedures. Front Surg 2022;9:935410. [Crossref] [PubMed]
7. Bekisz JM, Salibian AA, Frey JD, et al. Picking the Right Plane: A Comparison of Total Submuscular, Dual-Plane, and Prepectoral Implant-Based Breast Reconstruction. Plast Reconstr Surg 2022;150:737e-46e. [Crossref] [PubMed]
8. Bushong EE, Wesely N, Komorowska-Timek E. To acellular dermal matrix or not to acellular dermal matrix?-outcomes of pre-pectoral prosthetic reconstruction after nipple-sparing mastectomy with and without acellular dermal matrix. Gland Surg 2024;13:885-96.
9. Nolan IT, Farajzadeh MM, Boyd CJ, et al. Do we need acellular dermal matrix in prepectoral breast reconstruction? A systematic review and meta-analysis. J Plast Reconstr Aesthet Surg 2023;86:251-60. [Crossref] [PubMed]
10. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008-12. [Crossref] [PubMed]
11. Hajiesmaeili H, Shirazi S, Agrawal K, et al. A Comparative Study of One-Stage Pre-pectoral Implant Breast Reconstruction With and Without Mesh. Cureus 2024;16:e75896. [Crossref] [PubMed]
12. McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods 2021;12:55-61. [Crossref] [PubMed]
13. Higgins JPT, Thomas J, Chandler J, et al. editors. Cochrane handbook for systematic reviews of interventions. 2nd ed. Hoboken, NJ: Wiley-Blackwell; 2019:736.
14. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34. [Crossref] [PubMed]
15. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60. [Crossref] [PubMed]
16. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005;5:13. [Crossref] [PubMed]
17. Pires G, Marquez JL, Memmott S, et al. Early Complications after Prepectoral Tissue Expander Placement in Breast Reconstruction with and without Acellular Dermal Matrix. Plast Reconstr Surg 2024;153:1221-9. [Crossref] [PubMed]
18. Manrique OJ, Huang TC, Martinez-Jorge J, et al. Prepectoral Two-Stage Implant-Based Breast Reconstruction with and without Acellular Dermal Matrix: Do We See a Difference? Plast Reconstr Surg 2020;145:263e-72e. [Crossref] [PubMed]
19. Plotsker EL, Graziano FD, Rubenstein RN, et al. Early Complications in Prepectoral Breast Reconstructions with and without Acellular Dermal Matrix: A Preliminary Analysis of Outcomes. Plast Reconstr Surg 2024;153:786-93. [Crossref] [PubMed]
20. Safran T, Al-Badarin F, Al-Halabi B, et al. Aesthetic Limitations in Direct-to-Implant Prepectoral Breast Reconstruction. Plast Reconstr Surg 2022;150:22e-31e. [Crossref] [PubMed]
21. Safran T, Al-Halabi B, Viezel-Mathieu A, et al. Skin-Reducing Mastectomy with Immediate Prepectoral Reconstruction: Surgical, Aesthetic, and Patient-Reported Outcomes with and without Dermal Matrices. Plast Reconstr Surg 2021;147:1046-57. [Crossref] [PubMed]
22. Ibrahim AM, Koolen PG, Ashraf AA, et al. Acellular Dermal Matrix in Reconstructive Breast Surgery: Survey of Current Practice among Plastic Surgeons. Plast Reconstr Surg Glob Open 2015;3:e381. [Crossref] [PubMed]
23. Cook H, Zargaran D, Glynou SP, et al. Does the use of acellular dermal matrices (ADM) in women undergoing pre-pectoral implant-based breast reconstruction increase operative success versus non-use of ADM in the same setting? A systematic review protocol. Syst Rev 2024;13:153. [Crossref] [PubMed]
24. Mangialardi ML, Salgarello M, Cacciatore P, et al. Complication Rate of Prepectoral Implant-based Breast Reconstruction Using Human Acellular Dermal Matrices. Plast Reconstr Surg Glob Open 2020;8:e3235. [Crossref] [PubMed]
25. Wagner RD, Braun TL, Zhu H, et al. A systematic review of complications in prepectoral breast reconstruction. J Plast Reconstr Aesthet Surg 2019;72:1051-9. [Crossref] [PubMed]
26. Sbitany H. Important Considerations for Performing Prepectoral Breast Reconstruction. Plast Reconstr Surg 2017;140:7S-13S. [Crossref] [PubMed]
27. Sigalove S, Maxwell GP, Sigalove NM, et al. Prepectoral Implant-Based Breast Reconstruction and Postmastectomy Radiotherapy: Short-Term Outcomes. Plast Reconstr Surg Glob Open 2017;5:e1631. [Crossref] [PubMed]
28. Jones G, Yoo A, King V, et al. Prepectoral Immediate Direct-to-Implant Breast Reconstruction with Anterior AlloDerm Coverage. Plast Reconstr Surg 2017;140:31S-8S. [Crossref] [PubMed]
29. di Pompeo FS, Firmani G, Paolini G, et al. Immediate prepectoral breast reconstruction using an ADM with smooth round implants: A prospective observational cohort study. J Plast Reconstr Aesthet Surg 2023;80:56-65. [Crossref] [PubMed]
30. Kilmer LH, Challa S, Stranix JT, et al. Case-matched Comparison of Implant-based Breast Reconstruction with and without Acellular Dermal Matrix. Plast Reconstr Surg Glob Open 2024;12:e5660. [Crossref] [PubMed]
31. Onesti MG, Di Taranto G, Ribuffo D, et al. ADM-assisted prepectoral breast reconstruction and skin reduction mastectomy: Expanding the indications for subcutaneous reconstruction. J Plast Reconstr Aesthet Surg 2020;73:673-80. [Crossref] [PubMed]
32. Headon H, Kasem A, Manson A, et al. Clinical outcome and patient satisfaction with the use of bovine-derived acellular dermal matrix (SurgiMend™) in implant based immediate reconstruction following skin sparing mastectomy: A prospective observational study in a single centre. Surg Oncol 2016;25:104-10. [Crossref] [PubMed]
33. Maruccia M, Elia R, Tedeschi P, et al. Prepectoral breast reconstruction: an ideal approach to bilateral risk-reducing mastectomy. Gland Surg 2021;10:2997-3006. [Crossref] [PubMed]
34. Wazir U, Patani N, Heeney J, et al. Pre-pectoral Immediate Breast Reconstruction Following Conservative Mastectomy Using Acellular Dermal Matrix and Semi-smooth Implants. Anticancer Res 2022;42:1013-8. [Crossref] [PubMed]
35. Belmonte BM, Campbell CA. Safety Profile and Predictors of Aesthetic Outcomes After Prepectoral Breast Reconstruction With Meshed Acellular Dermal Matrix. Ann Plast Surg 2021;86:S585-92. [Crossref] [PubMed]
36. Poveromo LP, Franck P, Ellison A, et al. Prepectoral Breast Reconstruction Without the Use of Acellular Dermal Matrix: A 3-Year Review. Ann Plast Surg 2022;88:S205-8. [Crossref] [PubMed]
37. Urban C, González E, Fornazari A, et al. Prepectoral Direct-to-Implant Breast Reconstruction without Placement of Acellular Dermal Matrix or Mesh after Nipple-Sparing Mastectomy. Plast Reconstr Surg 2022;150:973-83. [Crossref] [PubMed]
38. Marquez JL, French M, Ormiston L, et al. Outcomes after tissue expander exchange to implant in two-stage prepectoral breast reconstruction with and without acellular dermal matrix: A retrospective cohort study. J Plast Reconstr Aesthet Surg 2024;89:97-104. [Crossref] [PubMed]
39. Qureshi AA, Broderick K, Funk S, et al. Direct Hospital Cost of Outcome Pathways in Implant-Based Reconstruction with Acellular Dermal Matrices. Plast Reconstr Surg Glob Open 2016;4:e831. [Crossref] [PubMed]
40. Krishnan NM, Chatterjee A, Rosenkranz KM, et al. The cost effectiveness of acellular dermal matrix in expander-implant immediate breast reconstruction. J Plast Reconstr Aesthet Surg 2014;67:468-76. [Crossref] [PubMed]
41. de Blacam C, Momoh AO, Colakoglu S, et al. Cost analysis of implant-based breast reconstruction with acellular dermal matrix. Ann Plast Surg 2012;69:516-20. [Crossref] [PubMed]
42. Viezel-Mathieu A, Alnaif N, Aljerian A, et al. Acellular Dermal Matrix-sparing Direct-to-implant Prepectoral Breast Reconstruction: A Comparative Study Including Cost Analysis. Ann Plast Surg 2020;84:139-43. [Crossref] [PubMed]