Two-stage breast reconstruction comparison between prepectoral tissue expander wrapped within acellular dermal matrix versus subpectoral placement: the prospective observational EX-BRAX study

Abstract

Background

Implant-based breast reconstruction (IBBR) has progressively shifted toward prepectoral techniques to improve cosmetic outcomes and reduce postoperative morbidity. However, comparative evidence between prepectoral and subpectoral tissue expander (TE) placement remains very limited. The aim of this study was to prospectively compare postoperative pain and early complications between prepectoral ADM-assisted and subpectoral tissue expander-based breast reconstruction in a real-world clinical setting.

Methods

This prospective monocentric observational study compared patients undergoing two-stage IBBR with either prepectoral TE wrapped within acellular dermal matrix (ADM) or subpectoral expanders without ADM. Primary outcomes included postoperative pain [Numeric Pain Rating Scale (NPRS)] and early complications (<30 days). Secondary variables included surgical data and hospital stay. Minimum follow-up: 6 months.

Results

Fifty-six patients (59 breasts) were included: 27 patients (29 breasts) in the prepectoral group and 29 patients (30 breasts) in the subpectoral group. Postoperative pain was significantly lower in the prepectoral group at all timepoints (day 1: 3.79±2.32 vs. 5.3 ± 1.82, P<0.01; day 7: 0.93±1.03 vs. 5.3±2.58, P<0.01; day 14: 0.28±0.53 vs. 4.06±2.58, P<0.01). Early complication rates were lower in the prepectoral group (3.45% vs. 23.3%), although this difference did not reach statistical significance (P=0.056). Baseline imbalances (prior radiotherapy: 11.1% vs. 34.5%, P=0.049) were documented and considered in interpretation.

Conclusions

Prepectoral breast reconstruction with ADM is associated with significantly reduced postoperative pain compared to subpectoral reconstruction, along with a trend toward lower early complication rates. However, given the non-randomized design, baseline imbalances, and limited sample size, these findings should be interpreted with caution and considered hypothesis-generating.

Highlight box.

Key findings

• Prepectoral two-stage breast reconstruction with acellular dermal matrix (ADM) significantly reduced postoperative pain at all timepoints and markedly decreased opioid consumption compared with the subpectoral approach.

• A faster expansion process was observed in the prepectoral group, shortening the time to implant exchange.

• Early postoperative complications showed a lower, although not statistically significant, incidence in the prepectoral cohort.

What is known and what is new?

• Subpectoral reconstruction has traditionally been the standard technique but is associated with pain, animation deformity, and longer recovery. Prepectoral approaches have recently gained popularity, with reported advantages in patient-reported outcomes.

• This study provides prospective real-world comparative data demonstrating a substantial opioid-sparing effect and significantly improved early postoperative pain profile with prepectoral reconstruction, alongside reduced expansion time.

What is the implication, and what should change now?

• Prepectoral reconstruction should be considered a preferred option in appropriately selected patients requiring two-stage IBBR, given its benefits in early recovery and patient comfort.

• Surgical decision-making should increasingly incorporate patient-centered outcomes such as pain and functional recovery.

Introduction

Breast cancer is the most common malignancy among females worldwide, with approximately 2.3 million new cases annually (1). Mastectomy followed by implant-based breast reconstruction (IBBR) is the most common reconstructive approach, with established benefits for psychosocial outcomes, body image, and quality of life (2).

Two-stage IBBR with tissue expanders (TE) remains the predominant technique globally, even if one-stage IBBR has been significantly increasing in numbers in recent decades. Historically, subpectoral placement offered muscle coverage but carried risks of postoperative pain, animation deformity (up to 86% of patients), and capsular contracture (3). More recently, prepectoral techniques enhanced by acellular dermal matrices (ADMs), such as Braxon, have emerged as an alternative approach (3-5).

Recent meta-analyses have demonstrated that prepectoral reconstruction offers significant advantages over subpectoral approaches, including reduced capsular contracture [odds ratio (OR) 0.54], animation deformity (OR 0.02–0.37), and prosthesis failure (OR 0.58), as well as improved postoperative pain control, enhanced BREAST-Q scores, and better upper arm function (6,7). In irradiated patients, capsular contracture rates are dramatically lower with prepectoral placement (OR 0.14) (6). ADMs theoretically reduce capsular contracture through modulation of foreign body response and decreased myofibroblast activation, particularly in irradiated fields (8,9). However, debate remains regarding the necessity and cost-effectiveness of ADM. Recent randomized trials demonstrated that prepectoral reconstruction with ADM is noninferior to reconstruction without ADM regarding major complications (13.2% vs. 13.1%), with comparable patient-reported outcomes (10). Meta-analyses show no significant differences in complication rates between ADM and non-ADM cohorts in appropriately selected patients with robust mastectomy flaps (6).

The success of prepectoral reconstruction is critically dependent on meticulous patient selection and intraoperative assessment (11,12). Key factors include mastectomy skin flap perfusion and thickness, patient comorbidities (obesity, smoking, diabetes), radiation status, and oncologic considerations (12,13). The National Comprehensive Cancer Network (NCCN) guidelines (14) recognize prepectoral, partial submuscular, and total submuscular TE placement as equally valid options, emphasizing that radiotherapy significantly increases the risk of capsular contracture, aesthetic deformity, and reconstructive failure regardless of implant plane. Recent evidence suggests that the choice between prepectoral and subpectoral approaches should balance infection risk against patient-reported outcomes, with decreasing muscle coverage associated with higher infection rates but more favorable physical well-being scores (8-13,15).

Study rationale

The aim of this study is to provide a preliminary comparison of early postoperative complications and outcomes between prepectoral and subpectoral TE-based breast reconstruction. Given the dramatic shift in clinical practice from predominantly subpectoral (96% in 2018) to predominantly prepectoral (90.2% in 2024) reconstruction (16), and the conflicting evidence regarding complication profiles, there is an urgent need for prospective comparative studies to guide evidence-based decision-making. High-quality comparative data remain limited, although propensity-matched analyses—such as the study by Nelson et al. (2022) (7)—have provided important insights, demonstrating reduced early postoperative pain in the prepectoral group at the expense of higher seroma rates. This study provides a prospective observational comparison of postoperative pain and early complications between prepectoral and subpectoral two-stage IBBR in a contemporary clinical setting, aiming to highlight both evidence-based data and real-world surgical choices.

Despite increasing adoption of prepectoral techniques, high-quality prospective comparative data remain limited, particularly regarding early postoperative pain and short-term complications in real-world clinical settings. We present this article in accordance with the TREND reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0328/rc).

Methods

Study design

This prospective monocentric observational non-randomized controlled study was conducted at the Breast and Plastic Surgery Units, Bologna University Hospital (Policlinico di Sant’Orsola IRCCS), Italy. Patients undergoing an oncologically indicated mastectomy or prophylactic mastectomy followed by two-stage breast reconstruction were enrolled between December 1st, 2024, and December 31st, 2025. The prepectoral group received TE IBBR wrapped within BRAXON®Fast ADM; this approach provides complete ADM coverage, addressing both biological and mechanical requirements by modulating the foreign body response across the entire implant surface and enhancing prosthesis stabilization (17,18). The subpectoral group received TE IBBR in the traditional total muscle coverage without ADM.

All reconstructive decisions were made through multidisciplinary discussion involving breast surgeons and plastic surgeons, addressing oncologic safety, anatomical considerations, and patient preferences.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by Comitato Etico di Area Vasta Emilia Centro (CE-AVEC) (No. 655/2025), and informed consent was obtained from all individual participants.

Study population

Patient allocation to two-stage versus direct-to-implant (DTI) reconstruction was based on individual risk profile and reconstructive considerations, rather than on implant plane selection. Lower-risk patients (favorable flap thickness >1.5 cm, as assessed on mammography; absence of significant ptosis; no prior radiotherapy; non-smokers) were preferentially selected for DTI reconstruction.

Higher-risk patients (unfavorable flap thickness <1.5 cm; mild-to-moderate ptosis; significant smoking history or active smoking; reduced skin envelope due to a skin-sparing mastectomy indication; small breast volume; prior radiotherapy) were treated with a two-stage reconstruction approach and were included in this study.

Allocation to the prepectoral or subpectoral groups was not randomized and was determined solely by the operating surgeon’s preference and expertise with the specific technique.

This non-randomized allocation may have introduced selection bias and baseline imbalances between groups.

Surgical techniques

The prepectoral group

After completion of the mastectomy, the surgical field was irrigated with sterile saline solution and meticulous hemostasis was achieved. A single drain (18-Fr tubular suction drain) was placed in the surgical site. An appropriately sized TE was then selected and completely wrapped in a BRAXON®Fast ADM [Expander-BRAXON(R)Fast = EX-BRAX], using interrupted absorbable sutures (Vicryl 3-0) to secure the free edges of the ADM. At this stage, the TE was partially inflated with air (Figure 1). The ADM-TE construct was then soaked in an antibiotic solution and positioned within the mastectomy pocket.

Figure 1.

Tissue expander wrapped in BRAXON®Fast ADM. The ADM is not tightly fitted around the expander; instead, it is prepared with sufficient slack to allow for subsequent expansion. The two edges of the ADM are approximated using interrupted sutures. (A) Frontal view; (B) posterior view; (C) the expander valve remains visible through the ADM, facilitating accurate positioning of the device. ADM, acellular dermal matrix.

Three to four interrupted sutures were placed superiorly and laterally, along the breast footprint and sometimes caudally at the level of the inframammary fold, to fix the ADM envelope to the surrounding tissues. The ADM was anchored to the fibrous ligaments at the edges of the mastectomy flaps, at their reflection toward the underlying muscular fascia. Additional sutures were placed to secure the ADM to the dome of the mastectomy flap, again engaging fibrous ligaments and avoiding adipose tissue, in order to reduce dead space.

The subpectoral group

After completion of the mastectomy, the surgical field was irrigated with sterile saline solution and hemostasis was achieved. A traditional subpectoral pocket was created by dissecting beneath the pectoralis major muscle. Laterally, the pocket was completed using the serratus anterior muscle or fascia to achieve full coverage of the TE.

Two drains (18-Fr tubular suction drains) were placed: one in the submuscular pocket and one in the subcutaneous space. An appropriately sized, empty TE was soaked in an antibiotic solution and then inserted into the submuscular pocket. The expander was secured by closing the pectoralis major muscle over it with a running suture, incorporating the serratus anterior muscle or fascia.

In both groups, the anaesthesiologists adopted a standard general anaesthesia approach, without any local block infiltration for pain control. For what concerns postoperative pain control, the standard regimen consisted of intravenous paracetamol 1,000 mg administered every 8 hours during the in-patient period, followed by oral paracetamol 1,000 mg administered as needed after discharge (maximum of 3 doses per day). Patients who experienced inadequate pain relief with paracetamol were permitted to use NSAIDs on an as-needed basis.

In addition, further analgesic support was provided for each patient based on the anesthesiologist’s indications and the patient’s reported level of pain. Available options included the use of a morphine-releasing elastomeric pump (prefilled with 2 fl of morphine in 50 cc of saline solution, administered at a rate of 2 cc/h for a total duration of 48 hours) and/or oxycodone 5 mg slow-release tablets.

Postoperative management was also standardized as for antibiotic therapy: 8 days of 1 g amoxicillin-clavulanic acid 3 times daily.

Expansion protocol

In the prepectoral group, the expander was initially filled with air rather than saline, as this allowed for a significantly lighter device, reducing mechanical stress on the mastectomy flaps and facilitating optimal flap recovery without additional tension.

The expander was maintained air-filled for approximately the first 3 weeks postoperatively. Thereafter, air was gradually replaced with saline solution, with minimal additional expansion (typically 30–60 cc beyond the initial volume), mainly aimed at optimizing contour and natural ptosis rather than achieving true tissue expansion.

With such an approach, expansion time was quite fast in the prepectoral group compared to the subpectoral group. In the latter, expanders were initially unfilled or minimally prefilled (approximately 0–30 cc of saline) and subsequently expanded in a stepwise manner with 30–60 cc increments every 3 weeks, until adequate soft tissue expansion was achieved to accommodate the definitive implant.

Inclusion/exclusion criteria

The prepectoral group: patients ≥18 years with breast cancer (therapeutic) or genetic predisposition (prophylactic) undergoing two-stage prepectoral reconstruction with Braxon ADM after mastectomy; not suitable for DTI reconstruction.

The subpectoral group: patients ≥18 years with breast cancer (therapeutic) or genetic predisposition (prophylactic) undergoing two-stage subpectoral reconstruction without ADM after mastectomy; not suitable for DTI reconstruction.

Exclusion criteria (both groups): metastatic disease, chronic/acute infections, autoimmune diseases, intraoperative ischemic areas, collagen/scarring disorders, microcirculation alterations, inability to complete 6-month follow-up.

Data collection

Clinical data were prospectively recorded from institutional medical records and operative reports, including: demographic information (age, BMI, comorbidities), oncologic features (staging, biological subtype, grading, therapies), surgical details (operative time, drainage volume, hospital stay), antibiotic use, postoperative complications (within 30 days), pain assessment [Numeric Pain Rating Scale (NPRS) at days 1, 7, 14], and device integration at follow-up.

Statistical analysis

Data are reported as means ± standard deviation, medians, ranges, and percentages. Patients with >10% missing data were excluded. Follow-up losses due to death or change of care center were documented. Minimum inclusion follow-up: 6 months. Significance level: P≤0.05. Group comparisons were performed using independent t-tests for continuous variables, Mann-Whitney U for non-normally distributed or ordinal variables, and Fisher or chi-squared tests for categorical variables. No multivariable adjustment or propensity score matching was performed due to the limited sample size.

Results

Fifty-six patients (59 breasts) were enrolled: the prepectoral group = 27 patients (29 breasts, 2 bilateral procedures); the subpectoral group = 29 patients (30 breasts, 1 bilateral procedure). All surgeries were therapeutic with the exception of two prophylactic procedures for BRCA positivity in the prepectoral group.

Baseline characteristics were largely comparable between groups (Table 1). However, the subpectoral group had significantly higher rates of prior radiotherapy (34.5% vs. 11.1%, P=0.049) and the prepectoral group patients were younger (mean age 49±10.2 vs. 55±10.11 years, P=0.03). BMI, smoking status, hypertension, diabetes, and previous rate of breast surgery were comparable. These baseline differences represent potential confounding factors and should be considered when interpreting comparative outcomes.

Table 1. Demographic characteristics.

Parameter	The prepectoral group (n=27)	The subpectoral group (n=29)	P value
Age (years)	49±10.2	55±10.11	0.03*
BMI	22.65±4.99	24.70±4.04	0.08
Smoking	9 (33.0)	10 (34.5)	>0.99
Hypertension	1 (3.7)	4 (13.8)	0.35
Diabetes	1 (3.7)	3 (10.3)	0.61
Prior radiotherapy	3 (11.1)	10 (34.5)	0.049*
Previous breast surgery	6 (22.2)	14 (48.3)	0.61

Data are presented as mean ± SD or n (%). *, P<0.05. BMI, body mass index; SD, standard deviation.

Operative variables were similar between groups (Table 2). Expander type and sizing were consistent within each group but tailored to individual anatomy. A non-significant trend toward increased drainage volume was noted in the prepectoral group (79.48±56.19 vs. 52.58±54.78 mL, P=0.06). Hospital stay was comparable, with discharge on postoperative days 3–4. The only important difference was in the choice of mastectomy performed; overall, in the prepectoral group, less invasive procedures are more commonly used (48.3% vs. 13.3% NSM).

Table 2. Surgical data.

Parameter	The prepectoral group	The subpectoral group	P value
Expander volume (mL)	407.06±65.21	425.34±78.15	0.33
Days with drainage	11.86±5.12	11.89±3.5	0.93
Final week drainage (mL)	79.48±56.19	52.58±54.78	0.06
Operating room time (min)	208.27±36.16	205.03±84.56	0.84
Nipple sparing	14 (48.3)	4 (13.3)	<0.001
Skin sparing	14 (48.3)	26 (86.7)	<0.001
Skin reducing	1 (3.4)	0	0.49

Data are presented as mean ± standard deviation or n (%).

The distribution of skin incision patterns differed substantially between groups. The prepectoral group more frequently underwent conservative access patterns such as S-shaped radial incision in upper outer quadrant, axillary-line, periareolar, and semicircular incisions, whereas the subpectoral group more commonly underwent elliptical and especially lozenge-shaped incisions, consistent with the higher proportion of skin-sparing procedures reported in this cohort (Table 3) (19-23).

Table 3. Surgical incision patterns.

Type of skin incision/surgical access	The prepectoral group (n=27), n (%)	The subpectoral group (n=29), n (%)
Radial S-shaped italic incision in upper outer quadrant	13 (48.1)	2 (6.9)
Anterior axillary line (upward inframammary fold extension)	4 (14.8)	2 (6.9)
Periareolar	3 (11.1)	0
Semicircular	4 (14.8)	0
Elliptical	5 (18.5)	8 (27.6)
Lozenge-shaped	0	18 (62.1)

Postoperative pain profiles differed significantly between groups (Table 4, all P<0.01). The prepectoral group reported substantially lower pain at all timepoints. On postoperative day 1, the prepectoral group reported lower pain scores compared to the subpectoral group (3.79±2.32 vs. 5.3±1.82). By day 7, patients in the prepectoral group were nearly asymptomatic (0.93±1.03), whereas those in the subpectoral group continued to report moderate pain (5.3±2.58). This difference persisted at day 14, with minimal, homogeneous pain levels in the prepectoral group (0.28±0.53) compared with persistently higher, more variable scores in the subpectoral group (4.06±2.58).

Table 4. Pain profile and complications.

Parameter	The prepectoral group	The subpectoral group	P value
Pain (NPRS 0–10)
Day 1	3.79±2.32	5.3±1.82	<0.001
Day 7	0.93±1.03	5.3±2.58	<0.001
Day 14	0.28±0.53	4.06±2.58	<0.001
Early complications
Any complication	1 (3.45)	7 (23.3)	0.056
Hematoma	1 (3.45)	4 (13.3)	0.36
Seroma	0	1 (3.3)	>0.99
Expander rupture	0	1 (3.3)	>0.99
Lymphocele	0	1 (3.3)	>0.99
Prior radiotherapy	0	4 (13.3)	0.50
No radiotherapy	1 (3.45)	3 (10.0)	0.31

Data are presented as mean ± standard deviation or n (%). NPRS, Numeric Pain Rating Scale.

Regarding in-patient postoperative analgesic therapy, in addition to the standard regimen of intravenous paracetamol 1,000 mg every 8 hours, a statistically significant increase in the need for additional opioid therapy was observed in the subpectoral group compared with the prepectoral group (96.6% vs. 44.4%, P<0.01) (Table 5).

Table 5. Opioid use.

Parameter	The prepectoral group, n (%)	The subpectoral group, n (%)	P value
Need for opioids	12 (44.4)	28 (96.6)	<0.001
Morphine-releasing elastomer	2 (7.4)	22 (75.9)	<0.001
Oxycodone 5 mg	11 (40.7)	12 (41.0)	>0.99
Elastomer plus oxycodone	0	6 (21.0)	<0.001

Specifically, virtually all patients in the subpectoral group required the use of a morphine-releasing elastomeric pump (28/29, 96.6%), prefilled with 2 fl in 50 cc of saline solution and administered at a rate of 2 cc/h for 48 hours, compared with only 2 patients (7.4%) in the prepectoral group who, when needed, received a single postoperative dose of the less potent oxycodone 5 mg (40.7%, 11/27).

In addition to the elastomeric pump, patients in the subpectoral group also required oxycodone administration in 41% of cases (12/29), in some instances in combination with the elastomeric device (21%, 6/29). This opioid-sparing effect may have important clinical implications, particularly in the context of enhanced recovery protocols and efforts to minimize opioid exposure in surgical patients.

The overall early complication rate was lower in the prepectoral group (3.45%) compared to the subpectoral group (23.3%), indicating a favourable trend that, although not statistically significant, approached significance (P=0.056, Table 4). In the prepectoral group, one patient developed a postoperative hematoma requiring prolonged antibiotic therapy and repeated outpatient drainage maintenance. In the subpectoral group, seven patients experienced early complications: four hematomas (requiring drainage and antibiotics), one seroma (managed conservatively), one lymphocele, and one expander rupture (requiring urgent surgical replacement). After excluding the lymphocele (which was related to the lymphadenectomy oncological surgical procedure), three of the remaining six patients with complications in the subpectoral group had a history of prior radiotherapy, consistent with established risk factors for postoperative wound healing complications. However, subgroup analyses showed no statistically significant differences in complication rates between irradiated patients in the prepectoral and subpectoral groups (P=0.50) or between non-irradiated patients in the two groups (P=0.31).

The prepectoral group patients also required a significantly lower period of time to complete expansion of the TE, with an average of 10.8±8.1 vs. 14.9±3.6 weeks in the subpectoral group (P<0.001).

Within the 6 months of follow-up no other complications requiring a surgical procedure, rather than the reintervention for TE rupture, were then registered. 6 patients in the prepectoral group underwent TE/implant exchange during the follow-up period uneventfully.

Discussion

In recent years, IBBR has progressively evolved toward less invasive, patient-centered approaches emphasizing postoperative pain reduction, functional recovery, and quality of life. Within this context, prepectoral reconstruction has gained significant attention as a muscle-sparing alternative to traditional submuscular techniques.

The present study contributes to this evolving field by providing a prospective comparison between prepectoral and subpectoral TE-based reconstruction in a contemporary clinical setting. The most consistent finding of our analysis is the significant reduction in postoperative pain observed in the prepectoral cohort. Patients undergoing prepectoral reconstruction reported significantly lower pain scores from the immediate postoperative period through the first two weeks, with a rapid decline over time, with a significant reduced use of opioids as well. This observation is in line with the underlying biological rationale of the technique, as preservation of the pectoralis major muscle avoids muscle elevation, reduces surgical trauma, and minimizes inflammation-related discomfort (11,12). These findings are consistent with those reported by Holland et al. (24), who, in a cohort of more than 300 patients followed over an 8-year period, demonstrated lower postoperative pain scores following prepectoral TE reconstruction. In the same study, patients undergoing subpectoral reconstruction also required significantly greater opioid consumption, further supporting the association between increased postoperative discomfort and greater analgesic requirements. Similarly, Copeland-Halperin et al. (25) found that there was a 33% reduction in days requiring postoperative opioid pain medication in patients undergoing prepectoral breast reconstruction compared with those undergoing dual-plane reconstruction.

However, postoperative pain is influenced by multiple factors beyond the reconstructive plane. The type of mastectomy performed may represent an additional confounding factor, as Holland et al. (24) identified skin-sparing mastectomy as an independent predictor of increased opioid consumption. In our cohort, skin-sparing mastectomy was performed more frequently in the subpectoral group (P<0.01); however, it was also performed in 48.3% of patients undergoing prepectoral reconstruction. Consequently, differences in mastectomy type alone are unlikely to fully explain the observed pain disparity, suggesting that the reconstructive plane itself may have contributed substantially to the differences in postoperative pain.

The influence of postoperative analgesic protocols should also be considered. The use of opioids during the immediate postoperative period may have affected NPRS assessments; however, opioid administration would be expected to reduce measured pain levels in the subpectoral cohort, potentially underestimating the difference between groups. Analgesic requirements were a consequence of the perceived pain burden, with patients experiencing greater discomfort requiring stronger analgesic interventions. Therefore, although differences in medication protocols represent a potential source of variability, they likely attenuated the true difference between the two groups.

Furthermore, the incision pattern itself may represent a minor confounding factor for postoperative pain. Postoperative pain is often localized to the incision site, and larger incisions may involve a greater area of tissue and nerve trauma, potentially contributing to increased early postoperative discomfort (26,27). However, a meta-analysis comparing inframammary and periareolar incisions found no significant differences in postoperative pain or changes in breast sensation (P=0.27), suggesting that the incision pattern is unlikely to have substantially influenced the differences observed between groups (27).

Overall, these findings are consistent with previous reports demonstrating improved early postoperative recovery and better patient-reported outcomes with prepectoral reconstruction (6,7). Recent literature has highlighted that minimizing muscular disruption may translate not only into reduced pain but also into improved upper limb function and faster return to daily activities (7,8,28,29). Although functional outcomes were not directly assessed in the present study, the observed pain profile may indirectly reflect these advantages.

With regard to postoperative complications, our results suggest a lower incidence in the prepectoral group. However, this finding should be interpreted with caution. The difference did not reach statistical significance and is likely influenced by baseline imbalances between groups, particularly the higher proportion of patients with prior radiotherapy and previous breast surgery in the subpectoral cohort (6). Radiotherapy is a well-established risk factor for postoperative and chronic pain, wound healing complications, infection, and reconstructive failure, and its uneven distribution represents a relevant confounding factor in our analysis (30-32). In particular, 3 out of the 7 complications recorded in the subpectoral group occurred in previously irradiated patients. At the same time, exploratory subgroup analyses did not demonstrate a statistically significant difference in complication rates between non-irradiated patients in the two groups (P=0.31). Nevertheless, these analyses were based on a very small number of patients and events and were therefore underpowered.

Differences in mastectomy characteristics may also have influenced postoperative complications. Nevertheless, the systematic review and meta-analysis by Clarijs et al. (33) found no significant difference in overall complication rates between nipple-sparing and skin-sparing mastectomy. Similarly, although previous reviews have suggested that incision pattern may influence nipple-areola complex perfusion, no nipple-areola complex-related complications occurred in our cohort. Consequently, while differences in mastectomy type and incision pattern cannot be completely excluded as sources of confounding, they are unlikely to fully account for the observed differences in complication rates.

Therefore, no definitive conclusions can be drawn regarding the comparative safety of the two techniques based on the present data. However, these findings show a consistent and encouraging trend, suggesting that a true effect may exist and should be explored further.

Several important limitations must be acknowledged. First, the non-randomized design introduces potential selection bias and baseline imbalances, particularly regarding prior radiotherapy and previous breast surgery. Second, the relatively small sample size limits statistical power and increases the risk of type II error. In particular, this study was not powered to detect differences in relatively infrequent outcomes such as postoperative complications, and the absence of statistically significant differences should therefore not be interpreted as evidence of equivalence between techniques. Third, the lack of multivariable adjustment prevents controlling for confounding factors. Additionally, postoperative analgesic administration was not fully standardized, which may have influenced pain outcomes.

Finally, the relatively short follow-up does not allow assessment of long-term outcomes such as capsular contracture, aesthetic results, or patient-reported outcomes.

Despite these limitations, this study reflects real-world clinical practice and provides prospective comparative data in a field where high-quality evidence remains limited. The consistency and magnitude of pain reduction in the prepectoral cohort represent a clinically meaningful finding, as pain is a key determinant of early recovery and patient experience. Moreover, a reduced expansion time in the postoperative period translates into less discomfort for the patients and fewer outpatient visits, with an obvious benefit for expenses and resources. Besides, this result entails the possibility of a faster exchange with the implant. Overall, our findings suggest that prepectoral two-stage TE-based reconstruction may offer meaningful advantages in postoperative comfort without clear evidence of increased early complications. Given the methodological constraints, these results should be considered hypothesis-generating rather than definitive.

This work reports early results on a completed patient cohort. Further prospective multicentric studies with larger cohorts, longer follow-up (minimum 12–24 months), and standardized outcome measures are needed to confirm these results, refine patient selection criteria, and evaluate long-term complications including capsular contracture and aesthetic satisfaction.

Conclusions

In this setting, when a two-stage implant-based reconstruction is indicated, the pre-pectoral approach may represent a preferable option in appropriately selected patients, offering improved postoperative comfort without compromising overall safety.

Supplementary

The article’s supplementary files as

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. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Comitato Etico di Area Vasta Emilia Centro (CE-AVEC) (No. 655/2025), and informed consent was obtained from all individual participants.

Data Sharing Statement

Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0328/dss

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DOI: 10.21037/gs-2026-0328