Methodological considerations in evaluating reconstructive strategies following postmastectomy radiotherapy

Kooijman and colleagues have recently investigated the potential advantages of immediate implant-based breast reconstruction (IBR) compared to delayed reconstruction in women undergoing postmastectomy radiotherapy (PMRT) for breast cancer (1). Their study found that nipple- or skin-sparing mastectomy [(N)SSM] combined with immediate implant-based reconstruction (IIBR) followed by PMRT was associated with a 22% rate of severe complications and an 8% rate of reconstruction failure. Nonetheless, (N)SSM/IIBR performed prior to PMRT required fewer subsequent interventions than delayed reconstruction after PMRT and was less time-consuming, even when excluding the initial mastectomy from consideration. Consequently, the authors concluded that the potential need for re-intervention should not deter clinicians or patients from pursuing immediate reconstruction in the context of anticipated PMRT.

While this study contributes meaningful insights into reconstructive strategies post-PMRT, several methodological limitations warrant critical evaluation to contextualize the findings and guide future research.

A major concern is the significant disparity in group sizes—372 patients in the IBR group versus only 18 in the delayed reconstruction group. Although the authors acknowledge this imbalance, it raises concerns regarding statistical power and limits the generalizability of the results. Future investigations utilizing larger and more balanced cohorts would allow for a more accurate comparison of outcomes.

Selection bias is another possible limitation. Although baseline characteristics were presented, important factors such as patient preference, surgeon recommendation, and psychosocial considerations—which could significantly influence the choice of reconstruction timing—were not thoroughly analyzed. Incorporating standardized decision-making frameworks or qualitative assessments in future studies could provide greater clarity on these influences.

Moreover, the study compares two inherently different reconstructive modalities—IIBR and delayed autologous reconstruction—thereby introducing a confounding variable that complicates the interpretation of outcomes. Prospective, randomized studies designed to isolate the effects of reconstruction timing from those of reconstruction type would be more informative.

A significant omission is the lack of patient-reported outcomes (PROs), including quality of life, aesthetic satisfaction, and psychological well-being. These metrics are essential for a holistic evaluation of reconstruction success and should be integral components of future research. Validated scoring systems such as the BREAST-Q, along with standardized photographic evaluation protocols, should be employed to ensure reproducibility and comparability of aesthetic outcomes. Additionally, objective assessments using three-dimensional surface imaging and volumetric analysis can enhance the reliability of aesthetic evaluation by providing quantifiable, observer-independent data on symmetry, volume retention, and contour.

Furthermore, aesthetic results should be evaluated systematically with consistent preoperative and postoperative photographic documentation—using standardized positioning, lighting, and follow-up intervals—to enable meaningful longitudinal comparisons. Given that both aesthetic outcomes and complication rates can evolve over time, long-term follow-up should be reported explicitly.

The absence of a formal cost-effectiveness analysis and the lack of consideration of contralateral procedures leave important gaps in understanding the broader economic and aesthetic implications of each reconstructive strategy. Including health economic assessments and comprehensive evaluations of symmetry and aesthetic outcomes would support more nuanced clinical decision-making.

Another notable limitation is that all patients in the study underwent subpectoral reconstruction using highly textured implants. However, there has been a global transition toward prepectoral implant placement using smooth surface implants, often combined with an acellular dermal matrix (ADM). This approach mitigates the risk of radiation fibrosis to the pectoralis muscle, reduces capsular contracture rates, and avoids muscle animation deformity (2,3). Notably, one study found nearly a significant reduction in capsular contracture rates in association with the use of the prepectoral and two stage IIBR compared with the subpectoral and direct to implant approaches in the setting of PMRT (4). Figure 1 illustrates the aesthetic result 3 years after bilateral nipple-sparing mastectomy performed through periareolar incisions using a prepectoral approach with smooth surface round implants and ADM. For clarity, we confirm that this patient did not undergo PMRT. Figure 2 illustrates the aesthetic outcome 5 years after bilateral SSM and IIBR and PMRT on the right side.

Figure 1 Aesthetic result at 3 years following bilateral nipple-sparing mastectomy through periareolar incisions using a prepectoral approach with smooth surface round implants and ADM. This patient did not undergo PMRT. ADM, acellular dermal matrix; PMRT, postmastectomy radiotherapy.

Figure 2 Aesthetic result at 5 years following bilateral skin-sparing mastectomy through circumareolar incisions and IIBR. This patient did undergo PMRT on the right side. IIBR, immediate implant-based reconstruction; PMRT, postmastectomy radiotherapy.

In addition, the discussion should acknowledge that while smooth surface implants are increasingly preferred—due to their association with a lower risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and improved integration in prepectoral placement—they may be associated with higher rates of implant mobility and malposition, especially in the absence of adequate ADM support. By contrast, textured implants, although declining in use due to BIA-ALCL risk, have historically provided greater positional stability in subpectoral pockets but may carry a higher risk of capsular contracture, particularly in irradiated tissues. Kaplan et al. showed that the use of Motiva Ergonomix breast implant was associated with a low incidence (2.2%) of capsular contracture in the context of PMRT (5). These trade-offs should be balanced carefully when selecting implant type and placement technique in the setting of PMRT.

Another important consideration is that having a tissue expander or implant in place at the time of radiation helps prevent the mastectomy flap from contracting tightly to the chest wall, thereby preserving the native breast skin and facilitating future reconstructive options with either prosthetic devices or autologous tissue.

The interval between surgery and the initiation of PMRT in the study averaged 10 weeks in the IBR group and 14 weeks in the delayed group—longer than the commonly recommended window. This is concerning, as the therapeutic benefit of PMRT may diminish significantly if delayed beyond 12 weeks post-surgery.

Importantly, even when delayed autologous reconstruction is planned, IIBR can serve as a useful interim strategy. This approach preserves the skin envelope, minimizes delays to adjuvant therapy, avoids radiation-induced injury to autologous flaps, and may improve long-term aesthetic and functional outcomes. A recent systematic review demonstrated comparable complication and success rates in autologous breast reconstruction patients who received radiation either before or after reconstruction (6). Based on these findings, immediate autologous reconstruction remains a viable option, even for patients likely to undergo PMRT.

Finally, in light of the increasing adoption of the 26 Gy in 5 fractions over one week radiotherapy regimen supported by the FAST-Forward trial (7), it is crucial that future research evaluates the impact of shorter-course PMRT on reconstructive outcomes. However, it is important to note that only about 1% of patients in that trial underwent IBR, which limits generalizability to this population.

In summary, the work by Kooijman et al. offers valuable data regarding reconstructive timing in patients receiving PMRT but should be interpreted with caution given its methodological constraints. Future prospective, multicenter studies that incorporate contemporary surgical techniques, comprehensive PROs, long-term follow-up, objective aesthetic assessments, and health economic analyses are needed to optimize outcomes for patients facing PMRT.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article has undergone external peer review.

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-221/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-221/coif). K.M. has received honoraria for offering academic and clinical advice to Q Medical Technologies. K.M. also received sponsorship from Establishment Labs to attend an academic conference. The other author has 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.

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