Optimal reconstructive strategies in the setting of post-mastectomy radiotherapy - A systematic review and network meta-analysis

Background: A third of breast cancer patients require mastectomy. In some high-risk cases postmastectomy radiotherapy (PMRT) is indicated, threatening reconstructive complications. Several PMRT and reconstruction combinations are used. Autologous flap (AF) reconstruction may be immediate (AF→PMRT), delayed-immediate with tissue expander (TE [TE→PMRT→AF]) or delayed (PMRT→AF). Implant-based breast reconstruction (IBBR) includes immediate TE followed by PMRT and conversion to permanent implant (PI [TE→PMRT→PI]), delayed TE insertion (PMRT→TE→PI), and prosthetic implant conversion prior to PMRT (TE→PI→PMRT). Aim: Perform a network metanalysis (NMA) assessing optimal sequencing of PMRT and reconstructive type. Methods: A systematic review and NMA was performed according to PRISMA-NMA guidelines. NMA was conducted using R packages netmeta and Shiny. Results: 16 studies from 4182 identified, involving 2322 reconstructions over three decades, met predefined inclusion criteria. Studies demonstrated moderate heterogeneity. Multiple comparisons combining direct and indirect evidence established AF-PMRT as the optimal approach to avoid reconstructive failure, compared with IBBR strategies (versus PMRT→TE→PI; OR [odds ratio] 0.10, CrI [95% credible interval] 0.02 to 0.55; versus TE→PMRT→PI; OR 0.13, CrI 0.02 to 0.75; versus TE→PI→PMRT OR 0.24, CrI 0.05 to 1.05). PMRT→AF best avoided infection, demonstrating significant improvement versus PMRT→TE→PI alone (OR 0.12, CrI 0.02 to 0.88). Subgroup analysis of IBBR found TE→PI→PMRT reduced failure rates (OR 0.35, CrI 0.15–0.81) compared to other IBBR strategies but increased capsular contracture. Conclusion: Immediate AF reconstruction is associated with reduced failure in the setting of PMRT. However, optimal reconstructive strategy depends on patient, surgeon and institutional factors. If IBBR is chosen, complication rates decrease if performed prior to PMRT. Prospero registration: CRD 42020157077.