Optimal localization strategies for non-palpable breast cancers –A network meta-analysis of randomized controlled trials

Purpose: Mammographic screening programmes have increased detection rates of non-palpable breast cancers. In these cases, wire-guided localization (WGL) is the most common approach used to guide breast conserving surgery (BCS). Several RCTs have compared WGL to a range of novel localization techniques. We aimed to perform a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing methods of non-palpable breast cancer localization. Methods: A NMA was performed according to PRISMA-NMA guidelines. Analysis was performed using R packages and Shiny. Results: 24 RCTs assessing 9 tumour localization methods in 4236 breasts were included. Margin positivity and reoperation rates were 16.9% (714/4236) and 14.3% (409/2870) respectively. Cryo-assisted localization had the highest margin positivity (28.2%, 58/206) and reoperation (18.9%, 39/206) rates. Compared to WGL (n = 2045 from 24 RCTs) only ultrasound guided localization (USGL) (n = 316 from 3 RCTs) significantly lowered margin positivity (odds ratio (OR): 0.192, 95% confidence interval (CI): 0.079–0.450) and reoperation rates (OR: 0.182, 95%CI: 0.069–0.434). Anchor-guided localization (n = 52, 1 RCT) significantly lowered margin positivity (OR: 0.229, 95%CI: 0.050–0.938) and magnetic-marker localization improved patient satisfaction (OR: 0.021, 95%CI: 0.001–0.548). There was no difference in operation duration, overall complications, haematoma, seroma, surgical site infection rates, or specimen size/vol/wt between methods. Conclusion: USGL and AGL are non-inferior to WGL for the localization of non-palpable breast cancers. The reported data suggests that these techniques confer reduced margin positivity rates and requirement for re-operation. However, caution when interpreting results relating to RCTs with small sample sizes and further validation is required in larger prospective, randomized studies.