Screening and Test Evaluation Program (STEP), The University of Sydney, Australia
Michael Luke Marinovich , Lamiae Azizi , Petra Macaskill , Les Irwig , Monica Morrow , Lawrence J. Solin , Nehmat Houssami
Background: There is no consensus on what constitutes adequate negative margins in breast-conserving surgery (BCS) for ductal carcinoma in-situ(DCIS). We systematically review the evidence on surgical margins in BCS for DCIS. Methods: Study-level meta-analysis of studies reporting local recurrence (LR) relative to microscopic margin status and threshold distance for negative margins. LR proportion was modelled using random-effects logistic meta-regression (frequentist) that dichotomised data using one margin distance, and network meta-analysis (Bayesian) that allows for multiple margin distances per study, adjusting for follow-up time. Results: Based on 33 studies (LR in 865 of 7,883), theodds of LR were associated with margin status (logistic: odds ratio (OR) 0.53 for negative vs positive/close [P<0.001]; network: OR=0.45 for negative vs positive). In logistic meta-regression models, relative to >0 or 1mm, ORs for 2mm (0.51), 3 or 5mm (0.42) and 10mm (0.60) thresholds showed comparable significant reductions in the odds of LR. Odds of LR did not differ between 2mm, 3 or 5mm, and 10mm (all P>0.40). Predicted probabilities of LR at 10 years were 18.1% (>0 or 1mm), 10.1% (2mm), 8.5% (3 or 5mm), and 11.7% (10mm). In the network analysis, ORs relative to positive margins for 2mm (0.32), 3mm (0.30) and 10mm (0.32) showed similar reductions in the odds of LR that were greater than for >0 or 1mm (0.45). There was weak evidence of lower odds at 2mm compared to >0 or 1mm (Relative OR=0.72, 95% credible interval [CrI] 0.47-1.08), and no evidence of a difference between 2mm and 10mm (Relative OR=0.99, 95% CrI 0.61-1.64). Adjustment for covariates (age; median recruitment year; and proportions with radiotherapy, endocrine therapy, or high grade DCIS), and analyses based only on studies using whole-breast radiotherapy, did not change findings. Conclusions: Negative margins in BCS for DCIS reduce the odds of LR; however, minimum margins distances above 2mm are not significantly associated with further reduced odds of LR in women receiving radiation.
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