A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial)

Abstract

Purpose Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. Methods This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness. Discussion This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy. We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety. Trial Registration ClinicalTrials.gov Identifier: NCT03975179 ; Clinical Research Information Service Identifier: KCT0004606

Updates and Debate Concerning Margin Adequacy and Management following Breast-Conserving Surgery

“…Conversely, in the case of in situ carcinoma (including both DCIS and pleiomorphic lobular carcinoma in situ), a radial evaluation of margin distances may be more appropriate with the aim to exclude a distance of the tumor from margins lower than 2 mm. However, intraoperative frozen-section analysis of margins is still contentious: some authors have recently proposed to omit this procedure, as there is some evidence that in selected cases can be omitted without burden the patient management [36].…”

Image-guided cancer surgery: a narrative review on imaging modalities and emerging nanotechnology strategies

“…Current techniques for evaluating margin statuses, such as frozen section, imprint cytology, and intraoperative ultrasound, are very useful tools for precision surgery but expensive in terms of time and costs and not always available to surgeons. Furthermore, not all hospitals have experts in the use of this instrumentation applied to tumours [ 5 , 6 ]. However, there is a clinical need for safe and accurate approaches to defining tumour margins intraoperatively [ 7 ].…”