MarginProbe System for Identifying Positive Margins during Breast Cancer Lumpectomy

The primary treatment for patients with early-stage breast cancer (e.g., ductal carcinoma in situ, stage I or II invasive carcinoma of the breast) is surgical resection of the cancerous tissue. Depending on the stage and level of their lymph node involvement, patients may be eligible for either breast-conserving surgery (e.g., lumpectomy) or mastectomy.1 Alternatively, patients who meet all criteria for breast-conserving surgery but whose tumor is too large may undergo neoadjuvant chemotherapy to reduce tumor size.1 Following surgical resection, pathologists perform histologic analysis of the resected tissue to assess tumor characteristics that may influence subsequent treatment. In particular, lumpectomy samples are tested to assess whether the resected tissue margins are cancer free.1 Patients with cancer-positive margins may undergo a subsequent surgical resection to remove further tissue and establish cancer-free margins. Optimal outcomes after breast-conserving surgery for early-stage breast cancer require that the margins of the excised tissue be clear of cancerous tissue. However, consistent intraoperative detection of cancer-positive margins is difficult, and many patients must undergo revision surgery after positive margins are identified by postsurgical histology.

Dune Medical Devices, Ltd. (Caesarea, Israel) has developed the MarginProbe System, a handheld device intended to improve positive-margin detection during surgery. The manufacturer purports that MarginProbe can differentiate between cancerous and noncancerous tissue using radiofrequency (RF) spectroscopy, by which the tissue's response to stimulation with an electromagnetic field is measured.2 Research findings suggest that RF spectroscopy can differentiate between normal and cancerous tissues based on bioelectric differences between the two, which may be due in part to changes in the cellular and tissue structure of cancer, including cell membrane depolarization, altered nuclear morphology, increased vascularity, and loss of cell-cell adhesion.2,3 Because RF spectroscopy detects only tissue response to the electromagnetic field near the sample's surface, it is considered appropriate for detecting clean margins, often defined as having a depth of normal (noncancerous) tissue of at least 1 or 2 mm.3 The system incorporates a diagnostic algorithm, based on a large number of comparisons between RF spectroscopy readings and pathology results, to differentiate between cancerous and noncancerous tissue.4 According to the company, MarginProbe measurements take about three to five minutes and provide surgeons with a binary answer indicating whether the assessed margin is clean.5 MarginProbe is intended for use during lumpectomy to potentially reduce the need for subsequent surgical procedures. The company is also investigating the system's efficacy in surgical margin assessment during a radical prostatectomy procedure.6

In April 2011, Dune Medical Devices released results from its pivotal clinical trial and announced in May 2011 that FDA had formally accepted its premarket approval (PMA) application for the MarginProbe System.7,8 Given that no device is available in the United States to perform intraoperative assessment of lumpectomy margins, FDA granted the system priority review.8 In June 2012, an FDA advisory panel voted 10 to 1 to approve MarginProbe based on research indicating that women whose surgeons used the technology during lumpectomy were 56% less likely to need more surgery compared with women whose surgeons did not.9 FDA issued an approvable letter for MarginProbe on November 19, 2012, stating that the PMA is approvable subject to final agreement on the design of the required postapproval study.10 On January 2, 2013, FDA approved the MarginProbe System for marketing.11 MarginProbe has been available for use in...