Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual
Policy #:	2013026
Category:	Surgery
Initiated:	August 2013
Last Review:	March 2024

Intraoperative Assessment of Tissue

Description:

Breast-conserving surgery as part of the treatment of localized breast cancer is optimally achieved by attaining margins around the surgical resection that are free from tumor cells. Failure to achieve clear margins will often require additional surgery to re-excise breast tissue. Currently, histologic examination of excised tissues after completion of surgery is the only method of definitively determining whether clear margins were achieved. Intra-operative methods of assessing surgical margins such as specimen imaging, frozen section pathology, and touch print cytology, are either not highly accurate, not commonly available, or require considerable time and resources.

A device to detect positive margins should have a high sensitivity, indicating the ability to accurately detect any tumor found in the margins, ideally above 95%. While specificity is less important, excess false-positive margin detection would lead to additional unnecessary tissue removal. A new device should have a specificity at least matching current standard best practices, estimated at 85% (Maloney, 2018).

MarginProbe® is an intraoperative device which uses radiofrequency spectroscopy to measure the dielectric properties of tissue into which it comes in contact. Cancer cells and normal breast tissues produce different signals. A handheld probe is applied to a small area of the lumpectomy specimen and analyzes whether the tissue is likely malignant or benign. The device gives a positive or negative reading for each touch. If any touch on a particular margin gives a positive reading, the margin is considered to be positive and more tissue should be re-excised if possible. The device can only be used on the main lumpectomy specimen, and it cannot be used on shavings or in the lumpectomy cavity in the patient’s breast. Use of the MarginProbe® device is intended to increase the probability that the surgeon will achieve clear margins in the initial operation, thus avoiding the need for a second surgery to excise more breast tissue.

Regulatory Status

In December 2012, MarginProbe® (Dune Medical Devices, Caesarea, Israel) was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval process as an adjunctive diagnostic tool for identification of cancerous tissue at the margins (≤ 1mm) of the main ex-vivo lumpectomy specimen following primary excision (P110014). It is indicated for intraoperative use in conjunction with standard methods (e.g., intraoperative imaging and palpation) for patients undergoing lumpectomy for previously diagnosed breast cancer. FDA product code: OEE.

In January 2019, SPY Elite™ Intraoperative Perfusion Assessment System (Novadaq Technologies ULC. (Now A Part of Stryker) was approved by the U.S. Food and Drug Administration (FDA, 2019) through the premarket approval (K182907) to be used with SPY AGENT™ GREEN for use in adult and pediatric patients one month of age and older. The SPY Elite System is indicated for fluorescence imaging of blood flow and tissue perfusion before, during, and after vascular, gastrointestinal, organ transplant, and plastic, micro- and reconstructive surgeries.

Coding

There is no specific CPT code for this spectroscopic assessment. A possible unlisted CPT code that might be used is 19499 unlisted procedure breast.

Policy/
Coverage:

Effective September 2023

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Handheld radiofrequency spectroscopy for intraoperative assessment of surgical margins during breast-conserving surgery does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

For members with contracts without primary coverage criteria, handheld radiofrequency spectroscopy for intraoperative assessment of surgical margins during breast-conserving surgery is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Fluorescence imaging angiography (eg, indocyanine green fluorescence angiography) for intraoperative assessment of skin flap perfusion and viability as part of breast-conserving surgery does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

For members with contracts without primary coverage criteria, Fluorescence imaging angiography (eg, indocyanine green fluorescence angiography) for intraoperative assessment of skin flap perfusion and viability as part of breast-conserving surgery is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

For non-ocular surgeries, use of intraoperative fluorescence imaging systems for assessment of vascular patency, tissue viability, organ identification, or tissue perfusion is considered an integral part of the surgical procedure and is not separately reimbursable.

Effective June 15, 2023 through August 2023

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Effective August 2021 through June 14, 2023

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

For members with contracts without primary coverage criteria, handheld radiofrequency spectroscopy for intraoperative assessment of surgical margins during breast-conserving surgery is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective Prior to August 2021

For members with contracts without primary coverage criteria, handheld radiofrequency spectroscopy for intraoperative assessment of surgical margins during breast-conserving surgery is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:

Evidence evaluating the efficacy of MarginProbe comes from FDA documents describing the clinical trial that led to FDA approval (FDA, 2012). The trial has not yet been published in a peer-reviewed journal as of May 2013. An earlier study evaluating its use did not use the same classification algorithm and may not represent the current performance of the device (Allweis, 2008). The reviewed study reports the most relevant patient outcomes available for evaluating MarginProbe® with the largest number of patients including a large proportion of US patients. In addition to clinical outcomes, the study allows assessments of diagnostic test performance of MarginProbe®, which will help inform judgments of its utility.

The pivotal study compared surgical processes and short-term outcomes in patients in whom MarginProbe® was used versus patients in whom margin probe was not used. The control strategy did not include intraoperative histologic techniques, but did include radiographic imaging of the main resection specimen in addition to inspection of the resection specimen. The pivotal study was a multicenter (21 sites) randomized study of 596 patients assigned equally to the two arms of the study.

Patients enrolled in the study met criteria mentioned in the FDA labeling, but also all had non-palpable lesions which required image-guided localization. The study design was complex, and included several steps in the study sequence in which additional shavings of breast tissue could be taken during the operation. The declared principal outcome of the trial was called complete surgical resection, in which positive margins were either re-excised or noted if not re-excised. It was not necessary for the re-excision to result in a clear margin. Thus this outcome is not fully clinically relevant, and appears to be biased against the control arm of the study.

For the principal outcome of complete surgical resection, MarginProbe® showed a rate of 71.8% versus 22.4% for controls, with positive margin subjects as the denominator, which is a large magnitude of difference and statistically significant. However, this outcome is biased against the control group and includes non-clinically relevant events as outcomes, such as positive margins that were not resected. Volume of tissue resected on both a relative and absolute scale were greater in the MarginProbe® group, but the data analysis only presents conclusions of a non-inferiority analysis. The non-inferiority margin for the normalized total tissue volume was not specified.

More clinically relevant outcomes include the proportion of patients with positive margins on final pathology after surgery, which was 31% for the MarginProbe® group and 42% in the control group (p=0.0082). Some patients with positive margins in the MarginProbe® group arise from subjects that did not have positive margins in their main specimen. However, due to false positive MarginProbe® readings, additional shavings were undertaken in which cancer tissue was found at the margin. Without these additional shavings taken in response to MarginProbe® assessment, these patients would have been considered to have a clear margin. This occurrence reflects the uncertainty of final pathology in trying to ascertain whether all cancer tissue has been removed. It complicates the comparison of outcomes between the two groups because a measure usually considered a poor outcome like a positive margin, in this case is not due to inadequate surgery but inadvertent discovery of residual cancer due to false positive MarginProbe® readings.

Re-excision rates using all patients enrolled in the study as the denominator showed about a 5% absolute reduction in the MarginProbe® group (28.5% vs. 23.8%), which was not statistically significant. The decision to re-operate was based on judgment of the surgeon based on patient and tumor characteristics and the totality of pathologic findings. The study does not assess outcomes beyond the short term outcome of the re-excision rate; thus it is unknown if the lower re-excision rates resulted in at least equivalent local recurrence rates. Without knowing if the recurrence rate is at least equivalent, a lower re-excision rate could reflect inadequate initial surgery.

The study also reports the diagnostic characteristics of MarginProbe. Out of 1,788 margins with final histopathology, MarginProbe® readings were valid or not missing in 1,750. Three hundred twenty seven margins were positive, and MarginProbe® was positive in 246 for a sensitivity of 75.2%. Out of 1423 negative margins, MarginProbe® was negative in 660 for a specificity of 46.4%. These performance characteristics showing moderate sensitivity and poor specificity are consistent with better than random capability of the device in detecting positive margins. Given the 19% (327/1750) prevalence of positive margins, the positive predictive value of a positive MarginProbe® test for a margin is 24%. In another analysis (apparently performed or requested by FDA) in which the location of the positive margin was ignored, and the test was considered positive if any margin tested positive, MarginProbe® was 96.3% sensitive but only 8.9% specific. Although this test performance characteristic is less clinically relevant, the low specificity in this study indicates that MarginProbe® was positive for at least one margin in almost every patient in the study, even though the prevalence of at least one positive margin was 52%.

Conclusions: The reviewed study showed a non-statistically significant difference in the re-excision rate in the two study arms. The declared principal outcome of the study, complete surgical resection, is not directly clinically relevant and is biased against the control arm of the study. The study does not follow patients long enough to assess the local recurrence rate, which would be important to assess when evaluating the adequacy of initial excision. The diagnostic characteristics of the device show only moderate sensitivity and poor specificity; thus the device will miss some cancers and have frequent false-positive results.

Ongoing Clinical Trials

No ongoing studies on MarginProbe® for assessment of surgical margins during breast conservation surgery are currently listed at online site ClinicalTrials.gov.

Summary

Breast-conserving surgery as part of the treatment of localized breast cancer is optimally achieved by attaining margins around the surgical resection that are free from tumor cells. Handheld radiofrequency spectroscopy for intraoperative assessment of surgical margins (i.e., MarginProbe®) is intended to increase the probability that the surgeon will achieve clear margins in the initial operation, thus avoiding the need for a second surgery to excise more breast tissue. The one clinical trial of MarginProbe® does not provide sufficient evidence that it improves the adequacy of initial surgical treatment of localized breast cancer. This device has not been assessed in comparison to other techniques of intraoperative margin assessment such as frozen section and touch-print cytology. There is a lack of evidence that the use of handheld radiofrequency spectroscopy for intraoperative assessment of surgical margins improves net health outcomes.

2014 Update

A literature search conducted through July 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.

Evidence evaluating the efficacy of MarginProbe® comes from FDA documents describing the pivotal trial that led to FDA approval (Schnabel, 2014; Rivera, 2012). The trial has not yet been published in a peer-reviewed journal as of May 2013. An earlier study evaluating its use did not use the same classification algorithm and may not represent the current performance of the device (Allweis, 2008). The reviewed trial reported the most relevant patient outcomes available for evaluating MarginProbe® with the largest number of patients including a large proportion of U.S. patients. In addition to clinical outcomes, the trial allows assessments of diagnostic test performance of MarginProbe®, which will help inform judgments of its utility.

A 2014 systematic review of techniques used for intraoperative assessment of margins in breast conserving therapy for ductal carcinoma in situ (DCIS) concluded that larger studies are needed to determine whether MarginProbe® has a role to play in breast-conserving surgery (Butler-Henderson, 2014). This conclusion was based on the pivotal trial reviewed above and earlier studies.

In 2014, Thill et al reported final results of a cohort study of MarginProbe® in DCIS (Thill, 2014; Thill, 2011). Forty-two (76%) of 55 patients enrolled from the general screening population at 3 centers in Germany were eligible for analysis. Patients underwent preoperative wire localization followed by breast-conserving surgery, with intraoperative assessment of the excised specimen by MarginProbe®, radiograph, and paraffinembedded pathological review. MarginProbe® also was used on additional shavings. Outcome measures were re-excision rate compared with a historical control rate of 39% and “procedure success,” defined as (1) negative margins after breast-conserving surgery, and (2) early identification of an extended lesion, with conversion to mastectomy rather than re-excision. Criteria for re-excision defined a negative margin of 5 mm. The historical cohort comprised 67 patients with DCIS who underwent breast-conserving surgery by the same surgeons involved in the study during the year before enrollment began. Because information about patient selection and baseline data were not provided for either cohort, it is unknown how comparable the 2 cohorts were. Re-excision rate was 17%, a statistically significant difference from the historical control rate (Fisher exact test, p=0.018), and “procedure success” occurred in 24 (57%) of 42 patients. Sensitivity was 57% (95 CI, 48 to 66), and specificity was 50% (95 CI, 42 to 58). It is possible that the observed reduction in the reduced re-excision rate was due to an increased incidence of mastectomies. A randomized trial that assesses recurrence is required to demonstrate improvement in net health outcome with MarginProbe®.

A subsequent study in women with DCIS showed poor sensitivity and specificity and suggested that more mastectomies may be performed with MarginProbe®. A randomized trial that assesses recurrence is required to demonstrate whether net health outcome is improved.

Two clinical studies of MarginProbe® provide insufficient evidence that the device improves initial surgical treatment of localized breast cancer or ductal carcinoma in situ (DCIS). The device has not been assessed in comparison with other techniques of intraoperative margin assessment. Lacking evidence for improved net health outcomes, use of handheld radiofrequency spectroscopy for intraoperative assessment of surgical margins during breast conservation surgery is considered investigational.

National Comprehensive Cancer Network (NCCN)

Current NCCN guidelines for breast cancer (version 3.2014) do not include recommendations for intraoperative assessment of surgical margins using radiofrequency spectroscopy for either DCIS or invasive breast cancer (NCCN, 2014).

2015 Update

A literature search conducted using the MEDLINE database did not reveal any new information that would prompt a change in the coverage statement. One new retrospective, multicenter study was identified. Sebastian and colleagues found a reduction in re-excision procedures from 26% to 10% after introduction of Margin Probe® (Sebastian, 2015). Investigators reviewed case records of 4 surgeons in 3 centers who used individual (nonstandardized), routine lumpectomy methods including criteria for reexcision (n=186 cases before MarginProbe®; n=165 cases with MarginProbe®). For each surgeon, reexcision rates with the use of MarginProbe® were compared with those from a historical set, comprising a consecutive series of cases from a time period shortly before each surgeon started using MarginProbe®. With use of the device, there were 28 cases in which the margin on the main specimen was clear, but the corresponding shaving contained cancer. Three (1.8%) of 165 patients in the “after” group underwent mastectomy; mastectomy rate in the “before” group was not reported. Performance characteristics (eg, sensitivity and specificity) of MarginProbe® cannot be calculated from these data. Other study limitations include lack of baseline description of the control (“before”) group, potential confounding by secular trends over time, and lack of recurrence outcomes.

2016 Update

A literature search conducted through June 2016 did not reveal any new information that would prompt a change in the coverage statement.

2017 Update

A literature search conducted through July 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.

A 2016 retrospective single-center study by Blohmer and colleagues compared the use of MarginProbe in 150 patients to a historical control group of 172 patients (Blohmer, 2016). The 2 groups had approximately similar proportions of patients with invasive breast cancer and DCIS. The historical control group underwent gross pathology examination and radiogram of the specimen as standard intraoperative procedures. The principal outcome of the study was re-excision rate. In patients for whom MarginProbe was used, the re-excision rate was 14.6%; in the historical control group, it was 29.7%. Nothing in the study assessed the performance of MarginProbe, the criteria for re-excision, or long-term patient outcomes. The difference in the amount of breast tissue removed between strategies was not reported.

A 2016 retrospective single-center study by Reid Coble compared the use of MarginProbe in 137 patients to a historical control group of 199 patients (Coble, 2016). The 2 groups had approximately similar demographic characteristics and proportions with invasive breast cancer and DCIS. The historical control group underwent standard lumpectomy followed by additional shavings taken circumferentially from all aspects of the cavity. The principal outcome of the study was re-excision rate. For procedures using MarginProbe, the re-excision rate was 6.6%; in the historical control group, the rate was 15.1%. The total volume of tissue (main specimen plus additional shavings) removed was also less in the MarginProbe cases (78 cm3 vs 116 cm3; p= 0.002).

2018 Update

A literature search was conducted through July 2018. There was no new information identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

A systematic review by St John et al of intraoperative techniques to assess margins following breast conservation surgery identified 55 studies, 35 of which were included in meta-analysis (St John, 2017). The primary end point was diagnostic accuracy of the various techniques, which was based on pooled sensitivity, specificity, and area under the receiver operating characteristic curve. Reviewers found only one prospective study on MarginProbe, which was found to have a diagnostic accuracy of 68.2%, based in part on sensitivity (71.4%) and specificity (67.7%). Re-excision rates were a secondary outcome: of 57 patients in the MarginProbe study, 15.8% required re-excision during the initial surgery. Because there was only 1 study on the MarginProbe, it was not included in the meta-analysis. Other intraoperative techniques included in meta-analysis had pooled specificity ranging from 81% to 96%, depending on the modality, and pooled sensitivity ranging from 53% to 91%. The meta-analysis was limited by heterogeneity between studies in methodology and varying criteria for diagnosis and assessment of margins. A number of studies identified for the review could not be included in meta-analysis because of missing raw data.

Kupstas et al retrospectively reviewed charts of patients from a single center who were treated with MarginProbe during lumpectomy for invasive carcinoma and DCIS; 120 patients were intraoperatively assessed using standard of care, and 120 patients were intraoperatively assessed using the MarginProbe device (Kupstas, 2017). Reviewers found an improvement in the device group for the primary outcome, re-excision rate (9.2% of patients treated with MarginProbe required re-excision surgery vs 18.2% of those treated with standard of care; p=0.039). Included in this re-excision group were those who needed a second lumpectomy¾5.8% (n=7) of the device group vs 15% (n=18) of the standard care group (p=0.020). The study population differed in initial specimen volume; the device group was with significantly smaller breast volume on average (p=0.032). It also differed in the number of shavings required, as those in the device group tended to receive 1.5 more shavings than their counterparts. The final mean volume of removed tissue was comparable between the device group (53.6 mL) and the standard of care group (53.5 mL; p=0.974). Study limitations included the absence of long-term outcomes.

2019 Update

A literature search was conducted through July 2019. There was no new information identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

A systematic review by Butler-Henderson et al of techniques used for intraoperative assessment of margins in breast-conserving therapy for DCIS concluded that larger studies are needed to determine whether MarginProbe has a role to play in breast-conserving surgery (Butler-Henderson, 2014). This conclusion was based on the pivotal trial previously reviewed and earlier studies.

A retrospective single-center study by Blohmer et al compared the use of MarginProbe in 150 patients with a historical control group of 172 patients (Blohmer, 2016). The 2 groups had approximately similar proportions of patients with invasive breast cancer and DCIS. The historical control group underwent gross pathology examination and radiogram of the specimen as standard intraoperative procedures. The principal outcome of the study was re-excision rate. In patients for whom MarginProbe was used, the re-excision rate was 14.6%; in the historical control group, it was 29.7%. T The study did not describe the criteria for re-excision, or include long-term patient outcomes. The difference in the amount of breast tissue removed between strategies was also not reported.

2020 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2020. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

Gooch et al. (2019) retrospectively reviewed charts of patients (n=341) from a single center who underwent breast-conserving surgery with the aid of the MarginProbe device during lumpectomy from 2013 to 2017 to elucidate the relationship between mammographic breast density and positive lumpectomy margins (Gooch, 2019). A main lumpectomy specimen served as the index lesion assessed via the device. The final margin status was defined as the conclusion of the surgery, taking into account any additional margins excised after removal of the main specimen with the aid of the MarginProbe device. Mammographic breast density was not correlated with the likelihood of a final positive margin (p=0.4564). Higher mammographic breast density was associated with younger age (p<0.0001) and lower body mass index (p<0.0001). The MarginProbe device identified 135 margin-positive main specimens. Final margins were positive in 34 (25.2%) patients and negative in 101 (74.8%) patients. The MarginProbe device identified 206 margin-negative main specimens. Final margins were positive in 17 (8.3%) and negative in 189 (91.7%) patients. These findings correspond to a sensitivity of 66.7% and a specificity of 65.2%. Positive margins on the main lumpectomy specimen were correlated with larger tumor size (p<0.001), more advanced disease stage at diagnosis (p=0.0247), the presence of a palpable mass (p=0.0010), and an increased likelihood of subsequent re-excision (p=0.0002). The overall re-excision rates were 11.3% and 8.0% for patients with BI-RADS category ratings of A-B or C-D, respectively.

2021 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

Geha et al. reported single-center results for the Columbia cohort (n = 46) (Geha, 2020). Following conventional lumpectomy and intraoperative assessment, margins in 23 patients were additionally evaluated with MarginProbe. Data were collected until the earliest of the following events: 2 months after last surgery, conversion to mastectomy, or initiation of chemotherapy. The re-excision rate in the device group was significantly lower compared to control (4.3% vs 34.8%; P = 0.022), The authors hypothesize that the device re-excision rate at their study site was lower than previously reported for the multicenter trial due to a higher number of patients with DCIS in the device group (30%) compared to control (8%) who were surgically-managed with thicker tissue shavings in the case of device-reported margin involvement. Long-term excision and local recurrence rates were not reported for this cohort.

A prospective single-center study by LeeVan et al compared the use of MarginProbe for breast-conserving surgery in 60 patients with a historical control group (LeeVan, 2020). Intraoperative margin assessment was performed with a surgical standard operating procedure consisting of specimen radiography and gross pathological examination. Re-excision surgery was defined as a return to the operating table for a subsequent procedure. However, criteria for re-excision surgery were not provided. While 8 patients (13.3%) had a final close or positive margin on pathology following use of MarginProbe, only 4 patients consented to re-excision surgery, yielding a re-excision rate of 6.6%. Four patients declined re-excision in favor of whole breast irradiation. Although this result was statistically lower compared to the historical re-excision rate of 8.6% (P < 0.01), the authors conclude that this difference is not clinically meaningful. The sensitivity, specificity, NPV, and PPV for the use of MarginProbe was 67%, 60%, 16%, and 94% respectively, which was similar to standard protocol alone. Long-term outcomes and complete demographic characteristics for each group were not reported.

2022 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

Cen et al. published a retrospective review of patients in a single center's institutional breast cancer database who received both neoadjuvant chemotherapy and breast-conserving surgery (N=61) between 2010 and 2018 (Cen, 2021). Median patient age was 51.8 years and the study population had diverse representation (White 43%, Black or African American 17%, Hispanic 24%, and Asian 17%). A complete response was achieved for 19 (31.1%) patients. Of the remaining 42 patients, 9 (21%) had margins that required re-excision. While the use of MarginProbe was associated with a lower re-excision rate (6% vs. 31%, respectively), this difference was not statistically significant. Long-term outcomes were not reported.

2023 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2023. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

Hoffman et al conducted a prospective cohort study of patients undergoing breast-conserving surgery with the use of MarginProbe (N=48) in a single-center general surgery department between 2018 and 2019 (Hoffman, 2022). Of the 48 patients included in the study, there were 51 total tumors analyzed. Out of 306 margins (in 51 tumors), 4 were not assessed by MarginProbe. MarginProbe correctly identified 3 of 13 positive margins; it also read 97 false positive readings of 289 true negative margins. These findings correspond to a sensitivity of 23.1% (95% CI, 5.0% to 53.8%), specificity of 66.4% (95% CI, 60.7% to 71.9%), positive predictive value of 3.0% (95% CI, 0.6% to 8.5%), and negative predictive value of 95.1% (95% CI, 91.1% to 97.6%).

2024 Update

Annual policy review completed with a literature search using the MEDLINE database through February 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

As part of the treatment of localized breast cancer, breast-conserving surgery is optimally achieved by attaining tumor-free margins around the surgical resection site (Schnitt, 2020). Failure to achieve clear margins will often require additional surgery to re-excise breast tissue. Currently, histologic examination of excised tissues after completion of surgery is the only method to determine definitively whether clear margins were achieved. Intraoperative methods of assessing surgical margins, such as specimen imaging, frozen section pathology, and touch print cytology, are either not highly accurate, not commonly available, or require considerable time and resources.

A systematic review with meta-analysis evaluated re-excision rates in studies of patients undergoing breast-conserving surgery for non-palpable DCIS or invasive breast cancer with intraoperative use of MarginProbe (Rossou, 2023). The authors included data from 4 RCTs and 8 nonrandomized studies comprising 2680 patients. Re-excision was reported in a mean of 10.93% (±5.49%) of patients whose evaluation included MarginProbe compared with 25.8% (±10.12%) of patients whose evaluation did not include use of MarginProbe (p=.001). Calculated mean specificity and sensitivity were 63.47% and 69.07%, respectively. Other clinical outcomes were not analyzed.

CPT/HCPCS:

References:

Allweis TM, Kaufman Z, Lelcuk S et al.(2008) A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast conserving surgery. Am J Surg 2008; 196(4):483-9.

Allweis TM, Kaufman Z, Lelcuk S, et al.(2008) A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery. Am J Surg. Oct 2008;196(4):483-489. PMID 18809049

American Society of Breast Surgeons.(2019) Performance and Practice Guidelines for Breast-Conserving Surgery/Partial Mastectomy. https://www.breastsurgeons.org/statements/guidelines/PerformancePracticeGuidelines_Breast-ConservingSurgery-PartialMastectomy.pdf. Accessed January 9, 2019.

Blohmer JU, Tanko J, Kueper J, et al.(2016) MarginProbe(c) reduces the rate of re-excision following breast conserving surgery for breast cancer. Arch Gynecol Obstet. Aug 2016;294(2):361-367. PMID 26796680

Blohmer JU, Tanko J, Kueper J, et al.(2016) MarginProbe(c) reduces the rate of re-excision following breast conserving surgery for breast cancer. Arch Gynecol Obstet. Aug 2016;294(2):361-367. PMID 26796680

Blue Cross and Blue Shield Association Technology Evaluation Center (TEC).(2013) Handheld Radiofrequency Spectroscopy for Intraoperative Margin Assessment During Breast-Conserving Surgery. TEC Assessments 2013, Volume 28, Tab TBD.

Butler-Henderson K, Lee AH, Price RI, et al.(2014) Intraoperative assessment of margins in breast conserving therapy: a systematic review. Breast. Apr 2014;23(2):112-119. PMID 24468464

Cen C, Chun J, Kaplowitz E, et al.(2021) Margin Assessment and Re-excision Rates for Patients Who Have Neoadjuvant Chemotherapy and Breast-Conserving Surgery. Ann Surg Oncol. Sep 2021; 28(9): 5142-5148. PMID 33635409

Coble J, Reid V(2016) Achieving clear margins. Directed shaving using MarginProbe, as compared to a full cavity shave approach. Am J Surg. Dec 30 2016. PMID 28049561

Geha RC, Taback B, Cadena L, et al.(2020) A Single institution's randomized double-armed prospective study of lumpectomy margins with adjunctive use of the MarginProbe in nonpalpable breast cancers. Breast J. Nov 2020; 26(11): 2157-2162. PMID 32772474

Gooch JC, Yoon E, Chun J, et al.(2019) The Relationship of Breast Density and Positive Lumpectomy Margins. Ann. Surg. Oncol., 2019 Mar 20;26(6). PMID 30888516

Gray RJ, Pockaj BA, Garvey E, Blair S.(2018) Intraoperative margin management in breast-conserving surgery: a systematic review of the literature. Ann Surg Oncol. 2018;25:18-27. PMID 28058560

Hoffman A, Ashkenazi I.(2022) The efficiency of MarginProbe in detecting positive resection margins in epithelial breast cancer following breast conserving surgery. Eur J Surg Oncol. Jul 2022; 48(7): 1498-1502. PMID 35219544

Kupstas A, Ibrar W, Hayward RD, et al.(2017) A novel modality for intraoperative margin assessment and its impact on re-excision rates in breast conserving surgery. Am J Surg. Nov 21 2017. PMID 29191356

LeeVan E, Ho BT, Seto S, et al.(2020) Use of MarginProbe as an adjunct to standard operating procedure does not significantly reduce re-excision rates in breast conserving surgery. Breast Cancer Res Treat. Aug 2020; 183(1): 145-151. PMID 32607640

Maloney BW, McClatchy DM, Pogue BW, et al.(2018) Review of methods for intraoperative margin detection for breastconserving surgery. J Biomed Optics. 2018;23(10). PMID 30369108

National Comprehensive Cancer Network (NCCN).(2014) Clinical practice guidelines in oncology: breast cancer, version http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed July 2014.

Pruimboom T, Schols RM, Van Kuijk SM, Van der Hulst RR, Qiu SS.(2020) Indocyanine green angiography for preventing postoperative mastectomy skin flap necrosis in immediate breast reconstruction. Cochrane Database Syst Rev. 2020 Apr 22;4(4):CD013280. doi: 10.1002/14651858.CD013280.pub2. PMID: 32320056; PMCID: PMC7175780.

Rivera RJ, Holmes DR, Tafra L.(2012) Analysis of the Impact of Intraoperative Margin Assessment with Adjunctive Use of MarginProbe versus Standard of Care on Tissue Volume Removed. Int J Surg Oncol. 2012;2012:868623. PMID 23326653

Schnabel F, Boolbol SK, Gittleman M, et al.(2014) A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies. Ann Surg Oncol. May 2014;21(5):1589-1595. PMID 24595800

Sebastian M, Akbari S, Anglin B, et al.(2015) The impact of use of an intraoperative margin assessment device on reexcision rates. Springerplus. 2015;4:198.

St John ER, Al-Khudairi R, Ashrafian H, et al.(2017) Diagnostic accuracy of intraoperative techniques for margin assessment in breast cancer surgery: a meta-analysis. Ann Surg. Feb 2017;265(2):300-310. PMID 27429028

Thill M, Dittmer C, Baumann K, et al.(2014) MarginProbe®--final results of the German post-market study in breast conserving surgery of ductal carcinoma in situ. Breast. Feb 2014;23(1):94-96. PMID 24291375

Thill M, Roder K, Diedrich K, et al.(2011) Intraoperative assessment of surgical margins during breast conserving surgery of ductal carcinoma in situ by use of radiofrequency spectroscopy. Breast. Dec 2011;20(6):579-580. PMID 21885281

U.S. Food and Drug Administration (FDA).(2012) Summary of safety and effectiveness data: MarginProbe® System. 2012. Accessed at http://www.accessdata.fda.gov/cdrh_docs/pdf11/P110014b.pdf

U.S. Food and Drug Administration.(2019) SPY Elite Intraoperative Perfusion Assessment System. K182907. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf18/K182907.pdf

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association.