National Medical Policy

National Medical Policy Subject: Breast Tomosynthesis (Digital), 3-D Mammography Policy Number: NMP 526 Effective Date: December 2013 Update: April 2016 This National Medical Policy is subject to the terms in the IMPORTANT NOTICE at the end of this document *For Medicaid Plans: Please refer to the appropriate Medicaid Manuals for coverage guidelines prior to applying Health Net Medical Policies The Centers for Medicare & Medicaid Services (CMS) For Medicare Advantage members please refer to the following for coverage guidelines first: Use Source Reference/Website Link X National Coverage Determination (NCD) NCD 220.2 Mammography http://www.cms.gov/medicare-coveragedatabase/details/ncddetails.aspx?ncdid=186&ncdver=1&bc=aaaaqaaaa AAA& National Coverage Manual Citation Local Coverage Determination (LCD)* Article (Local)* X Other http://www.cms.gov/outreach-and- Education/Medicare-Learning-Network- MLN/MLNMattersArticles/Downloads/MM8874.pdf None Instructions Medicare NCDs and National Coverage Manuals apply to ALL Medicare members in ALL regions. Medicare LCDs and Articles apply to members in specific regions. To access your specific region, select the link provided under Reference/Website and follow the search instructions. Enter the topic and your specific state to find the coverage determinations for your region. *Note: Health Net must follow local coverage determinations (LCDs) of Medicare Administration Contractors (MACs) located outside their service area when those MACs have exclusive coverage of an item or service. (CMS Manual Chapter 4 Section 90.2) If more than one source is checked, you need to access all sources as, on occasion; an LCD or article contains additional coverage information than contained in the NCD or National Coverage Manual. If there is no NCD, National Coverage Manual or region specific LCD/Article, follow the Health Net Hierarchy of Medical Resources for guidance. Breast Tomosynthesis April 2016 1

Current Policy Statement Note: Please refer to specific state regulation for coverage information as it may vary by state and product line. Digital breast tomosynthesis (DBT) is considered investigational for all indications as there currently is insufficient evidence in the medical literature to recommend this technology for routine screening or diagnosis at this time. Codes Related To This Policy ICD-10 C50.011-C50.019 Malignant neoplasm of nipple and areola, female (code range) C50.111-C50.119 Malignant neoplasm of central portion of breast, female (code range) C50.211-C50.219 Malignant neoplasm of upper-inner quadrant of breast, female (code range) C50.311-C50.319 Malignant neoplasm of lower-inner quadrant of breast, female (code range) C50.411-C50.419 Malignant neoplasm of upper-outer quadrant of breast, female (code range) C50.511-C50.519 Malignant neoplasm of lower-outer quadrant of breast, female (code range) C50.611-C50.619 Malignant neoplasm of axillary tail of breast, female (code range) C50.811-C50.819 Malignant neoplasm of overlapping sites of breast, female (code range) C50.911-C50.919 Malignant neoplasm of breast of unspecified site, female (code range) C79.81 Secondary malignant neoplasm of breast C79.89 Secondary malignant neoplasm of other specified sites C79.9 Secondary malignant neoplasm of unspecified site D05.00-D05.92 Lobular carcinoma in situ of breast (code range) D48.60-D48.62 Neoplasm of uncertain behavior of other and unspecified sites (code range) D49.3 Neoplasm of unspecified behavior of breast R92.8 Other abnormal and inconclusive findings on diagnostic imaging of breast Z12.31 Encounter for screening mammogram for malignant neoplasm of breast Z12.39 Encounter for other screening for malignant neoplasm of breast Z80.3 Family history of malignant neoplasm of breast Z85.3 Personal history of malignant neoplasm of breast CPT Codes 77061 Digital breast tomosynthesis; unilateral 77062 Digital breast tomosynthesis; bilateral 77063 Screening digital breast tomosynthesis, bilateral (List separately in addition to code for primary procedure) HCPCS Codes G0279 Diagnostic digital breast tomosynthesis, unilateral or bilateral (list separately in addition to G0204 or G0206) Background Digital breast tomosynthesis (DBT) also known as 3-dimensional (3-D) mammography is a modification of digital (2-D) mammography. The difference is that DBT uses a rotating X-ray tube to acquire multiple image slices at several angles. The patient s breast is placed on a digital flat-panel detector and lightly compressed while the X-ray tube rotates around the breast in an arc. It is rotated about +/-15 degrees, and 11 exposures are made every 3 degrees or so during a total scan. Data from the X-ray projections are then reconstructed by computer software to produce a 3D map of the breast, similar to the methods used in computed tomography. The DBT cross-sectional images are approximately 1 millimeter in thickness and can be viewed individually or in a dynamic movie mode. According to the FDA, traditional 2-D imaging has its limitations as about 10 percent of women receive further testing after the initial screening for abnormalities later determined to be noncancerous. DBT is proposed to resolve the issue of tissue overlap that can occur Breast Tomosynthesis April 2016 2

in 2-D breast imaging that may hide cancerous lesions or cause benign masses to appear as suspicious, which are the major reasons for recalls and requests for additional imaging. Scientific Rationale - May 2016 HAYES (2015) identified 25 prospective or retrospective comparative cohort studies from January 2000 thru August 2015, evaluating digital breast tomosynthesis for screening, diagnosis, or characterization of breast lesions. Studies populations ranged from 100 to 100 to 454,850 patients and included adult women with no indications of breast cancer undergoing routine screening, or undergoing targeted or additional breast imaging to investigate known or suspected breast cancer. Studies compared digital breast tomosynthesis alone or in combination with digital mammography (DM) or ultrasonography (US). In women undergoing screening, outcomes included recall, biopsy, and cancer detection rates. Comparing the results of the best available studies led to the conclusion that for breast cancer detection, tomosynthesis is not consistently better than conventional DM unless it is combined with conventional DM. These imaging methods differ in that tomosynthesis combines multiple low-radiation dosage images while DM captures a single higher-dosage image. These differing image collection techniques may be complementary, allowing the combination of the 2 techniques to provide better breast imaging than either technique alone. However, additional studies are needed to confirm this conclusion and to determine whether the apparent benefits of combining tomosynthesis and conventional DM offset the increase in radiation dosage and additional time needed to collect and interpret the results of tomosynthesis and DM imaging. A particular concern is that most of the studies did not compare tomosynthesis with conventional DM that included spot compression and magnified and angled views. The two largest studies are noted here. Friedewald et al (2014) studied 454,850 women in 13 radiology practices to determine if mammography combined with tomosynthesis is associated with better performance of breast screening programs in the United States. The study took place in two time periods ad the mean age was 56.2 years.. Outcomes included recall rate for additional imaging, cancer detection rate and positive predictive values for recall and for biopsy. Period 1 included one full year of screening with digital mammography alone, ending on the date of 3D introduction at each institution. Period 2 included screening with digital mammography and tomosynthesis (2D) + 3D). Of the 454,850 examinations, 281,187 (period 1) received digital mammography; 173,663 (period 2) received digital mammography + tomosynthesis. With digital mammography, 29,726 patients were recalled and 5056 biopsies resulted in cancer diagnosis in 1207 patients (n=815 invasive; n=392 in situ). With digital mammography + tomosynthesis, 15,541 patients were recalled and 3285 biopsies resulted in cancer diagnosis in 950 patients (n=707 invasive; n=243 in situ). Results were reported as model-adjusted rates per 1000 screens. For recall rates: 107 (95%CI, 89-124) with digital mammography vs 91 (95%CI, 73-108) with digital mammography + tomosynthesis; difference, 16 (95%CI, 18 to 14; P <.001); For biopsies: 18.1 (95%CI, 15.4-20.8) with digital mammography vs 19.3 (95%CI, 16.6-22.1) with digital mammography + tomosynthesis; difference, 1.3 (95%CI, 0.4-2.1; P =.004); For cancer detection: 4.2 (95%CI, 3.8-4.7) with digital mammography vs 5.4 (95%CI, 4.9-6.0) with digital mammography + tomosynthesis; difference, 1.2 (95%CI, 0.8-1.6; P <.001); and For invasive cancer detection: 2.9 (95%CI, 2.5-3.2) with digital mammography vs 4.1 (95%CI, 3.7-4.5) with digital mammography + tomosynthesis; difference, 1.2 (95%CI, 0.8-1.6; P <.001). Breast Tomosynthesis April 2016 3

In situ cancer detection: 1.4 (95%CI, 1.2-1.6) per 1000 screens with both methods. Adding tomosynthesis was associated with an increase in the positive predictive value for recall from 4.3%to 6.4%(difference, 2.1%; 95%CI, 1.7%-2.5%; P <.001) and for biopsy from 24.2%to 29.2%(difference, 5.0%; 95%CI, 3.0%-7.0%; P <.001). The authors noted study limitations include the lack of prospective randomization and a lack of follow-up over several years but concluded that the addition of tomosynthesis to digital mammography was associated with a decrease in recall rate and an increase in cancer detection rate. Further studies are needed to assess the relationship to clinical outcomes. Greenberg et al (2014) performed a retrospective comparative cohort study to evaluate breast DM plus tomosynthesis vs DM alone for detection of breast cancer in a community based radiology practice in 59, 617 women. Performance outcomes measures were assessed for 14 radiologists who interpreted more than 500 screening mammography 3D DBT studies after the initiation of tomosynthesis. Outcomes from screening mammography during the study period between August 9, 2011, and November 30, 2012, using 3D DBT (n = 23,149 patients) versus 2D DM (n = 54,684 patients) were compared. For patients screened with 3D DBT, the relative change in recall rate was 16.1% lower than for patients screened with 2D DM (p > 0.0001). The overall cancer detection rate (CDR), expressed as number of cancers per 1000 patients screened, was 28.6% greater (p = 0.035) for 3D DBT (6.3/1000) compared with 2D DM (4.9/1000). The CDR for invasive cancers with 3D DBT (4.6/1000) was 43.8% higher (p = 0.0056) than with 2D DM (3.2/1000). The positive predictive value for recalls from screening (PPV1) was 53.3% greater (p = 0.0003) for 3D DBT (4.6%) compared with 2D DM (3.0%). No significant difference in the positive predictive value for biopsy (PPV3) was found for 3D DBT versus 2D DM (22.8% and 23.8%, respectively) (p = 0.696). The authors concluded that in community-based radiology practice, mammography screening with 3D DBT yielded lower recall rates, an increased CDR for cancer overall, and an increased CDR for invasive cancer compared with 2D DM. The PPV1 was significantly greater in the group screened using 3D DBT. Society Positions/Recommendations United States Preventative Services Task Force (USPSTF). January 2016 The USPSTF concludes that the evidence on DBT as a primary screening method for breast cancer is insufficient, and the balance of benefits and harms cannot be determined: All women Women with dense breasts The USPSTF concludes that the current evidence is insufficient to assess the benefits and harms of digital breast tomosynthesis (DBT) as a primary screening method for breast cancer. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, magnetic resonance imaging, DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. These recommendations apply to asymptomatic women aged 40 years or older who do not have preexisting breast cancer or a previously diagnosed high-risk breast lesion and who are not at high risk for breast cancer because of a known underlying genetic mutation (such as a BRCA1 or BRCA2 Breast Tomosynthesis April 2016 4

gene mutation or other familial breast cancer syndrome) or a history of chest radiation at a young age. National Comprehensive Cancer Network (NCCN) January 2015 According to the National Comprehensive Cancer Network, Early studies show promise for tomosynthesis mammography. Two large trials showing a combined use of digital mammography and tomosynthesis resulted in improved cancer detection and decreased call back rates; of note, this is double the dose of radiation and is a factor in recommending this modality. Definitive studies are still pending. American College of Obstetricians and Gynecologists (ACOG) 2013 Clinical data suggest that digital mammography with tomosynthesis produces a better image, improved accuracy, and lower recall rates compared with digital mammography alone. Further study will be necessary to confirm whether digital mammography with tomosynthesis is a cost-effective approach capable of replacing digital mammography alone as the first-line screening modality of choice for breast cancer screening. ACOG 2015: Current published evidence does not demonstrate meaningful outcome benefits (eg, reduction in breast cancer mortality) with supplemental tests (eg, ultrasonography and magnetic resonance imaging) to screening mammography or with alternative screening modalities (eg, breast tomosynthesis or thermography) in women with dense breasts who do not have additional risk factors. Evidence is lacking to advocate for additional testing until there are clinically validated data that indicate improved screening outcomes. American College of Radiology November 2014 A new digital technology, breast tomosynthesis has shown to be an advance over digital mammography, with higher cancer detection rates and fewer patient recalls for additional testing. This is extremely important. Lower recall rates result in fewer patients who may experience short-term anxiety awaiting test results. This is important evidence that tomosynthesis will have a positive impact on patient care. As this technology is used in clinical practice, we anticipate that further studies will clarify its impact on long-term clinical outcomes, including reduced mortality. It will also be important to further elucidate which subgroups of women might benefit most from these exams (by age, breast density, frequency of examination, etc.). To facilitate such large scale outcome data collection, the technology must be widely available. Availability is greatly impacted by reimbursement for the service provided. The College applauds the decision by the Centers for Medicare and Medicaid Services (CMS) to facilitate access to these exams by covering beneficiaries for tomosynthesis and urges private payers to do the same. To be clear: tomosynthesis is no longer investigational. Tomosynthesis has been shown to improve key screening parameters compared to digital mammography. While the College encourages more studies to clarify the clinical role(s) of tomosynthesis and its long-term outcomes, it is clear that tomosynthesis represents an advance in breast imaging. The ACR will continue to update members and external stakeholders on this important matter. American Cancer Society October 2015 Although digital breast tomosynthesis units are steadily being introduced in mammography facilities, at the time the protocol for the evidence review was developed, there was too little data on digital breast tomosynthesis to include comparisons to 2D mammography. The issue will continue to be revisited and will be updated as evidence emerges. Breast Tomosynthesis April 2016 5

American Society of Breast Disease (no date noted) DBT is an advanced imaging technology for breast cancer screening and diagnosis. The DBT technology produces cross-sectional images by using multiple, low-dose acquisitions with total radiation exposure and breast compression similar to that used for conventional 2D digital mammography. The addition of DBT to conventional DM improves the accuracy of diagnostic mammographic interpretation. This improvement in diagnostic accuracy can be achieved by enhanced detection of lesion, improvement in the analysis of the margins of a lesion and precise localization of a lesion. DBT with DM has a higher sensitivity than DM alone. Published studies showed an increase cancer detection rate of 27-30% at screening. Single center studies have shown that DBT and DM have increased specificity compared to DM alone. Multiple studies noted reduction in the recall rates of screening mammography with the addition of DBT. Recent studies suggest that young women with dense mammographic breast tissue may benefit the most from DBT and may have the greatest reduction in the recall rates. The three largest published DBT screening studies demonstrate a 40-50% increase in cancer detection rates. American Society of Breast Surgeons Consensus Statement: Oct 2015 Multiple large screening trials are currently underway comparing the utility of screening patients with 2D + 3D tomosynthesis to 2D conventional mammography alone. Recent data from the Screening with Tomosynthesis OR standard Mammography (STORM) study demonstrated a 17.1% reduction in false positive recalls and a 33.9% increase in the cancer detection rate by adding 3D tomosynthesis to screening. Another study reported similar results, with a 15% decrease in false positives and a 27% increase in the cancer detection rate. Of note, another study found that the increased sensitivity of tomosynthesis was largest for invasive cancers where 15-22% of cases were invasive versus 3% being in situ. Neither the USPSTF or ACS guidelines provide specific recommendations for type of mammogram but recognize that all prior randomized trials used film screen mammography. Breast tomography may be considered for screening a. Early data shows promise in higher sensitivity rates and specificity rates b. May increase detection rates and decrease false positive rates especially in women with dense breast tissue c. Data from large randomized clinical trials is pending Scientific Rationale December 2014 In the 2014 BCBS TECH assessment on the use of digital breast tomosynthesis (DBT) with mammography for breast cancer screening or diagnosis, six studies were identified. The strongest evidence for the use of both services for screening comes from a large trial in Norway involving 12,621 women where 121 screening-detected cancers were identified. The cancer detection rate was 6.1 per 1000 screening with mammography alone and 8.0 per 1000 women with both mammography and DBT. The authors noted that they did not ascertain any improvement in detecting Ductal Carcinoma In Situ (DCIS) by adding breast tomosynthesis. The false-positive rate was 61.1 per 1,000 screenings for mammography alone and 53.1 per 1,000 screenings for mammography plus breast tomosynthesis. Such a reduction in the false-positive rate would decrease the number of women recalled for additional imaging or biopsy. The authors noted that for this interim analysis, only limited data were available about interval cancers, so they could not estimate conventional absolute sensitivity and specificity. The second study (STORM) examined comparative cancer detection for traditional mammography with or without breast tomosynthesis in a general asymptomatic screening population of 7,292 Italian women. The reference standard was pathology for women Breast Tomosynthesis April 2016 6

undergoing biopsies; women with negative results on both mammography and breast tomosynthesis were not followed to detect interval cancers that might have been missed during screening, so neither the sensitivity nor specificity could be calculated. Mammography plus breast tomosynthesis detected 59 cancers; 20 of these cancers were missed by traditional mammography alone (p<0.0001). The incremental improvement in cancer detection using both modalities was 2.7 cancers per 1,000 screens (95% CI: 1.7 to 4.2). There were 395 false-positive results: 181 occurred using mammography and both imaging modalities together; an additional 141 occurred using mammography only; and 73 occurred using mammography and breast tomosynthesis combined (p<0.0001) (but not by mammography alone). In preplanned analyses, the researchers found that the combined results of mammography and digital breast tomosynthesis yielded more cancers in patients either younger or older than 60 years old and for both breast density categories (1 and 2 vs. 3 and 4, with 1 being least dense and 4 being most dense). The third study compared results before and after the introduction of breast tomosynthesis at their multisite center. In this apparently retrospective study, the subjects did not serve as their own controls. The addition of tomosynthesis reduced the recall rate from 8.7% to 5.5% (p<0.001). Breast cancer detection rates did not differ between the two periods (4.04 per 1,000 screenings to 5.37 per 1,000 with tomosynthesis; p=0.18). The positive predictive value for recalls increased from 4.7% with mammography alone to 10.1% with the addition of tomosynthesis (p<0.001). The improvement in recall rates was similar across breast density categories, ranging from 32.4% (densest) to 41.0% (least dense). The TEC Assessment concluded that the evidence suggests that use of mammography plus breast tomosynthesis may modestly increase the number of cancers detected, with a large decrease in the number of women who undergo unnecessary recalls or biopsies. However, the studies were nonrandomized and the lack of long-term follow-up prevents assessment of false negative results and full assessment of test performance. Further, overall impacts on health outcomes are unknown. Long-term effects of additional radiation exposure also are unknown and therefore digital breast tomosynthesis is considered investigational. A trial that randomizes women to digital mammography with or without tomosynthesis, or performs both screening methods in the same woman, is required to demonstrate that improvements in screening are due to tomosynthesis and not to confounding variables, eg, patient characteristics or radiologist experience in tomosynthesis interpretation. The utility of adding DBT to diagnostic mammography (such as spot views) to reduce the number of women who undergo unnecessary biopsies by screening out some fraction of women with false-positive results is also being evaluated. The TEC Assessment evaluated 3 studies as follows: In a study of 158 women consecutively recalled after screening mammography, breast tomosynthesis was evaluated as a possible triage tool to reduce the number of false-positive results. The results of the diagnostic assessment (including ultrasound and needle biopsy when performed) were used as the reference standard. Breast tomosynthesis eliminated 102 of the 158 recalls, all of which were unnecessary (i.e., false-positive results on mammography). No cancers were missed on breast tomosynthesis. The performance of breast tomosynthesis did not vary by breast density or age group, but the reduction in recalls was greater for asymmetric densities and distortions, and nodular opacities with regular margins. The authors noted that the decline in recall rates following the use of breast tomosynthesis was higher in this study than in blinded comparisons of digital mammography and breast tomosynthesis. Another study compared diagnostic mammography to breast tomosynthesis among women with abnormalities on screening mammography with no calcifications in a simulated clinical setting. The breast tomosynthesis rating was based on 2 readers ratings and their confidence that no additional studies were needed, as well as ultrasound results in some Breast Tomosynthesis April 2016 7

cases. The reference standard was either the results of the entire clinical workup, including biopsy if performed, or follow- up for women not undergoing biopsy (86.1% of the entire sample). There was no statistically significant difference in sensitivity or specificity between diagnostic mammography and breast tomosynthesis. The third study evaluated 738 women with 759 lesions who were recalled after screening with film mammography. In this unblinded study, the incremental value of adding breast tomosynthesis to film and digital mammography was assessed. The reference standard consisted of pathology results or follow-up for 18 to 36 months. Adding breast tomosynthesis to film and digital mammography results increased the area under the curve (AUC) from 0.895 (0.871-0.919) to 0.967 (0.957-0.977) (p=0.001). The complete sensitivity (counting ratings of 3-5 as positive) increased from 39.7% for digital mammography to 58.3% when breast tomosynthesis was added; no confidence intervals or p values were reported. The specificity increased from 51% to 74.2% when breast tomosynthesis was added to digital mammography. The difference in AUC after the addition of breast tomosynthesis was statistically significant for soft-tissue lesions, but not for micro calcifications. The authors noted that ultrasound and MRI are used during the diagnostic work-up so studies comparing diagnostic mammography and DBT may not allow a good comparison and a different research design would be needed to accurately assess how DBT compares to these modalities. They conclude that the evidence currently available on the use of breast tomosynthesis plus diagnostic mammography versus diagnostic mammography alone for a diagnostic workup is insufficient to permit conclusions regarding the effect on health outcomes of adding breast tomosynthesis. In November 2014, the American College of Radiology issued a statement to regard DBT as an advancement over digital mammography because of higher cancer detection rates and fewer patient recalls for additional testing. The ACR also states that further studies are needed to clarify its impact on long-term clinical outcomes, including reduced mortality and to further elucidate which subgroups of women might benefit most from these exams (by age, breast density, frequency of examination, etc.). Scientific Rationale - Initial Chen et al. (2007) carried out a small pilot study of 13 women recruited between April 2005 and November 2005 to assess the clinical feasibility of contrast enhanced (CE) DBT as an adjunct to digital mammography, and to correlate lesion enhancement characteristics and morphology obtained with CE-DBT to digital mammography, magnetic resonance (MR) and ultrasound (US). After undergoing breast imaging evaluation (including digital mammography, US, and MR) as part of the parent multimodality breast imaging study (NCIfunded grant [PO1-CA85484]) the participants were evaluated with CEDBT. Eleven of the 13 participants had pathology proven malignancies, (6 invasive ductal carcinoma, 4 ductal carcinoma in situ, 1 invasive lobular carcinoma). Suspicious lesions were demonstrated with CE-DBT in 10 of 11 cases of proven breast malignancy. The researchers concluded that when used in conjunction with diagnostic mammography, CE-DBT may be a potential alternative tool for breast lesion morphologic and vascular characterization. A 2007 study by Poplack et al. assessed the image quality of DBT with that of conventional mammography and to estimate the recall rate of screening when tomosynthesis is used in addition to mammography. A total of 98 consecutive women between 34 and 85 years of age with an abnormal digital screening mammogram were included in the study. During the initial evaluation each woman underwent a DBT examination using a research prototype tomosynthesis unit (Genesis, Hologic) and screening mammography using full-field digital technology. The image quality of DBT was subjectively rated as equivalent in 52% (51/99) or superior 37% (37/99) to diagnostic mammography in 89% (88/99) of cases. In the identification of masses, DBT image quality was rated as equivalent in 26% (5/19) or Breast Tomosynthesis April 2016 8

superior to diagnostic mammography in 68% (13/19) of cases. Calcifications usually showed better image quality on diagnostic mammography than on DBT. The authors concluded that "tomosynthesis has comparable or superior image quality to that of film-screen mammography in the diagnostic setting, and it has the potential to decrease the recall rate when used adjunctively with digital screening mammography." However, limitations of the study included the small sample size and the fact that the study was unblinded, nonrandomized and uncontrolled. DBT may perform differently in a general screening population than in the study group of women who were recruited because of a breast screening abnormality. In this study group, only 5% (5/98) of women had fatty breast composition; the remainder, 95% (93/98), had higher density compositions. In a population with a greater proportion of fatty breast composition, DBT may prove to be less effective. A 2008 study by Goode et al. evaluated issues associated with digital tomosynthesis image interpretation. Nine board certified radiologists were asked to review the breast images from 30 women who underwent digital mammography and digital tomosynthesis to look for masses and micro calcification clusters from each film. Nine board certified radiologists independently reviewed the 30 cases 3 times: as displayed as digital mammography, as 11 low-dose projections prior to reconstruction of tomosynthesis images, and the reconstructed digital tomosynthesis examination. They were then asked to rate each image set for the presence or absence detect and rate masses and micro calcification clusters. When compared to digital mammography, the reconstructed DBT examination took much longer to review and interpret. Three of the 9 radiologists perceived the tomosynthesis frame mode to be better than digital mammography, and 6 of the 9 radiologists perceived the reconstructed tomosynthesis examination to be better than digital mammography. The detection rate of malignancies was slightly better for the reconstructed digital tomosynthesis examination than for digital mammography (93.9% versus 90%), and the recall rate for nonmalignancies was slightly lower (62.6% versus 64.3%). The researchers noted that better visualization and training tools will need to be developed before digital tomosynthesis can be used efficiently in a screening environment and additional studies are needed before this imaging approach finds its optimal role in the clinical environment. Andersson et al. (2008) conducted an unblinded study of 36 women to compare breast cancer visibility in one-view breast tomosynthesis (BT) to cancer visibility in one- or twoview digital mammography (DM). Forty breast cancers were found in 37 breasts. The authors found that cancer visibility on breast tomosynthesis was greater in 22 of 40 cancers found compared to single view digital mammography. Thirteen of the remaining 18 cancers were equally visible/clearly visible on single view digital mammography and breast tomosynthesis. While it appears that breast tomosynthesis identifies some cases of breast cancer, in over half of the patients accuracy of diagnosis was not increased and therefore it can not be concluded what type of patient should have breast tomosynthesis and at what stage in the screening process this should occur. The study is also limited by small sample size and non-blinded study design. Gur et al. (2009) conducted a retrospective observer study that compared digital tomosynthesis with digital mammography from 125 selected breast examinations from 8 experienced radiologists. In 35 examinations, cancer had been verified, and the other 90 showed no evidence of cancer. The combination of digital mammography with digital tomosynthesis was associated with a 30% reduction in recalls for the cancer-free examinations compared with the use of digital mammography alone. Digital tomosynthesis alone reduced recall rates by approximately 10%. Digital tomosynthesis did not substantially improve sensitivity. The authors acknowledged that while initial results are promising, further work is needed before DBT finds its optimal role in the clinical environment. Breast Tomosynthesis April 2016 9

Teertstra et al (2010) assessed mammography and DBT in 513 women with an abnormal screening mammogram or with clinical symptoms. The ACR BI-RADS criteria were used to classify the cases. In 112 newly detected cancers, DBT and mammography were each falsenegative in 8 cases (7%). In three cases, both mammography and DBT failed to detect the carcinoma. The sensitivity of both techniques for the detection of breast cancer was 92.9%, and the specificity of mammography was 86.1% and 84.4% for DBT. The authors concluded that DBT can be used as an additional technique to mammography in individuals referred with an abnormal screening mammogram or with clinical symptoms. They also acknowledged that the additional lesions detected by DBT are also likely to be detected by other techniques used in the clinical work-up of these individuals. A retrospective study by Spangler et al. (2011) compared the ability of digital breast tomosynthesis and full field digital mammography (FFDM) to detect and characterize calcifications in 100 paired examinations. There were 20 biopsy-proven cancers, 40 biopsy proven benign calcifications and 40 randomly selected negative screening studies reviewed. Overall calcification detection sensitivity was higher for digital mammography (84%) than for digital breast tomosynthesis (75%). Of the calcifications accurately detected using digital mammography, 14 cancers and 38 benign calcifications were not detected with digital breast tomosynthesis. Of the calcifications accurately detected using digital breast tomosynthesis, 4 cancers and 13 benign calcifications were not detected with FFDM. The authors concluded that digital mammography appears to be slightly more sensitive than digital breast tomosynthesis for the detection of calcification. This study is limited by retrospective design and a small study sample. Skaane et al. (2013) presented results of a clinical trial comparing digital mammography to digital mammography with plus DBT in a population-based screening program in Norway. The results of the 12,631 female participants, detection rates, including those for invasive and in situ cancers, were 6.1 per 1000 examinations for mammography alone and 8.0 per 1000 examinations for mammography plus tomosynthesis. False-positive rates before arbitration were 61.1 per 1000 examinations with mammography alone and 53.1 per 1000 examinations with mammography plus tomosynthesis (15% decrease, adjusted for reader; P <.001). After arbitration, positive predictive values for recalled patients with cancers verified later were comparable (29.1% and 28.5%, respectively, with mammography alone and mammography plus tomosynthesis; P =.72). Twenty-five additional invasive cancers were detected with mammography plus tomosynthesis (40% increase, adjusted for reader; P <.001). The mean interpretation time was 45 seconds for mammography alone and 91 seconds for mammography plus tomosynthesis (P <.001). The researchers found the use of mammography plus tomosynthesis in a screening environment resulted in a significantly higher cancer detection rate and enabled the detection of more invasive cancers. Rafferty et al (2013) conducted a study to compare radiologists' diagnostic accuracy and recall rates for breast tomosynthesis combined with digital mammography versus digital mammography alone. Mediolateral oblique and craniocaudal digital mammographic and tomosynthesis images of both breasts were obtained from 1192 subjects. Two studies were performed to compare digital mammography with tomosynthesis against digital mammography alone. Study 1 comprised 312 cases (48 cancer cases) with images read by 12 radiologists; study 2, 312 cases (51 cancer cases) with 15 radiologists. Study 1 readers recorded only that an abnormality requiring recall was present; study 2 readers had additional training and recorded both lesion type and location. Diagnostic accuracy was compared with receiver operating characteristic analysis. Recall rates of noncancer cases, sensitivity, specificity, and positive and negative predictive values determined by analyzing Breast Imaging Reporting and Data System scores were compared for the two methods. The authors report that diagnostic accuracy for combined tomosynthesis and digital mammography was superior to that of digital mammography alone. Average difference in Breast Tomosynthesis April 2016 10

area under the curve in study 1 was 7.2% (95% confidence interval [CI]: 3.7%, 10.8%; P <.001) and in study 2 was 6.8% (95% CI: 4.1%, 9.5%; P <.001). All 27 radiologists increased diagnostic accuracy with addition of tomosynthesis. Recall rates for noncancer cases for all readers significantly decreased with addition of tomosynthesis (range, 6%- 67%; P <.001 for 25 readers, P <.03 for all readers). Increased sensitivity was largest for invasive cancers: 15% and 22% in studies 1 and 2 versus 3% for in situ cancers in both studies. Limitations of this study noted by the authors include that reader studies were enriched, almost all the patients with cancer where scheduled for biopsy as they had been detected on conventional mammogram. Therefore, it is likely that the study results underestimate the potential gains in sensitivity that might occur in clinical practice. Additional studies done in the clinical environment are needed to confirm the performance of tomosynthesis combined with digital mammography versus digital mammography alone Physician Organizations and Other Recommendations National Comprehensive Cancer Network According to the National Comprehensive Cancer Network Breast Cancer Screening and Diagnosis (V1.2015): Early studies show promise for tomosynthesis mammography. Two large trials showing a combined use of digital mammography and tomosynthesis resulted in improved cancer detection and decreased call back rates. Of note, this is double the dose of radiation and is a factor in recommending this modality. The radiation dose can be minimized by 2-D synthetic reconstruction. Definitive studies are still pending. The Society of Breast Imaging (SBI) and the American College of Radiology (ACR) statement on the on Skaane et al was published on their the ACR website in January 2013 Tomosynthesis Breast Cancer Screening Study states the following "While the study results are promising, they do not provide adequate information to define the role of tomosynthesis in clinical practice Although the cancer detection rate was higher when tomosynthesis was added to mammography alone, it is not known if an equal incremental benefit will be realized in a second screening round. This small study does not supply statistical information regarding subgroups of women that might benefit, or might not benefit from adding tomosynthesis. How the technology will affect screening accuracy among women of different ages, risk profiles and parenchymal density is uncertain. In addition, how this technology would affect reader performance among U.S. radiologists with varying practice patterns and expertise is also uncertain. Other questions include whether computer aided detection will provide any further benefit, and if reconstructed images can be used, in lieu of standard full field digital images, to reduce radiation dose" Guidelines on breast cancer screening from the American College of Obstetricians and Gynecologists (ACOG, 2011) considered, but did not recommend, breast tomosynthesis. The guidelines concluded that "[c]olor Doppler ultrasonography, computer-aided detection, positron emission tomography, scintimammography, and digital breast tomosynthesis have shown promise in selected clinical situations or as adjuncts to mammography for breast cancer diagnosis. However, these technologies are not considered alternatives to routine mammography." In November 2013, the California Technology Assessment Forum (CTAF) voted that the evidence supports supplemental screening of women at high risk for breast cancer, and that screening with MRI had the strongest evidence for use. In addition, the majority of CTAF members voted that MRI and ABUS (Automated Breast Ultrasound) represented high or Breast Tomosynthesis April 2016 11

reasonable value and DBT represented low value compared to HHUS (Hand Held Ultrasound). Review History December 2013 December 2014 May 2016 Medical Advisory Council initial review Updated Scientific Rationale and added new CPT codes Republished policy Evidence Based Sources 1. American College of Obstetricians-Gynecologists. Practice bulletin no. 122: Breast cancer screening. Obstet Gynecol. 2011; 118(2 Pt 1):372-382. Available at: http://www.guideline.gov/content.aspx?id=34275&search=breast+tomosynthesis. Accessed on November 20, 2013 2. American College of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 625: Management of women with dense breasts diagnosed by mammography. Obstet Gynecol. 2015;125(3):750-751. 3. American College of Radiology. Press Releases.ACR, SBI Statement on Skaane et al Tomosynthesis Breast Cancer Screening Study (2013). Available at: http://www.acr.org/about-us/media-center/press-releases/2013-press- Releases/20130110ACR-SBI-Statement-on-Skaane-et-al. Accessed on November 20,2013 4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology Breast Cancer Screening and Diagnosis (V.1.2015). NCCN website: http://www.nccn.org/index.asp. References - May 2016 1. Greenberg JS, Javitt MC, Katzen J, Michael S, Holland AE. Clinical performance metrics of 3D digital breast tomosynthesis compared with 2D digital mammography for breast cancer screening in community practice. AJR Am J Roentgenol. 2014;203(3):687-693. 2. Friedewald SM, Rafferty EA, Rose SL, et al. Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA. 014;311(24):2499-2507. 3. United States Preventive Services Task Force Breast Cancer: Screening Jan 2016 http://www.uspreventiveservicestaskforce.org/page/document/updatesummaryfinal /breast-cancer-screening1 4. Winifred Hayes Digital Breast Tomosynthesis for Breast Cancer Diagnosis or Screening Hayes Medical Technology Directory Published September 24, 2015 5. American College of Breast Surgeons Consenus Statement on Screening Mammography https://www.breastsurgeons.org/statements/pdf_statements/screening_mammogra phy.pdf 6. American Society of Breast Disease. Statement of Digital Breast Tomosynthesis http://www.areyoudenseadvocacy.org/worxcms_files/asbd_statement_on_tomosyn thesis12-16-13.pdf References December 2014 1. BCBS Technology Assessment (January 2014) Use of Breast Digital Tomosynthesis with Mammography for Breast Cancer Screening and Diagnosis. Volume 28 No. 6. Accessed on December 3, 2014 at http://www.bcbs.com/blueresources/tec/vols/28/28_06.pdf 2. American College of Radiology (November 24, 2014) Position Statement on Breast Tomosynthesis. Accessed December 2014 at http://www.acr.org/about-us/media- Center/Position-Statements/Position-Statements-Folder/20141124-ACR-Statementon-Breast-Tomosynthesis Breast Tomosynthesis April 2016 12

References Initial 1. Andersson I, Ikeda DM, Zackrisson S, et al. Breast tomosynthesis and digital mammography: a comparison of breast cancer visibility and BIRADS classification in a population of cancers with subtle mammographic findings. Eur Radiol. 2008; 18(12):2817-2825. 2. Chen S, Carton AK, Albert M, et al. Initial Clinical Experience with Contrast-Enhanced Digital Breast Tomosynthesis. Acad Radiol. 2007; 14(2): 229 238. 3. Good, WF, Abrams GS, Catullo VJ, et al. Digital breast tomosynthesis: a pilot observer study. AJR Am J Roentgenol. 2008; 190(4):865-869. 4. Gur D, Abrams GS, Chough DM, Ganott MA. Digital breast tomosynthesis: observer performance study. AJR Am J Roentgenol. 2009; 193(2): 586-591. 5. Michell MJ, Iqbal A, Wasan RK, et al. A comparison of the accuracy of film-screen mammography, full-field digital mammography, and digital breast tomosynthesis. Clin Radiol. 2012; 67(10):976-981. 6. Poplack SP, Tosteson TD, Kogel CA, Nagy HM. Digital breast tomosynthesis: initial experience in 98 women with abnormal digital screening mammography. AJR Am J Roentgenol. 2007; 189(3):616-623. 7. Rafferty EA, Park JM, Philpotts LE, et al. Assessing radiologist performance using combined digital mammography and breast tomosynthesis compared with digital mammography alone: results of a multicenter, multireader trial. Radiology. 2013; 266(1):104-113. 8. Skaane P, Bandos AI, Gullien R, et al. Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Radiology. 2013; 267(1):47-56. 9. Spangler ML, Suley ML, Sumkin JH, et al. Detection and classification of calcifications on digital breast tomosynthesis and 2D digital mammography: a comparison. Am J Roentgenol. 2011; 196(2): 320-324. 10. Teertstra HJ, Loo CE., van den Bosch MA, et al. Breast tomosynthesis in clinical practice: initial results. Eur Radiol. 2010; 20(1):16-24. 11. California Technology Assessment Forum. September 25, 2103. Supplemental Cancer Screening for Women with Dense Breasts. Accessed at: http://www.ctaf.org/assessments/supplemental-cancer-screening-women-densebreasts Important Notice General Purpose. Health Net's National Medical Policies (the "Policies") are developed to assist Health Net in administering plan benefits and determining whether a particular procedure, drug, service or supply is medically necessary. The Policies are based upon a review of the available clinical information including clinical outcome studies in the peerreviewed published medical literature, regulatory status of the drug or device, evidence-based guidelines of governmental bodies, and evidence-based guidelines and positions of select national health professional organizations. Coverage determinations are made on a case-by-case basis and are subject to all of the terms, conditions, limitations, and exclusions of the member's contract, including medical necessity requirements. Health Net may use the Policies to determine whether under the facts and circumstances of a particular case, the proposed procedure, drug, service or supply is medically necessary. The conclusion that a procedure, drug, service or supply is medically necessary does not constitute coverage. The member's contract defines which procedure, drug, service or supply is covered, excluded, limited, or subject to dollar caps. The policy provides for clearly written, reasonable and current criteria that have been approved by Health Net s National Medical Advisory Council (MAC). The clinical criteria and medical policies provide guidelines for determining the medical necessity criteria for specific procedures, equipment, and services. In order to be eligible, all services must be medically necessary and otherwise defined in the member's benefits contract as described this "Important Notice" disclaimer. In all cases, final benefit determinations are based on the applicable contract language. To the extent there are any conflicts between medical policy guidelines and applicable contract language, the contract language prevails. Medical policy is not intended to override the policy that defines the member s benefits, nor is it intended to dictate to providers how to practice medicine. Policy Effective Date and Defined Terms. Breast Tomosynthesis April 2016 13

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