Latest Review Date: April 2024

Category:  Radiology                                                             

POLICY:

Positron emission mammography (PEM) is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

Positron emission mammography (PEM) is a form of positron emission tomography (PET) that uses a high-resolution, mini-camera detection technology for imaging the breast. As with PET, PEM provides functional rather than anatomic information on the breast.  PEM has been studied primarily for use in pre-surgical planning and evaluation of breast lesions.

Positron Emission Mammography

Positron emission mammography (PEM) is a form of positron emission tomography (PET) that uses a high-resolution, mini-camera detection technology for imaging the breast. As with PET, a radiotracer, (usually fluorine 18 fluorodeoxyglucose [FDG]) is administered and the camera is used to provide a higher resolution image of a limited section of the body than would be achievable with FDG-PET. Gentle compression is used, and the detector(s) are mounted directly on the compression paddle(s).

PEM was developed to overcome the limitations of PET for detecting breast cancer tumors.  Patients usually are supine for PET procedures and the breast tissue may spread above the chest wall, making it potentially difficult to differentiate breast lesions from other organs that take up the radiotracer.  PET’s resolution is generally limited to approximately 5mm, which may not detect early breast cancer tumors. PEM allows for the detection of lesions as small as two to three millimeters and creates images that are more easily compared with mammography because they are acquired in the same position. Three-dimensional reconstruction of the PEM images is also possible. As with PET, PEM provides functional rather than anatomic information about the breast. In studies of PEM, exclusion criteria included some patients with diabetes.

Radiation Dose Associated with PEM

The label-recommended dose of FDG for PEM is 370 MBq (10 mCi). Hendrick (2010) calculated mean glandular doses, and from those, lifetime attributable risk (LAR) of cancer for film mammography, digital mammography, breast-specific gamma imaging (BSGI), and PEM. The author used BEIR VII Group risk estimates to gauge the risks of radiation-induced cancer incidence and mortality from breast imaging studies. Estimated LAR of cancer for a patient with average-sized compressed breast during mammography of 5.3 cm (risks would be higher for larger breasts) for a single breast procedure at age 40 years is:

• 5 per 100,000 for digital mammography (breast cancer only);
• 7 per 100,000 for screen film mammography (breast cancer only);
• 55 to 82 per 100,000 for BSGI (depending on the dose of technetium Tc 99m sestamibi); and
• 75 per 100,000 for PEM.

The corresponding LAR of cancer mortality at age 40 years is:

• 1.3 per 100,000 for digital mammography (breast cancer only);
• 1.7 per 100,000 for screen film mammography (breast cancer only);
• 26 to 39 per 100,000 for BSGI; and
• 31 per 100,000 for PEM.

A major difference in the impact of radiation between mammography and BSGI or PEM is that in mammography radiation dose is limited to the breast; whereas with BSGI and PEM, all organs are irradiated. Furthermore, as one ages, the risk of cancer induction from radiation exposure decreases more rapidly for the breast than for other radiosensitive organs. Organs at highest risk for cancer are the bladder with PEM and the colon with BSGI; these cancers, along with lung cancer, are also less curable than breast cancer. Thus, the distribution of radiation throughout the body adds to the risks associated with BSGI and PEM. Hendrick concluded that:

“results reported herein indicate that BSGI and PEM are not good candidate procedures for breast cancer screening because of the associated higher risks for cancer induction per study compared with the risks associated with existing modalities such as mammography, breast US [ultrasound], and breast MR (magnetic resonance) imaging. The benefit-to-risk ratio for BSGI and PEM may be different in women known to have breast cancer, in whom additional information about the extent of disease may better guide treatment.”

O’Connor et al (2010) estimated the LAR of cancer and cancer mortality from use of digital mammography, screen film mammography, PEM, and molecular breast imaging (MBI). Only results for digital mammography and PEM are reported here. The study concluded that in a group of 100,000 women at age 80 years, a single digital mammogram at age 40 years would induce 4.7 cancers with 1.0 cancer deaths; 2.2 cancers with 0.5 cancer deaths for a mammogram at age 50; 0.9 cancers with 0.2 cancer deaths for a mammogram at age 60; and 0.2 cancers with 0.0 cancer deaths for a mammogram at age 70. Comparable numbers for PEM would be 36 cancers and 17 cancer deaths for PEM at age 40; 30 cancers and 15 cancer deaths for PEM at age 50; 22 cancers and 12 cancer deaths for PEM at age 60; and 9.5 cancers and 5.2 cancer deaths for PEM at age 70. The authors also analyzed the cumulative effect of annual screening between ages 40 and 80, as well as between ages 50 and 80. For women at age 80 who were screened annually from ages 40 to 80, digital mammography would induce 56 cancers with 15 cancer deaths; for PEM, the analogous numbers were 800 cancers and 408 cancer deaths. For women at age 80 who were screened annually from ages 50 to 80, digital mammography would induce 21 cancers with 6 cancer deaths; for PEM, the analogous numbers were 442 cancers and 248 cancer deaths. However, background radiation from age 0 to 80 is estimated to induce 2174 cancers and 1011 cancer deaths.

These calculations, like all estimated health effects of radiation exposure, are based on several assumptions. Comparing digital mammography and PEM, two conclusions are clear: Many more cancers are induced by PEM than by digital mammography; and for both modalities, adding annual screening from 40 to 49 roughly doubles the number of induced cancers. In a benefit/risk calculation performed for digital mammography but not for PEM, O’Connor et al nevertheless reported that the benefit-risk ratio of annual screening is still approximately 3 to 1 for women in their 40s, although it is much higher for women 50 and older. Like Hendrick, the authors concluded that “if molecular imaging techniques [including PEM] are to be of value in screening for breast cancer, then the administered doses need to be substantially reduced to better match the effective doses of mammography.”

The American College of Radiology (ACR) has assigned a relative radiation level (effective dose) of 10 to 30 mSv to PEM. The College also stated that, because of radiation dose, PEM and BSGI in their present form are not indicated for screening.

Because the use of BSGI and MBI has been proposed for women at high risk of breast cancer, it should be noted that there is controversy and speculation whether some women (e.g., those with BRCA variants) have heightened radiosensitivity. If women with BRCA variants are more radiosensitive than the general population, the previous estimates may underestimate the risks they face from breast imaging with ionizing radiation (i.e., mammography, BSGI, MBI, PEM, single-photon emission computed tomography, breast-specific computed tomography, and tomosynthesis; ultrasound and MRI do not use radiation). More research will be needed to resolve this issue. Also, risks associated with radiation exposure will be greater for women at high risk of breast cancer, regardless of whether or not they are more radiosensitive, because they start screening at a younger age when risks associated with radiation exposure are increased.

KEY POINTS:

The most recent literature review was performed through April 2, 2024.

Summary of Evidence

For individuals who are being screened for breast cancer the evidence includes a retrospective study. The relevant outcomes are OS, disease-specific survival, test accuracy and validity, and resource utilization. It has not been demonstrated that PEM provides better diagnostic accuracy than the relevant comparators nor has PEM been shown to provide clinical utility. In addition, without demonstrated advantages in clinical utility, the relatively high radiation dosage associated with PEM does not favor its use given that alternative tests deliver lower doses. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals with clinically localized breast cancer undergoing pre-surgical evaluation, the evidence includes prospective studies. The relevant outcomes are OS, disease-specific survival, test accuracy and validity, and resource utilization. It has not been demonstrated that PEM provides better diagnostic accuracy than the relevant comparators nor has PEM been shown to provide clinical utility. In addition, without demonstrated advantages in clinical utility, the relatively high radiation dosage associated with PEM does not favor its use given that alternative tests deliver lower doses. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals with a suspicious breast lesion on conventional breast cancer evaluation, the evidence includes prospective studies as well as a meta-analysis. The relevant outcomes are OS, disease-specific survival, test accuracy and validity, and resource utilization. It has not been demonstrated that PEM provides better diagnostic accuracy than the relevant comparators nor has PEM been shown to provide clinical utility. In addition, without demonstrated advantages in clinical utility, the relatively high radiation dosage associated with PEM does not favor its use given that alternative tests deliver lower doses. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

American College of Radiology

The American College of Radiology (2017) has included positron emission mammography (PEM) in its criteria on breast screening. PEM was rated as “usually not appropriate” for screening women at average- or high-risk for breast cancer. The College has also assigned a relative radiation level (effective dose) of 10 to 30 mSv to PEM and stated that PEM is limited “by radiation dose and lack of evidence in large screening population.”

National Comprehensive Cancer Network

Current NCCN (version 2.2024) guidelines for breast cancer screening and diagnosis do not include PEM.

U.S. Preventive Services Task Force Recommendations

No U.S. Preventive Services Task Force recommendations for PEM have been identified.

KEY WORDS:

Positron emission tomography (PEM), the PEM 2400 PET Scanner

APPROVED BY GOVERNING BODIES:

In 2003, the PEM 2400 PET Scanner (PEM Technologies, Ridgefield, NJ) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. The FDA determined that this device was substantially equivalent to existing devices for use in “medical purposes to image and measure the distribution of injected positron emitting radiopharmaceuticals in human beings for the purpose of determining various metabolic and physiologic functions within the human body.”

In 2009, FDA cleared the Naviscan PEM Flex™ Solo II ™ High Resolution PET Scanner (Naviscan, Inc.; San Diego, California) for marketing through the 510(k) process for the same indication. The PEM 2400 PET Scanner was the predicate device. The newer device is described by the manufacturer as “a high spatial resolution, small field-of-view PET imaging system specifically developed for close-range, spot, i.e., limited field, imaging.”

In 2013, Naviscan was acquired by Compañía Mexicana de Radiología SA (Queretaro, Mexico), which currently markets the Naviscan Solo II™ Breast PET Scanner in the United States (CMR Naviscan Corp., Carlsbad, CA).

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. 

CURRENT CODING:

CPT Codes:

There are no specific CPT codes for PEM.

The most appropriate codes would be:

Or the PET imaging limited area code might be used:

REFERENCES:

1. American Cancer Society. Breast Cancer Early Detection and Diagnosis. 2022. Available online at: www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/experimental-breast-imaging.html
2. American College of Radiology (ACR). ACR Appropriateness Criteria® breast microcalcifications — initial diagnostic workup. 2009. Available online at: www.acr.org/~/media/ACR/Documents/AppCriteria/Diagnostic/BreastMicrocalcifications.pdf.
3. American College of Radiology (ACR). ACR Appropriateness Criteria® breast cancer screening. 2016. Available online at: www.acr.org/~/media/ACR/Documents/AppCriteria/Diagnostic/BreastCancerScreening.pdf.
4. Berg WA, Madsen KS, Schilling K et al. Breast cancer: Comparative effectiveness of positron emission mammography and MR imaging in presurgical planning for the ipsilateral breast. Radiology 2011; 258(1):59-72.
5. Berg WA, Madsen KS, Schilling K et al. Comparative effectiveness of positron emission mammography and MRI in the contralateral breast of women with newly diagnosed breast cancer. AJR Am J Roentgenol 2012; 198(1):219-32.
6. Berg WA, Weinberg IN, Narayanan D et al. High-resolution fluorodeoxyglucose position emission tomography with compression (“position emission mammography”) is highly accurate in depicting primary breast cancer. Breast J 2006; 12(4):309-23.
7. Berrington de Gonzalez A, Berg CD, Visvanathan K et al. Estimated risk of radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers. J Natl Cancer Inst 2009; 101(3):205-9.
8. Birdwell RL, Mountford CE, Iglehart JD. Molecular imaging of the breast. AJR Am J Roentgenol 2009; 193(2):367-76.
9. Caldarella C, Treglia G, Giordano A. Diagnostic Performance of Dedicated Positron Emission Mammography Using Fluorine-18-Fluorodeoxyglucose in Women With Suspicious Breast Lesions: A Meta-analysis. Clin Breast Cancer 2014;14(4):241-248.
10. Crystal Clear Collaboration. Clear PEM sonic, 2011. Available online at: crystalclear.web.cern.ch/node/17
11. Eo JS, Chun IK, Paeng JC et al. Imaging sensitivity of dedicated positron emission mammography in relation to tumor size. Breast 2012; 21(1):66-71.
12. Ernestos B, Nikolaos P, Koulis G et al. Increased chromosomal radiosensitivity in women carrying BRCA1/BRCA2 mutations assessed with the G2 assay. Int J Radiat Oncol Biol Phys 2010; 78(4):1199-205.
13. Expert Panel on Breast Imaging, American College of Radiology, Slanetz PJ, et al. ACR Appropriateness Criteria®: Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer. 2017; acsearch.acr.org/docs/3099208/Narrative/.
14. FDA. 510(k) summary: PEM 2400 PET scanner, 08/13/2003. Available online at: www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm?db=pmn&id=K032063.
15. Fikes BJ. Naviscan's assets sold to Mexican company. The San Diego Union-Tribune, 12/11/2013. Available online at: www.utsandiego.com/news/2013/Dec/11/naviscan-sold-mexican-cmr-positron/.
16. Gold LS, Lee CI, Devine B, et al. Imaging Techniques for Treatment Evaluation for Metastatic Breast Cancer [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Oct. (Technical Briefs, No. 17.). www.ncbi.nlm.nih.gov/books/NBK253155/.
17. Hendrick RE. Radiation doses and cancer risks from breast imaging studies. Radiology 2010; 257(1):246-53.
18. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
19. Kalinyak JE, Berg WA, Schilling K et al. Breast cancer detection using high-resolution breast PET compared to whole-body PET or PET/CT. Eur J Nucl Med Mol Imaging 2014; 41(2):260-75.
20. Khatcheressian JL, Hurley P, Bantug E et al. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013; 31(7):961-5.
21. Li Z, Gao Y, Gong H, et al. Different Imaging Modalities for the Diagnosis of Axillary Lymph Node Metastases in Breast Cancer: A Systematic Review and Network Meta-Analysis of Diagnostic Test Accuracy. J Magn Reson Imaging. 2023;57(5):1392-1403.
22. Mainiero MB, Lourenco A, Mahoney MC et al. ACR Appropriateness Criteria Breast Cancer Screening. J Am Coll Radiol 2013; 10(1):11-4.
23. Moy L, Heller SL, Bailey L, et al. ACR Appropriateness Criteria(R) Palpable Breast Masses. J Am Coll Radiol. May 2017; 14(5s): S203-s224.
24. Muller FH, Farahati J, Muller AG, et al. Positron emission mammography in the diagnosis of breast cancer. Is maximum PEM uptake value a valuable threshold for malignant breast cancer detection? Nuklearmedizin. 2016; 55(1):15-20.
25. Narayanan D, Madsen KS, Kalinyak JE et al. Interpretation of positron emission mammography: feature analysis and rates of malignancy. AJR Am J Roentgenol 2011; 196(4):956-70.
26. Narayanan D, Madsen KS, Kalinyak JE et al. Interpretation of positron emission mammography and MRI by experienced breast imaging radiologists: performance and observer reproducibility. AJR Am J Roentgenol 2011; 196(4): 971-81.
27. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis, version 1.2021. Available online at: www.nccn.org/professionals/physician_gls/f_guidelines.asp#detection
28. O’Connor MK, Li H, Rhodes DJ et al.  Comparison of radiation exposure and associated radiation-induced cancer risks from mammography and molecular imaging of the breast.  Med Phys 2010; 37(12):6187-98.
29. Prekeges J. Breast imaging devices for nuclear medicine. J Nucl Med Technol 2012; 40(2):71-8.
30. Research Council of the National Academies. Health risks from exposure to low levels of ionizing radiation: BEIR VII, Phase 2—Committee to Assess Health Risks for Exposure to Low Levels of Ionizing Radiation. Washington, DC: National Academies Press, 2006.
31. Schilling K, Narayanan D, Kalinyak JE et al. Positron emission mammography in breast cancer presurgical planning: comparisons with magnetic resonance imaging. Eur J Nucl Med Mol Imaging 2011; 38(1):23-36.
32. Shkumat NA, Springer A, Walker CM et al. Investigating the limit of detectability of a positron emission mammography device: a phantom study. Med Phys 2011; 38(9):5176-85.
33. Tafra L, Cheng Z, Uddo J et al. Pilot clinical trial of 18F-fluorodeoxyglucose positron-emission mammography in the surgical management of breast cancer. Am J Surg 2005; 190(4):628-32.
34. Tafreshi NK, Kumar V, Morse DL et al. Molecular and functional imaging of breast cancer. Cancer Control 2010; 17(3):143-55.
35. Yamamoto Y, Ozawa Y, Kubouchi K, et al. Comparative analysis of imaging sensitivity of positron emission mammography and whole-body PET in relation to tumor size. Clin Nucl Med. Jan 2015; 40(1):21-25.
36. Yamamoto Y, Tasaki Y, Kuwada Y, et al. A preliminary report of breast cancer screening by positron emission mammography. Ann Nucl Med. Feb 2016; 30(2):130-137.

POLICY HISTORY:                                                           

Medical Policy Panel, January 2011

Medical Policy Group, January 2011 (2)

Medical Policy Administration Committee, February 2011

Available for comment February 9 – March 25, 2011

Medical Policy Panel, June 2012

Medical Policy Group, July 2012 (2): Updated Key Points and References

Medical Policy Panel, June 2013

Medical Policy Group, September (2): No change in policy statement.  Key Points and References updated.

Medical Policy Panel, June 2014

Medical Policy Group, June 2014 (3): 2014 Updates to Key Points, Governing Bodies & References; add as a clarification to the policy statement “for all indications” – no change in context.

Medical Policy Panel, June 2015

Medical Policy Group, July 2015 (3): 2015 Updates to Key Points, Approved Governing Bodies, and References; No change to policy statement.

Medical Policy Panel, September 2016

Medical Policy Group, September 2016 (3): 2016 Updates to Description, Key Points, Approved by Governing Bodies, and References. No change to policy statement

Medical Policy Panel, September 2017

Medical Policy Group, October 2017 (3): 2017 Updates to Description, Key Points & References; No change to policy statement

Medical Policy Panel, September 2018

Medical Policy Group, September 2018 (9): 2018 Updates to Description, Key Points. No change to policy statement.

Medical Policy Panel, September 2019

Medical Policy Group, October 2019 (2): Updates to Key Points and References. No change in Policy Statement.

Medical Policy Panel, October 2020

Medical Policy Group, October 2020 (2): Updates to Key Points. No change in Policy Statement.

Medical Policy Group, March 2022 (2): Reviewed by consensus. No new literature identified that would alter coverage statement at this time. Policy statement updated to remove “not medically necessary;” no change to intent.

Medical Policy Group, April 2023 (2): Updates to Key Points, Benefit Application, and References; no change to Policy Statement. Reviewed by consensus. No new literature identified that would alter coverage statement at this time.

Medical Policy Group, April 2024 (2): Reviewed by consensus. Updates to Key Points; Practice Guidelines and Position Statements, and References. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

   3. The technology must improve the net health outcome;

   4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.