Archived Policies - Radiology


Positron Emission Tomography (PET)

Number:RAD605.001

Effective Date:03-01-2016

End Date:04-14-2017

Coverage:

Oncologic Applications

Positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) may be considered medically necessary for Initial Treatment Strategy Planning and Subsequent Treatment Strategy Planning for known or suspected malignancy (but not for Screening or Surveillance) when the following criteria are met:

Initial Treatment Strategy Planning

One PET or PET/CT study may be considered medically necessary for Initial Treatment Strategy Planning for patients who have solid tumors that are biopsy proven, or suspected based on other diagnostic testing, when a PET or PET/CT study is needed to determine the location and/or extent of the tumor for the following therapeutic purposes related to the initial treatment strategy to determine:

Whether or not the patient is an appropriate candidate for an invasive diagnostic or therapeutic procedure; OR

The optimal anatomic location for an invasive procedure; OR

The anatomic extent of tumor when the recommended anti-tumor treatment reasonably depends on the extent of the tumor.

NOTE: BREAST CANCER, MELANOMA, AND PROSTATE CANCER HAVE SPECIFIC EXCLUSIONS FOR PET OR PET/CT, AS NOTED BELOW

Breast Cancer

PET or PET/CT is considered experimental, investigational and/or unproven for:

Diagnosis or evaluation in patients with suspicious breast lesions; OR

Initial staging of axillary lymph nodes in patients with breast cancer.

Melanoma

PET or PET/CT is considered experimental, investigational and/or unproven for evaluation of patients with clinically localized melanoma who are candidates to undergo sentinel node biopsy.

Prostate Cancer

PET or PET/CT is considered experimental, investigational and/or unproven to determine initial anti-tumor treatment in patients with adenocarcinoma of the prostate.

Subsequent Treatment Strategy Planning

PET or PET/CT imaging for subsequent treatment strategy planning may be considered medically necessary when the initial diagnostic PET criteria were met and PET is needed:

For the purpose of detecting residual disease within 12 months after completion of therapy for lymphoma or within 6 months after completion of therapy for all other malignancies; OR

During the course of chemotherapy or radiation treatment when clinical signs and symptoms are significant and suggestive of disease progression or worsening despite treatment and the results are necessary to plan a new course of treatment; OR

To determine the extent of a known recurrence established by other diagnostic modalities; OR

To monitor tumor response to treatment during the planned course of therapy when a change in therapy is anticipated.

Surveillance of Asymptomatic Patients After Completion of Therapy for Malignancy

PET or PET/CT is considered not medically necessary for patients ≥12 months after completion of therapy for lymphoma, or ≥6 months after completion of therapy for all other malignancies, unless the patient demonstrates signs, symptoms, laboratory or other objective findings suggestive of recurrence or spread of the original malignancy.

NOTE: Surveillance utilizing PET or PET/CT is defined as a scan performed for patients without signs or symptoms of cancer recurrence who are six (6) months or more from completion of cancer treatment or 12 months or more from completion of treatment for lymphoma.

Screening of Asymptomatic Patients

PET or PET/CT is considered not medically necessary as a screening test (i.e., for evaluation of patients without specific signs and symptoms of disease).

Cardiac Applications

Myocardial Perfusion

Cardiac PET scanning may be considered medically necessary as a technique to assess myocardial perfusion defects when the patient has at least intermediate risk* for coronary artery disease AND the following criteria are met:

Indeterminate noninvasive imaging tests (e.g., single-photon emission computed tomography (SPECT) scan, myocardial perfusion imaging, stress echocardiogram); OR

Patients for whom SPECT could be reasonably expected to be suboptimal in quality due to body habitus (for example, including but not limited to:

o Moderate to severe obesity, i.e., BMI > 35 kg/m2; or

o Large breasts and/or implants; or

o Left mastectomy; or

o Chest wall deformity; or

o Any other technical problems (e.g., indeterminant prior SPECT, extensive prior MI, etc).

* Intermediate risk is discussed in the Description section.

Myocardial Viability

Cardiac PET scanning may be considered medically necessary to assess the myocardial viability in patients with severe left ventricular dysfunction as a technique to determine candidacy for a revascularization procedure

Cardiac Sarcoidosis

Cardiac PET scanning may be considered medically necessary for the diagnosis of cardiac sarcoidosis in patients who are unable to undergo magnetic resonance imaging (MRI) scanning. Examples of patients who are unable to undergo MRI include, but are not limited to, patients with pacemakers, automatic implanted cardioverter-defibrillators (AICDs), or other metal implants.

Quantification of Myocardial Blood Flow

Cardiac PET scanning is considered experimental, investigational and/or unproven for quantification of myocardial blood flow in patients diagnosed with CAD.

Miscellaneous (noncardiac, nononcologic) Indications

Positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) may be considered medically necessary for the following:

Diagnosis of chronic osteomyelitis;

Assessment of selected patients with epileptic seizures who are candidates for surgery. NOTE: Appropriate candidates are those patients who have complex partial seizures that have failed to respond to medical therapy and who have been advised to have a resection of a suspected epileptogenic focus located in a region of the brain accessible to surgery. Conventional techniques for seizure localization must have been tried and provided data that suggested a seizure focus, but were not sufficiently conclusive to permit surgery.

Electroencephalogram’s (EEG's) AND PET EXAMINATION: The purpose of the PET examination should be to avoid subjecting the patient to extended pre-operative electroencephalographic recording with implanted electrodes.

Positron Emission Mammography (PEM)

Positron emission mammography (PEM) is considered experimental, investigational and/or unproven for breast cancer screening, diagnosis or management.

Positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) is considered experimental, investigational and/or unproven for all other indications.

Sodium 18F-Fluoride (NaF-18) Radiotracer for Positron Emission Tomography (PET) Bone Scans

Sodium 18F-Fluoride (NaF-18) radiotracer for positron emission tomography (PET) bone scans is considered experimental, investigational and/or unproven for non-oncologic indications, including but not limited to osteomyelitis.

Description:

Positron emission tomography (PET) scans are based on the use of positron emitting radionuclide tracers coupled to organic molecules, such as glucose, ammonia, or water. The radionuclide tracers simultaneously emit two high-energy photons in opposite directions that can be simultaneously detected (referred to as coincidence detection) by a PET scanner, consisting of multiple stationary detectors that encircle the area of interest.

A variety of tracers are used for PET scanning, including oxygen-15, nitrogen-13, carbon-11, and fluorine-18. Because of their short half-life, tracers must be made locally, the majority requiring an on-site cyclotron.

This policy only addresses the use of radiotracers detected with the use of dedicated PET scanners. There is a similar procedure to PET that uses the radiotracer 2-[F-18] - fluorodeoxyglucose (FDG) may be referred to as FDG-SPECT (fluorodeoxyglucose-single photon emission computed tomography), metabolic SPECT, or PET using a gamma camera. In this procedure radiotracers such as FDG may be detected using SPECT cameras.

Surveillance is closely monitoring a patient's condition, looking for sign(s) that a cancer has returned, but withholding treatment until symptoms appear or change; also called observation, watchful waiting, and expectant management.

The purpose of a cancer screening test is to identify the presence of a specific cancer in an individual who does not demonstrate any symptoms. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate).

Positron Emission Tomography/Computed Tomography – (PET/CT Fusion Imaging)

PET/CT Fusion Imaging is a new diagnostic tool for the staging and restaging of cancer. Patients can be examined with both PET and CT in a single examination. This new technology correlates two simultaneous imaging modalities for a comprehensive examination that combines anatomic data with functional or metabolic information. The CT images are used for anatomic reference of the tracer uptake patterns images in PET, as well as for attenuation correction of the PET data.

Positron Emission Mammography (PEM)

Positron-emission mammography (PEM) is a specialized imaging modality utilizing radiopharmaceuticals and PET technology to detect breast cancer. PEM was developed to overcome the limitation of whole-body PET in detecting smaller breast lesions, and to improve visualization of fibrodense breast tissue and breasts with fibrocystic disease. With PEM, two high-resolution detector heads are placed on opposite sides of a compressed breast, and the data is integrated with conventional mammography.

The PEM Flex™ Solo II, the first commercially available U.S. Food and Drug Administration (FDA)-cleared, high-resolution PET scanner, is designed to image small body parts and can be used with other imaging modalities. Solo II utilizes PEM to allow physicians to visualize and characterize lesions as small as 1.5-2.0 mm, about the diameter of a mammary duct. In November 2008, the FDA granted 510(k) clearance for the Stereo Navigator™, which is the first commercially available breast PET-guided biopsy feature, to be used with PEM Flex Solo II. The FDA approval states “it is intended for the localization of lesions in female breasts, as identified on a PET image. By using the Stereo Navigator, the physician is able to guide compatible interventional devices towards the PET abnormality as medically indicated. The Stereo Navigator also provides a means to confirm localization of the lesion in advance of the interventional procedure.”

Cardiac PET Scan

In terms of myocardial perfusion studies, patient selection criteria for PET scans involve an individual assessment of the pretest probability of coronary artery disease (CAD), based on both patient symptoms and risk factors. Patients at low risk for CAD may be adequately evaluated with exercise electrocardiography. Patients at high risk for CAD may not benefit from a non-invasive assessment of myocardial perfusion, since, in this setting, a negative test may represent a false negative result. These patients may be immediately referred to coronary angiography.

Patient selection criteria for PET scans for myocardial viability are typically those patients with severe left ventricular dysfunction who are under consideration for a revascularization procedure. A PET scan may determine whether the left ventricular dysfunction is related to viable or nonviable myocardium. Patients with viable myocardium may benefit from revascularization, while those with non-viable myocardium will not. As an example, PET scans are commonly performed in potential heart transplant candidates to rule out the presence of viable myocardium.

For both perfusion and viability study indications, a variety of studies have suggested that the PET scans are only marginally more sensitive or specific than SPECT scans. Therefore, the choice between a PET scan (which may not be available locally) and a SPECT scan represents another clinical issue. PET scans may provide the greatest advantage over SPECT scans in obese patients where tissue attenuation of tracer is of greater concern.

Studies of quantitative myocardial blood flow and myocardial flow reserve in patients with CAD indicates that these methods are in a developmental stage for clinical use. Current evidence is insufficient to permit conclusions about the impact on net health outcome in these patients.

Risk for Cardiovascular Heart Disease

In 1999, the American College of Cardiology (ACC) and American Heart Association (AHA) released a joint scientific statement describing the assessment of cardiovascular or coronary heart disease (CHD) risk to categorize patients for selection of appropriate interventions (available in the ACC website <http://www.acc.org>). The statement defines CHD, as derived from the Framingham Heart Study, to include angina pectoris, unstable angina or coronary insufficiency, and unrecognized myocardial infarction (MI) (defined by electrocardiogram[EKG]). The ACC/AHA scientific statement further states, “The first step in determining the patient’s risk is to calculate the number of Framingham points for each risk factor”, by using the Framingham Global Risk Assessment Scoring:

Risk Factor

Risk Points

Men

Women

Age by year:

Less than 34

-1

9

35 – 39

0

-4

40 – 44

1

0

45 – 49

2

3

50 – 54

3

6

55 – 59

4

7

60 – 64

5

8

65 – 69

6

8

70 - 74

7

8

Total Cholesterol, mg/dL*:

Less than 160

-3

-2

169 – 199

0

0

200 – 239

1

1

240 – 279

2

2

Greater than or equal to 280

3

3

HDL cholesterol, mg/dL*:

Less than 35

2

5

35 – 44

1

2

45 – 49

0

1

50 – 59

0

0

Greater than or equal to 60

-2

-3

Systolic blood pressure, mm Hg**:

Less than 120

0

-3

120 – 129

0

0

130 – 139

1

1

140 – 159

2

2

Greater than 160

3

3

Diabetes:

No

0

0

Yes

2

4

Smoker:

No

0

0

Yes

2

2

* mg dL = milligrams/deciliter

** mm Hg = millimeter of mercury as it relates to a unit of pressure equal to 0.001316 atmosphere

Adding Up the Points

Age:

Cholesterol:

HDL – C:

Blood Pressure:

Diabetes:

Smoker:

Total Points:

Additionally the 1999 ACC/AHA scientific statement explained the following tables as demonstrating the relative and absolute risk estimates for CHD in men and women as determined for Framingham scoring, including this explanation for table information, “Relative risk estimates for each age range are compared with baseline risk conferred by age alone (in the absence of other major risk factors).” Additionally described was, “Average risk refers to that observed in the Framingham population. Absolute risk estimates are given in the two right hand columns. Absolute risk is expressed as the percentage likelihood of developing CHD per decade. Total CHD risk equates to all forms of clinical CHD, whereas hard CHD includes clinical evidence of MI and coronary death. Hard CHD estimates are approximated from published Framingham data.”

In the following grids, the intermediate risk estimates (classified as moderately above average risk) will be identified as bolded and high risk as underlined. Following the last grid (for women), the keys for these symbols “*”, “#”, “++”, and “**” will be defined.

MEN

Age

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

Low Risk Level*

(2%)

(3%)

(3%)

(4%)

(5%)

(7%)

(8%)

(10%)

(13%)

Absolute Risk

Absolute Risk ++

Points#

Total CHD++

Hard CHD**

0

1.0

2%

2%

1

1.5

1.0

1.0

3%

2%

2

2.0

1.3

1.3

1.0

4%

3%

3

2.5

1.7

1.7

1.3

1.0

5%

4%

4

3.5

2.3

2.3

1.8

1.4

1.0

7%

5%

5

4.0

2.6

2.6

2.0

1.6

1.1

1.0

8%

6%

6

5.0

3.3

3.3

2.5

2.0

1.4

1.3

1.0

10%

7%

7

6.5

4.3

4.3

3.3

2.6

1.9

1.6

1.3

1.0

13%

9%

8

8.0

5.3

5.3

4.0

3.2

2.3

2.0

1.6

1.2

16%

13%

9

10.0

6.7

6.7

5.0

4.0

2.9

2.5

2.0

1.5

20%

16%

10

12.5

8.3

8.3

6.3

5.0

3.6

3.1

2.5

1.9

25%

20%

11

15.5

10.3

10.3

7.8

6.1

4.4

3.9

3.1

2.3

31%

25%

12

18.5

12.3

12.3

9.3

7.4

5.2

4.6

3.7

2.8

37%

30%

13

22.5

15.0

15.0

11.3

9.0

6.4

5.6

4.5

3.5

45%

35%

>14

26.5

>17.7

>17.7

>13.3

>10.6

>7.6

>6.6

>5.3

>4.1

>53%

>45%

WOMEN

Age

40-44

45-49

50-54

55-59

60-64

65-69

70-74

 

 

Low Risk Level*

(2%)

(3%)

(5%)

(7%)

(8%)

(8%)

(8%)

Absolute Risk

Absolute Risk ++

Points#

 

 

 

 

 

 

 

Total CHD++

Hard CHD**

0

1.0

 

 

 

 

 

 

2%

1%

1

1.0

 

 

 

 

 

 

2%

1%

2

1.5

1.0

 

 

 

 

 

3%

2%

3

1.5

1.0

 

 

 

 

 

3%

2%

4

2.0

1.3

 

 

 

 

 

4%

2%

5

2.0

1.3

 

 

 

 

 

4%

2%

6

2.5

1.7

1.0

 

 

 

 

5%

2%

7

3.0

2.0

1.2

 

 

 

 

6%

3%

8

3.5

2.3

1.4

1.0

 

 

 

7%

3%

9

4.0

2.7

1.6

1.1

1.0

1.0

1.0

8%

3%

10

5.0

3.3

2.0

1.4

1.3

1.3

1.3

10%

4%

11

5.5

3.7

2.2

1.6

1.4

1.4

1.4

11%

7%

12

6.5

4.3

2.6

1.9

1.6

1.6

1.6

13%

8%

13

7.5

5.0

3.0

2.1

1.9

1.9

1.9

15%

11%

14

9.0

6.0

3.6

2.6

2.3

2.3

2.3

18%

13%

15

10.0

6.7

4.0

2.9

2.5

2.5

2.5

20%

15%

16

12.0

8.0

4.8

3.4

3.0

3.0

3.0

24%

18%

>17

>13.5

>9.0

>5.4

>3.9

5.4

5.4

5.4

>27%

>20%

Symbols Key:

* Low absolute risk level = 10-year risk for CHD end points for the person the same age, blood pressure less than 120 mm Hg systolic and less than 80 mm Hg diastolic, serum total cholesterol - 160 to 199 mg/dL, LDL-C - 100 to 129 mg/dL (LDL = low-density lipoprotein), HDL-C - greater or equal to 45 mg/dL in men and greater or equal to 55 mg/dL in women, nonsmoker, and no diabetes mellitus. Percentages show 10-year absolute risks for total CHD endpoints.

# Points = number of points estimated from the Framingham Global Risk Assessment Scoring.

++ 10-year absolute risk for total CHD end points estimated from the Framingham data corresponding to the Framingham (Global Risk Assessment Scoring) points.

** 10-year absolute risk for hard CHD end points approximated from the Framingham data corresponding to the Framingham (Global Rish Assessment Scoring) points.

Sodium 18F-Fluoride (NaF-18) Radiotracer

NaF-18 is a diagnostic molecular imaging agent used for identification of new bone formation. Although NaF-18 was approved by the FDA in 1972, it was listed as a discontinued drug in 1984. NaF-18 is now being marketed again by PETNET Solutions (a network of PET radiopharmacies). NaF-18 is injected intravenously, and is used to define areas of altered osteogenic activity.

Rationale:

This policy was originally developed in 1990 and has been updated with searches of scientific literature through August 18, 2015. This section of the current policy has been substantially revised. The following is a summary of the key literature to date.

Oncologic Applications

This policy is based on multiple evaluations of PET, including Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessments. In the TEC Assessments, PET scanning was considered an adjunct to other imaging methods (i.e., CT, MRI, ultrasonography), often used when previous imaging studies are inconclusive or provide discordant results. In this setting, the clinical value of PET scans is the rate of discordance among imaging techniques and the percentage of time that PET scanning results in the correct diagnosis, as confirmed by tissue biopsy. Development of this medical policy also included consideration of other systematic reviews, meta-analyses, decision analyses, and cost-effectiveness analyses, including those conducted by Centers for Medicare and Medicaid Services (CMS) and the National Comprehensive Cancer Network (NCCN), as well as guidelines from the American College of Radiology, the Society for Nuclear Medicine, and others.

Breast Cancer

The 2001 TEC Assessment (19) focused on multiple applications of PET scanning in breast cancer, including characterization of breast lesions, staging axillary lymph nodes, detection of recurrence, and evaluating response to treatment. The 2003 TEC Assessment (16) reexamined all of these indications except for its role in characterizing breast lesions.

A 2013 meta-analysis by Hong et al. reported sensitivity and specificity of PET/CT in diagnosing distant metastases in breast cancer patients of 0.96 (95% confidence interval [CI], 0.90 to 0.98) and 0.95 (95% CI, 0.92 to 0.97), respectively, when 8 studies totaling 748 patients were included. (93) When the meta-analysis included 6 comparative studies totaling 664 patients, sensitivity and specificity were 0.97 (95% CI, 0.84 to 0.99) and 0.95 (95% CI, 0.93 to 0.97), compared with 0.56 (95% CI, 0.38 to 0.74) and 0.91(95% CI, 0.78 to 0.97) with conventional imaging.

Rong et al. (94) meta-analyzed 7 studies totaling 668 patients and reported that PET/computed tomography (CT) sensitivity and specificity were greater compared with bone scintigraphy for detecting bone metastasis in breast cancer patients. PET/CT sensitivity and specificity were 0.93 (95% CI, 0.82 to 0.98) and 0.99 (95% CI, 0.95 to 1.00), respectively, compared with 0.81 (95% CI, 0.58 to 0.93) and 0.96 (95% CI, 0.76 to 1.00), respectively, for bone scintigraphy.

In a meta-analysis of 8 studies (total N=873) of fludeoxyglucose F18 (FDG-PET) in women with suspicious breast lesions, Caldarella et al. (95) reported pooled sensitivity and specificity of 0.85 (95% CI, 0.83 to 0.88) and 0.79 (95% CI, 0.74 to 0.83), respectively, on a per-lesion basis. As previously noted, a false-negative rate of 15% (1 - sensitivity) may be considered unacceptable given the relative ease of breast biopsy.

A 2007 National Comprehensive Cancer Network (NCCN) review of PET concluded that PET is optional and may be useful for staging and restaging regional or distant metastasis when suspicion is high and other imaging is inconclusive. Current NCCN guidelines include an optional category 2B recommendation for FDG-PET/CT in the work-up of clinical stage IIIA breast cancer. (96) NCCN recommends against FDG-PET/CT for lower stage breast cancer due to high false-negative rates in detecting low-grade lesions or lesions less than 1 cm; low sensitivity in detecting axillary node metastasis; low prior probability of detectable metastases in these patients; and high false-positive rates. PET or PET/CT is considered most helpful when “standard staging studies are equivocal or suspicious, especially in the setting of locally advanced or metastatic disease.” Additionally, NCCN guidelines do not recommend routine use of PET scans in asymptomatic patients for surveillance and follow-up after breast cancer treatment.

Two 2012 meta-analyses pooled studies, on use of FDG PET to predict pathologic response to neoadjuvant therapy before surgery for locally advanced breast cancer. (97) These articles reported similar pooled point estimates of both sensitivity and specificity. They both concluded that PET has reasonably high sensitivity and relatively low specificity. Neither article described how PET should be used to influence patient management decisions and therefore whether health outcomes would be changed relative to decisions not based on PET results. Thus, it is unclear whether PET improves outcomes for predicting pathologic response to neoadjuvant therapy for locally advanced breast cancer.

Melanoma

In their review of management of malignant melanoma, Kumar et al. concluded that FDG-PET is of limited use in patients with early-stage disease and cannot replace sentinel node biopsy, which is more sensitive in detecting microscopic lymph node metastases. Wagner et al (17). compared FDG-PET to conventional imaging studies and concluded that FDG PET is an insensitive indicator of occult melanoma lymph node metastases in patients with melanoma because of minute tumor volumes in this population, and does not have a primary role for staging regional lymph nodes in patients with clinically localized melanoma.

In a meta-analysis of 9 studies (total N=623), Rodriquez Rivera et al. reported pooled sensitivity and specificity of FDG-PET for detecting systemic metastases in patients with stage III cutaneous melanoma of 0.89 (95% CI, 0.65 to 0.98) and 0.89 (95% CI, 0.77 to 0.95), respectively. (98)

Current NCCN guidelines for melanoma indicate that PET/CT may be used for staging and restaging for more advanced disease, such as stage III, in the presence of specific signs and symptoms. PET/CT is not recommended for stage I or II disease. (99) PET/CT also is listed as an option for surveillance screening for recurrent or metastatic disease.

UpToDate (2015) notes the following concerning PET for melanoma. (122) "We favor the use of PET/CT every six months in very high-risk melanoma patients, such as those with clinical stage III and IV (rendered disease-free by surgery). Patients, however, should be informed that the imaging studies and blood work is yet to be of proven value in terms of its impact on overall survival. In light of the new and more effective systemic therapies, additional studies are needed to better define the role of imaging in the follow-up of patients with melanoma.”

Prostate Cancer

Both a 2009 NCCN Task Force Report (98) and a 2008 Agency for Healthcare Research and Quality (AHRQ) systematic review (99) did not find sufficient evidence to support the use of PET for any indication in patients with prostate cancer. Reports showed significant overlap between benign prostatic hyperplasia, malignant tumor, local recurrence, and postoperative scarring. PET may have limited sensitivity in detecting distant metastatic disease. The AHRQ report identified only 4 studies of PET for the indications of restaging and recurrence, none of which addressed the effect of PET on management decisions.

In a 2013 meta-analysis by Umbehr et al. of 10 studies (total N=637) of initial prostate cancer evaluation, pooled sensitivity was 0.84 (95% CI, 0.68 to 0.93), and specificity was 0.79 (95% CI, 0.53 to 0.93).(100) In meta-analysis of 12 studies (total N=1055) of patients with biochemical failure after local treatment, pooled sensitivity was 0.85 (95% CI, 0.79 to 0.89), and specificity was 0.88 (95% CI, 0.73 to 0.95).

In a 2014 meta-analysis by von Eyben and Kairemo, pooled sensitivity and specificity of choline PET/CT for detecting prostate cancer recurrence in 609 patients was 0.62 (95% CI, 0.51 to 0.66) and 0.92 (95% CI, 0.89 to 0.94), respectively.(101) In an evaluation of 280 patients from head-to-head studies comparing choline PET/CT with bone scans, PET/CT identified metastasis significantly more often than did bone scanning (127 [45%] vs 46 [16%], respectively; odds ratio, 2.8; 95% CI, 1.9 to 4.1; p<0.001). The authors also reported that choline PET/CT changed treatment in 381 (41%) of 938 patients. Complete prostate specific antigen (PSA) response occurred in 101 (25%) of 404 patients.

Mohsen et al. (102) conducted a meta-analysis of 23 studies on C-11-acetate PET imaging for primary or recurrent prostate cancer. Pooled sensitivity for primary tumor evaluation was 0.75 (95% CI, 0.70 to 0.80), and pooled specificity was 0.76 (95% CI, 0.72 to 0.79). For detection of recurrence, pooled sensitivity was 0.64 (95% CI, 0.59 to 0.69), and pooled specificity was 0.93 (95% CI, 0.83 to 0.98). Although study quality was considered poor, low sensitivities and specificities appeared to limit the utility of C-11-acetate imaging in prostate cancer. C-11-acetate is not currently FDA-approved. Current NCCN guidelines for prostate cancer indicate that C-11-choline PET may be considered for biochemical failure after primary treatment, i.e., radiotherapy or radical prostatectomy, although further study is needed to determine the best use of this imaging modality in men with prostate cancer. (103) FDG or fluoride PET should not be used routinely, for initial assessment or in other settings, due to limited evidence of clinical utility.

The European Association of Urology (EAU) guidelines for prostate cancer indicate that C-11-choline PET/CT has limited value unless PSA levels exceed 1.0 ng/mL. (104) In meta-analysis of 14 studies (total N=1667) of radiolabelled choline PET/CT for restaging prostate cancer, Treglia et al. (105) reported a maximum pooled sensitivity of 0.77 (95% CI, 0.71 to 0.82) in patients with PSA rate of increase greater than 2 ng/mL per year. Pooled sensitivity was lower for patients with PSA rate of increase less than 2 ng/mL per year or with PSA doubling time of 6 months or less. In meta-analysis of 11 studies (total N=609) of radiolabelled choline PET/CT for staging or restaging prostate cancer, Von Eyben et al. reported pooled sensitivity and specificity of 0.59 (95% CI, 0.51 to 0.66) and 0.92 (95% CI, 0.89 to 0.94), respectively.80 Pooled positive predictive value (PPV) and negative predictive value (NPV) were 0.70 and 0.85, respectively.

Surveillance and Screening

Prevalence of PET Used for Surveillance

It is unknown how frequently and for which cancers PET is used for surveillance. An unsystematic attempt to find studies in which PET was apparently used for surveillance reveals some literature. Unger et al. (2004) reports the findings of 26 asymptomatic patients after treatment for cervical cancer among a larger series of patients who underwent PET in order to detect recurrence. The scans were done at a mean of 7.8 months after treatment, but the range was 2-40 months. Chung et al. (2006) reports the findings of 30 women undergoing surveillance PET among a larger series of other patients with clinical indications of recurrence of cervical cancer.

The only study that was found through unsystematic searches, and that solely examined use of surveillance PET, was by Ryu et al. (2003). In this study from Korea, 249 patients with no evidence of recurrent cervical cancer at least six months after treatment received PET scans at a variable time after treatment. Thirty-two percent of patients had positive scans, and 11.2% were clinically or histologically confirmed as having recurrences. The calculated sensitivity and specificity were 90.3% and 76.1%, respectively. Subsequent treatment and survival are not reported in this study.

Registries of PET utilization and analyses of claims data do not report, and do not appear to be capable of counting, PET scans used for surveillance.

Principles of Surveillance

Surveillance has also been called “tertiary prevention” or “monitoring.” Tertiary preventive services are those that are provided to persons who clearly have or have had a disease in order to prevent further complications. Although some might not consider surveillance for recurrent disease to be prevention, the principles of surveillance are actually similar, if not identical to, those of traditional screening tests used for initial early detection of disease.

The purpose of a regimen of surveillance is to detect recurrence or progression earlier than would have otherwise. The diagnostic characteristics of the surveillance test for patients without suspected recurrence should be consistent with a reasonable degree of accuracy for both accurate and efficient identification of recurrence. In addition, recognizing the recurrence or progression earlier than it would have without the surveillance regimen should result in clinical interventions that produce a better outcome than would have if the recurrence had been detected clinically. Thus, the cancer must be biologically more responsive to treatment at the time that it is detected with the surveillance test than it is when it is detected clinically. For example, if PET detects the recurrence at a point in time in which distant metastasis is less likely, then it is possible that a treatment of the local recurrence may be more likely to benefit the patient. This implies that the surveillance test must be able to detect the cancer at a meaningful, rather than trivially earlier, interval in time than clinical detection.

As in screening, evaluating surveillance is complicated by several potential biases when trying to determine its efficacy. Analyses of outcomes from observational data can be misleading. Lead-time bias can result in apparent longer survival in surveillance-detected cases simply due to the additional increment of time between asymptomatic detection and clinical detection of recurrence. Lead-time effects could be particularly harmful for cancer recurrence due to adverse effects of treatment.

Length-time bias and over diagnosis bias result from the preferential detection of slow-growing recurrences by surveillance tests, again resulting in an apparent, but not real, improvement in survival when comparing the outcomes of surveillance-detected cases to historical controls or to clinically detected cases. If treatments for recurrence are started simply based on the results of surveillance tests without some kind of confirmation of recurrence, an extreme form of over-diagnosis bias can occur if the surveillance tests are falsely positive. Thus, it is difficult to determine the efficacy of surveillance regimens using most kinds of observational data, such as case series data. These biases have long been recognized for traditional screening tests, leading to the recognition that randomized, clinical trials are often necessary to demonstrate the efficacy of screening tests.

However, the evidence supporting any surveillance regimen after cancer treatment is scant. Most recommended surveillance strategies appear to be recommended based on consensus, rather than rigorous trials. However, for colorectal cancer at least, recommended surveillance guidelines have some support from randomized, clinical trials. The American Society of Clinical Oncology (ASCO) guidelines recommending abdominal CT after treatment for colon cancer cite randomized, clinical trials as providing some support for this particular surveillance test (Desch et al. 2005). However, the evidence is less than definitive, as the guidelines acknowledge that several other organizations do not recommend any routine imaging studies.

Several clinical trials were completed comparing clinical visits and mammography to more intensive surveillance regimens that included bone scans, chest x-rays, and laboratory tests for women after treatment for breast cancer. The separate results of the trials and a systematic review of all trials concluded that the more intensive regimens did not improve survival (Rojas et al. 2009). Thus, for at least a few diseases, surveillance regimens have been evaluated with randomized, clinical trials leading to guidelines which in one case (colon cancer) support a particular surveillance test (CT) while in another case (breast cancer) do not recommend a particular test (bone scan).

Use of PET for surveillance may be thought to be effective without rigorous proof because it may be believed that PET is a sensitive and specific diagnostic test for cancer. In the absence of clinical trials or a rigorous trail of evidence supporting the full chain of logic that supports the utility of surveillance, and the desire to do some sort of surveillance, physicians may opt to perform what they believe is the most sensitive test. Certain literature reviews may reinforce this emphasis on the diagnostic characteristics of the test rather than evidence of improved health outcome. For example, an AHRQ technology assessment on PET appears to focus almost solely on the calculation of diagnostic characteristics of PET for various cancers (University of Alberta Evidence-based Practice Center 2008).

A published guideline statement on the use of PET for colorectal cancer cites numerous systematic reviews and meta-analyses that seem to suggest that PET has superior sensitivity and specificity to CT in detecting colorectal hepatic metastases (Fletcher et al. 2007). A cursory look at some of the studies included in these meta-analyses reveals that these conclusions may, in fact, be flawed. In one of these studies by Valk et al. (1999), patients were included in the study for suspicion of recurrence, of which one of the indications for suspicion was an abnormal CT scan. If having a positive test on one of the tests being analyzed is one of the referral criteria for being in the study, then its performance cannot be estimated in an unbiased fashion. In fact, the authors state themselves “…an unbiased determination of the accuracy of PET and CT cannot be obtained from studies of this type, in which many patients are selected for PET imaging because of positive CT findings.” However, the conclusion of the authors is that PET is more sensitive and specific than CT for detection of recurrent colorectal cancer. Another reason for viewing these results with caution is that the PET diagnostic characteristics were determined in the setting of suspected recurrence, not routine surveillance. In addition to the probability of recurrence being higher in this situation than in the surveillance setting, differences in the detectability of the recurrence, so-called “spectrum biases,” may mean that the results are not generalizable to the surveillance setting.

The justification of the use of PET for detection of suspected recurrence as stated in many guidelines tends not to be because of the additional identification of more curable or treatable recurrence (early detection), but in more accurate staging of suspected recurrence (restaging), which then often changes the treatment plan when the recurrence is discovered to be more extensive than originally thought. In this scenario, then, the improved outcome of the patients is generally not because of the overall superior outcomes of treating the recurrence (although the subset of patients that are more accurately identified as having only local recurrence will appear to have superior survival), but in the avoidance of the morbidity of radical attempts at cure. This is clearly a different scenario than that of disease surveillance; the probability of recurrent disease is high or close to one, negating for the most part the problem of false positive results. The avoidance of futile radical curative treatments is an unambiguous benefit for patients who have more extensive disease found by using PET.

A 2009 BlueCross Blue Shield Association's special report on PET for post-treatment surveillance of cancer (23) noted that there is simply inadequate direct and indirect evidence supporting the effectiveness of PET scanning for the purpose of surveillance. Reflecting this lack of evidence, current practice guidelines appear unanimously to recommend against the use of PET for surveillance. No strong support of the use of PET for surveillance was found in editorials, case reports, or other studies. The report concluded that given such problems such as lead time bias, length bias, and the uncertain diagnostic characteristics of PET in the surveillance setting, it would be difficult to determine if the effectiveness of PET for surveillance could be determined with observational data.

In summary, several biases inherent in the evaluation of surveillance as a type of screening make it difficult to assess the efficacy of PET used in this situation. Rigorous trials evaluating PET as a method of cancer surveillance to improve patient outcomes have not been carried out. Lacking such evidence, belief that PET scan is a sensitive and specific test may drive its use. However, the sensitivity and specificity of PET scan in the surveillance setting is probably unknown, and the scientific literature may very well be flawed in comparisons of PET to other imaging techniques. Use of PET to make treatment decisions may result in the appearance of superior outcomes for certain subsets of patients, but aggregate outcomes for all patients subjected to PET scanning should be accounted for.

Potential Harms of PET Surveillance

While there is potential benefit of early detection of recurrence that ideally should be demonstrated in a rigorous trial, these would need to be greater than the potential harms of such surveillance. Such harms would include any adverse effects from further testing, treatments, or procedures resulting from false-positive tests.

The test itself has substantial radiation exposure and potential for inducing cancer. A study by Huang et al. (2009) estimated that radiation doses ranged from 13.5 mSv to 32.3 mSv for a whole-body PET/CT scan depending on the particular scanning protocol and the gender of the patient. A lifetime attributable risk for cancer of up to 0.514% for a scan in a 20-year old woman was estimated, very similar to an estimate from another study analyzing the potential risk from coronary CT angiography (Einstein et al. 2007). Another study by Brix et al. (2005) estimated a radiation dose from a whole-body PET/CT scan to be about 25 mSv, consistent with the estimates from Huang et al. (2009). These estimates were based on the risk of a single scan. The potential harms mentioned above are multiplied over time when surveillance tests are repeated.

Guideline Statements and Systematic Reviews Regarding PET for Surveillance in Oncology

Guideline statements regarding the use of PET for cancer surveillance were reviewed. Statements or evidence reviews supporting the use of PET for surveillance were rarely found for any cancer. The following Guidelines and Reviews were included:

• National Comprehensive Cancer Network (NCCN) Task Force Reports regarding use of PET;

• NCCN guidelines on treatment of selected specific cancers;

• AHRQ Technology Assessment on PET;

• Technology Assessment by the National Health Service Research & Development Health Technology Assessment Programme;

• CMS Technology Assessment in support of proposed coverage decision;

• American Society of Clinical Oncology (ASCO)—Convened Panel Recommendation Statement;

• Canadian Agency for Drugs and Technologies in Health (CADTH) Health Technology Assessment;

• The American College of Chest Physicians.

There is simply inadequate direct and indirect evidence supporting the efficacy of PET scanning for the purpose of surveillance. Reflecting this lack of evidence, current practice guidelines appear unanimously to recommend against the use of PET for surveillance. No strong support of the use of PET for surveillance was found in editorials, case reports, or other studies. Given such problems as lead-time bias, length-time bias, and the uncertain diagnostic characteristics of PET in the surveillance setting, it would be difficult to determine whether the efficacy of PET for surveillance could be determined with observational data. Clinical trials may be necessary to determine whether PET surveillance is effective in improving health outcomes.

Clinical utility of PET scanning in surveillance, (i.e., in performing follow-up PET scans in asymptomatic patients to detect early disease recurrence), is not well-studied. (For this policy, a scan is considered a surveillance scan if performed more than 6 months after therapy [but 12 months for lymphoma].) The 2009 NCCN Task Force report (89) stated, “PET as a surveillance tool should only be used in clinical trials.”

Additionally, NCCN guidelines for various malignancies often note that PET scans are not recommended in asymptomatic patients. For example, current NCCN guidelines for breast cancer comment that PET scans (as well as many other imaging modalities) provide no advantage in survival or ability to palliate recurrent disease and are not recommended. (98)

Positron Emission Mammography (PEM)

PEM has shown promising results in detecting primary ductal carcinoma in situ and recurrent breast disease, as well as for directing biopsy of suspicious lesions.

Raylman et al. found initial testing of the PEM/PET scanner revealed that the imaging capabilities of the system are excellent; more advanced testing is ongoing.

Berg et al. prospectively assessed the diagnostic performance of PEM scanning at four centers on 94 consecutive women with known breast cancer or suspicious breast lesions. Readers were provided clinical histories and x-ray mammograms (when available). After excluding inevaluable cases and two cases of lymphoma, PEM lesions were correlated with histopathology for 92 lesions in 77 women. Overall, PEM sensitivity for detecting cancer was 90%, specificity 86%, (PPV) 88%, (NPV) 88%, accuracy 88%, and area under the receiver-operating characteristic curve (Az) 0.918. In three patients, cancer foci were identified only on PEM, significantly changing patient management. Excluding eight diabetic subjects and eight subjects whose lesions were characterized as clearly benign with conventional imaging, PEM sensitivity was 91%, specificity 93%, PPV 95%, NPV 88%, accuracy 92%, and Az 0.949 when interpreted with mammographic and clinical findings. The study concluded that FDG PEM has high diagnostic accuracy for breast lesions, including DCIS (ductal carcinoma in situ).

The National Institutes of Health (NIH) have several studies underway for PEM. An ongoing phase IV study (identified as NCT00484614) is a prospective multi-center clinical trial to evaluate the role of high resolution PEM, used in combination with the radiotracer FDG, for pre-surgical planning in women with newly diagnosed breast cancer who are considered candidates for breast conserving surgery (i.e., lumpectomy) after full routine workup (including mammography, clinical breast exam, and additional ultrasound). Participants undergo both contrast enhanced MRI and PEM imaging. In order to control for potential bias in interpretation of the second examination (i.e., PEM or MRI), the order of interpretation of these examinations is randomly assigned at study entry. The primary objective of the study is to determine changes in surgical management resulting from PEM or MRI or both, separately and in conjunction with conventional imaging, and to determine whether these changes were appropriate (i.e., to excise malignancy) or inappropriate (e.g., wider excision or mastectomy for what proved to be benign disease).

A phase III trial (NCT00896649) is studying PEM to see how well it works compared with standard mammography in women with dense breast tissue or who are at high risk of breast cancer. This study is currently accepting participants.

Another study (NCT00981812) is not yet open for participant recruitment. The purpose of this research study is to evaluate the ability to perform breast biopsies using PEM and the Stereo Navigator software and to see whether PEM and Stereo Navigator help the doctors obtain results sooner (in fewer clinical visits) than if they use MRI, mammography and/or ultrasound.

In September 2009, the National Cancer Institute et al. of the NIH made a presentation titled “Diagnosis and Management of Ductal Carcinoma In Situ (DCIS)” at the NIH State-of-the-Science Conference. In their summary of future research directions they stated, “…Work must be continued with attention to newer imaging technologies, such as tomosynthesis, breast computed tomography, breast positron emission mammography, breast-specific gamma imaging, and others still in earlier phases of development.”

Caldarella et al. (95) conducted a systematic review with meta-analysis of PEM studies in women with newly discovered breast lesions suspicious for malignancy. Literature was searched through January 2013. Eight studies (total N=873) of 10 or more patients (range, 16-388) that used histological review as criterion standard, including the 3 studies described in detail next, were included. Pooled sensitivity and specificity were 85% (95% CI, 83 to 88; I2=74%) and 79% (95% CI, 74 to 83; I2=63%), respectively. Pooled PPVs and NPVs were 92% and 64%, respectively. Comparator arms were not pooled. Other limitations of the study included substantial statistical heterogeneity in meta-analyses and lack of blinding of both PEM and histopathology readers in individual studies.

Other Indications for PEM

No full-length, published studies were identified that addressed other indications for PEM, including management of breast cancer and evaluation for recurrence of breast cancer.

In 2014, the AHRQ published a technical brief on imaging techniques for treatment evaluation of metastatic breast cancer. (106) PEM was not included.

Yamamoto et al. (107) in Japan conducted a retrospective review of 54 women younger than 50 years (mean age, 43 years) who were suspected of or diagnosed with breast cancer (n=45) or presented for screening (n=9). The objective of the study was to evaluate performance characteristics of PEM compared with WBPET. All women underwent both tests. Imaging sensitivity overall was statistically greater with PEM (79% vs 48%), driven by increased sensitivity for tumors 1 cm or smaller (67% vs 13%). That is, sensitivity for larger tumors did not differ statistically between groups. Specificity of PEM and WBPET was comparable (91% vs 94%, respectively). Major limitations of this study include its small size, data-driven (and unreported) threshold for PEM positivity, and uninformative comparator.

Cardiac Applications

In 2003, the American College of Cardiology (ACC) and the American Heart Association (AHA) published updated guidelines for cardiac radionuclide imaging. Cardiac applications of PET scanning were included in these guidelines. The ACC/AHA guidelines categorize specific indications for PET scanning:

Class I is defined as conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective.

Class IIa is defined as conditions for which there is conflicting evidence or a divergence of opinion but the weight of evidence/opinion is in favor of usefulness/efficacy.

Class IIb is similar to Class IIa except that the usefulness/efficacy is less well established by evidence/opinion.

The medically necessary indications for PET myocardial perfusion studies in this policy are consistent with Class I and Class IIa indications in the ACC guidelines.

Myocardial Viability

PET has perhaps been most thoroughly researched as a technique to assess myocardial viability to determine candidacy for a coronary revascularization procedure. For example, a patient with a severe stenosis identified by coronary angiography may not benefit from revascularization if the surrounding myocardium is non-viable. A fixed perfusion defect, as imaged on SPECT scanning or stress thallium echocardiography, may suggest non-viable myocardium. However a PET scan may reveal metabolically active myocardium, suggesting areas of hibernating myocardium that would indeed benefit from revascularization. The most common PET technique for this application consists of N-13 ammonia as a perfusion tracer and FDG as a metabolic marker of glucose utilization. A pattern FDG uptake in areas of hypoperfusion (referred to as FDG/blood flow mismatch) suggests viable, but hibernating myocardium. The ultimate clinical validation of this diagnostic test is the percentage of patients who experience improvement in left ventricular dysfunction after revascularization of hibernating myocardium, as identified by PET scanning.

SPECT scanning may also be used to assess myocardial viability. For example, while initial myocardial uptake of thallium-201 reflects myocardial perfusion, redistribution after prolonged periods can be used as a marker of myocardial viability. Initial protocols required redistribution imaging after 24 to 72 hours. While this technique was associated with a strong positive predictive value, there was a low negative predictive value, i.e., 40% of patients without redistribution nevertheless showed clinical improvement after revascularization. The negative predictive value has improved with the practice of thallium reinjection. Twenty-four to 72 hours after initial imaging, patients receive a reinjection of thallium and undergo redistribution imaging.

The ACC/AHA guidelines conclude that PET imaging “appears to have slightly better overall accuracy for predicting recovery of regional function after revascularization in patients with left ventricular (LV) dysfunction than single photon techniques (i.e., SPECT scans).” However, the ACC guidelines indicate that either PET or SPECT scans are Class I indications for predicting improvement in regional and global LV function and natural history after revascularization, and thus do not indicate a clear preference for either PET or SPECT scans in this situation.

Further supporting the equivalency of these two testing modalities, Siebelink and colleagues performed a prospective randomized study comparing management decisions and outcomes based on either PET imaging or SPECT imaging in 103 patients with chronic coronary artery disease and left ventricular dysfunction who were being evaluated for myocardial viability. Management decisions included drug therapy or revascularization with either angioplasty or coronary artery bypass grafting. This study is unique in that the diagnostic performance of the two studies was tied to the actual patient outcomes. No difference in patient management or cardiac event-free survival was demonstrated between management based on the two imaging techniques. The authors concluded that either technique could be used for management of patients considered for revascularization with suspicion of jeopardized myocardium.

Myocardial Perfusion

In patients with symptoms suggestive of coronary artery disease (CAD), a central clinical issue is to determine whether a coronary angiogram is necessary for further work-up. A variety of non-invasive imaging tests, including PET (using rubidium-82) and SPECT scans, have been investigated as a means of identifying reversible perfusion defects, which may reflect coronary artery disease, and thus identify patients who may benefit from further work-up with an angiogram. The following table summarizes the ACC guidelines for myocardial reperfusion for both SPECT and PET scans in patients with an intermediate risk of coronary artery disease

Indication

SPECT Class

PET Class

Identify extent, severity, and location of ischemia (SPECT protocols vary according to whether patient can exercise).

I

IIA

Repeat test after 3–5 years after revascularization in selected high-risk asymptomatic patients (SPECT protocols vary according to whether patients can exercise).

IIa

As initial test in patients who are considered to be at high risk (i.e., patients with diabetes or those with a more than 20% 10-year risk of a coronary disease event) (SPECT protocols vary according to whether patients can exercise).

IIa

Myocardial perfusion PET when prior SPECT study has been found to be equivocal for diagnostic or risk stratification purposes.

NA

I

As noted in the table, the data and consensus opinion (as reflected by a Class I designation) favors limiting a PET scan to those situations in which a prior SPECT scan is inconclusive. In the text summary, the guidelines note, “Overall, because of the higher resolution of PET and the routine application of attenuation correction, it is probable that sensitivity and specificity are slightly higher for PET compared with SPECT, but there is not a robust database of head-to-head comparisons.” The previous 1995 version of the guidelines stated, “PET is an expensive imaging modality, and whether the greater cost of PET is justified by a possible improvement in diagnostic accuracy requires further rigorous study. Thus, until data from large-scale, definitive studies are published, PET is considered an effective modality for the noninvasive diagnosis of coronary artery disease but should be considered for routine diagnostic purposes only if the costs of PET are equivalent to or less than the costs of SPECT imaging in the same community.” This discussion of the relative costs of PET and SPECT has been eliminated in the 2003 version of the guidelines.

Studies continued to show the equivalence of SPECT and PET. As one example, Slart and colleagues concluded that there was overall good agreement between SPECT and PET for the assessment of myocardial viability in patients with severe LV dysfunction. Comparative studies reported on test accuracy and did not address impact on clinical outcomes.

While comparative studies were identified for SPECT compared to PET in the evaluation of CAD, the comparative data are still limited. Using a thorax-cardiac phantom, Knesaurek concluded that PET was better at detecting smaller defects. In this study, a 1 cm (centimeter) insert was not detectable by SPECT, yet it was detectable using PET. Merhige reported on outcomes of non-contemporaneous patients with similar probabilities of CAD who were evaluated by SPECT or PET. In this study involving PET scans done at one center compared to those evaluated by SPECT, those receiving PET evaluations had lower rates of angiography (13% versus 31%) and revascularization (6% versus 11%) with similar rates of death and MI at one year of follow-up. These results were viewed as preliminary and additional comparative studies showing impact on outcomes are needed. Another publication also described the PAREPET study, which will determine whether the amount of viable dysfunctional myocardium and/or sympathetic dysinnervation is associated with the risk of sudden cardiac death.

The sensitivity and specificity of PET may be slightly better than SPECT. However, their diagnostic utilities are similar in terms of altering disease risk in a manner affecting subsequent decision making among patients with intermediate pretest probability of CAD. For example, a patient with a 50% pretest probability of CAD would have a 9% post-test probability of CAD following a negative PET scan compared to 13% after a negative SPECT. In either case, further testing would not likely be pursued.

Another consideration is that there are fewer indeterminate results with PET than SPECT. A retrospective study by Bateman et al. matched 112 SPECT and 112 PET studies by gender, body mass index, and presence and extent of CAD, and they were compared for diagnostic accuracy and degree of interpretative certainty (age 65 years; 52% male; mean body mass index (BMI) = 32 kg/m2; 76% with CAD diagnosed on angiography). Eighteen of 112 (16%) SPECT studies were classified as indeterminate compared to 4 of 112 (4%) PET studies. Liver and bowel uptake were believed to affect 6 of 112 (5%) PET studies, compared to 46 of 112 (41%) SPECT studies. In obese patients (BMI > 30), the accuracy of SPECT was 67% versus 85% for PET; accuracy in nonobese patients was reported to be 70% for SPECT and 87% for PET. Therefore, for patients with intermediate pretest probability of coronary artery disease, one should start with SPECT testing and only proceed to SPECT in indeterminate cases. Additionally, since obese patients are more prone to liver and bowel artifact, PET testing is advantageous over SPECT in severely obese patients.

In 2005, a joint statement from the Canadian Cardiovascular Society, Canadian Association of Radiologists, Canadian Association of Nuclear Medicine, Canadian Nuclear Cardiology Society, Canadian Society of Cardiac Magnetic Resonance recommended (Class I recommendation, level B evidence) “PET scanning for patients with intermediate pretest probability of CAD who have nondiagnostic noninvasive imaging tests or where such a test does not agree with clinical diagnosis, or may be prone to artifact that could lead to an equivocal other test, such as obese patients.”

While comparative studies were identified for SPECT compared to PET in the evaluation of coronary artery disease, the comparative data are still limited. Using a thorax-cardiac phantom, Knesaurek and Machac concluded that PET was better at detecting smaller defects. In this study, a 1-cm insert was not detectable by SPECT yet it was detectable using PET. Merhige and colleagues reported on outcomes of non-contemporaneous patients with similar probabilities of coronary artery disease that were evaluated by SPECT or PET. In this study involving PET scans done at one center compared to those evaluated by SPECT, those receiving PET evaluations had lower rates of angiography (13% versus 31%) and revascularization (6% and 11%) with similar rates of death and myocardial infarction at one year of follow-up. These results are viewed as preliminary and additional comparative studies showing impact on outcomes are needed. Another publication also described the PAREPET study that will determine whether the amount of viable dysfunctional myocardium and/or sympathetic dysinnervation is associated with the risk of sudden cardiac death.

A review by Di Carli and Hachamovitch describes the current and potential diagnostic uses of cardiac PET and is in agreement with the policy statements. The Study of Perfusion and Anatomy’s Role in CAD (SPARC) trial is recruiting patients to evaluate the role of cardiac PET/CT for the diagnosis of coronary artery disease. To date, there are no articles from the PAREPET or SPARC trials.

Published evidence on the utility of PET scanning for cardiac sarcoidosis is limited due to the relatively small numbers of patients with this condition. A recent review article concluded that imaging studies had incremental value when combined with clinical evaluation and/or myocardial biopsy in the diagnosis of cardiac sarcoidosis. This review reported that cardiac magnetic resonance imaging (MRI) was the more established imaging modality in diagnosing sarcoidosis, with an estimated sensitivity of 100% and specificity of 80%. There is limited evidence to define the sensitivity, specificity or predictive value of PET scanning for this purpose, but it appears to have reasonably good accuracy based on small series of patients.

In 2011, BCBSA requested clinical input from physician specialty societies and academic medical centers. Based on the input BCBSA received, coverage was expanded for an additional indication on the workup of cardiac sarcoidosis. Also, clinical input received in June 2011 was generally in agreement on the medical necessity of PET for myocardial viability or for patients with an indeterminate SPECT scan. However, input varied on using a strict BMI cutoff to define patients in whom a SPECT scan would be expected to be suboptimal. Therefore, the BMI requirements have been removed and replaced with suboptimal quality SPECT scan on the basis of body habitus.

Quantified Myocardial Blood Flow

Several publications describe the use of PET imaging to quantify both myocardial blood flow and MFR (MFR, defined as stress myocardial blood flow/rest myocardial blood flow). (108, 109) However, as noted in an accompanying editorial (110) and by subsequent reviewers, (111) larger prospective clinical trials are needed to understand the clinical utility of these approaches. For example, Stuijfzand et al. (2015) used 15-O [H2O] PET imaging in 92 patients with 1-2 vessel disease to quantify myocardial blood flow, myocardial flow reserve, and “relative flow reserve” (defined as stress myocardial blood flow in a stenotic area/stress myocardial blood flow in a normal perfused area). (112) Relative flow reserve was evaluated as a potential noninvasive alternative to fractional flow reserve (FFR) on coronary angiography. Using optimized cut points for PET detection of hemodynamically significant CAD (FFR as reference standard), AUC analysis showed similar diagnostic performance for all 3 measures (0.76 [95% CI, 0.66 to 0.86] for myocardial blood flow; 0.72 for MFR [95% CI, 0.61 to 0.83]; and 0.82 [95% CI, 0.72 to 0.91] for relative flow reserve; p>0.05 for all comparisons).

Taqueti et al. (2015) evaluated the association between MFR (called coronary flow reserve in this study) and cardiovascular outcomes in 329 consecutive patients referred for invasive coronary angiography after stress PET perfusion imaging. (113) Patients with a prior history of coronary artery bypass grafting (CABG) or heart failure, or with left ventricular ejection fraction (LVEF) less than 40%, were excluded. Patients underwent rubidium-82 (Rb-82) or N-13 ammonia PET imaging and selective coronary angiography. MFR was calculated as the ratio of stress to rest myocardial blood flow for the whole left ventricle. The primary outcome was a composite of cardiovascular death and hospitalization for heart failure. These outcomes were chosen because they are thought to be related to microvascular dysfunction, which impacts PET myocardial blood flow measures, as opposed to obstructive CAD, which characteristically presents with myocardial infarction and/or revascularization. Patients were followed for a median of 3.1 years (interquartile range, 1.7-4.3) for the occurrence of major adverse cardiovascular events (MACE, comprising death, cardiovascular death, and hospitalization for heart failure or myocardial infarction). During follow-up, 64 patients (19%) met the primary composite end point. In a multivariate model that included pretest clinical score (to determine the pretest probability of obstructive, angiographic CAD), LVEF, left ventricular ischemia, early revascularization (within 90 days of PET imaging), and Coronary Artery Disease Prognostic Index, MFR was statistically associated with the primary outcome (hazard ratio [HR] per 1 unit decrease in continuous MFR score, 2.02 [95% CI, 1.20 to 3.40]). Using binary classification defined by median MFR, incidence of the primary outcome was 50% in patients with low or high CFR. A statistically significant interaction between CFR and early revascularization by CABG was observed: Event-free survival for patients with high CFR who underwent early revascularization was similar in groups who received CABG (n=17) or percutaneous coronary intervention (PCI; n=72) or no revascularization (n=79); among patients with low CFR who underwent early revascularization, event-free survival was significantly better in the CABG group (n=22) compared with the PCI group (n=85; adjusted log-rank test, p=0.006) and the no-revascularization group (n=57; adjusted log-rank test, p=0.001).

In 2011, Ziadi et al. reported a prospective study of the prognostic value of myocardial flow reserve (MFR) with Rb-82 PET in 704 consecutive patients assessed for ischemia. (114) Ninety-six percent of patients (n=677) were followed for a median of 387 days; most (90%) were followed up by telephone. The hypothesis tested was that patients with reduced flow reserve would have higher cardiac event rates and that Rb-82 MFR would be an independent predictor of adverse outcomes. Primary outcome was the prevalence of hard cardiac events (myocardial infarction and cardiac death); secondary outcome was prevalence of MACE (comprising cardiac death, myocardial infarction, later revascularization, and cardiac hospitalization). Patients with a normal summed stress score (SSS) but impaired MFR had a significantly higher incidence of hard events (2% vs 1.3%) and MACE (9% vs 3.8%) compared with patients who had preserved MFR. Patients with abnormal SSS and impaired MFR had a higher incidence of hard events (11.4% vs 1.1%) and MACE (24% vs 9%) compared with patients who had preserved MFR. Rb-82 MFR was an independent predictor of cardiac hard events (HR: 3.3) and MACE (HR=2.4) over SSS. Three patients (0.4%) were classified up and 0 classified down with MFR in the multivariate model (p=0.092).

Murthy et al. (2011) examined the prognostic value of Rb-82 PET MFR (called coronary flow reserve in this study) in a retrospective series of 2783 patients referred for rest/stress PET myocardial perfusion imaging. (115) Coronary flow reserve was calculated as the ratio of stress to rest myocardial blood flow using semi quantitative PET interpretation. Primary outcome was cardiac death over a median follow-up of 1.4 years. Prognostic modeling was done with a Cox proportional hazards model. Adding MFR to a multivariate model containing clinical covariates (e g., CAD risk factors and CAD history) significantly improved model fit and improved the c index, a measure of discrimination performance, from 0.82 to 0.84 (p=0.02). MFR was a significant independent predictor of cardiac mortality and resulted in improved risk reclassification. In 2012, these authors reported that the added value of PET MFR was observed in both diabetic and nondiabetic patients.

Studies of quantitative myocardial blood flow and myocardial flow reserve in patients with CAD indicates that these methods are in a developmental stage for clinical use. Current evidence is insufficient to permit conclusions about the impact on net health outcome in these patients.

Evidence from the medical literature supports the use of PET scanning to assess myocardial viability in patients with severe LV dysfunction who are being considered for revascularization. Results of primary studies and recommendations from specialty societies conclude that PET scanning is at least as good as, and likely superior, to SPECT scanning for this purpose. For assessing myocardial perfusion in patients with suspected coronary artery disease, PET scanning is less likely than SPECT scanning to provide indeterminate results. Therefore, PET scanning is also useful in patients with an indeterminate SPECT scan, as well as in patients whose body habitus is likely to result in indeterminate SPECT scans, for example patients with moderate to severe obesity. For patients who are undergoing a workup for cardiac sarcoidosis, MRI is the preferred initial test. However, for patients who are unable to undergo MRI, such as patients with a metal implant, PET scanning is the preferred test.

Miscellaneous (noncardiac, nononcologic) Indications

Review articles have discussed the potential applications for PET in various neurological and psychological conditions. Henry and Van Heertum (50) suggested that “interictal FDG PET can be used in presurgical epilepsy evaluations to reliably: 1) determine the side of anterior temporal lobectomy, and in children the area of multilobar resection, without intracranial electroencephalographic recording of seizures; 2) select high-probability sites of intracranial electrode placement for recording ictal onsets; and 3) determine the prognosis for complete seizure control following anterior temporal lobe resection.” The performance data for PET localization of seizure foci has already been established. It is suggested that FDG PET might also be used to localize and minimize the placement of intracranial electrodes that could reduce the morbidity associated with intracranial monitoring, even if invasive monitoring was not avoided altogether.

Parsey and Mann state that “brain imaging is not yet part of clinical practice in psychiatry,” and describe the various PET tracers and applications currently being investigated. PET radiotracers include the use of 18F-FDG to track metabolic activity, 15-O-water as a marker for cerebral blood flow, and a variety of 11-C tagged neuroreceptor markers to study serotonergic or dopaminergic activity as well as psychotropic drug effects.

A scientific statement from the AHA provides guidelines and recommendations for perfusion imaging in cerebral ischemia. The authors state that “although the development of these techniques has been fascinating, their role in evaluating a variety of diseases of the CNS [central nervous system] is controversial.” This report mentions that “oxygen extraction fraction (OEF) as measured with PET scanning” is being used in a new national trial to help “define the patient population with occlusive vascular disease at risk for stroke and the potential of an EC-IC [extracranial-intracranial] bypass to decrease that risk.” This report further states that “other types of perfusion imaging with challenge tests may act as surrogate techniques for the more elaborate and expensive PET-OEF technique.”

Two additional studies were identified exploring the use of FDG PET to assist in the differential diagnosis of infection in musculoskeletal conditions. Schmitz et al. evaluated 16 consecutive subjects with suspected spondylodiscitis on the basis of clinical and imaging findings who underwent surgical histopathological evaluation. Interpretation of FDG PET was blinded to clinical information and final diagnosis. This study reported that FDG PET was able to identify the presence of spondylodiscitis in all 12 subjects who had surgically proven infection (100% sensitivity). Among the four cases without evidence of infection at surgery, PET was truly negative in three cases with either degenerative changes or fracture and falsely positive in one patient who had a spinal sarcoma but no associated infection (75% specificity). A study by Manthey et al. explored the use of FDG-PET for differentiating synovitis, loosening, and infection in 23 patients who had 14 hip and 14 knee prostheses, but PET interpretations were not clearly blinded. Results found that PET identified four of four cases with periprosthetic infection and four of five cases with periprosthetic loosening, and there were true-negative PET results in three cases without evidence of infection, loosening, or synovitis. Confirmation of these favorable preliminary results in well-designed, prospective studies including larger numbers of patients is needed.

In a systematic review and meta-analysis of diagnostic imaging to assess chronic osteomyelitis, the authors reviewed studies through July 2003 on six imaging approaches to chronic osteomyelitis, including fluorodeoxyglucose PET. The study concluded that PET is the most accurate mode (pooled sensitivity = 96% [95% CI: 88%-99%]; pooled specificity = 91% [95% CI: 81%-95%]) for diagnosing chronic osteomyelitis. Leukocyte scintigraphy is adequate in the peripheral skeleton (sensitivity = 84% [95% CI: 72%-91%]; specificity = 80% [95%CI: 61%-91%]), but is inferior in the axial skeleton (sensitivity = 21% [95% CI: 11%-38%]; specificity = 60% [95%CI: 39%-78%]). The assessment of PET is based on four prospective, European studies published between 1998 and 2003, with a total of 1,660 patients. However, the study populations vary and include the following: 1) 57 patients with suspected spinal infection referred for FDG PET and who had previous spinal surgery, but not “recently;” 2) 22 trauma patients scheduled for surgery who had suspected metallic implant-associated infection; 3) 51 patients with recurrent osteomyelitis or osteomyelitis symptoms for more than six weeks, 36 in the peripheral skeleton and 15 in the central skeleton; and 4) 30 consecutive non-diabetic patients referred for possible chronic osteomyelitis. The results appear to be robust across fairly diverse clinical populations, which strengthen the conclusions. A clinical trial funded by the U.S. National Institutes of Health at the University of Pennsylvania to look at the use of FDG PET in the complicated diabetic foot started in 2002 and began enrolling patients in March 2007, toward a target of 240 patients. This trial may provide additional information on the use of PET in this specific population.

Alzheimers Disease (AD) and Dementia

The role of PET in dementia is an active area for research. In a quasi-systematic review (quality assessment of included studies was not reported), Davison et al. 2014 (34) reported diagnostic performance of FDG-PET in 3 studies (total N=197) that used histopathology as reference standard. ) In patients with or without a clinical diagnosis of AD, sensitivity was 84%, and specificity was 74%; in patients with memory loss or dementia, sensitivity was 94%, and specificity was approximately 70%. In comparison, in 173 patients with memory loss or dementia (3 studies), sensitivity and specificity of SPECT were 63% to 87% and 73% to 90%, respectively. For predicting conversion from mild cognitive impairment (MCI) to AD, sensitivity and specificity of PET were 82% to 89% and 78% to 85%, respectively, compared with 81% to 84% and 70% to 90%, respectively, for SPECT. Information about health outcomes in patients undergoing PET or SPECT imaging was not reported.

Research continues on efforts to use PET to identify AD and differentiate it from other types of dementia. For example, a 2008 multicenter, international study with 548 patients, including normal patients and those with MCI, AD, frontotemporal dementia, and dementia with Lewy bodies, used Neurological Statistical Image Analysis (Neurostat, University of Washington) to process the results. (35) Excluding patients with MCI, the sample was split in half, with key PET findings identified on half of the data set and validated on the second half of the data set. Disease-specific PET patterns correctly classified 94% of unimpaired patients, 95% AD, 92% dementia with Lewy bodies, and 94% frontotemporal dementia (p<0.001). PET patterns were also 98% sensitive and 92% specific (p<0.001) in distinguishing MCI from unimpaired patients. While interesting, these findings need to be replicated on a less selected sample, i.e. one that includes patients with MCI. Also, the reference standard used was clinical diagnosis, so the incremental value, if any, of PET imaging over clinical judgment alone could not be determined. More generally, evidence of clinical utility would require demonstrating that PET improved diagnostic accuracy and that earlier or more accurate diagnosis led to treatment changes that improved health outcomes.

One of the challenges in evaluating the use of PET to distinguish among dementias is identifying what serves as the reference standard. Durand-Martel et al. noted in 2010 that the sensitivity of clinical diagnosis for AD varies between 75% and 98%, with an average of 82%. (116) Therefore, comparing PET results with clinical diagnosis can be confounded by the fact that the clinical diagnosis itself may not be accurate. Durand-Martel et al. asserted that autopsy results should serve as the reference standard in studies on the use of FDG-PET for dementia; they identified only 5 studies with 20 patients or more in which results of both FDG-PET imaging and autopsy were presented.

Another recent research interest is the potential use of PET scan results as a biomarker for progression to AD. It is difficult to evaluate treatments that may prevent or delay the onset of dementia in individuals with MCI because a relatively small number of study participants will progress to AD during the follow-up period. A 2011 prospective study by Herholz et al. in the U.K. used a quantitative PET score previously devised by this research group to evaluate disease progression; a software program was available to calculate the score.(117) The study included 94 patients with MCI: 40 patients with mild AD, and 44 healthy controls. Participants received 4 PET scans and clinical assessments over 2 years. By the 2-year followup, 30 (32%) of 94 patients with mild MCI had progressed to MCI: 7 (7%) reverted to normal cognitive function, and 57 (61%) remained MCI. Two (4.5%) of 44 healthy controls had progressed to MCI. All of the individuals with AD at baseline remained in that category. The proportion of patients with abnormal PET scores at baseline was 85% in the AD group, 40% in the MCI group, and 11% in the control group. An abnormal PET score at baseline had a sensitivity to predict disease progression of 0.57 and a specificity of 0.67. The area under the ROC curve was 0.75 for PET scores. Areas under the ROC curve for predicting disease progression for the outcome measures MMSE and the Alzheimer’s disease Assessment Scale?Cognitive were 0.66 and 0.68, respectively. Conclusions about the utility of using this PET score in clinical practice cannot be drawn from the Herholz study; additional research is needed to evaluate whether patient management decisions using the PET score results in improved health outcomes.

A 2012 meta-analysis (118) pooled 7 studies of FDG PET and 6 studies of PET with carbon-11 Pittsburgh Compound B (PIB) for prediction of conversion to AD among patients with MCI. Areas under the receiver operating characteristic (ROC) curve were 0.88 for FDG PET and 0.85 for PIB-PET. This report lacked comparisons with other means of predicting conversion from MCI to AD. It also lacked a discussion of how PET might influence treatment decisions and whether use of PET improves health outcomes.

In 2014, these researchers published a Cochrane review addressing the same question. (119) Literature was searched through 2012, and 9 cohort studies of PIB-PET in patients with MCI were included (total N=274). Study quality was limited due to poor reporting. Across all trials, 112 patients (41%) converted to AD. Range of reported sensitivities and specificities was 83% to 100% and 46% to 88%, respectively. Because of heterogeneity across trials in the conduct of PIB-PET and in cutoffs used to indicate a positive test, meta-analysis was not done. It should be noted that much of the present interest in detecting AD early is to develop and test treatments that may affect disease progression. This is clearly an important goal, but several important challenges must be overcome before PET imaging is used routinely in clinical practice to detect preclinical AD, so that treatment can be started. Additionally, other methods of diagnosing AD that do not involve imaging are being explored. Due to the lack of direct evidence that this imaging technique will result in a change in management that will improve patient outcomes, PET for AD and dementia would be considered experimental, investigational and/or unproven.

Vasculitis

In 2011, Treglia et al. published a systematic review of PET and PET/CT in patients with large-vessel vasculitis. (26) The investigators identified 32 studies with a total of 604 vasculitis patients. The authors did not pool findings of the studies. They concluded that PET and PET/CT may be useful for initial diagnosis and assessment of severity of disease and that the role of these imaging methods in monitoring treatment response is unclear. They also concluded that “given the heterogeneity between studies with regard to PET analysis and diagnostic criteria, a standardization of the technique is needed.” The studies cited in support of using PET for diagnosing large vessel vasculitis had small sample sizes; 1 study included (25) vasculitis patients and 44 controls; the others had total sample sizes of fewer than 20 patients. Lehmann et al. in Germany published a study after the Treglia review (2011). (120) PET scans of 20 patients with giant cell arteritis or Takayasu arteritis, and 20 healthy controls were retrospectively reviewed by 2 experienced nuclear medicine experts on a blinded basis. PET was found to have a sensitivity of 65% and a specificity of 80% for identifying patients with a diagnosis of large vessel vasculitis. The 2 reviewers agreed on the diagnosis in 34 (85%) of 40 of scans; interrater agreement (Cohen’s) was 0.70. The authors concluded that, due to low sensitivity and specificity, the diagnosis of large vessel vasculitis should not be based solely on PET findings. Study limitations included its retrospective study design and exclusion of individuals with suspected, rather than established, large vessel vasculitis.

The Lehmann study previously described was included in a 2014 systematic review of FDG-PET in giant cell arteritis. (121) A standardized method for assessing vascular inflammation based on the intensity of FDG uptake is currently lacking, and the investigators sought to compare the diagnostic performance of qualitative and semiquantitative methods. Of 19 included studies, 10 used qualitative FDG uptake criteria to characterize inflammation, 6 used semiquantitative criteria, and 3 (including the Lehmann study) used both. Overall, qualitative methods were more specific but less sensitive than semiquantitative methods. Diagnostic performance varied by vessel and by thresholds (cutoffs) for positivity. For qualitative methods, sensitivity and specificity were 56% to 77% and 77% to 100%, respectively; positive predictive value (PPV) and negative predictive value (NPV) were 93% to 100% and 70% to 82%, respectively. For semiquantitative methods, sensitivity and specificity were 58% to 90% and 42% to 95%, respectively; PPV and NPV were 79% to 89% and 95% to 98%, respectively. For mixed methods, sensitivity and specificity were 65% to 100% and 45% to 100%, respectively.

PET for selected patients with epilepsy and patients with chronic osteomyelitis may be considered medically necessary. There is insufficient evidence on the value of PET for other miscellaneous (noncardiac, nononcologic) indications. Studies are needed that demonstrate that PET will result in a change in management that will improve patient outcomes to determine that it is a clinically useful test.

Sodium 18F-Fluoride (NaF-18) Radiotracer

Although there are ongoing trials to compare NaF-18 to traditional technetium bone scan for oncologic use, literature is sparse on uses of NaF-18 for other indications, such as osteomyelitis. The Society of Nuclear Medicine (SNM) Guideline for Sodium18 F-Fluoride PET/CT Bone Scans state that no appropriateness criteria have been developed to date, but that PET/CT 18F bone scans may be used to identify skeletal metastases. However, insufficient information exists to recommend in other conditions, which they list, including back pain, osteomyelitis, arthritis, osteonecrosis of the mandible, complications of prosthetic joints, etc.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

78459, 78491, 78492, 78608, 78609, 78811, 78812, 78813, 78814, 78815, 78816

HCPCS Codes

A9515, A9580, A9587, A9588, A9597, A9598, C9461, G0219, G0235, G0252

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessments: Chicago, IL:

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Policy History:

Date Reason
3/1/2016 Document updated with literature review. The following coverage language criterion, specific to lymphoma was changed under subsequent treatment strategy planning for oncologic indications to now read: “PET or PET/CT imaging for subsequent treatment strategy planning may be considered medically necessary when the initial diagnostic PET criteria were met and PET is needed: for the purpose of detecting residual disease within 12 months after completion of therapy for lymphoma or within 6 months after completion of therapy for all other malignancies”. In addition, the following note was added under surveillance of asymptomatic patients after completion of therapy for malignancy: “NOTE: Surveillance utilizing PET or PET/CT is defined as a scan performed for patients without signs or symptoms of cancer recurrence who are six (6) months or more from completion of cancer treatment or 12 months or more from completion of treatment for lymphoma”.
10/15/2015 Document updated with literature review. The following was added as an experimental, investigational and/or unproven indication for cardiac applications of positron emission tomography: Cardiac positron emission tomography scanning is considered experimental, investigational and/or unproven for quantification of myocardial blood flow in patients diagnosed with coronary artery disease. The following editorial clarification made to investigational, experimental and unproven exclusions specific to melanoma to note: PET or PET/CT is considered experimental, investigational and/or unproven for evaluation of patients with clinically localized melanoma who are candidates to undergo sentinel node biopsy.
1/1/2014 The following was added to Coverage: Sodium 18F-Fluoride (NaF-18) radiotracer for positron emission tomography (PET) bone scans is considered experimental, investigational and unproven for non-oncologic indications, including but not limited to osteomyelitis.
1/1/2012 Document updated with literature review for cardiac applications of PET. The following changes were made: 1) Requirements for cardiac PET scanning to assess myocardial perfusion defects was revised to eliminate the BMI cutoff and replace it with the phrase “in patients for whom SPECT could be reasonably expected to be suboptimal in quality on the basis of body habitus”; 2) An additional indication for PET scanning was added: “Cardiac PET scanning may be considered medically necessary for the diagnosis of cardiac sarcoidosis in patients who are unable to undergo MRI scanning. Examples of patients who are unable to undergo MRI include, but are not limited to, patients with pacemakers, automatic implanted cardioverter-defibrillators (AICDs) or other metal implants” ; 3) Criteria for breast cancer, prostate cancer, and melanoma were revised to only include the individual exclusions.
6/1/2011 Document updated with literature review. The following change was made: PET or PET/CT imaging for subsequent treatment strategy planning may be considered medically necessary when the initial diagnostic PET criteria were met, and the listed conditions are also met. (The list of specific diagnoses has been removed).
6/15/2010 Revised/updated document with literature review. The following changes were made: 1) New medical necessity criteria for oncologic uses of PET or PET/CT include: a) initial treatment strategy planning when criteria are met (with additional criteria and exclusions for breast cancer, melanoma, and prostate cancer); and b) subsequent treatment strategy planning for cancers of the breast, cervix, colon and rectum, esophagus, head and neck, non-small cell lung, lymphoma, melanoma, myeloma, ovary, and thyroid; c) PET or PET/CT is considered experimental, investigational and unproven for subsequent treatment strategy planning for any other tumor/cancer not listed above. (This includes, but is not limited to pancreatic cancer); d) PET or PET/CT is considered not medically necessary for patients ≥12 months after completion of therapy for lymphoma, or ≥6 months after completion of therapy for all other malignancies, unless the patient demonstrates signs, symptoms, laboratory or other objective findings suggestive of recurrence or spread of the original malignancy. 2) Positron emission mammography (PEM) was added to coverage: PEM is considered experimental, investigational and unproven for breast cancer screening, diagnosis or management. 3) The AHA/ACC Joint Statement for assessment of cardiovascular risk was added to the Description section to assist determination of intermediate risk.
10/1/2009 Revised/updated entire document
7/1/2009 Policy revised to allow coverage of PET for ovarian cancer, pancreatic cancer, small cell lung cancer, and soft tissue sarcoma.
3/1/2008 Revised/Updated Entire Document
2/1/2005 Revised/Updated Entire Document
10/16/2004 Revised/Updated Entire Document
10/1/2003 Codes Revised/Added/Deleted
8/1/2003 Revised/Updated Entire Document
5/1/2000 Codes Revised/Added/Deleted
1/1/2000 Codes Revised/Added/Deleted
9/1/1999 Codes Revised/Added/Deleted
4/1/1999 Codes Revised/Added/Deleted
5/1/1996 Codes Revised/Added/Deleted
10/1/1994 Codes Revised/Added/Deleted
10/1/1992 Codes Revised/Added/Deleted
7/1/1992 Codes Revised/Added/Deleted
1/1/1992 Codes Revised/Added/Deleted
5/1/1990 New Medical Document

Archived Document(s):

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