Coverage Policy Manual
Policy #: 2012027
Category: Radiology
Initiated: June 2012
Last Review: January 2024
  PET Scan for Multiple Myeloma, Plasmacytoma
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 2 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, some tracers must be made locally using and onsite cyclotron.  The radiotracer most commonly used in oncology imaging has been fluorine-18 coupled with fluorodeoxyglucose (FDG), which has a metabolism related to glucose metabolism. FDG has been considered useful in cancer imaging, since tumor cells show increased metabolism of glucose.  The most common malignancies studied have been melanoma, lymphoma, lung colorectal, and pancreatic cancer.
 
Definitions
 
Screening – testing in the absence of an established or clinically suspected diagnosis
 
Diagnosis - testing based on a reasonable clinical suspicion of a particular condition or disorder
 
Diagnostic Workup – initial staging of documented malignancy
 
Management – testing to direct therapy of an established condition, which may include preoperative or postoperative imaging, or imaging performed to evaluate the response to nonsurgical intervention. In oncologic imaging, management applies to patients with measurable disease and to imaging performed before or after planned treatment intervention, therapy response, restaging or clinically suspected recurrence.
 
Surveillance – periodic assessment following completion of therapy. In oncologic imaging, surveillance applies to asymptomatic patients in remission and/or without measurable disease
 
Cannot be performed or is nondiagnostic – applies when the test:
    • Is positive or indeterminate for clinically significant pathology when the information provided about the abnormality by the test is not sufficient to direct subsequent management
    • Is negative when the negative likelihood ratio of the test is both insufficient to confidently exclude the absence of suspected disease and unable to direct subsequent management. This typically applies in scenarios with moderate to high clinical pretest probability with negative testing or low pretest probability with clear evidence for net benefit
    • Has been previously nondiagnostic because of a persistent clinical factor (e.g., body habitus, immobility) that is very likely to make retesting nondiagnostic as well Cannot be performed due to a medical contraindication (e.g., contrast nephrotoxicity, allergy, or in highly radiation sensitive populations such as pediatrics and pregnancy) or reasonable unavailability related to lack of local expertise or service availability
Standard or conventional imaging: Refers to imaging that does not require a PET/CT. Depending on the clinical scenario and individual patient circumstances, this may include computed tomography, magnetic resonance imaging, ultrasound and/or scintigraphy.
Policy/
Coverage:
Effective April 09, 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
FDG-PET/CT for patients with solitary plasmacytoma and multiple myeloma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
Diagnostic Workup:
        • Indicated for initial workup/staging of active myeloma, smoldering myeloma, or solitary plasmacytoma  
Management
Indicated for ANY of the following scenarios:
        • Multiple myeloma; or
        • Smoldering myeloma or solitary plasmacytoma: restaging/treatment response, or follow-up every 12 months
 
For all fully insured contracts, all self-funded church-sponsored health plans and all self-funded government-sponsored health plans other than the Arkansas State and Public School Employees program, the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET/CT for patients with solitary plasmacytoma and multiple myeloma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any indication or any circumstance other than those listed above including but not limited to:
    • Surveillance*
For contracts without primary coverage criteria, PET/CT for patients with solitary plasmacytoma and multiple myeloma is considered investigational and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • Surveillance*
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
*For all fully insured contracts, all self-funded church-sponsored health plans and all self-funded government-sponsored health plans other than the Arkansas State and Public School Employees program, the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.  
 
Note: Standard or conventional imaging: Refers to imaging that does not require a PET/CT. Depending on the clinical scenario and individual patient circumstances, this may include computed tomography, magnetic resonance imaging, ultrasound and/or scintigraphy
 
Effective March 13, 2022 to April 08, 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
FDG-PET/CT for patients with solitary plasmacytoma and multiple myeloma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
Diagnostic Workup:
      • Indicated for initial workup/staging of active myeloma, smoldering myeloma, or solitary plasmacytoma  
Management:
      • Indicated for restaging/treatment response of active myeloma, smoldering myeloma, or solitary plasmacytoma
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET/CT for patients with solitary plasmacytoma and multiple myeloma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any indication or any circumstance other than those listed above including but not limited to:
    • Surveillance*
For contracts without primary coverage criteria, PET/CT for patients with solitary plasmacytoma and multiple myeloma is considered investigational and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • Surveillance*
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
*For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Note: Standard or conventional imaging: Refers to imaging that does not require a PET/CT. Depending on the clinical scenario and individual patient circumstances, this may include computed tomography, magnetic resonance imaging, ultrasound and/or scintigraphy
 
Effective Prior to March 13, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
FDG-PET/CT for patients with solitary plasmacytoma and multiple myeloma meets member benefit certificate primary coverage criteria of effectiveness for improving health outcomes for:
 
Diagnostic Workup
As clinically indicated in EITHER of the following:
    • Initial work-up of solitary plasmacytoma when skeletal survey and/or whole body MRI is negative for bone involvement; or
    • Differentiate smoldering myeloma from active myeloma when skeletal survey and/or whole body MRI is negative for bone involvement.
Management
    • As clinically indicated when routine evaluation with laboratory findings or bone survey suggests recurrence or progression of disease.
 
For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET/CT for patients with solitary plasmacytoma and multiple myeloma does not meet member benefit certificate primary coverage criteria of effectiveness for improving health outcomes for:
    • Screening and surveillance*;
    • Any other indication not specifically listed as covered above.
 
 *For all fully insured contracts, all self-funded church-sponsored health plans, and all self-funded government-sponsored health plans (e.g., state and public-school employee plans), other than the Federal Employee Health Benefit Program and Medicare Advantage plans, as required by Act 583 of the Arkansas Legislature, please see ABCBS policy 2021004, Surveillance and Other PET Oncologic Applications.
 
For members with contracts without primary coverage criteria, PET/CT for patients with solitary plasmacytoma and multiple myeloma is considered investigational for:
    • Screening and surveillance;
    • Any other indication not specifically listed above
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior to August 2021
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
FDG-PET/CT for patients with solitary plasmacytoma and multiple myeloma meets member benefit certificate primary coverage criteria of effectiveness for improving health outcomes for:
 
Diagnostic Workup
As clinically indicated in EITHER of the following:  
    • Initial work-up of solitary plasmacytoma when skeletal survey and/or whole body MRI is negative for bone involvement; or
    • Differentiate smoldering myeloma from active myeloma when skeletal survey and/or whole body MRI is negative for bone involvement.
Management
As clinically indicated when routine evaluation with laboratory findings or bone survey suggests recurrence or progression of disease.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
PET/CT for patients with solitary plasmacytoma and multiple myeloma does not meet member benefit certificate primary coverage criteria of effectiveness for improving health outcomes for:
    • Screening and surveillance;
    • Any other indication not specifically listed as covered above.  
For members with contracts without primary coverage criteria, PET/CT for patients with solitary plasmacytoma and multiple myeloma is considered investigational for:
    • Screening and surveillance;
    • Any other indication not specifically listed above  
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective October 2018 to May 2021
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
PET for multiple myeloma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following:
 
1. Initial treatment strategy (diagnosis) of tumors that are biopsy proven or strongly suspected based on other diagnostic testing to determine the location and/or extent of the tumor for the following therapeutic purposes related to the initial treatment strategy:
 
        • To determine if patient is an appropriate candidate for an invasive diagnostic or therapeutic procedure, or  
        • To determine the optimal anatomic location for an invasive procedure, or  
        • To determine the anatomic extent of tumor when the recommended anti-tumor treatment reasonably depends on the extent of the tumor.  
 
2. Subsequent treatment strategy (monitoring response to treatment when a change in treatment is anticipated) for known (diagnosed) myeloma for patient who has recently completed treatment AND no PET scan obtained after treatment;
 
3. Subsequent treatment strategy (Restaging) for known (diagnosed) myeloma AND has new signs or symptoms indicative of recurrent disease.
 
4. Staging or restaging of multiple myeloma, particularly if the skeletal survey is negative.
 
PET for plasmacytoma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
1. Initial treatment strategy (Diagnosis) of tumors that are biopsy proven or strongly suspected based on other diagnostic testing to determine the location and/or extent of the tumor for the following therapeutic purposes related to the initial treatment strategy:
 
        • To determine if patient is an appropriate candidate for an invasive diagnostic or therapeutic procedure, or  
        • To determine the optimal anatomic location for an invasive procedure, or  
        • To determine the anatomic extent of tumor when the recommended anti-tumor treatment reasonably depends on the extent of the tumor.  
 
2. Subsequent treatment strategy (restaging) for diagnosed plasmacytoma AND new signs and/or symptoms are indicative of recurrent disease.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET for myeloma or plasmacytoma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following:
 
        • In lieu of biopsy to establish a diagnosis of cancer (Podoloff, 2009);
        • As a surveillance tool (i.e., routine scanning post treatment in asymptomatic patients)(Podoloff, 2009; NCCN Guidelines, V1.2012);
        • As a monitoring tool post therapy to predict outcome or prognosis.  
 
For members with contracts without primary coverage criteria, PET for myeloma or plasmacytoma is considered investigational for the following:
 
        • In lieu of biopsy to establish a diagnosis of cancer (Podoloff, 2009);
        • As a surveillance tool (i.e., routine scanning post treatment in asymptomatic patients)(Podoloff, 2009; NCCN Guidelines, V1.2012);
        • As a monitoring tool post therapy to predict outcome or prognosis.  
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
There is inconsistency in medical literature about the use of PET for multiple myeloma or plasmacytoma in these non-covered circumstances, though many authors consider PET imaging “promising”.
 
Effective prior to October 2018
 
PET for myeloma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
1. Initial treatment strategy (Diagnosis) of tumors that are biopsy proven or strongly suspected based on other diagnostic testing to determine the location and/or extent of the tumor for the following therapeutic purposes related to the initial treatment strategy:
 
    • To determine if patient is an appropriate candidate for an invasive diagnostic or therapeutic procedure, or  
    • To determine the optimal anatomic location for an invasive procedure, or  
    • To determine the anatomic extent of tumor when the recommended anti-tumor treatment reasonably depends on the extent of the tumor.  
 
2. Subsequent treatment strategy (monitoring response to treatment when a change in treatment is anticipated) for known (diagnosed) myeloma for patient who has recently completed treatment AND no PET scan obtained after treatment;
 
3. Subsequent treatment strategy (Restaging) for known (diagnosed) myeloma AND has new signs or symptoms indicative of recurrent disease.
 
PET for plasmacytoma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
1. Initial treatment strategy (Diagnosis) of tumors that are biopsy proven or strongly suspected based on other diagnostic testing to determine the location and/or extent of the tumor for the following therapeutic purposes related to the initial treatment strategy:
 
    • To determine if patient is an appropriate candidate for an invasive diagnostic or therapeutic procedure, or  
    • To determine the optimal anatomic location for an invasive procedure, or  
    • To determine the anatomic extent of tumor when the recommended anti-tumor treatment reasonably depends on the extent of the tumor.  
 
2. Subsequent treatment strategy (restaging) for diagnosed plasmacytoma AND new signs and/or symptoms are indicative of recurrent disease.
 
PET, for myeloma or plasmacytoma, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes; or for members with contracts without primary coverage criteria, is considered investigational in the following circumstances:
 
    • In lieu of biopsy to establish a diagnosis of cancer (Podoloff, 2009);
    • As a surveillance tool (i.e., routine scanning post treatment in asymptomatic patients)(Podoloff, 2009; NCCN Guidelines, V1.2012);
    • As a monitoring tool post therapy to predict outcome or prognosis.  
 
There is inconsistency in medical literature about the use of PET for multiple myeloma or plasmacytoma in these non-covered circumstances, though many authors consider PET imaging “promising”.
 
Rationale:
Bird et al., 2011, in guidelines for the diagnosis and management of multiple myeloma, state the skeletal survey remains the screening technique of choice at diagnosis (Bird, 2011). CT and MRI should be used to clarify ambiguous plain film findings such as equivocal lytic lesions, especially in parts of the skeleton that are hard to visualize on plain films. “There is insufficient evidence to recommend the routine use of positron-emission tomography (PET) or 99mTechnetium sestamibi (MIBI) imaging. Either technique may be useful in selected cases for clarification of previous imaging findings preferably within the context of a clinical trial.”
 
Chua et al., 2009, reported on the role of SPECT and PET for the imaging of bone mestastases for specific cancers and said this about multiple myeloma: “MIBI imaging and 18F-FDG-PET have both shown considerable promise in this area and although they remain under evaluation, both techniques are recommended within certain clinical scenarios in guidelines for the use of imaging in myeloma published by the British Committee for Standards in Hematology” (Chua, 2009).  18F-FDG-PET may detect active foci or marrow involvement in patients with plasmacytoma. 18F-FDG-PET may be helpful in selected cases requiring clarification of previous imaging findings. The authors states an important limitation of PET scanning is its limited spatial resolution. A false-negative result could be related to the inability of PET to detect lesions smaller than 1 cm in size. Recent chemotherapy or radiotherapy or inflammation could result in false-positive results secondary to increased cellular turnover. “It is therefore advisable to avoid 18F-FDG-PET within 4 weeks of chemotherapy or 3 months of radiotherapy.”
 
Derlin et al, 2012, reported results of 197 whole body PET scans in 99 myeloma patients who were post allogeneic or autologous SCT (Derlin, 2012). Focal osseous and extramedullary lesions (597) were detected in 79 scans. Diffuse bone marrow involvement was detected in 17 patients. PET had sensitivity of 54.6%, specificity of 82.1%, positive predictive value of 82.3%, a negative predictive value of 54.2% and overall accuracy of 65.5%.
 
Fonti, et al., 2008, reported on 33 newly diagnosed patients, diagnosed and staged by standard criteria who then had whole body PET/CT, whole body (99m)Tc-MIBI, and MRI of spine and pelvis.within 10 days. PET/CT: positive in 32 patients; 16 focal, 3 diffuse, 13 focal and diffuse (Fonti, 2008). 178 focal lesions in bones, 18 in soft tissues, 121 in districts other than spine and pelvis; 35 focal spinal lesions, 30 focal pelvic lesions. (99m)Tc-MIBI: positive in 30 patients; 6 focal, 11 diffuse, 13 focal and diffuse. 60 focal lesions in bones, 3 in soft tissues, 53 in districts other than spine and pelvis; 1 focal spinal lesion, 9 focal pelvic lesions. MRI: positive in 27 patients; 6 focal, 13 diffuse, 8 focal and diffuse; 40 in spine, 11 in pelvis.
 
Hur et al., 2008 reported a comparison of PET and MRI in 22 untreated myeloma patients, 9 were stage I, 3 were stage II, and 10 were stage III, PET detected 29 of 37 lesions and MRI detected 32 of 37 lesions in patients with Stages I & II disease, not statically significant (P=0.317) (Hur, 2008). In stage III patients PET detected 81 of 101 lesions while MRI detected 93 of 101 lesions, statistically significant (P=0.038).
 
Nanni et al., 2006, reported comparison of PET findings with those of whole body x-ray (WBXR) and MRI in 28 newly diagnosed myeloma patients (Nanni, 2006). PET vs WBXR: PET detected more skeletal bone lesions in 16/28 patients, of these 9 had completely negative WBXR. In 12/28 patients the two imaging methods yielded equivalent findings. PET vs MRI: PET detected more lytic lesions in 7/28, all of which were located outside the MRI field of view. PET and MRI found the same number of lesions in the spine and pelvis in 14/28 patients. MRI detected an infiltrative pattern in the spine in 7/28 whereas PET was negative. These authors recommended evaluation of myeloma bone disease at diagnosis should include MRI of the spine and PET.
 
A systematic review by van Lemmeren-Venema and colleagues concluded the performance of PET in the clinical staging and response monitoring of multiple myeloma is promising after noting that restaging after initial therapy for response monitoring has been performed in a very small number of studies (van Lemmeren-Venema, 2012), . Generally PET has a higher sensitivity for myeloma bone lesions than WBXR but direct comparisons suggest MRI may surpass PET. “Future studies have to validate the additive value of myeloma-related bone disease detected on 18FDG-PET-CT in predicting outcome. However, it is essential that these studies use uniform guidelines for standardization of the acquisition and interpretation of 18FDG-PET-CT images to generalize the results.”
 
2015 Update
A literature search conducted through June  2015 did not reveal any new information that would prompt a change in the coverage statement.  The key identified literature is summarized below.
 
Dammacco and colleagues reported on a review of diagnostic and prognostic features in multiple myeloma and related disorders (Dammacco, 2015). Conventional radiographic skeletal survey has been for many years the gold standard to detect the occurrence of osteolytic lesions in patients with multiple myeloma (MM). However, the introduction of more sensitive imaging procedures has resulted in an updated anatomic and functional Durie and Salmon "plus" staging system and has remarkably changed the diagnostic and prognostic approach to this tumor. It is now established that (18)fluorine-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography (PET) combined with low-dose computed tomography (CT), shortly designated PET/CT, exhibits a higher screening and diagnostic sensitivity and specificity over the skeleton X-ray. In patients with monoclonal gammopathy of undetermined significance and in those with smoldering MM, PET/CT is consistently unable to detect focal and/or diffuse marrow abnormalities. Conversely, based on a systematic review of 18 studies comprising almost 800 MM patients, PET/CT was able to detect MM osteolytic lesions with a sensitivity of approximately 80-90% and a specificity of 80-100%. Importantly, a poor degree of concordance has also been emphasized between PET/CT and whole-body magnetic resonance imaging (WB-MRI) in that when both techniques were applied to the same patients, double-positive results were recorded in approximately 30% of the cases, but in the majority of them, a higher number of lesions were revealed with PET/CT than with MRI. Double-negative results, on the other hand, were found in about 22% of the patients. Because PET/CT is able to identify tumor foci throughout the body, it can be usefully applied to the study of solitary bone plasmacytoma and extra-medullary plasmacytoma: In both conditions, the detection of additional, previously overlooked sites of skeletal involvement would falsify the diagnosis of single-district disease, upstage the tumor, and therefore require a different therapeutic approach. In addition, although PET/CT is poorly sensitive to diffuse bone marrow infiltration, it can anticipate a site of impending fracture throughout the body and can discriminate old from new pathologic fractures. MRI should, however, be preferred when vertebral bodies are suspected to be involved and the risk of vertebral fracture is to be assessed. PET/CT is a sensitive and reliable procedure to evaluate the response to chemotherapy and/or radiotherapy, which is shown by a remarkable reduction and sometimes total disappearance of FDG accumulation in the involved bony structures, although these structures remain morphologically abnormal. Conversely, an increased focal uptake of FDG in apparent remission patients often precedes clinically overt relapse. PET/CT should be preferred to other imaging techniques to assess the remission status after autologous stem cell transplantation. In patients with primary and remission-induced non-secretory MM, the use of PET/CT may help to early detect single or multiple districts of focal non-secretory relapse. Osteonecrosis of the jaw, its location, and extent in MM patients receiving bis-phosphonates are better defined by both PET/CT and contrast-enhanced MRI compared with dental panoramic views derived from cone beam CT imaging. Little is known as to the possible role of PET/CT in the assessment of disease extension, tumor load, and response to therapy in patients with Waldenström's macroglobulinemia (WM). In a study conducted on 35 WM patients, comparative PET/CT before and after therapy was able to detect positive findings in 83% of the patients, in contrast with the previous results achieved with conventional imaging that reported visceral involvement in much lower percentages. Similarly scanty are the data on the use of PET/CT in localized and systemic amyloidosis, given the small number of patients studied so far. A retrospective study has shown that, at variance from (123)Iodine-serum amyloid P component ((123)I-SAP) scintigraphy, which was found to be positive in about one-third of the patients with localized amyloidosis, an increased FDG uptake was detected at the amyloid site in virtually all of them. On the contrary, none of the patients with systemic amyloidosis showed an increased FDG uptake in sites of known deposition, whereas (123)I-SAP scintigraphy tested positive in the large majority of them. In another study, however, no such remarkable difference of positive PET/CT scans between localized and systemic amyloidosis was reported. Finally, false-positive and false-negative PET/CT findings can occur in different conditions that should be kept in mind to avoid wrong or omitted diagnoses.
 
Solitary plasmacytoma (SP) is a localized proliferation of monoclonal plasma cells in either bone or soft tissue, without evidence of multiple myeloma (MM), and whose prognosis is marked by a high risk of transformation to MM. Fouquet and colleagues studied the impact of FDG-PET/CT (2[18F]fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography) on the risk of transformation of SP to overt MM among other markers in a series of 43 patients diagnosed with SP (Fouquet, 2014).  Median age was 57.5 years; 48% of patients had an abnormal involved serum-free light chain (sFLC) value, and 64% had an abnormal sFLC ratio at diagnosis. Thirty-three percent had two or more hypermetabolic lesions on initial PET/CT, and 20% had two or more focal lesions on initial MRI. With a median follow-up of 50 months, 14 patients transformed to MM with a median time (TTMM) of 71 months. The risk factors that significantly shortened TTMM at diagnosis were two or more hypermetabolic lesions on PET/CT, abnormal sFLC ratio and involved sFLC, and to a lesser extent at completion of treatment, absence of normalized involved sFLC and PET/CT or MRI. In a multivariate analysis, abnormal initial involved sFLC [OR = 10; 95% confidence interval (CI), 1-87; P = 0.008] and PET/CT (OR = 5; 95% CI, 0-9; P = 0.032) independently shortened TTMM. An abnormal involved sFLC value and the presence of at least two hypermetabolic lesions on PET/CT at diagnosis of SP were the two predictors of early evolution to myeloma in our series. This data analysis will need confirmation in a larger study, and the study of these two risk factors may lead to a different management of patients with SP in the future.
 
2016 Update
A literature search conducted through April 2016 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Lin and colleagues investigated the potential value of (11)C-acetate (ACT) PET/CT in characterizing multiple myeloma (MM) compared with (18)F-FDG PET/CT (Lin, 2014). Bone marrow histological and whole-body (WB) MRI findings served as the reference standards. 15 untreated MM patients (10 men and 5 women, age range 48-69 years) underwent dual-tracer (11)C-ACT and (18)F-FDG PET/CT and WB MRI for pretreatment staging, and 13 of them had repeated examinations after induction therapy. Diffuse and focal bone marrow uptake was assessed by visual and quantitative analyses, including measurement of the maximum standardized uptake value (SUVmax). Between-group differences and correlations were assessed with the Mann-Whitney U test and the Pearson test. At staging, all 15 patients had diffuse myeloma involvement upon bone marrow examination with 30-90 % of plasma cell infiltrates. Diffuse infiltration was detected in all of them (100 %) using (11)C-ACT with a positive correlation between bone marrow uptake values and percentages of plasma cell infiltrates (r = +0.63, p=0.01). In contrast, a diagnosis of diffuse infiltration could be established using (18)F-FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both (11)C-ACT PET/CT and WB MRI, and in 10 patients on (18)F-FDG PET/CT. Focal lesions demonstrated (11)C-ACT uptake with a mean SUVmax of 11.4 ± 3.3 (range 4.6-19.6, n=59), which was significantly higher than the (18)F-FDG uptake (mean SUVmax 6.6 ± 3.1, range 2.3-13.7, n=29; p<0.0001). After treatment, the diffuse bone marrow (11)C-ACT uptake showed a mean SUVmax reduction of 66 % in patients with at least a very good partial response versus 34 % in those with at most a partial response only (p=0.01).
 
July 2017
A literature search conducted using the MEDLINE database did not reveal any new literature that would prompt a change in the coverage statement.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2018. No new literature was identified that would prompt a change in the coverage statement.
  
2018 Update
A literature search was conducted through September 2018.  The key identified literature is summarized below.
 
MULTIPLE MYELOMA
 
Guidelines
Current NCCN guidelines for multiple myeloma added PET/CT to the list of imaging techniques that may be useful under certain circumstances, to discern active from smoldering myeloma, particularly if the skeletal survey is negative (NCCN, 2018). PET/CT may also be considered to detect disease progression.
 
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2019. No new literature was identified that would prompt a change in the coverage statement.
 
2020 Update
A literature search was conducted through February 2020.  There was no new information identified that would prompt a change in the coverage statement.  
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2021. No new literature was identified that would prompt a change in the coverage statement.
 
2022 Update
A literature review was performed through September 2021. Following is a summary of the key literature to date.
 
DIAGNOSTIC WORKUP
The International Staging System and the Durie-Salmon Staging System are both used in staging. Recent advances in low dose CT technology have improved detection rates of lytic bone lesions with a radiation dose comparable to that of a skeletal survey. (1, 2) In a prospective study comparing whole body low-dose CT (WBCT) and whole body X-ray, WBCT performed markedly better and resulted in a change in management in 18% of patients. (3) In a recent large retrospective study, WBCT detected 25% more lytic lesions than conventional bone radiography. (4) MRI is the most sensitive modality for detection of bone lesions; when compared head to head, MRI detected lesions in 74% of patients compared to 56% with whole body X-ray. In patients with negative skeletal surveys, MRI detected lesions in 52% of patients, while 20% of patients with a negative MRI were discovered to have focal lesions on skeletal survey. (5)
In patients thought to have a solitary plasmacytoma, MRI detected additional disease and led to a change of management in 25% of those studied. (6) In a similar study of indolent myeloma, MRI detected 28% more lesions. (7) While MRI is superior for detection of bone disease, PET/CT may be more sensitive for extramedullary involvement. The majority of patients with active myeloma will have positive results on PET scan, and PET imaging may detect early bone marrow involvement in patients with solitary plasmacytoma. (8, 9) In a prospective study using PET/CT to stage solitary plasmacytoma and multiple myeloma, 14% of patients had a change in management as a result of information gleaned from PET imaging. (8) NCCN recommends either WBCTor FDG PET/CT for initial workup of active myeloma,
smoldering myeloma or solitary plasmacytoma (level of evidence category 2A); if negative, whole body MRI with contrast can be considered to discern smoldering from multiple myeloma. (5) The European Society for Medical Oncology (ESMO) similarly recommends WBCT (FDG PET/CT deemed optional if carried out instead of WBCT, if available) and whole body MRI for WBCT-negative cases (if FDG PET/CT not carried out). (10)
 
MANAGEMENT
MRI may be able to detect early treatment response based on the pattern of marrow response, but false positive results are common due to persistent nonviable lesions. (11) In one study, the overall accuracy of whole body MRI was 79% with a sensitivity of 64%, specificity of 86%, positive predictive value of 70%, and negative predictive value of 83%. MRI had only moderate agreement with routinely performed laboratory tests for determining remission. (12) PET imaging, however, does provide early assessment of response as well as prognostic information for lesions smaller than 5 mm. (13) In a head-to-head study comparing MRI and PET/CT for treatment evaluation of multiple myeloma, PET/CT was less accurate but was able to detect treatment responses earlier.14 In the IMAJEM study, normalization of PET following induction therapy with lenalidomide/bortezomib/dexamethasone (RVD) regimen was associated with improved progression-free survival (30-month progression-free survival, 78.7% vs56.8%, respectively) (15) whereas normalization of MRI findings was not found to correlate with improved outcome measures.
 
The NCCN panel recommends considering using the same imaging modality used during the initial workup for the follow-up assessments. (16) The ESMO recommends FDG PET/CT to confirm imaging minimum residual disease (MRD) at treatment response assessment, and every 12 months for follow-up of bone marrow MRD-negative patients. (10) AIM guidelines are in accordance with the NCCN Guidelines for Multiple Myeloma and the European Society for Medical Oncology (ESMO). (10,16)
 
Current References
    1. Regelink JC, Minnema MC, Terpos E, et al. Comparison of modern and conventional imaging techniques in establishing multiple myeloma-related bone disease: a systematic review. Br J Haematol. 2013;162(1):50-61. PMID: 23617231
    2. Pianko MJ, Terpos E, Roodman GD, et al. Whole-body low-dose computed tomography and advanced imaging techniques for multiple myeloma bone disease. Clin Cancer Res. 2014;20(23):5888-97. PMID: 25294899
    3. Kropil P, Fenk R, Fritz LB, et al. Comparison of whole-body 64-slice multidetector computed tomography and conventional radiography in staging of multiple myeloma. Eur Radiol. 2008;18(1):51-8. PMID: 17924119
    4. Hillengass J, Moulopoulos LA, Delorme S, et al. Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myeloma Working Group. Blood Cancer J. 2017;7(8):e599. PMID: 28841211
    5. Walker R, Barlogie B, Haessler J, et al. Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol. 2007;25(9):1121-8. PMID: 17296972
    6. Moulopoulos LA, Dimopoulos MA, Weber D, et al. Magnetic resonance imaging in the staging of solitary plasmacytoma of bone. J Clin Oncol. 1993;11(7):1311-5. PMID: 8315427
    7. Hillengass J, Fechtner K, Weber MA, et al. Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol. 2010;28(9):1606-10. PMID: 20177023
    8. Schirrmeister H, Bommer M, Buck AK, et al. Initial results in the assessment of multiple myeloma using 18F-FDG PET. Eur J Nucl Med Mol Imaging. 2002;29(3):361-6. PMID: 12002711
    9. Kato T, Tsukamoto E, Nishioka T, et al. Early detection of bone marrow involvement in extramedullary plasmacytoma by whole-body F-18 FDG positron emission tomography. Clin Nucl Med. 2000;25(11):870-3. PMID: 11079582
    10. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(3):309-22. PMID: 33549387
    11. Hillengass J, Ayyaz S, Kilk K, et al. Changes in magnetic resonance imaging before and after autologous stem cell transplantation correlate with response and survival in multiple myeloma. Haematologica. 2012;97(11):1757-60. PMID: 22689673
    12. Bannas P, Hentschel HB, Bley TA, et al. Diagnostic performance of whole-body MRI for the detection of persistent or relapsing disease in multiple myeloma after stem cell transplantation. Eur Radiol. 2012;22(9):2007-12. PMID: 22544292
    13. Zamagni E, Nanni C, Mancuso K, et al. PET/CT improves the definition of complete response and allows to detect otherwise unidentifiable skeletal progression in multip le myeloma. Clin Cancer Res. 2015;21(19):4384-90. PMID: 26078390
    14. Spinnato P, Bazzocchi A, Brioli A, et al. Contrast enhanced MRI and 18F-FDG PET-CT in the assessment of multiple myeloma: a comparison of results in different phases of the disease. Eur J Radiol. 2012;81(12):4013-8. PMID: 22921683
    15. Moreau P, Attal M, Caillot D, et al. Prospective evaluation of magnetic Resonance imaging and 18fluorodeoxyglucose positron emission tomography-computed tomography at diagnosis and before maintenance therapy in symptomatic patients with multiple myeloma included in the IFM/DFCI 2009 trial: results of the IMAJEM study. J Clin Oncol. 2017;35(25):2911-8. PMID: 28686535
    16. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma (Version .2021). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2021.  
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2022.
 
The NCCN (2022) panel recommends considering using the same imaging modality used during the initial workup for the follow-up assessments. Since the risk of progression of solitary plasmacytoma into multiple myeloma or relapse is relatively high (14%-48% within first 3 years of diagnosis), the NCCN (2022) recommends yearly follow-up with the same imaging used at first diagnosis for the first 5 years; the NCCN (2022) also recommends advanced whole-body imaging (ie MRI, low-dose CT, FDG PET/CT) annually for follow-up of smoldering myeloma.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2023. No new literature was identified that would prompt a change in the coverage statement.
 
 
NCCN Guidelines for Multiple Myeloma (Version 1.2024) were reviewed with no change from Version 5.2022 with regard to PET applications in Multiple Myeloma.
CPT/HCPCS:
78811Positron emission tomography (PET) imaging; limited area (eg, chest, head/neck)
78812Positron emission tomography (PET) imaging; skull base to mid thigh
78813Positron emission tomography (PET) imaging; whole body
78814Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; limited area (eg, chest, head/neck)
78815Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; skull base to mid thigh
78816Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; whole body
References: American College of Radiology.(2011) American College of Radiology Appropriateness Criteria, Positron emission tomography. Accessed at http://ac.search.acc.org.

Bird JM, Owen RG, et al.(2011) Guidelines for the diagnosis and management of multiple myeloma 2011. Brit J Haematology, 2011, 154:32-75.

Chua S, Gnanasegaran G, Cook G.((2009) Miscellaneous cancers (lung, thyroid, renal cancer, myeloma, and neuroendocrine tumors): role of SPECT and PET in imaging bone metastases. Semin Nucl Med, 2009; 39:416-430.

Dammacco F, Rubini G, Ferrari C, et al.(2015) ¹8F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders. Clin Exp Med. 2015 Feb;15(1):1-18.

Derlin T, Weber C, et al.(2012) 18F-FDG PET/CT for detection and localization of residual or recurrent disease in patients with multiple myeloma after stem cell transplantation. Eur J Nucl Med Mol Imaging, 2012; 39:493-500.

Dimopoulos M, Terpos E, et al.(2009) International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple myeloma. Leukemia, 2009; 23:1545-56.

Fletcher JW, Djulbegovic B, Soares HP, et al.(2008) Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med, 2008; 49:480-508.

Fonti R, Salvatore B, et al.(2008) 18F-FDG PET/CT, 99mTc-MIBI, and MRI in evaluation of patients with multiple myeloma. J Nucl Med, 2008; 49:195-200.

Fouquet G, Guidez S, Herbaux C, et al.(2014) Impact of initial FDG-PET/CT and serum-free light chain on transformation of conventionally defined solitary plasmacytoma to multiple myeloma. Clin Cancer Res. 2014 Jun 15;20(12):3254-60.

Hughes M, Soutar R, et al.(2009) Guidelines on the diagnosis and management of solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas: 2009 update. http://ukmf.org.uk/guidelines.htm. Accessed Jun 2012.

Hur J, Yoon CS, et al.(2008) Comparative study of fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for the detection of spinal bone marrow infiltration in untreated patients with multiple myeloma. Acta Radiol, 2008; 49:427-35.

Lin C, Ho CL, Ng SH, et al.(2014) C-acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment. Eur J Nucl Med Mol Imaging. 2014 Jan;41(1):41-9

Mujoomdar M, Moulton K, Nkansah E.(2010) Positron emission tomography in oncology: A systematic review of clinical effectiveness and indications for use. Ottawa: Canadian Agency for Drugs and Technologies in Health. Ottawa: Canadian Agency for Drugs and Technologies in Health. http://www.cadth.ca. Accessed Jun 2012.

Nanni C, Zamagni E, et al.(2006) Role of 18F-FDG PET/CT in the assessment of bone involvement in newly diagnosed multiple myeloma: preliminary results. Eur J Nucl Med Mol Imaging, 2006; 33:525-31.

National Comprehensive Cancer Network (NCCN) Guidelines™ .(2012) Version 1.2012. www.nccn.org. Last accessed June 2012

National Comprehensive Cancer Network (NCCN).(2018) NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 1.2019. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed August 2, 2018.

National Comprehensive Cancer Network(2022) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma (Version 5.2022). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2022.

National Comprehensive Cancer Network.(2024) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma (Version 1.2024). Available at http://www.nccn.org.

Podoloff DA, Ball DW, en-Josef E, et al.(2009) NCCN task force report: Clinical utility of PET in a variety of tumor types. JNCCN, 2009; 7 (Suppl 2):S1-S23.

Univ of Alberta Evidence-based Practice Center, Edmonton, Canada.(2008) Positron Emission Tomography for nine cancers (bladder, brain, cervical, kidney, ovarian, pancreatic, prostate, small cell lung, testicular). http://www.AHRQ Technology Assessment Program. http://www.ahrq.gov/clinic/techix.htm#completed.

van Lammeren-Venema D, , Regelink JC, et al.(2012) 18F-Fluoro-deoxyglucose Positron Emission Tomography in assessment of myeloma-related bone disease: A systematic review. Cancer, 2012; 118:1971-81.
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