Coverage Policy Manual
Policy #: 2001039
Category: Radiology
Initiated: December 1999
Last Review: March 2019
  PET or PET/CT for Neuroendocrine Tumors

Description:
Note:  This policy is intended for those members with contracts that do not have requirements for prior approval for imaging procedures through an independent imaging review organization.
 
 
 
Diagnosis: Refers to use of PET as part of the testing used in establishing whether or not a patient has cancer.
 
Initial Staging: Refers to use of PET to determine the stage (extent) of the cancer at the time of diagnosis, before any treatment is given. Imaging at this time is generally to determine whether or not the cancer is localized. This may also be referred to as “staging”.
 
Restaging: Refers to imaging following treatment in 2 situations. Restaging is part of the evaluation of a patient in whom a disease recurrence is suspected based on signs and/or symptoms. Restaging also includes determining the extent of malignancy following completion of a full course of treatment.
 
Surveillance:  Refers to use of imaging in asymptomatic patients (patients without objective signs or symptoms of recurrent disease). This imaging is completed 6 months or more (12 months or more for lymphoma) following completion of treatment.
 
Monitoring: Refers to the assessment of early treatment response (i.e. during active treatment cycle for cancer, prior to completion of the treatment cycle, to determine whether the treatment being given should be maintained or changed).
 
Positron Emission Tomography (PET) imaging uses radiotracers that can reveal both anatomical and physiological information.  There are few radioisotopes that are approved by the FDA for PET imaging.  A radioisotope that is not FDA approved cannot be marketed; however, radioisotopes can be manufactured and used, without FDA approval, at the site of manufacture.  The FDA approved PET radioisotope, 18 Fluoro-1-deoxy-D-glucose (FDG), which is used for most oncologic imaging, is not an effective imaging agent in well differentiated neuroendocrine tumors.  (Primary Neuroendocrine Tumors [NETs] may arise in the bronchi of the lung, in the thyroid gland, the thymus, the pancreas, the ileum of the small bowel, in paraganglioma, and from unknown sites. These tumors may be well differentiated, poorly differentiated, and intermediate in differentiation.  The well and intermediate differentiated tumors contain somatostatin receptors [SSRs] in abundant quantity).  
 
The somatostatin analogue octreotide has been known to be taken up by somatostatin receptors, and can be visualized on photon imaging equipment.  A newer analogue (DOTATOC) has shown increased specificity for well differentiated and intermediate differentiated neuroendocrine tumors, whereas FDG uptake is seen primarily in poorly differentiated tumors that do not have somatostatin receptors.
 
“PET scan” refers to FDG PET or PET/CT.
 
 

Policy/
Coverage:
Effective October 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
PET scan imaging with 68 Gallium for staging neuroendocrine tumors either during initial staging or restaging at follow-up meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
PET scan imaging using fluorine 18 FDG radioisotope for initial staging to aid in identification of sites of involvement of poorly differentiated NETs meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
PET scan imaging using fluorine 18 FDG restaging of patients who had FDG avid neuroendocrine tumor found on initial staging meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
PET scan imaging using DOTATOC radioisotope for initial staging to aid in identification of sites of involvement of NETs that produce somatostatin receptors meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
PET scan imaging using DOTATOC radioisotope restaging of patients who had DOTATOC avid neuroendocrine tumor found on initial staging meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET scan imaging using any radioisotope for initial diagnosis does not meet member certificate of benefit Primary Coverage Criteria for effectiveness because PET scan imaging is not recommended above tissue histology for initial diagnosis of neuroendocrine tumors. For members with contracts without primary coverage criteria, this indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
PET scan imaging using either fluorine 18 FDG or DOTATOC or other radioisotopes does not meet member certificate of benefit Primary Coverage Criteria for effectiveness for surveillance of patients with neuroendocrine tumor who do not have clinical, laboratory, or radiological evidence of recurrent disease, as this use is presently under study to determine effectiveness (NCT00646022). For members with contracts without primary coverage criteria, this indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
PET scan imaging using either fluorine 18 FDG, DOTATOC, or other radioisotopes does not meet member certificate of benefit Primary Coverage Criteria for effectiveness for monitoring response to therapy, as monitoring has not been shown to improve health outcomes, and this use is being studied in ongoing clinical trials (NCT01338090). For members with contracts without primary coverage criteria, this indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective prior to October 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
PET scan imaging using fluorine 18 FDG radioisotope for initial staging meets member certificate of benefit Primary Coverage Criteria for effectiveness to aid in identification of sites of involvement of poorly differentiated NETs.  
 
PET scan imaging using fluorine 18 FDG meets member certificate of benefit Primary Coverage Criteria for effectiveness for restaging of patients who had FDG avid neuroendocrine tumor found on initial staging.
 
PET scan imaging using DOTATOC radioisotope for initial staging meets member certificate of benefit Primary Coverage Criteria for effectiveness to aid in identification of sites of involvement of NETs that produce somatostatin receptors.
 
PET scan imaging using DOTATOC radioisotope meets member certificate of benefit Primary Coverage Criteria for effectiveness for restaging of patients who had DOTATOC avid neuroendocrine tumor found on initial staging.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET scan imaging using any radioisotope for initial diagnosis does not meet member certificate of benefit Primary Coverage Criteria for effectiveness because PET scan imaging is not recommended above tissue histology for initial diagnosis of neuroendocrine tumors. For members with contracts without primary coverage criteria, this indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
PET scan imaging using either fluorine 18 FDG or DOTATOC or other radioisotopes does not meet member certificate of benefit Primary Coverage Criteria for effectiveness for surveillance of patients with neuroendocrine tumor who do not have clinical, laboratory, or radiological evidence of recurrent disease, as this use is presently under study to determine effectiveness (NCT00646022). For members with contracts without primary coverage criteria, this indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
PET scan imaging using either fluorine 18 FDG, DOTATOC, or other radioisotopes does not meet member certificate of benefit Primary Coverage Criteria for effectiveness for monitoring response to therapy, as monitoring has not been shown to improve health outcomes, and this use is being studied in ongoing clinical trials (NCT01338090). For members with contracts without primary coverage criteria, this indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 

Rationale:
Neuroendocrine tumors span a spectrum from well-to poorly-differentiated phenotypes, with well-differentiated NETs closely resembling normal neuroendocrine cells, and the patient exhibiting an indolent course.  Even in this latter group, however, the secretion of hormones can lead to morbidity and mortality.  The use of octreotide, a long acting analogue of somatostatin, labeled with indium-11, which was taken up by the somatostatin receptors on the neuroendocrine tumor cells, when used with Single Photon Emission Computed Tomography became the accepted imaging test (Krenning, 1989).  PET scan imaging with fluorine 18 FDG has been known to be of limited value in imaging neuroendocrine tumors which are poorly differentiated and do not exhibit SST receptors (Adams, 1998).  More recently, PET imaging using gallium-68 DOTA conjugates to octreotide or octreotate which have a higher avidity for somatostatin receptors, have improved the specificity and sensitivity of imaging in those patients with SST receptor positive tumors (Buchmann, 2007; Srirajaskanthan, 2010; Poeppel, 2011).  Fluorine 18 FDG imaging remains the test of choice for those poorly differentiated tumors.  Hofman, 2012).  Poorly differentiated tumors (SSR avid), as might be expected, have a worse prognosis (Binderup, 2010).
 
“Patients with FDG positive but SSRT PET negative disease cannot be effectively targeted with either octreotide or peptide receptor radionuclide therapy, as the negative SSTR PET indicates that the obligatory target is not expressed.  Such patients may benefit from conventional chemotherapy or newer biologic agents such as everolimus or sunitinib, which inhibit m-TOR and tyrosine kinase, two pathways involved in NET proliferation, respectively (Hofman, 2012).
 
2014 Update
A literature search conducted through September 2014 did not reveal any new information that would prompt a change in the coverage statement.
 
2015 Update
A literature search conducted through September 2015 did not reveal any new information that would prompt a change in the coverage statement.
 
January 2018
A literature search conducted using the MEDLINE database through December 2017 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.
 
October 2018 Update
A literature search was conducted through September 2018.  The key identified literature is summarized below.
 
NEUROENDOCRINE TUMORS
 
Systematic Reviews
 
68Ga-PET and 68Ga-PET/CT
Barrio et al conducted a systematic review and meta-analysis on the impact of gallium 68 (68Ga) PET/CT on management decisions in patients with neuroendocrine tumors (Barrio, 2017). Reviewers selected 14 studies (N=1561 patients). Change in management occurred in 44% of the patients following 68Ga-PET/CT. Clinical outcomes were not reported.
 
Guidelines
Current NCCN guidelines for neuroendocrine have recommended somatostatin receptor-based imaging with PET/CT, using 68Ga-dotatate as the radioactive tracer (NCCN, 2018). The guidelines note that 68Ga-PET/CT is more sensitive than somatostatin receptor scintigraphy for determining somatostatin receptor status. 68Ga-PET/CT is recommended for diagnosis, staging, and restaging. FDG-PET may be considered in poorly differentiated carcinomas only in biopsy proven neuroendocrine tumors of unknown primary. Neither 68Ga-PET/CT nor FDG-PET are recommended for surveillance. 18F-DOPA PET/CT is not discussed in the guidelines.
 
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.

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
A9587Gallium ga-68, dotatate, diagnostic, 0.1 millicurie

References: Adams S, Baum R, Rink T, et al.(1998) Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med, 1996; 25:79-83.

Barrio M, Czernin J, Fanti S, et al.(2017) The impact of somatostatin receptor-directed PET/CT on the management of patients with neuroendocrine tumor: a systematic review and meta-analysis. J Nucl Med. May 2017;58(5):756-761. PMID 28082438

Binderup T, Knigge U, Loft A, et al.(2010) 18F-flurodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res, 2010; 16:978-985.

Buchmann I, Henze M, Engelbrecht S, et al.(2007) Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (OctreoScan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging, 2007; 34:1617-1626.

Hofman MS, Hicks RJ.(2012) Changing paradigms with molecular imaging of neuroendocrine tumors. www.discovery medicine.com/Michael S Hofman/2012/07/26. Accessed 2012-10-22.

Krenning EP, Bakker WH, Breeman WA, et al.(1989) Localization of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet, 1989; 1(8632):242-244.

National Comprehensive Cancer Network (NCCN).(2018) NCCN Clinical Practice Guidelines in Oncology: Neuroendocrine and Adrenal Tumors. Version 2.2018. https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Accessed August 2, 2018.

NCT00646022.(2012) Natural history of familial carcinoid tumor. www.clinicaltrials.gov. Accessed 2012-10-22.

NCT01338090.(2012) 89Zr-bevacisymab PET imaging in patients with neuroendocrine tumors. www.clinicaltrials.gov. Accessed 2012-10-22.

Poeppel TD, Binse I, Petersenn S, et al.(2011) 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. J Nucl Med, 2011; 52:1864-1870.

Srirajaskanthan R, Kayani I, Quigley AM, et al.(2010) The role of 68Ga-DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 111In-DTPA-Octreotide scintigraphy. J Nucl Med, 2010; 51:875-882.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.