Coverage Policy Manual
Policy #: 2001039
Category: Radiology
Initiated: December 1999
Last Review: December 2023
  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.
 
 
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 MARCH 13, 2023
 
FDG-PET/CT
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
PET/CT using fluorine 18 FDG for patients with neuroendocrine cancer meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
Poorly-differentiated Neuroendocrine Tumors
(For poorly differentiated neuroendocrine tumors of the lung, refer to Small Cell Lung Cancer section)
 
Diagnostic Workup:
          • Indicated when standard imaging cannot be performed or is nondiagnostic for metastatic disease  
 
Management:
          • Indicated to assess treatment response when PET used for initial staging
 
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 using fluorine 18 FDG for patients with neuroendocrine cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
      • Surveillance*
 
For members with contracts without primary coverage criteria, PET/CT using fluorine 18 FDG for patients with neuroendocrine tumors is considered investigational and is not covered for any indication or any circumstance other than those listed above. 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.
 
Somatostatin Receptor-Based PET (eg. using Gallium 68 or Copper 64)
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
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.
 
PET using somatostatin receptor-based imaging (eg. using Gallium 68 or Copper 64) for patients with neuroendocrine cancer meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
Well-differentiated Neuroendocrine Tumors
(Including carcinoid tumors of the gastrointestinal tract, lung or thymus, and pheochromocytoma or Paraganglioma)
 
Diagnostic Workup:
            • Indicated in EITHER of the following scenarios:
            • Biopsy-proven well-differentiated neuroendocrine tumor; or
            • Suspected well-differentiated neuroendocrine tumors (based on endoscopy, conventional imaging**, or biochemical markers***) that are not amenable to biopsy
 
** Conventional imaging includes MRI or contrast-enhanced CT.
*** Biochemical evidence for suspected neuroendocrine umors may include elevated levels of chromogranin A, pancreatic polypeptide, neuron-specific enolase, vasoactive intestinal polypeptide, serotonin (urinary 5-HIAA), gastrin, somatostatin, catecholamines, metanephrines, calcitonin, fasting insulin, C-peptide (proinsulin), or glucagon
 
Management:
            • Indicated in EITHER of the following scenarios:
            • Prior to planned peptide receptor radioligand therapy (PRRT) for well-differentiated neuroendocrine tumor
OR
            • When identification of more extensive disease will change management and ANY of the following criteria are met:
            • Equivocal findings of disease progression on conventional imaging; or
            • Clinical or biochemical progression with negative conventional imaging; or
            • When the original disease was only detectable by somatostatin receptor-based imaging
 
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 using somatostatin receptor-based imaging for patients with neuroendocrine cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes:  
        • Surveillance*
 
For members with contracts without primary coverage criteria, PET using somatostatin receptor-based imaging for patients with neuroendocrine tumors is considered investigational and is not covered for any indication or any circumstance other than those listed above. 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.
 
Effective August 2021 through March 12, 2023
  
FDG-PET/CT
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
PET/CT using fluorine 18 FDG for patients with neuroendocrine cancer meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
Poorly-differentiated Neuroendocrine Tumors
Diagnostic Workup
      • Indicated when standard imaging cannot be performed or is nondiagnostic for metastatic disease.
Treatment Management
      • As clinically indicated.
 
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 using fluorine 18 FDG for patients with neuroendocrine cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
    • For screening and surveillance*: or
    • For any other indication not specifically listed 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.
 
 
Somatostatin Receptor-Based PET (eg. using Gallium 68 or Copper 64)
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
PET using somatostatin receptor-based imaging (eg. using Gallium 68 or Copper 64) for patients with neuroendocrine cancer meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
Well-differentiated Neuroendocrine Tumors
Diagnostic Workup
Indicated in EITHER of the following:
        • Biopsy-proven well-differentiated neuroendocrine tumor; or
        • Suspected well-differentiated neuroendocrine tumor (based on endoscopy, conventional imaging*, or biochemical markers**) that are not amenable to biopsy.
 
* Conventional imaging includes MRI or contrast-enhanced CT.
** Biochemical evidence for suspected neuroendocrine cancers may include elevated levels of chromogranin A, pancreatic polypeptide, neuron-specific enolase, vasoactive intestinal polypeptide, serotonin (urinary 5-HIAA), gastrin, somatostatin, catecholamines, metanephrines, calcitonin, fasting insulin, C-peptide (proinsulin), or glucagon.
 
Treatment Management:
Indicated in EITHER of the following:
        • Prior to planned peptide receptor radioligand therapy (PRRT) for well-differentiated neuroendocrine tumor; or
        • When identification of more extensive disease will change management and ANY of the following criteria are met:
        • Equivocal findings of disease progression on conventional imaging; or
            • Clinical or biochemical progression with negative conventional imaging; or
            • When the original disease was only detectable by somatostatin receptor-based imaging.
 
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 using somatostatin receptor-based imaging for patients with neuroendocrine cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes:  
    • For screening and surveillance*; or
    • For any other indication not specifically listed 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 using somatostatin receptor-based imaging for patients with neuroendocrine cancer is considered investigational:
    • For screening and surveillance; or
    • For any other indication not specifically listed above.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
 
Effective June 15, 2021 to July 2021
 
FDG-PET/CT
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
PET/CT using fluorine 18 FDG for patients with neuroendocrine cancer meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
Poorly-differentiated Neuroendocrine Tumors
 
Diagnostic Workup
 
Indicated when standard imaging cannot be performed or is nondiagnostic for metastatic disease.
 
Treatment Management
 
As clinically indicated.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET/CT using fluorine 18 FDG for patients with neuroendocrine cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
    • For screening and surveillance: or
    • For any other indication not specifically listed above.
 
Somatostatin Receptor-Based PET
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
PET using somatostatin receptor-based imaging for patients with neuroendocrine cancer meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
 
Well-differentiated Neuroendocrine Tumors
 
Diagnostic Workup
 
Indicated in EITHER of the following:
 
        • Biopsy-proven well-differentiated neuroendocrine tumor; or
        • Suspected well-differentiated neuroendocrine tumor (based on endoscopy, conventional imaging*, or biochemical markers**) that are not amenable to biopsy.
 
* Conventional imaging includes MRI or contrast-enhanced CT.
** Biochemical evidence for suspected neuroendocrine cancers may include elevated levels of chromogranin A, pancreatic polypeptide, neuron-specific enolase, vasoactive intestinal polypeptide, serotonin (urinary 5-HIAA), gastrin, somatostatin, catecholamines, metanephrines, calcitonin, fasting insulin, C-peptide (proinsulin), or glucagon.
 
Treatment Management:
 
Indicated in EITHER of the following:
 
      • Prior to planned peptide receptor radioligand therapy (PRRT) for well-differentiated neuroendocrine tumor; or
      • When identification of more extensive disease will change management and ANY of the following criteria are met:
 
          • Equivocal findings of disease progression on conventional imaging; or
          • Clinical or biochemical progression with negative conventional imaging; or
          • When the original disease was only detectable by somatostatin receptor-based imaging.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET using somatostatin receptor-based imaging for patients with neuroendocrine cancer does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes:
 
    • For screening and surveillance; or
    • For any other indication not specifically listed above.
 
For members with contracts without primary coverage criteria, PET using somatostatin receptor-based imaging for patients with neuroendocrine cancer is considered investigational:
 
    • For screening and surveillance; or
    • For any other indication not specifically listed above.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective October 2018 to June 15, 2021
 
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 that there be scientific evidence of 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 that there be scientific evidence of 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 benefit certificate primary coverage criteria for effectiveness that there be scientific evidence 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.
 
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.
 
December 2021 Update
A literature review was performed through September 2021. Following is a summary of the key literature to date.
 
DIAGNOSTIC WORKUP
Neuroendocrine tumor is staged using the American Joint Committee on Cancer TNM system. The World Health Organization classification scheme also takes into account proliferation rate (Ki-67) in grading of tumors. Neuroendocrine tumors of the GI tract, lung and thymus are highly vascular tumors and multiphasic imaging (abdominal +/- pelvic multiphasic CT or MRI per NCCN), including arterial phase imaging, should be used to improve detection.1, 2 MRI is more sensitive than CT for detection of liver metastases. (3) Smaller lesions, especially in the small bowel and appendix, may be difficult to visualize with either modality.
 
Somatostatin receptor (SSR) imaging is recommended by multiple professional societies including ACR, NCCN, and ENTS as a part of initial staging of well-differentiated neuroendocrine tumors when indicated. SSR-PET/CT is generally preferred. A 2018 systematic review of 15 studies with 679 patients evaluating comparing the diagnostic accuracy of SSTR-PET with OctreoScan, 18FDG PET or CT/MRI, Hope et al. reported that SSTR-PET was associated with greater sensitivity than OctreoScan (difference in sensitivity ranged from 14% to 56%) as well as CT and/or MRI (differences in sensitivity ranged from 12% to 49%). (4)
 
Multiple prospective trials confirm the overall superiority of 68Ga DOTATATE PET to somatostatin receptor scintigraphy. Several systematic reviews, a meta-analysis, and prospective studies of variable quality have consistently shown that 68Ga dotatate has a moderate to high diagnostic accuracy for the staging of de novo, recurrent, or suspected neuroendocrine cancer with a moderate to high positive likelihood ratio and a high negative likelihood ratio to exclude neuroendocrine cancer. (4-9)
 
64Cu-DOTATATE was also found to have non-inferior diagnostic accuracy (corrected sensitivity/specificity of 100% and 96.8%, respectively) compared to 68Ga-DOTATATE. (10, 11)
FDG-PET for staging of poorly differentiated neuroendocrine tumor remains controversial. In a limited number of small studies, FDG-PET appears to be useful in detecting poorly differentiated neuroendocrine tumors and well-differentiated neuroendocrine tumors with high Ki-67. (12-14)
 
MANAGEMENT
Imaging to assess disease response to therapy should be performed with the same modality used to detect the initial abnormality and the same modality should be used over time. For most cases, CT chest and abdominal +/- pelvic multiphasic CT or MRI is sufficient. There is limited evidence supports for the use of SRT-PET for monitoring disease during treatment. Somatostatin analog receptor imaging is vital prior to PRRT. Based on the increased sensitivity for detection of somatostatin receptors and expected change in management, 68Ga dotatate also appears to play a role prior to therapy. 68Ga dotatate changed management in 13%-60% of patients, with a wide variation depending on the clinical scenario in which the radiotracer is used. No study has compared the utility of SSTR-PET with alternative imaging modalities for predicting response to PRRT or somatostatin analog therapy. (15)
 
SURVEILLANCE
Poorly differentiated tumors have a higher risk of recurrent disease after definitive treatment; therefore, routine surveillance imaging may include CT chest, abdomen, and pelvis. Limited evidence supports the use of SRT-PET for monitoring disease after completion of treatment.
 
Current References
    1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Neuroendocrine and Adrenal Tumors (Version 2.2020). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2020.
    2. Paulson EK, McDermott VG, Keogan MT, et al. Carcinoid metastases to the liver: role of triple-phase helical CT. Radiology. 1998;206(1):143-50. PMID: 9423664
    3. Dromain C, de Baere T, Lumbroso J, et al. Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J Clin Oncol. 2005;23(1):70-8. PMID: 15625361
    4. Hope TA, Bergsland EK, Bozkurt MF, et al. Appropriate use criteria for somatostatin receptor PET imaging in neuroendocrine tumors (2020): Society of Nuclear Medicine & Molecular Imaging (SNMMI). Available from: http://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=23260.
    5. Albanus DR, Apitzsch J, Erdem Z, et al. Clinical value of 68Ga-DOTATATE-PET/CT compared to stand-alone contrast enhanced CT for the detection of extra-hepatic metastases in patients with neuroendocrine tumours (NET). Eur J Radiol. 2015;84(10):1866-72. PMID: 26152870
    6. Deppen SA, Blume J, Bobbey AJ, et al. 68Ga-DOTATATE compared with 111In-DTPA-octreotide and conventional imaging for pulmonary and gastroenteropancreatic neuroendocrine tumors: a systematic review and meta-analysis. J Nucl Med. 2016;57(6):872-8. PMID: 26769864
    7. Menda Y, O'Dorisio TM, Howe JR, et al. Localization of unknown primary site with 68Ga-DOTATOC PET/CT in patients with metastatic neuroendocrine tumor. J Nucl Med. 2017;58(7):1054-7. PMID: 28153957
    8. Sadowski SM, Millo C, Cottle-Delisle C, et al. Results of (68)Gallium-DOTATATE PET/CT scanning in patients with multiple endocrine neoplasia type 1. J Am Coll Surg. 2015;221(2):509-17. PMID: 26206648
    9. Sadowski SM, Neychev V, Millo C, et al. Prospective study of 68Ga-DOTATATE positron emission tomography/computed tomography for detecting gastro-entero-pancreatic neuroendocrine tumors and unknown primary sites. J Clin Oncol. 2016;34(6):588-96. PMID: 26712231
10. Delpassand ES, Ranganathan D, Wagh N, et al. 64Cu-DOTATATE PET/CT for imaging patients with known or suspected somatostatin receptor-positive neuroendocrine tumors: results of the first U.S. prospective, readermasked clinical trial. J Nucl Med. 2020;61(6):890-6. PMID: 31924723
11. Johnbeck CB, Knigge U, Loft A, et al. Head-to-head comparison of 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT: a prospective study of 59 patients with neuroendocrine tumors. J Nucl Med. 2017;58(3):451-7. PMID: 27660147
12. Abgral R, Leboulleux S, Deandreis D, et al. Performance of (18)fluorodeoxyglucose-positron emission tomography and somatostatin receptor scintigraphy for high Ki67 (>=10%) well-differentiated endocrine carcinoma staging. J Clin Endocrinol Metab. 2011;96(3):665-71. PMID: 21193541
13. Adams S, Baum R, Rink T, et al. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med. 1998;25(1):79-83. PMID: 9396878
14. Pasquali C, Rubello D, Sperti C, et al. Neuroendocrine tumor imaging: can 18F-fluorodeoxyglucose positron emission tomography detect tumors with poor prognosis and aggressive behavior? World J Surg. 1998;22(6):588-92. PMID: 9597933
15. U.S. Food & Drug Administration (FDA). NETSPOT (kit for the preparation of gallium Ga 68 dotatate injection), for intravenous use. (2016 [revised 4/2018]). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208547s011lbl.pdf
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2022. No new literature was identified that would prompt a change in the coverage statement.
 
NCCN Guidelines Neuroendocrine and Adrenal Tumors (Version 4.2021) were reviewed with no change from Version 2020 with regard to PET applications in Neuroendocrine and Adrenal cancer.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through November 2023. 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
A9592Copper cu-64, dotatate, diagnostic, 1 millicurie
A9800Gallium ga-68 gozetotide, diagnostic, (locametz), 1 millicurie
C9067Gallium ga 68, dotatoc, diagnostic, 0.01 mci
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

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