| Coverage Policy Manual | |
| Policy #: | 2002015 |
| Category: | Radiology |
| Initiated: | August 2002 |
| Last Review: | December 2024 |
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| PET or PET/CT for Carcinoma of Unknown Primary (CUP) | |
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| 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.
“PET scan” refers to FDG PET or PET/CT.
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, including carcinoma of undetermined primary (CUP) is addressed in this policy for the following indications:
Carcinoma of unknown primary (CUP) represents a heterogeneous group of metastatic malignancies for which no primary tumor site can be identified after extensive diagnostic workup. Failure to identify the primary site has been attributed to negatively impact patient management. Evaluation of PET for CUP has been divided into two categories: 1) CUP in lymph nodes of the cervical area (Head & Neck), and 2) CUP of any area below the cervical region.
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:
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.
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Policy/ Coverage: |
Act 583 applies to all contracts subject to AR state law (this includes fully insured contracts, self-funded church sponsored health plans, and self-funded state and local government sponsored health plans except the Arkansas State and Public School Employees program). For a list of the plans subject to AR state law, please see policy guidelines below.
As required by Act 583 of the Arkansas Legislature, positron emission tomography to screen for or to diagnose cancer in a patient upon the recommendation of the patient's physician when the patient has a prior history of cancer is covered when the following criteria are met:
a) Documentation of the malignancy by pathologic or equivalent report, and
b) Performed no more often than every 6 months, and
c) Ordered by or in consultation with a specialist trained in pediatric oncology for an individual under the age of 18 (given the enhanced risk of radiation exposure in young).
Special Note regarding “prior history of cancer”: In applying Act 583 to any PET scan prior approval or coverage decision for those fully-insured contracts and self-funded church or government plans to which Act 583 applies, the patient-member will be considered to have a “prior history of cancer” as referenced in Act 583 if the patient-member either (a) has active cancer at the time a prior approval request is submitted, as documented by a pathologic or equivalent report or (b) previously had cancer, whether or not in remission at the time the prior approval request is submitted, as documented by a pathologic or equivalent report.
For additional information, please see policy 2021004 (PET or PET/CT for Cancer Surveillance and Other Oncologic Applications)
Policy Guidelines
List of Plans subject to Act 583:
As stated above, this does not apply to Arkansas State and Public School Employee health plan participants and beneficiaries. For Arkansas State and Public School Employee health plan participants and beneficiaries, please see policy 2023025 (PET or PET/CT for Oncologic Applications for ASE/PSE Contracts) for additional information.
For Federal Employee Health Benefit Program and Medicare Advantage plan participants please use the appropriate policy set to review.
For other requests for PET or PET/CT scans, the following policy/coverage criteria applies:
Effective March 13, 2022
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
FDG-PET/CT for patients with Cancers of Unknown Primary and Cancers Not Otherwise Specified meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for patients for:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
PET/CT for patients with Cancers of Unknown Primary does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any other indication not listed as covered above including but not limited to:
For contracts without primary coverage criteria, PET/CT for patients with Cancers of Unknown Primary is considered investigational and is not covered for any indication or any circumstance other than those listed above including but not limited to:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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 Cancers of Unknown Primary meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
Diagnostic Workup
Treatment Management
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 Cancers of Unknown Primary does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
*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 Cancers of Unknown Primary is considered investigational for:
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 Cancers of Unknown Primary meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
Diagnostic Workup
Treatment Management
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
PET/CT for patients with Cancers of Unknown Primary does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:
For members with contracts without primary coverage criteria, PET/CT for patients with Cancers of Unknown Primary is considered investigational for:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective Prior to June 15, 2021
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
PET scan imaging as an aid in detection and initial staging of the primary site of tumor in patients with carcinoma of unknown primary metastatic to cervical nodes meets member certificate of benefit Primary Coverage Criteria for effectiveness.
PET scan imaging for restaging of carcinoma of unknown primary metastatic to cervical nodes meets member certificate of benefit Primary Coverage Criteria for effectiveness assuming the tumor is FDG-avid.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
PET scan imaging as an aid in detection of primary site of tumor in patients with extracervical carcinoma of unknown primary does not meet member certificate of benefit Primary Coverage Criteria based on the results of a clinical trial (MØller, 2012), an ongoing clinical trial (NCT01469026), and NCCN Guidelines (Version 1.2013).
For members with contracts without primary coverage criteria, PET scan imaging as an aid in detection of primary site of tumor in patients with extracervical carcinoma of unknown primary is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
PET scan imaging for surveillance of carcinoma of unknown primary metastatic to cervical nodes does not meet member certificate of benefit Primary Coverage Criteria for effectiveness based on lack of evidence of effectiveness and Expert Opinion (Podoloff, 2009; NCCN Guidelines on surveillance PET scan imaging)
For members with contracts without primary coverage criteria, PET scan imaging for surveillance of carcinoma of unknown primary metastatic to cervical nodes is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
PET scan imaging for monitoring of carcinoma of unknown primary of any site does not meet member certificate of benefit Primary Coverage Criteria for effectiveness based on lack of evidence of effectiveness, and Expert Opinion (Podoloff, 2009; NCCN Guidelines on monitoring with PET scan imaging).
For members with contracts without primary coverage criteria, PET scan imaging for monitoring of carcinoma of unknown primary of any site is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
NCCN Clinical Guidelines, Head & Neck Cancer/Occult Primary. Version 1.2012. www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf Accessed 2012-10-30
NCCN Clinical Guidelines, Occult Primary. Version 1.2013. www.nccn.org/professionals/physician_gls/pdf/occult/pdf Accessed 2012-10-30
For initial evaluation, NCCN deleted a previous “2B” recommendation for PET/CT, and present guidelines state, “Routine use of PET/CT is not recommended. PET/CT may be warranted in some situations.”
Canadian Agency for Drugs and Technologies in Health (Mujoomdar, 2010)
The April 2010 Canadian Agency for Drugs and Technologies in Health assessment of PET in Oncology does not include an assessment of PET for carcinoma of unknown primary.
NCCN Task Force Report (Podoloff DA, 2009)
The Podoloff, et al review does not address carcinoma of unknown primary.
Expert Panel Review (Fletcher, et al, 2008)
“The panel concluded that 18F-FDG PET should routinely be added to the conventional work-up or patients with unknown primary cancer.” This decision was based on 2 systematic reviews enrolling a total of 298 and 302 patients, with over 50% of the Delgado-Bolton study being patients with cervical node cancer, and all of the Rusthoven paper being patients with cervical lymph node metastases.
National Oncologic PET Registries Reports, 2008, 2009, and 2011 (Hillner, 2008, 2009, 2011)
None of these studies addresses carcinoma of unknown primary
AHRQ University of Alberta Evidence Based Practice Center assessment (2008)
No discussion of carcinoma of unknown primary
Specific Study: A Prospective Comparison of 18F-FDG PET/CT and CT as Diagnostic Tools to Identify the Primary Tumor Site in Patients with Extracervical Carcinoma of Unknown Primary Site (MØeller, 2012). 136 newly diagnosed CUP patients with extracervical metastases underwent FDG PET/CT, and compared to a standard of reference and CT. Standard of reference identified a primary tumor site in 66 CUP patients (48.9%). PET/CT identified 38 true positive tumor sites and CT identified 43 true positive primary tumor sites. No statistically significant differences were observed between 18F-FDG PET/CT and CT alone in regard to sensitivity, specificity, and accuracy.
Specific Study: 18F-FDG PET/CT as a Diagnostic Tool in Patients with Extracervical Carcinoma of Unknown Primary Site: A Literature Review (Moller AKH, 2011). This review found 4 publications involving 152 patients which evaluated 18F-FDG PET/CT in CUP patients with extracervical metastases. All studies were retrospective and heterogeneous in inclusion criteria, study design, and diagnostic workup prior to 18F-FDG PET/CT. PET/CT detected the primary tumor in 39.5% of patients with extracervical CUP. The most frequent site of the primary was in the lung. The pooled estimates of sensitivity, specificity, and accuracy of PET/CT with FDG in detection of the primary site were 8%, 88%, and 87.5%, respectively. The authors concluded, “The present review of currently available data indicates that 18F-FDG PET/CT might contribute to the identification of the primary tumor site in extracervical CUP. However, prospective studies with more uniform inclusion criteria are required to evaluate the exact role of this diagnostic tool.”
Specific Study: Clinical Applications of FDG PET and PET/CT in Head and Neck Cancer (Al-Ibraheem A, 2009). This meta-analysis of PET/CT in head & neck cancer included an analysis of CUP in cervical nodes in studies published between 2000-2009. PET & PET/CT detected the primary tumor in 51 of 180 patients. There were 30 false positives. PET alone was not distinguished from PET/CT.
Specific Study: The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor (Rusthoven KE, 2004). This was a review of 302 patients (PET scan imaging only) described in 16 studies published between 1994 and 2003. 18F-FDG PET detected 24.5% of tumors that were not apparent after conventional workup.
2013 Update
A search of the MEDLINE database through October 2013 did not reveal any new literature that would prompt a change in the coverage statement.
Cizmarevic and colleagues published the results of a study done to determine the survival rate of patients with carcinoma of unknown primary (CUP) in relation to lymph node status and eventual later identification of the primary tumor and to investigate the impact of PET-CT on identification of the primary tumor (Cizmarevic, 2012). This study included 97 patients with diagnosis of metastasis of unknown primary tumor. All susceptible patients had a surgery and postoperative radiation therapy. After treatment was completed they were followed up at ENT department. With preoperative examinations 48 primary tumors were discovered. Only in one case of 13 the PET-CT detected the primary tumor not confirmed with other examination methods. After the treatment primary tumors we found were found in 10 patients. In 39 patients we didn't discover any primary tumor. The authors concluded that PET-CT method was not particularly useful in detecting primary tumors in patients with metastasis with unknown primary.
Ongoing Clinical Trials
2014 Update
A literature search conducted through October 2014 did not reveal any new information that would prompt a change in the coverage statement.
2015 Update
A literature search conducted through January 2015 did not reveal any new information 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.
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
For malignancy of unknown origin involving the cervical lymph nodes but suspected to be of Head/Neck origin, please see “Head and Neck Cancer” coverage policy and guidelines.
The initial work-up for cancers of unknown primary should include a history and physical, laboratory evaluation, and imaging studies. CT of the chest, abdomen, and pelvis is commonly used to identify the primary cancer, assess extent of disease, and select for sites amenable to biopsy. (3) PET imaging is increasingly being used as part of the diagnosis of CUP. A meta-analysis and systematic review on the use of PET/CT in patients with CUP found that primary tumors were detected in 37% of 433 patients from 11 studies, with pooled sensitivity and specificity both at 84%. (4) Another study found that PET/CT detected more primary sites (24%-40%) than CT or MRI (20%-27%). (5) NCCN, however, does not recommend routine use of PET imaging for CUP due to a lack of prospective randomized studies comparing PET imaging to conventional imaging. (6) Special consideration should be given to patients presenting with a solitary metastasis where localized intervention is planned and to cervical nodal metastases of unknown origin. In a comprehensive review of patients with a solitary metastasis, PET imaging changed management in 34% of patients relative to conventional imaging. Fourteen percent of patients underwent surgery with curative intent. (7) In a systematic review and meta-analysis of patients with cervical nodal metastases of unknown origin, the primary tumor detection rate, sensitivity, and specificity of PET-CT were 0.44 (95% CI, 0.31-0.58), 0.97 (95% CI, 0.63-0.99), and 0.68 (95% CI,0.49-0.83). Area under the curve was 0.83 (95% CI, 0.80-0.86). (8) The initial work-up of patients with cancer not otherwise specified should include imaging of the primary neoplastic process and assessment for systemic involvement if warranted. Specific imaging recommendations vary with underlying pathologic diagnosis, staging, and patient factors. Because of the many nuances associated with cancer evaluation, peer-to-peer discussions will often be necessary to determine appropriateness of advanced imaging.
MANAGEMENT
For patients with either active disease or localized disease in remission, follow-up frequency should be determined by clinical need with additional diagnostic tests based on symptomatology. (6) Subsequent imaging strategy for cancer not otherwise specified varies with underlying pathologic diagnosis and staging. In general terms, imaging used in the initial detection of the cancer may be used to assess for treatment response.
SURVEILLANCE
For patients with either active disease or localized disease in remission, follow-up frequency should be determined by clinical need with additional diagnostic tests based on symptomatology. (6) The type and frequency of surveillance imaging for cancer not otherwise specified is dependent on the underlying pathologic diagnosis and staging. When indicated, CT imaging can be used in most cancers, with PET rarely indicated for surveillance.
Current References
2023 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 for Occult Primary (Cancer of Unknown Primary [CUP]) (Version 2022) were reviewed with no change from Version 2021 with regard to PET applications in Occult Primary.
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 Occult Primary (Cancer of Unknown Primary [CUP]) (Version 1.2024) were reviewed with no change from Version 2.2022 with regard to PET applications in Occult Primary.
Additional 2024 Update
Annual policy review completed with a literature search using the MEDLINE database through November 2024. No new literature was identified that would prompt a change in the coverage statement.
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| CPT/HCPCS: | |
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| References: |
Al-Ibraheem A, Buck A, Krause BJ, et al.(2009) Clinical applications of FDG PET and PET/CT in head and neck cancer. J of Oncology, 2009. BE Hillner, BA Siegel. Hanna L, et al.(2012) Impact of 18F-FDG PET used after initial treatment of cancer: comparison of the Nationl Oncologic PET Registry 2006 and 2009 cohorts. J Nucl Med, 2012; 53:831-837. Cizmarevic B, Lanisnik B, Dinevski D.(2012) Cervical lymph node metastasis of squamous cell carcinoma from unknown primary tumor. Coll Antropol. 2012 Nov;36 Suppl 2:27-32. Delgado-Bolton RC, Fernández-Pérez C, González-Maté A, et al.(2003) Meta-analysis of the performance of 18F-FDG PET in primary tumor detection in unknown primary tumors. J Nucl Med, 2003; 44:1301-1314. 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. Hillner BE, Siegel BA, Shields AF, et al.(2008) Relationship between cancer type and impact of PET and PET/CT on intended management: Findings of the National Oncologic PET Registry. J Nucl Med, 2008; 49:1928-1935. Hillner BE, Siegel BA, Shields AF, et al.(2009) The impact of positron emission tomography (PET) on expected management during cancer treatment. Cancer, 2009; 115:410-418. Moller AK, Loft A, Berthelsen AK, et al.(2011) 18F-FDG PET/CT as a diagnostic tool in patients with extracervical carcinoma of unknown primary site: A literature review. The Oncologist, 2011; 16:445-451. Møller AK, Loft A, Berthelsen AK, et al.(2012) A prospective comparison of 18F-FDG PET/CT and CT as diagnostic tools to identify the Primary Tumor Site in Patients with extracervical carcinoma of unknown primary site. Oncologist. 2012;17(9):1146-54. Mujoomdar M, Moulton K, Nkansah E.(2010) Positron emission tomography (PET) in oncology: A systematic review of clinical effectiveness and indications for use. Canadian Agency for Drugs and Technologies in Health, April 2010. National Comprehensive Cancer Network(2022) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Occult Primary (Cancer of Unknown Primary [CUP]) (Version 2.2022). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2022. National Comprehensive Cancer Network.(2024) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Occult Primary (Cancer of Unknown Primary [CUP]) (Version 1.2024). Available at http://www.nccn.org. NCCN Guidelines.(2013) Occult Primary, Version 1.2013. www.nccn.org/professionals/physician_gls/pdf/occult. Accessed 2012-10-30. NCT00530283.(2012) PET-CT for squamous cell carcinoma of the neck nodes unknown primary. Alberta Health Services. Completed, not yet reported. www.clinicaltrials.gov.Accessed 2012-10-30 NCT01469026.(2012) CUP project PET/CT. Odense University Hospital. Not yet open for participant recruitment. www.clinicaltrials.gov.Accessed 2012-10-30 Podoloff DA, Ball DW, Ben-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. Rusthoven KE, Koshy M, Paulino AC.(2004) The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor. Cancer, 2004; 101:2641-2649. |
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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 © 2025 American Medical Association. |
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