Coverage Policy Manual
Policy #: 2001030
Category: Radiology
Initiated: February 2002
Last Review: October 2023
  PET or PET/CT for Esophageal or Esophagogastric Junction (EGJ) Cancer
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.
 
Positron Emission Tomography (PET) imaging uses radiotracers that can reveal both anatomical and physiological information.  The glucose analog, 2-[fluorine-18]-Fluoro-2-deoxy-D-glucose (FDG) is useful in cancer imaging because it has been found that tumor cells show increased utilization of glucose compared to non-malignant tissue and is the most common radiotracer that is utilized. For certain malignancies PET scans have been shown to be more accurate than other non-invasive tests in detecting malignant disease.  However, as with all diagnostic tests, PET scans do not detect cancer 100% of the time that cancer is present (a false negative test), nor do all positive PET scans represent the presence of malignant disease (a false positive test).  A false negative test may occur because a critical volume of malignant cells is necessary for a PET scan to be positive. PET scans may be false positive in the presence of inflammation or granulomatous disease.
 
Upper gastrointestinal (GI) tract cancers originating in the esophagus, esophagogastric junction (EGJ) and stomach constitute a major health problem around the world.   In Western countries, the most common site of esophageal cancer is in the lower third of the esophagus, which often involves the EGJ.  Esophageal cancer is the eighth most common cancer worldwide.  An estimated 17,460 new cases and 15,070 deaths from esophageal cancer will occur in the United States in 2012.
 
Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma.  Adenocarcinoma of the esophagus may be associated with a better long-term prognosis after resection than SCC.  SCC is the most common in the endemic regions of the world and adenocarcinoma is most common in nonendemic areas, such as North America and many Western European countries.  Both SCC and adenocarcinoma are more common in men.  Tobacco and alcohol abuse are major risk factors for SCC whereas the use of tobacco is a moderate established risk factor for adenocarcinoma.  Obesity and high body mass index have been established as strong risk factors for adenocarcinoma of the esophagus.  
 
Gastroesophageal reflux disease (GERD) and Barrett’s esophagus are the other two major risk factors for adenocarcinoma of the esophagus.
 
PET scans for patients with esophageal cancer have been studied for six indications:
            •   Detecting primary esophageal cancer;
            •   Initial staging of patients with recently diagnosed disease;
            •   Restaging of disease in symptomatic patients;
            •   Monitoring response to therapy;
            •   Predicting prognosis in patients undergoing surgery; and
            •   Surveillance of patients with Barrett’s metaplasia of the esophagus to determine if malignancy has developed.
 
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, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
FDG-PET/CT for Esophageal and Gastroesophageal Junction cancer meets primary coverage criteria and is covered for:
 
Diagnostic Workup
Indicated when standard imaging cannot be performed or does not demonstrate distant (M1) metastatic disease
 
Management
Indicated in ANY of the following scenarios:
        • Radiation planning for preoperative or definitive treatment only
        • Single assessment of response to chemoradiation (as definitive treatment or prior to surgery) when performed at least 5 weeks after completion of therapy
        • Standard imaging cannot be performed or is nondiagnostic for recurrent or progressive disease.
 
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 Esophageal and Gastroesophageal Junction cancer does not meet member certificate of benefit Primary Coverage Criteria for effectiveness and is not covered for any indication or any circumstance other than those listed above including but not limited to:
    • Surveillance*
 
For members with contracts without primary coverage criteria, PET/CT for Esophageal and Gastroesophageal Junction cancer 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 Plan exclusions.
 
 
*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 Prior to March 13, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Positron emission tomography (PET) scanning meets primary coverage criteria for effectiveness and is covered for patients with esophageal or esophagogastric junction (EGJ) cancer for:
 
Initial treatment:
    • When standard imaging has been performed and has not demonstrated metastatic disease.  
Subsequent treatment:
    • To assess response to chemoradiation (as definitive treatment prior to surgery) at least 5 weeks post-treatment; OR
    • If recurrence is suspected based on signs/symptoms and standard modalities are equivocal
 
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
 
The following uses of PET scanning does not meet member certificate of benefit Primary Coverage Criteria for effectiveness and are not covered:
    • Monitoring patients with Barrett’s esophagus (there are no evidence-based studies indicating the effectiveness of this monitoring/surveillance in improving health outcomes.)
    • 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 contracts without primary coverage criteria, the following uses of PET scanning are considered investigational and are not covered:
    • Monitoring patients with Barrett’s esophagus (there are no evidence-based studies indicating the effectiveness of this monitoring/surveillance in improving health outcomes.)
    • Any other indication not specifically listed as covered above.
Investigational services are exclusions in the member certificate of coverage.
 
Effective Prior to August 2021
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Positron emission tomography (PET) scanning meets primary coverage criteria for effectiveness and is covered for patients with esophageal or esophagogastric junction (EGJ) cancer for:
 
Initial treatment: When standard imaging has been performed and has not demonstrated metastatic disease.
 
Subsequent treatment:
 
    • To assess response to chemoradiation (as definitive treatment prior to surgery) at least 5 weeks post-treatment; OR
    • If recurrence is suspected based on signs/symptoms and standard modalities are equivocal
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The following uses of PET scanning does not meet member certificate of benefit Primary Coverage Criteria for effectiveness and are not covered:
 
    • Monitoring patients with Barrett’s esophagus (there are no evidence-based studies indicating the effectiveness of this monitoring/surveillance in improving health outcomes.)
    • Any other indication not specifically listed as covered above.
 
For contracts without primary coverage criteria, the following uses of PET scanning are considered investigational and are not covered:
 
    • Monitoring patients with Barrett’s esophagus (there are no evidence-based studies indicating the effectiveness of this monitoring/surveillance in improving health outcomes.)
    • Any other indication not specifically listed as covered above.
 
Investigational services are exclusions in the member certificate of coverage.
 
Effective Prior to October 2019
 
PET scan” refers to FDG PET or PET/CT.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
PET scan meets member certificate of benefit Primary Coverage Criteria for effectiveness for:
 
        • Preoperative staging of carcinoma of the esophagus or esophagogastric junction (Meta-Analysis)
        • Restaging following surgery, or after completion of radiotherapy, chemotherapy, or any combination of the three
        • Monitoring response to neo-adjuvant chemotherapy to allow early surgery for non-responders (Clinical Trial Results)
        • Predicting survival of patients treated for carcinoma of the esophagus or esophagogastric junction
 
For contracts without primary coverage criteria, the following uses of PET scanning are covered for:
 
        • Preoperative staging of carcinoma of the esophagus or esophagogastric junction (Meta-Analysis)
        • Restaging following surgery, or after completion of radiotherapy, chemotherapy, or any combination of the three
        • Monitoring response to neo-adjuvant therapy to allow early surgery for non-responders (Clinical Trial Results)
        • Predicting survival of patients treated for carcinoma of the esophagus
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
PET scan does not meet member certificate of benefit Primary Coverage Criteria for effectiveness for:
 
        • Monitoring patients with Barrett’s esophagus or esophagogastric junction ( there are no evidence-based studies indicating the effectiveness of this monitoring/surveillance in improving health outcomes.)
        • Monitoring response to neo-adjuvant chemoradiotherapy to allow early response to non-responders (Clinical Trial Results). (Effective April 2013)
        • Initial diagnosis of primary esophageal and esophagogastric junction cancer. (Effective May 2014)
 
For contracts without primary coverage criteria, the following uses of PET scanning are considered investigational and are not covered:
 
        • Monitoring patients with Barrett’s esophagus ( there are no evidence-based studies indicating the effectiveness of this monitoring/surveillance in improving health outcomes.)
        • Monitoring response to neo-adjuvant chemoradiotherapy to allow early response to non-responders (Clinical Trial Results). (Effective April 2013)
        • Initial diagnosis of primary esophageal cancer. (Effective May 2014)
 
Investigational services are an exclusion in the member certificate of coverage.
 
 
Rationale:
PET is generally not considered a test for initial diagnosis of primary esophageal tumors, and evidence is lacking on its use to differentiate between esophageal cancer and benign conditions.
 
An NCCN Task Force report found studies showing that PET is more sensitive than other diagnostic imaging in detecting stage IV disease with distant lymph node involvement. A meta-analysis described in the report found a 67% pooled sensitivity, 97% specificity, and small added value after conventional staging in detecting distant metastasis (Podoloff, 2009).
 
Another use of PET in esophageal cancer is in determining whether to continue chemotherapy for potential curative resection. The NCCN Task Force Report describes several studies in which response to chemotherapy as defined as a decline in standardized uptake values (SUV) correlated with long-term survival (Podoloff, 2009).   Patients who do not respond to chemotherapy may benefit by this test by being spared futile and toxic chemotherapy. However, this treatment strategy of PET-directed chemotherapy does not appear to have been validated with randomized clinical trials showing improved overall health outcomes.
 
Non-invasive diagnostic tests that have commonly been used to initially diagnose disease in patients with suspected cancer of the esophagus include endoscopy, endoscopic ultrasound, computed tomography, and magnetic resonance imaging.  A concern with these techniques is that extent of disease is not recognized prior to curative surgery.  Only one published study evaluated the benefit of PET for the diagnosis of primary esophageal cancer, and although the sensitivity was high for some subsets of patients, the sensitivity for superficial (T1) lesions was only 70%. For this reason, PET is not recommended for initial detection of cancer of the esophagus.
 
The studies presently available on the use of PET for staging esophageal cancer show little difference in the sensitivity and specificity for PET (51% and 89%) and Computed Tomography (42% and 87%), and wide overlapping confidence intervals for both techniques.  Both false positive and false negative results occur in the evaluation of loco-regional metastases.  PET does appear to be superior to other diagnostic tests in determining resectability of the primary tumor, and may improve health outcomes.  Studies looking at the detection of distant metastases suggest that PET is superior to CT in this regard, but there are significant methodologic problems with the studies.
 
PET has not been shown to result in a significant number of false positive results (28%) in restaging disease after therapy.  In one small study (14 patients) using PET to monitor response to therapy, PET was better than CT in evaluating response to therapy; however, only 43% of these patients actually had biopsy of tissue to confirm the result of the PET scan.  In another study on neoadjuvant radiotherapy and chemotherapy showed that those patients whose PET scan demonstrated a response to therapy, histologic evaluation revealed less than 10% viable tumor cells in 13 patients, and more than 10% viable tumor cells in non-responders.  Whether this finding has any relevance to improvement in health outcomes has not been demonstrated.
 
PET scans have not been shown to be effective in detecting early conversion of Barrett’s metaplasia to carcinoma of the esophagogastric junction, or to improving survival in this group of patients.
 
NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers, Version 1.2013
  •   Staging studies such as endoscopic ultrasound (EUS) and integrated positron emission tomography (PET) and computed tomography (CT) scans are utilized to select patients for surgery, to exclude metastatic disease and to identify and quantify lymph node involvement.
  •   Clinical staging using EUS (with fine needle aspiration (FNA, if indicated), chest and abdomen CT scan, and PET scan (integrated PET/CT preferred over PET alone) should be performed before surgery to assess resectability.
  •   The review of CT and PET scans prior to EUS is recommended to become familiar with the nodal distribution for a possible FNA biopsy.   
 
 
Combined PET/CT has many advantages over PET scan alone:
    •   Significantly improves the diagnostic accuracy
    •   Useful for initial staging and evaluation of patients after chemoradiation prior to surgery
    •   May be useful for detection of distant lymphatic and hematogenous metastases.
    •   Shown to improve lymph node staging and the detection of stage IV esophageal cancer
    •   Predictor of overall survival in patients with non-metastatic esophageal cancer.
 
Additional studies are needed to assess the efficacy of combined PET/CT scan in esophageal cancer.  PET evaluation is preferred if there is no evidence of metastatic disease.
 
The prognostic value of metabolic response defined by PET scan after preoperative chemotherapy has been evaluated in retrospective and prospective studies.  Some studies have reported that PET scan could predict histopathological complete response and outcome after definitive or preoperative chemoradiation in patients with locally advanced esophageal cancer, other studies have shown conflicting results.
 
Based on the available evidence, the guidelines recommend consideration of PET/CT or PET only for the assessment of response to preoperative or definitive chemoradiation therapy before surgery or initiation of postoperative treatment (category 2B).  However, the guidelines emphasize that PET scans should not be used for the selection of patients to surgery following preoperative chemoradiation.
 
Response assessment with PET/CT or PET scan (category 2B) should be done 5-6 weeks after Start date of September 2011 with estimated enrollment of 204 and completion date of June 2017. detection of residual esophageal tumor.  However, PET/CT when used in combination with endoscopy was found to be useful in identifying patients with a high risk of residual tumor following preoperative chemoradiation.
 
Clinical Trials:
    •   NCT01836913 - Value of PET-CT in Radiation Treatment Planning for Patients With Esophageal Cancer (RESPECT).  This prospective study is ongoing, but not recruiting participants. Study was started in May 2009 with an enrollment of 90 and expected completion date of December 2013. (Netherlands)
 
    •   NCT01333033 - Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer. This interventional study is still recruiting participants.  Start date of September 2011 with estimated enrollment of 204 and completion date of June 2017. (Sponsored by NCI)
 
    • NCT00833625 - FDG-PET-CT and Biomarkers to Assess Pathologic Response in Surgical Specimens of Patients With Localized Esophageal Cancer After Chemoradiation.  This safety/efficacy study is ongoing, but not recruiting participants. Start date of February 2009 with estimated enrollment of 95 and completion date of March 2014.  The goal of this clinical research study is to learn if the results of a positron emission tomography/computed tomography (PET/CT) scan done 10-14 days after beginning chemotherapy and radiation (chemoradiation) can predict how a patient with cancer of the esophagus will respond to chemoradiation. Researchers also want to learn if biomarkers (substances in the body associated with cancer) found in tumor tissue can predict response to chemoradiation (MD Anderson).
 
2014 Update
Regarding initial diagnosis, PET is generally not considered a test for detecting primary esophageal tumors, and evidence is lacking on its use to differentiate between esophageal cancer and benign conditions.
 
In a 2013 meta-analysis of 245 patients with esophageal cancer from 6 studies, Shi et al. reported that for detection of regional nodal metastases, FDG PET-CT had a sensitivity of 0.55 (95% CI, 0.34 to 0.74) and specificity of 0.76 (95% CI, 0.66 to 0.83) (Shi, 2013).  The NCCN guideline on esophageal cancer indicates PET-CT may be considered if there is no evidence of M1 disease (distant metastasis) (NCCN, V.2.2013).
 
As noted above, another use of PET in esophageal cancer is in determining whether to continue chemotherapy for potential curative resection. The NCCN guideline on esophageal cancer indicates PET-CT may be considered to assess treatment response 5-6 weeks after preoperative therapy (NCCN, V.2.2013).
 
2015 Update
 
A literature search conducted through February 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers, Version 3.2015 were reviewed with no change from Version 1.2013 with regard to PET applications in Esophageal and Esophagogastric Junction (EGJ) cancer.
 
Fuster et al (2015) published research on the role for PET/CT with EGJ adenocarcinoma. His findings indicated that the value of 18F-FDG PET/CT in the initial diagnosis and in the locoregional staging of esophagogastric junction adenocarcinoma is not fully established. However, 18F-FDG PET/CT is widely accepted as the best modality for identification of suspected metastases in staging of the disease. Li and Rice (2012) also performed research on the diagnosis and staging of esophagus and EGJ cancer. Their findings concluded that the current best clinical staging modalities is endoscopic ultrasonography for tumor and lymph node involvement and CT/PET for metastasis.
 
Lundsgaard et al (2014) published the results of a prospective study to evaluate whether early reductions in CT perfusion parameters predict response to pre-operative chemotherapy prior to surgery for GEJ and gastric cancer. The results showed that a decrease in tumor permeability after one series of hemotherapy was positively correlated with clinical response after three series of chemotherapy. Significant changes in permeability and tumor volume were apparent after three series of chemotherapy in both clinical and histological responders. Early decrease in permeability is correlated with the likelihood of clinical response to pre-operative chemotherapy in GEJ and gastric cancer. However, the authors noted that as a single diagnostic test, CT perfusion only has moderate sensitivity and specificity in response assessment of preoperative chemotherapy making it insufficient for clinical decision purposes.
 
Schollaert et al (2014) studied the predictive value of 18F-FDG/PET for assessing disease-free (DFS) and overall survival (OS) in esophageal and esophagogastric junction cancer. The study was a metaanalysis for DFS and OS using the hazard (HRs) as outcome measure. Sources of heterogeneity study were also explored. The authors found that despite methodological and clinical heterogeneity, metabolic response on 18F-FDG/PET was still a significant predictor of long-term survival data.
 
Clinical Trials:
  • NCT01333033 – PET Scan Imaging in Assessing Response in Patients With Esophageal Cancer Receiving Combination Chemotherapy. This interventional study is still recruiting participants. The purpose of this randomized phase II trial is to study PETscan imaging in assessing response in patients with esophageal cancer receiving combination chemotherapy. Start date of September 2011 with estimated enrollment of 204 and completion date of June 2017. (Sponsored by NCI)
  • NCT00833625 - FDG-PET-CT and Biomarkers to Assess Pathologic Response in Surgical Specimens of Patients With Localized Esophageal Cancer After Chemoradiation. This safety/efficacy study is ongoing, but not recruiting participants. Start date of February 2009 with estimated enrollment of 95 and completion date of March 2016. The goal of this clinical research study is to learn if the results of a positron emission tomography/computed tomography (PET/CT) scan done 10-14 days after beginning chemotherapy and radiation (chemoradiation) can predict how a patient with cancer of the esophagus will respond to chemoradiation. Researchers also want to learn if biomarkers (substances in the body associated with cancer) found in tumor tissue can predict response to chemoradiation (MD Anderson).
  • NCT01927978. Using “PET Response Criteria in Solid Tumors (PERCIST)" in Evaluating Response to Neoadjuvant Chemoradiotherapy for esophageal cancer. This prospective observational study is currently recruiting participants . The purpose of the trial is to look at whether CT-PET changes therapies and outcomes of esophageal cancer. Start date of September 2011 with estimated enrollment of 204 and completion date of June 2017.(Sponsored by Taiwan University Hospital)
  • NCT02385604. The Predictive Value of CT-PET in Esophageal Cancer. This retrospective observational study is ongoing, but not recruiting participants. The aim of this study is to determine the accuracy of CT-PET for prediction of histopathologic response and/or oncologic outcome for patients with esophageal cancer. Study was started in January 2014 with an enrollment of 250 and expected completion date of January 2016. (Sponsored by St. James’s Hospital, Ireland).
 
2017 Update
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. The key identified literature is summarized below.
 
ESOPHAGEAL CANCER AND 18F-FDG-PET AND 18F-FDG-PET/CT
For initial diagnosis, PET is generally not considered for detecting primary esophageal tumors, and evidence is lacking on its ability to differentiate between esophageal cancer and benign conditions.
 
In 2016, a meta-analysis evaluating the predictive value of 18F-FDG-PET and -PET/CT for tumor response during or after neoadjuvant chemoradiotherapy in patients with esophageal cancer was conducted (Cong, 2016). The literature search, conducted through January 2016, identified 4 studies (n=192 patients) in which PET or PET/CT was performed during neoadjuvant chemoradiotherapy and 11 studies (n=490 patients) in which PET or PET/CT was performed after neoadjuvant chemoradiotherapy. All studies scored between 9 and 12 using the QUADAS tool. Pooled sensitivity and specificity for PET and PET/CT performed during NRCT is 85% (95% CI, 76% to 91%) and 59% (95% CI, 48% to 69%), respectively. Pooled sensitivity and specificity for PET and PET/CT performed after neoadjuvant chemoradiotherapy were 67% (95% CI, 60% to 73%) and 69% (95% CI, 63% to 74%), respectively.
 
In 2016, Goense et al published a systematic review evaluating 18F-FDG-PET and -PET/CT for the
detection of recurrent esophageal cancer after treatment with curative intent (Goense, 2016). The literature search, conducted through December 2014, identified 8 studies (total N=486 patients) for inclusion. The quality of the studies was considered reasonable using the QUADAS tool, with low risk of bias for a majority of the studies, and high risk of bias in a few studies for patient selection. Pooled estimates of sensitivity and specificity of 18F-FDG-PET and -PET/CT combined were 96% (95% CI, 93% to 97%) and 78% (95% CI, 66% to 86%), respectively. Subgroup analysis by technique (PET alone and PET/CT) was not possible for sensitivity due to heterogeneity. Specificity subgroup analysis showed no statistical difference between PET alone and PET/CT in detecting recurrent esophageal cancer.
 
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 January 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.
 
October 2021 Update
A literature review was performed through September 2021. Following is a summary of the key literature to date.
 
DIAGNOSTIC WORKUP
Esophageal cancer is staged using the American Joint Committee on Cancer TNM system. The role of endoscopic ultrasound is to evaluate tumor depth and lymph node involvement. The overall accuracy of endoscopic ultrasound (EUS) for this component of staging is in the 80% to 90% range. In a meta-analysis which also included high grade esophageal dysplasia, surgical or endoscopic mucosal resection pathologic staging compared to EUS had a T-stage concordance of only 65%.2 Nonetheless, EUS is still considered superior to CT, MRI, and PET for locoregional staging.3-5 The National Comprehensive Cancer Network (NCCN) recommends chest/abdominal CT with oral and IV contrast for initial workup; pelvic CT with contrast only as clinically indicated.(6)
 
While CT is the most widely used modality for detection of distant metastases (M1 disease), the addition of FDG-PET improves detection of lesions that may remain occult on CT, allowing proper patient selection for surgical resection. A meta-analysis of 31 articles found PET/CT to be more accurate than CT for identifying metastatic disease: sensitivity and specificity were 71% (95% CI, 0.62-0.79) and 93% (95% CI, 0.89-0.97) for FDG-PET and 52% (95% CI, 0.33-0.71) and 91% (95% CI, 0.86-0.96) for CT, respectively.(3) In the prospective American College of Surgeons Oncology Group trial Z0060, PET scan identified an additional 5% of biopsy-confirmed distant metastatic disease as compared to conventional imaging.(7) In 2 additional studies, PET/CT resulted in avoidance of futile surgery in up to 17% of patients and change in management of 38.2% of cases.(8)
 
MANAGEMENT
Metabolic response by PET/CT has been suggested as a surrogate marker for prognosis. In the largest of these studies, the prospective MUNICON phase II trial (N=110) showed that post-treatment PET correlated with treatment response and event-free survival (29.7 months in metabolic responders and 14.1 months in nonresponders, Hazard Ratio, 2.18, P= .002).(9) Conversely, in a review from 2017 that included 13 studies (N = 697), Cremonesi et al. noted that 8 studies supported interim PET, while 5 studies found no benefit in terms of pathological complete response and/or outcome.(10)The NCCN) recommends PET/CT as a preferred modality after preoperative or definitive chemoradiation (level 2Arecommendation), at least 5-8 weeks after completion of therapy.(6)
 
SURVEILLANCE
The majority of esophageal and gastroesophageal junction cancer recurrences present as distant metastases within the first 1 to 3 years. Based on the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers, surveillance imaging can be considered for up to 3 years if the patient is likely to tolerate additional curative-intent therapy for recurrence. (6)
 
 
Current References
    1. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349(23):2241-52. PMID: 14657432
    2. Young PE, Gentry AB, Acosta RD, et al. Endoscopic ultrasound does not accuratel y stage early adenocarcinoma or high-grade dysplasia of the esophagus. Clin Gastroenterol Hepatol. 2010;8(12):1037-41. PMID: 20831900
    3. van Vliet EP, Heijenbrok-Kal MH, Hunink MG, et al. Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer. 2008;98(3):547-57. PMID: 18212745
    4. Keswani RN, Early DS, Edmundowicz SA, et al. Routine positron emission tomography does not alter nodal staging in patients undergoing EUS-guided FNA for esophageal cancer. Gastrointest Endosc. 2009;69(7):1210-7. PMID: 19012886
    5. Flamen P, Lerut A, Van Cutsem E, et al. Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol. 2000;18(18):3202-10. PMID: 10986052
    6. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Cancers (Version 2.2021). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2021.
    7. Meyers BF, Downey RJ, Decker PA, et al. The utility of positron emission tomography in staging of potentially operable carcinoma of the thoracic esophagus: results of the American College of Surgeons Oncology Group Z0060 trial. J Thorac Cardiovasc Surg. 2007;133(3):738-45. PMID: 17320575
    8. Flanagan FL, Dehdashti F, Siegel BA, et al. Staging of esophageal cancer with 18F-fluorodeoxyglucose positron emission tomography. AJR Am J Roentgenol. 1997;168(2):417-24. PMID: 9016218
    9. Lordick F, Ott K, Krause BJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8(9):797-805. PMID: 17693134
    10. Cremonesi M, Garibaldi C, Timmerman R, et al. Interim 18F-FDG-PET/CT during chemo-radiotherapy in the management of oesophageal cancer patients. a systematic review. Radiother Oncol. 2017;125(2):200-12. PMID: 29029833
 
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 for Esophageal and Esophagogastric Junction Cancers, Version 2.2022 were reviewed with no change from Version 2021 with regard to PET applications in Esophageal and Esophagogastric Junction (EGJ) cancer.
 
2023 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.
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: Block MI, Patterson GA, Sundaresan RS, et al.(1997) Improvement in staging of esophageal cancer with the addition of positron emission tomography. Ann Thor Surg 1997; 64:770-777.

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