Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual
Policy #:	2012022
Category:	Radiology
Initiated:	June 2012
Last Review:	January 2024

PET or PET/CT for Urological Cancers

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.

Renal cell carcinoma (RCC) comprises approximately 2-3% of all malignancies, with a median age at

diagnosis of 65 years. The rate of RCC has increased by 2% per year for the past 65 years. The

reason for the increase is unknown. Approximately 90% of renal tumors are RCC, and 85% of these

are clear cell tumors.

18F-2-fluoro-2-deoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) is a useful non-invasive tool to evaluate glucose metabolic status, which can be the index of biological activity of cancer. Although PET has not been generally used for the screening of renal cell carcinoma (RCC0 due to the urinary excretion of the radiotracer, which can mask the presence of primary lesions, several investigators have reported that FDG-PET/CT had sufficient potential to evaluate advanced RCCs. (Ueno, 2012)

In the United States, around 55,000 men and 17,000 women are diagnosed with bladder cancer every year. Of those diagnosed around 11,000 men and 5,000 women die from the disease. The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma. Smoking, genetic factors, and exposure to certain chemicals are all risk factors for bladder cancer.

Bladder Cancer For individuals who have suspected or diagnosed bladder cancer in need of staging or restaging information who receive fluorine 18 (18F) coupled with fluorodeoxyglucose (FDG) PET or FDGPET/computed tomography (CT), the evidence includes a systematic review and meta-analysis. The relevant outcome is test validity. Pooled analyses showed relatively high sensitivity and specificity. Clinical guidelines include PET and PET/CT as considerations in staging bladder cancer, though CT, magnetic resonance imaging, and chest radiographs are also appropriate techniques for staging purposes. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who are asymptomatic after completing bladder cancer treatment who receive FDG-PET or FDG-PET/CT, there is no evidence. The relevant outcome is test validity. The evidence is insufficient to determine the effects of the technology on health outcomes.

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

Bladder, Renal Pelvis, and Ureter Cancers:

Noninvasive

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

PET/CT for patients with for patients with Noninvasive Bladder, Renal Pelvis, and Ureter Cancers does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any indication. *

For contracts without primary coverage criteria, PET/CT for patients with for patients with Noninvasive Bladder, Renal Pelvis, and Ureter Cancers is considered investigational. 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.

Invasive

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

FDG-PET/CT meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for patients with Invasive Bladder, Renal Pelvis, and Ureter Cancers for:

Diagnostic Workup:

Indicated in EITHER of the following:

Evaluation of stage II or stage III bladder cancer prior to definitive treatment when standard imaging cannot be performed or is nondiagnostic for metastatic disease
When bone metastasis is suspected based on signs and symptoms and standard imaging cannot be performed or is nondiagnostic

Management:

Indicated in the following scenario:

Standard imaging cannot be performed or is nondiagnostic for recurrent or progressive disease

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

PET/CT for Invasive Bladder, Renal Pelvis, and Ureter Cancers 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:

Surveillance*

For contracts without primary coverage criteria, PET/CT for Invasive Bladder, Renal Pelvis, and Ureter Cancers is considered investigational for any other indication not listed as covered 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.

Kidney Cancer (including renal cell carcinoma, Wilms tumor/nephroblastoma)

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

PET/CT for patients with for patients with Kidney Cancer (including renal cell carcinoma, Wilms tumor/nephroblastoma) does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any indication. *

For contracts without primary coverage criteria, PET/CT for patients with for patients with Kidney Cancer (including renal cell carcinoma, Wilms tumor/nephroblastoma) is considered investigational. 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

Renal Cell Carcinoma

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

PET/CT for patients with renal cell carcinoma does not meet member benefit certificate of effectiveness in improving health outcomes for any indication.

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 renal cell carcinoma for any indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Bladder, Renal Pelvis, and Ureter Cancers

Non-invasive

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

PET/CT for patients with non-invasive bladder, renal pelvis, and ureter cancers is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any indication.

For members with contracts without primary coverage criteria, PET/CT for patients with non-invasive bladder, renal pelvis, and ureter cancers for any indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Invasive

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

FDG-PET/CT for patients with invasive bladder, renal pelvis and ureter cancers meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:

Diagnostic Workup

As clinically indicated in EITHER of the following:

Evaluation of stage II or stage III bladder cancer prior to surgery;
When bone metastasis is suspected based on signs and symptoms and standard imaging has not demonstrated bone lesions.

Management

As clinically indicated in EITHER of the following:

Standard imaging studies are equivocal or nondiagnostic for recurrent or progressive disease;
When objective signs or symptoms of disease are present AND CT or MRI has not clearly demonstrated recurrence or progression.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

PET/CT for patients with invasive bladder, renal pelvis, and ureter cancers does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for:

Screening and surveillance*;
Any other indication not specifically listed as covered above.

For members with contracts without primary coverage criteria, PET/CT for patients with invasive bladder, renal pelvis, and ureter cancers is considered investigational for:

Screening and surveillance;
Any other indication not specifically listed as covered above.

Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective October 2018 to May 2021

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

PET or PET/CT for Renal Cell Carcinoma:

PET or PET/CT for Renal Cell Carcinoma meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following:

Initial staging, only as an adjunct test when CT scans are equivocal; OR
Follow-up (restaging) as an adjunct test when CT scans are equivocal.

PET or PET/CT for Bladder Cancer:

PET or PET/CT for Bladder Cancer meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the staging or restaging of muscle-invasive bladder cancer when CT or MRI are not indicated or remained inconclusive on distant metastasis.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

PET or PET CT does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following:

Evaluation of indeterminate renal mass (ACR Appropriateness, 2010; Podoloff, 2009)
Surveillance for pulmonary or other organ metastases in asymptomatic patients (ACR Appropriateness, 2010; Podoloff, 2009)
To determine if patient is an appropriate candidate for an invasive diagnostic or therapeutic procedure (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
To determine the optimal anatomic location for an invasive procedure (NCCN, 2011; McEwan, 2008; Powles, 2007);
To determine the anatomic extent of tumor when the recommended anti-tumor treatment reasonably depends on the extent of the tumor (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
For restaging of tumor following therapy (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
To monitor the effect of chemotherapy, biologic therapy, or vaccine therapy (Revheim, 2011; Heidenreich, 2010; Podoloff, 2009);
As a surveillance tool (i.e., routine monitoring in asymptomatic patients no longer on therapy) (Podoloff, 2009);
Detection of brain metastasis (NCCN 2011; Podoloff, 2009);
In lieu of biopsy to establish a diagnosis of cancer (Podoloff, 2009);
In patients with stable disease when PET findings alone are used to recommend therapy (Podoloff, 2009).
For bladder tumors that have not invaded the muscle (stage < cT2).

For members with contracts without primary coverage criteria, PET or PET/CT is considered investigational for the following:

Evaluation of indeterminate renal mass (ACR Appropriateness, 2010; Podoloff, 2009)
Surveillance for pulmonary or other organ metastases in asymptomatic patients (ACR Appropriateness, 2010; Podoloff, 2009)
To determine if patient is an appropriate candidate for an invasive diagnostic or therapeutic procedure (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
To determine the optimal anatomic location for an invasive procedure (NCCN, 2011; McEwan, 2008; Powles, 2007);
To determine the anatomic extent of tumor when the recommended anti-tumor treatment reasonably depends on the extent of the tumor (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
For restaging of tumor following therapy (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
To monitor the effect of chemotherapy, biologic therapy, or vaccine therapy (Revheim, 2011; Heidenreich, 2010; Podoloff, 2009);
As a surveillance tool (i.e., routine monitoring in asymptomatic patients no longer on therapy) (Podoloff, 2009);
Detection of brain metastasis (NCCN 2011; Podoloff, 2009);
In lieu of biopsy to establish a diagnosis of cancer (Podoloff, 2009);
In patients with stable disease when PET findings alone are used to recommend therapy (Podoloff, 2009).
For bladder tumors that have not invaded the muscle (stage < cT2).

Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective prior to October 2018

PET or PET/CT meets member benefit certificate primary coverage criteria for:

Initial staging, only as an adjunct test when CT scans are equivocal; OR
Follow-up (restaging) as an adjunct test when CT scans are equivocal.

PET or PET CT does not meet member benefit certificate primary coverage criteria for the following indications:

Evaluation of indeterminate renal mass (ACR Appropriateness, 2010; Podoloff, 2009)
Surveillance for pulmonary or other organ metastases in asymptomatic patients (ACR Appropriateness, 2010; Podoloff, 2009)
To determine if patient is an appropriate candidate for an invasive diagnostic or therapeutic procedure (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
To determine the optimal anatomic location for an invasive procedure (NCCN, 2011; McEwan, 2008; Powles, 2007);
To determine the anatomic extent of tumor when the recommended anti-tumor treatment reasonably depends on the extent of the tumor (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
For restaging of tumor following therapy (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
To monitor the effect of chemotherapy, biologic therapy, or vaccine therapy (Revheim, 2011; Heidenreich, 2010; Podoloff, 2009);
As a surveillance tool (i.e., routine monitoring in asymptomatic patients no longer on therapy) (Podoloff, 2009);
Detection of brain metastasis (NCCN 2011; Podoloff, 2009);
In lieu of biopsy to establish a diagnosis of cancer (Podoloff, 2009);
In patients with stable disease when PET findings alone are used to recommend therapy (Podoloff, 2009).

For members with contracts without primary coverage criteria, PET or PET/CT is considered investigational for the following indications:

Evaluation of indeterminate renal mass (ACR Appropriateness, 2010; Podoloff, 2009)
Surveillance for pulmonary or other organ metastases in asymptomatic patients (ACR Appropriateness, 2010; Podoloff, 2009)
To determine if patient is an appropriate candidate for an invasive diagnostic or therapeutic procedure (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
To determine the optimal anatomic location for an invasive procedure (NCCN, 2011; McEwan, 2008; Powles, 2007);
To determine the anatomic extent of tumor when the recommended anti-tumor treatment reasonably depends on the extent of the tumor (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
For restaging of tumor following therapy (NCCN, 2011; Heidenreich, 2010; McEwan, 2008; Powles, 2007);
To monitor the effect of chemotherapy, biologic therapy, or vaccine therapy (Revheim, 2011; Heidenreich, 2010; Podoloff, 2009);
As a surveillance tool (i.e., routine monitoring in asymptomatic patients no longer on therapy) (Podoloff, 2009);
Detection of brain metastasis (NCCN 2011; Podoloff, 2009);
In lieu of biopsy to establish a diagnosis of cancer (Podoloff, 2009);
In patients with stable disease when PET findings alone are used to recommend therapy (Podoloff, 2009).

Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:

PET or PET/CT for renal cell carcinoma is controversial. The following are statements from expert panels and systematic reviews:

Expert Panel Review (Fletcher JW, 2008):

The March 2008 “Recommendations on the Use of FDG-PET in Oncology by a number of “experts” from the U.S. and England, did not review kidney cancer because “Other neoplasms that have been reported and generally recognized as non-FDG-avid (e.g., renal, prostate, and hepatocellular cancer) were not addressed.”

Technology Assessment – Agency for Healthcare Research & Quality (McEwan AJ, 2008):

“Because of the high sensitivities and specificities reported in prospective studies of diagnostic accuracy, the application of FDG-PET to at least initial staging of renal cancer seems to be worthy of additional study by well-designed prospective trials. There is insufficient evidence to support its widespread adoption at this time.”

NCCN Task Force Report (Podoloff DA, 2009):

FDG-PET may be considered in detecting metastasis in kidney cancer…Currently, FDG-PET should only be considered an adjunct to, and not a replacement for, other conventional imaging techniques (i.e., MRI/magnetic resonance spectroscopy, CT, and bone scintigraphy…Because of its high specificity but low sensitivity, PET may be most useful in resolving diagnostic dilemmas in advanced disease.

Technology Assessment - Canadian Agency for Drugs and Technologies in Health (Mujoomdar M, 2010):

The April 2010 Canadian Agency for Drugs and Technologies in Health technology assessment of PET in Oncology, does not include assessment of PET for kidney cancer.

Expert Panel Review (Heidenreich, 2010):

“Contrast enhanced CT remains the standard imaging technique for monitoring of pulmonary, hepatic and lymph node metastases. For clinical trials it might be replaced by PET-CT.”

2013 Update:

A review of literature on PubMed through December 2012 was performed. There were no published

articles identified that would prompt a change in the coverage statement.

Ueno D, Yao M, Tateishi U, et al. (2012)

These authors reported previously that 18F-2-fluoro-2-deoxyglucose FDG PET/CT had potential for evaluating early response to treatment by tyrosine kinase inhibitors (TKIs) in advanced renal cell carcinoma (RCC). This study investigated the relation of the early assessment by FDG PET/CT to long-term prognosis with an expanded number of patients and period of observation.

Thirty-five patients for whom TKI treatment for advanced RCC was planned were enrolled (sunitinib 19 cases, sorafenib 16 cases). The patients with RCC showing high SUVmax in pretreatment FDG PET/CT demonstrated short progression free survival (PFS) (P =0.024, hazard ratio 1.137, 95% CI 1.017-1.271) and short overall survival (OS) (P =0.004, hazard ratio 1.210 95% CI 1.062-1.379). The patients were classified into three response groups: good responder (diameter sum did not increase, and SUVmax decreased≥20%), intermediate responder (diameter sum did not increase, and SUVmax decreased<20%), and poor responder (diameter sum increased, or one or more new lesions appeared). The median PFS of good, intermediate, and poor responders were 458±146days, 131±9days, and 88±26days (good vs. intermediate P=0.0366, intermediate vs. poor P=0.0097, log-rank test). Additionally the mean OSs were 999±70days, 469±34days, and 374±125days, respectively (good vs. intermediate P=0.0385, intermediate vs. poor P=0.0305, log-rank test). The authors concluded that the evaluation of RCC response to TKI by tumor size and FDG uptake using FDG PET/CT after 1month can predict PFS and OS.

Harrison MR and George DJ (2011)

Sunitinib treatment benefits patients with metastatic renal cell carcinoma (mRCC), but response duration can vary widely and resistance is not predicted by standard measures. FDG-PET uptake is variable in mRCC, but changes in FDG-PET uptake may be useful in monitoring disease progression. Further work is needed to personalize treatment for patients with mRCC.

Khandani AH, Rathmell WK (2012)

PET has revolutionized cancer imaging. FDG PET is used in the majority of malignant tumors with a few exceptions. Renal cell carcinoma (RCC) is one of those exceptions because of its variable uptake of FDG, although this variable uptake may actually be an asset in predicting response to some targeted agents. The purpose of Khandani’s review was to summarize the current status of PET usage in RCC and point out its potentials and future directions.

One study discussed was by Ozulker et al who prospectively examined 18 patients with “suspicious” renal masses detected on CE, MRI, or ultrasound (US) with sizes ranging from 2 to 17 cm. FDG-PET/CT was performed within 4 weeks of CT/MRI/US. All patients underwent nephrectomy or surgical resection of the renal mass within the 2 weeks after completion of imaging studies. A renal mass was classified malignant when its intensity on PET was greater than the intensity of uptake in the renal parenchyma and it was distinct from the physiological excretion in the collecting system. Histology was used as gold standard after surgical resection of the mass. PET was true positive for malignancy in 7 of the 15 lesions and false negative in 8 lesions, true negative in 2 lesions and false-positive in 1 lesion. A useful conclusion of thee data is that about half of clear cell histology (ccRCC) tumors are positive on FDG-PET.

FDG-PET in Staging and Restaging of RCC

About 30% of patients diagnosed with renal cancer have evidence of metastatic disease at the time of diagnosis. Traditionally, contrasted CT of the chest, abdomen, and pelvis is performed to stage RCC patient with RCC. The reported sensitivity of FDG-PET for detecting RCC metastases is higher than for the primary RCC. Kand et all studied 66 patients to assess the value of FDG-PET for primary RCC, metastatic disease, and local recurrence. PET detected 66.9% of distant metastases and 75% of retroperitoneal metastases/local recurrences versus only 60% of the primary RCC tumors. On a patient base, there were only 6 out of 52 patients (11.6%) in whom all metastatic lesions were missed on PET. In the remaining 46 patients (88.4%) PET detected at least some of the distant metastases, but failed to identify others. The authors attributed this to variable intensities of different metastatic lesions on FDG-PET.

Nakatani et al studied the value of FDG-PET to detect recurrence disease in 23 postsurgical RCC patients. PET correctly detected all cases of intra-abdominal and bone recurrence. There was a trend for better 5-year survival in PET-negative patients compared with PET-positive patients of 83% versus 40%, respectively. This underlines the fact that FDT-PET has probably a prognostic value in RCC.

The largest study addressing the value of FDG-PET in assessing the response to a targeted drug in RCC was conducted by Kayani et al. They studied prospectively 44 treatment-naïve ccRCC patients only, which were part of a phase II multicenter trial of sunitinib. FDG-PET scans were performed before treatment and at 4 and 16 weeks. The findings of the study were along the same experience as Khandani et al that ccRCC tumors with a lower pretherapy uptake on FDG-PET demonstrate a larger size decrease on CT after treatment with tyrosine kinase inhibitors.

Khandani AH, Cowey CL, Moore DT, et al. (2012)

The objective of this study was to collect preliminary data on the predictive value of pretherapy 18F-FDG PET in primary RCC patients undergoing neoadjuvant therapy with sorafenib.

As part of a clinical trial to assess the safety and feasibility of using neoadjuvant sorafenib in patients with RCC, 26 patients [19 with clear cell RCC (ccRCC), seven with non-clear cell RCC (non-ccRCC)] underwent 18F-FDG PET with concurrent CT before commencing sorafenib therapy and 17 (13 ccRCC, four non-ccRCC) of them also at the end of sorafenib therapy. The maximal standard uptake value at baseline (SUV base) and its change from baseline after therapy (SUV diff and SUV rel) were recorded and correlated with therapy response, measured as percentage size change on CT, using Spearman's rank and Pearson's correlation coefficients. In neither group was there a statistically significant correlation between change in SUV and size after commencement of treatment. All findings were limited by the small number of samples included in this analysis. The conclusion was that primary ccRCC tumors with lower SUV base are more likely to respond to neoadjuvant sorafenib, whereas this trend was not observed for non-ccRCC tumors.

NCCN Guidelines: Kidney Cancer (Version 1.2013):

The value of PET in RCC remains to be determined. Currently, PET alone is not a tool that is standardly used to diagnose kidney cancer or follow for evidence of relapse after nephrectomy.

American College of Radiology Appropriateness Guidelines (June 2012) for FDG PET/CT imaging:

(Rating Scale: 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate)

Evaluation of indeterminate renal mass

Not included in appropriateness recommendation

Follow-up of renal cell carcinoma (asymptomatic patient with no known metastasis)

Appropriateness rating: 1 (May have role when CT and/or bone scan findings are equivocal)

Screening for pulmonary metastasis (primary malignancy: renal cell carcinoma)

Appropriateness rating:1

Staging of renal cell carcinoma less than or equal to 3cm

Appropriateness rating: 1

Staging of renal cell carcinoma greater than 3cm

Appropriateness rating:1

2014 Update

A literature was conducted using the MEDLINE database through December 2013. There was no new information identified that would prompt a change in the coverage statement.

2017 Update

A literature search conducted through January 2017 did not reveal any new information that would prompt a change in the coverage statement.

2018 Update

A literature search conducted through January 2018 revealed no 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.

October 2018 Update

A literature search was conducted through September 2018. The key identified literature is summarized below.

BLADDER CANCER

Systematic Reviews

A systematic review and meta-analysis (10 studies, total N=433 patients) by Zhang et al evaluated the diagnostic accuracy of FDG-PET and FDG-PET with CT (FDG-PET/CT) in patients with urinary bladder cancer (Zhang, 2015). The 10 studies were assessed for quality using the 14-item Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Median QUADAS score was 9 (range, 7-10). Nine of the 10 studies used FDG-PET/CT and 1 used FDG-PET. Nine studies were retrospective and 1 prospective.

Meta-analyses showed relatively high sensitivity (82%; 95% confidence interval [CI], 75% to 88%) and specificity (92%; 95% CI, 87% to 95%) in the diagnosis of bladder cancer, with the reference test of pathology results. The meta-analysis funnel plots showed some asymmetry, indicating a potential for publication bias.

Guidelines

American College of Radiology

The American College of Radiology issued an Appropriateness Criteria for pretreatment staging of muscle-invasive bladder cancer (ACR, 2018). ACR stated that FDG-PET/CT “may be appropriate” for the pretreatment staging of muscle-invasive bladder cancer. However, the ACR cited CT, MRI, and chest radiographs as the most appropriate imaging techniques for pretreatment staging.

National Comprehensive Cancer Network

Current National Comprehensive Cancer Network (NCCN) guidelines for bladder cancer state that PET/CT “may be beneficial in selected patients with T2 (muscle-invasive disease) and in patients with ≥cT3 disease”(category 2B)” (NCCN, 2018). According to the guidelines, PET/CT may also be considered if metastasis is suspected in high-risk patients (category 2B). However, the guidelines note that “PET/CT should not be used to delineate the anatomy of the upper urinary tract” or in patients with non-muscle invasive bladder cancer.

Section Summary: Bladder Cancer

Evidence for the use of FDG-PET and FDG-PET/CT for the diagnosis and for the staging and restaging of muscle-invasive bladder cancer consists of a systematic review and meta-analysis of several studies.

Pooled analyses have shown that PET/CT is effective in the staging of muscle-invasive bladder cancer.

The evidence supports the use of FDG-PET/CT for the diagnosis and staging and restaging of muscle invasive bladder cancer.

The evidence does not support the use of FDG-PET/CT for non-muscle invasive bladder 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 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.

Bladder, Renal Pelvis, and Ureter

DIAGNOSTIC WORKUP

Staging utilizes the American Joint Committee on Cancer TNM system. Bladder cancer is further classified as muscle invasive or non-muscle invasive. Imaging is used to further assess the local tumor, lymph nodes, and distant metastases.

CT abdomen and pelvis with excretory imaging can be used for staging of invasive locally advanced bladder cancer. (1) Although CT provides adequate visualization of tumors and allows for assessment of the upper urinary tract, it does not have the same capability as MRI pelvis for local staging of bladder cancer. Compared to CT, MRI has the added benefit of high soft tissue contrast and direct multiplanar imaging capabilities, allowing for accurate tumor evaluation and better visualization of the bladder dome, trigone, and adjacent structures. The reported accuracy of MRI in overall staging of bladder cancer varies from 60% to 85%, whereas local staging ranges from 73% to 96%.(2) Both CT and MRI have comparable accuracy for staging lymph nodes: 73% to 90%.(3) The National Comprehensive Cancer Network (NCCN) does not recommend routine evaluation of bone metastases for non-muscle invasive urothelial cancer, and only recommends bone scintigraphy for muscle invasive urothelial cancer in symptomatic, high-risk patients or those with laboratory indicators of bone metastasis.(4)

The utility of PET/CT prior to planned cystectomy has been studied prospectively. In a study by Goodfellow et al, PET/CT was able to detect metastatic disease outside the pelvis with a sensitivity of 54% compared to 41% for the staging CT (N = 207). Both modalities had similar specificities of 97% and 98%. (5) In 2 additional studies, management was changed in 6%-27% of the patients based on new findings on PET/CT not detected by conventional CT. (6, 7) A meta-analysis of PET/CT in urinary bladder cancer showed pooled sensitivity and specificity of PET/CT for primary lesion detection were 90% and 100%, respectively. The authors concluded that diagnostic accuracy of PET/CT was good in metastatic lesions of urinary bladder cancer, but due to the small number of patients and limited number of studies

analyzed, the diagnostic capability of FDG-PET or PET/CT in detection of primary bladder wall lesions could not be assessed.8 Although PET shows promise as a useful clinical tool for staging of bladder cancer outside of the pelvis, currently its use is a National Comprehensive Cancer Network (NCCN) category 2B recommendation. (4)

Additional metastatic workup with MRI of the brain and bone scan should not be routinely ordered unless localizing labs or symptoms are present. (9, 10) The imaging recommendations for renal pelvis and urothelial carcinoma of the ureter for <T1 disease should be guided by recommendations for noninvasive bladder cancer and for ≥ T2 disease should be guided by recommendations for invasive bladder cancer. (11)

MANAGEMENT

There is limited evidence to favor one imaging modality over another for tumor evaluation following initial therapy. Results for the bladder cohort from the national oncologic PET registry showed that FDG-PET used for chemotherapy monitoring changed management in 52% of patients.12 This study included all disease stages and did not report the comparative effects of other imaging modalities on treatment.

SURVEILLANCE

The majority of recurrences after cystectomy are asymptomatic and routine surveillance is indicated. The most common sites of recurrence are the peritoneum, lymph nodes, liver, bone, lungs, and adrenal glands with late recurrences occurring in the upper urinary tract. (13) Early detection of asymptomatic recurrence has been shown to positively impact survival. (14)

Current References (Bladder, Renal Pelvis, and Ureter)

Chang SS, Bochner BH, Chou R, et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline. J Urol. 2017;198(3):552-9. PMID: 28456635
Tekes A, Kamel I, Imam K, et al. Dynamic MRI of bladder cancer: evaluation of staging accuracy. AJR Am J Roentgenol. 2005;184(1):121-7. PMID: 15615961
Barentsz JO, Jager GJ, van Vierzen PB, et al. Staging urinary bladder cancer after transurethral biopsy: value of fast dynamic contrast-enhanced MR imaging. Radiology. 1996;201(1):185-93. PMID: 8816542
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer (Version 12.2021). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2021.
Goodfellow H, Viney Z, Hughes P, et al. Role of fluorodeoxyglucose positron emission tomography (FDG PET)-computed tomography (CT) in the staging of bladder cancer. BJU Int. 2014;114(3):389-95. PMID: 24341486
Kollberg P, Almquist H, Blackberg M, et al. [18F] Fluorodeoxyglucose - positron emission tomography/computed tomography improves staging in patients with high-risk muscle-invasive bladder cancer scheduled for radical cystectomy. Scand J Urol. 2015;49(4):296-301. PMID: 25623843
Kibel AS, Dehdashti F, Katz MD, et al. Prospective study of [18F] fluorodeoxyglucose positron emission tomography/computed tomography for staging of muscle-invasive bladder carcinoma. J Clin Oncol. 2009;27(26):4314-20. PMID: 19652070
Lu YY, Chen JH, Liang JA, et al. Clinical value of FDG PET or PET/CT in urinary bladder cancer: a systemic review and meta-analysis. Eur J Radiol. 2012;81(9):2411-6. PMID: 21899971
Shinagare AB, Ramaiya NH, Jagannathan JP, et al. Metastatic pattern of bladder cancer: correlation with the characteristics of the primary tumor. AJR Am J Roentgenol. 2011;196(1):117-22. PMID: 21178055
Anderson TS, Regine WF, Kryscio R, et al. Neurologic complications of bladder carcinoma: a review of 359 cases. Cancer. 2003;97(9):2267-72. PMID: 12712482
Roupret M, Babjuk M, Comperat E, et al. European guidelines on upper tract urothelial carcinomas: 2013 update. Eur Urol. 2013;63(6):1059-71. PMID: 23540953
Hillner BE, Siegel BA, Hanna L, et al. Impact of 18F-FDG PET used after initial treatment of cancer: comparison of the National Oncologic PET Registry 2006 and 2009 cohorts. J Nucl Med. 2012;53(5):831-7. PMID: 22448033
Soukup V, Babjuk M, Bellmunt J, et al. Follow-up after surgical treatment of bladder cancer: a critical analysis of the literature. Eur Urol. 2012;62(2):290-302. PMID: 22609313
Giannarini G, Kessler TM, Thoeny HC, et al. Do patients benefit from routine follow-up to detect recurrences after radical cystectomy and ileal orthotopic bladder substitution? Eur Urol. 2010;58(4):486-94. PMID: 20541311

Kidney Cancer

DIAGNOSTIC WORKUP

Kidney cancer is staged using the American Joint Committee on Cancer TNM system. In a study comparing triphasic helical CT and fast MRI, renal cell carcinoma was correctly staged 67% of the time. (1) In another prospective study, accuracy of MRI was 78%-87%, and the accuracy of CT was 80%-83%. (2) Both modalities, however, are poor at detecting invasion of perinephric fat and assessing tumor extension into the renal veins or inferior vena cava. For the evaluation of renal vein involvement, MRI and CT appear to have approximately the same accuracy of 72%-76% and 78%-88%, respectively. (3) In the evaluation of primary renal cell carcinoma, PET accuracy was only 50%. The utility of PET/CT is adversely affected by poor FDG avidity and background uptake from the kidney. Although a poor staging modality, specificity of PET was found to approach 100% in 2 separate studies. (4, 5) The NCCN and ACR notes that the value of PET in renal cell carcinoma remains to be determined.6, 7 Current evidence suggests that imaging of the pelvis is of low yield and does not affect overall management.8, 9Forchest imaging, radiography is preferred, although CT is more sensitive in patients with symptoms, advanced-stage disease, anemia, or thrombocytopenia. (10, 11)

Guidelines are in accordance with recommendations from the National Comprehensive Cancer Network Guidelines for Kidney Cancer, American College of Radiology ACR Appropriateness Criteria® for Renal Cell Carcinoma Staging, and European Association of Urology. (6,7)

MANAGEMENT

Imaging (CT or MRI) with contrast can be done when clinically indicated following ablative techniques, and as baseline imaging after partial or radical nephrectomy (NCCN level of evidence category 2B). (6, 12)

SURVEILLANCE

Active surveillance can be considered in select T1b patients. Imaging (CT or MRI) should be done with contrast when clinically indicated if no contraindication. Active surveillance entails serial abdominal imaging with timely intervention should the mass demonstrate growth (e.g. tumor size, growth rate, infiltrative pattern) indicative of increasing metastatic potential. No single follow-up plan is appropriate for all patients. Follow-up frequency and duration should be individualized based on patient requirements and may be extended beyond 5 years at the discretion of the physician. The choice to perform imaging follow-up is level of evidence category 2B as designated by the National Comprehensive Cancer Network. (6, 12)

Current References (Kidney Cancer)

Walter C, Kruessell M, Gindele A, et al. Imaging of renal lesions: evaluation of fast MRI and helical CT. Br J Radiol. 2003;76(910):696-703. PMID: 14512329
Hallscheidt PJ, Bock M, Riedasch G, et al. Diagnostic accuracy of staging renal cell carcinomas using multidetector-row computed tomography and magnetic resonance imaging: a prospective study with histopathologic correlation. J Comput Assist Tomogr. 2004;28(3):333-9. PMID: 15100536
Hallscheidt PJ, Fink C, Haferkamp A, et al. Preoperative staging of renal cell carcinoma with inferior vena cava thrombus using multidetector CT and MRI: prospective study with histopathological correlation. J Comput Assist Tomogr. 2005;29(1):64-8. PMID: 15665685
Kang DE, White RL, Jr., Zuger JH, et al. Clinical use of fluorodeoxyglucose F 18 positron emission tomography for detection of renal cell carcinoma. J Urol. 2004;171(5):1806-9. PMID: 15076281
Majhail NS, Urbain JL, Albani JM, et al. F-18 fluorodeoxyglucose positron emission tomography in the evaluation of distant metastases from renal cell carcinoma. J Clin Oncol. 2003;21(21):3995-4000. PMID: 14581422
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer (Version 23.2021). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2021.
Vikram R, Beland MD, Blaufox MD, et al. ACR Appropriateness Criteria® renal cell carcinoma staging. J Am Coll Radiol. 2016;13(5):518-25. PMID: 27016804
Fielding JR, Aliabadi N, Renshaw AA, et al. Staging of 119 patients with renal cell carcinoma: the yield and cost effectiveness of pelvic CT. AJR Am J Roentgenol. 1999;172(1):23-5. PMID: 9888732
Khaitan A, Gupta NP, Hemal AK, et al. Is there a need for pelvic CT scan in cases of renal cell carcinoma? Int Urol Nephrol. 2002;33(1):13-5. PMID: 12090319
Lim DJ, Carter MF. Computerized tomography in the preoperative staging for pulmonary metastases in patients with renal cell carcinoma. J Urol. 1993;150(4):1112-4. PMID: 8371366
Larcher A, Dell'Oglio P, Fossati N, et al. When to perform preoperative chest computed tomography for renal cancer staging. BJU Int. 2017;120(4):490-6. PMID: 27684653
Donat SM, Diaz M, Bishoff JT, et al. Follow-up for clinically localized renal neoplasms: AUA Guideline. J Urol. 2013;190(2):407-16. PMID: 23665399

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 Bladder Cancer (2022) and Kidney Cancer (2022) were reviewed with no change from 2021 versions with regard to PET applications.

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 Bladder Cancer (3.2023) and Kidney Cancer (1.2024) were reviewed with no change from 2022 versions with regard to PET applications.

The European Society for Medical Oncology (ESMO) recommends cross-sectional upper tract imaging

with either CT or MR urography to assess for concurrent upper tract urothelial carcinoma. They recommend that, in patients with invasive disease, regional and distant staging should be done with CT chest and either CT or MRI abdomen/pelvis. There was no consensus reached on the utility of PET/CT (Prowles et al, 2022).

Professional society guidelines including the American College of Radiology Appropriate Use Criteria recommend post-treatment surveillance in patients with muscle-invasive bladder cancer, and those with nonmuscle invasive bladder cancer and symptoms or risk factors (Expert Panel on Urological Imaging: Allen et al, 2021).

In 2022, ACR updated its appropriateness criteria for staging of renal cell carcinoma and continued to note that the value of PET in renal cell carcinoma remains to be determined (Expert Panel on Urological Imaging: Ganeshan et al, 2023).

CPT/HCPCS:

78811	Positron emission tomography (PET) imaging; limited area (eg, chest, head/neck)
78812	Positron emission tomography (PET) imaging; skull base to mid thigh
78813	Positron emission tomography (PET) imaging; whole body
78814	Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; limited area (eg, chest, head/neck)
78815	Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; skull base to mid thigh
78816	Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; whole body

References:

ACR Appropriateness Criteria.(2011) Evaluation of indeterminate renal mass. http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria.aspx; accessed 2013-01-28.

ACR Appropriateness Criteria.(2011) Follow-up of renal cell carcinoma. http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria.aspx; accessed 2013-01-28.

ACR Appropriateness Criteria.(2011) Positron emission tomography. Available at http:/ac.search.acc.org; accessed 2011-10-05.

ACR Appropriateness Criteria.(2011) Renal cell carcinoma staging. http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria.aspx; accessed 2013-01-28.

ACR Appropriateness Criteria.(2011) Screening for pulmonary metastasis. http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria.aspx; accessed 2013-01-28.

Expert Panel on Urologic Imaging, van der Pol CB, Sahni VA, et al.(2018) ACR Appropriateness Criteria((R)) pretreatment staging of muscle-invasive bladder cancer. J Am Coll Radiol. May 2018;15(5S):S150-S159. PMID 29724418

Expert Panel on Urological Imaging: Allen BC, Oto A, Akin O, et al. ACR(2021) Appropriateness Criteria® post-treatment surveillance of bladder cancer: 2021 update. J Am Coll Radiol. 2021;18(5S):S126-S38.

Expert Panel on Urological Imaging: Ganeshan D, Khatri G, Ali N, et al.(2023) ACR Appropriateness Criteria® staging of renal cell carcinoma: 2022 update. J Am Coll Radiol. 2023;20(5S):S246-S64.

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

Heidenreich A, Albers P, Classen J, et al.(2010) Imaging studies in metastatic urogenital cancer patients undergoing systemic therapy: Recommendations of multidisciplinary consensus meeting of the association of urological oncology of the German cancer society. Urological Internationalis, 2010; 85:1-10.

Khandani AH, Cowey CL, Moore DT, et al.(2012) Primary renal cell carcinoma: relationship between 18F-FDG uptake and response to neoadjuvant sorafenib. Nucl Med Commun. 2012 Sep;33(9):967-73.

Khandani AH, Rathmell WK.(2012) Positron emission tomography in renal cell carcinoma: an imaging biomarker in development. Semin Nucl Med. 2012 Jul;42(4):221-30.

McEwan AJ, Gulenchyn K, Oprina MB, et al.(2008) Positron emission tomography for nine cancers (bladder, brain, cervical, kidney, ovarian, pancreatic, prostate, small cell lung, testicular). University of Alberta Evidence-based Practice Center, Edmonton, Canada. AHRQ Technology Assessment Program, December 1, 2008; pp136-144.

Mjoomdar M, Moulton K, Nkansah E.(2010) Positron emission tomography in oncology: A systematic review of clinical effectiveness and indications for use. Ottawa: Canadian Agency for Drugs & Technologies in Health, 2010.

National Comprehensive Cancer Network (NCCN).(2018) NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer Version 5.2018. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed August 16, 2018.

National Comprehensive Cancer Network(2022) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer (Version 1.2022). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2022.

National Comprehensive Cancer Network(2022) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer (Version 2.2022). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2022.

National Comprehensive Cancer Network.(2023) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer (Version 3.2023). Available at http://www.nccn.org.

National Comprehensive Cancer Network.(2023) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer (Version 2.2023). Available at http://www.nccn.org.

National Comprehensive Cancer Network®.(2012) Kidney cancer. NCCN Practice Guidelines. NCCN Guidelines, version 1.2013 (accessed 01/28/2013).

Podoloff DA, Ball DW, en-Josef E, et al.(2008) NCCN task force report: Clinical utility of PET in a variety of tumor types. JNCCN, 2008; 7 (Suppl 2):S9 – S10.

Powles T, Bellmunt J, Comperat E, et al.(2022) Bladder cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(3):244-58.

Ueno D, Yao M, Tateishi U, et al.(2012) Early assessment by FDG-PET/CT of patients with advanced renal cell carcinoma treated with tyrosine kinase inhibitors is predictive of disease course BMC Cancer. 2012; 12: 162.

Zhang H, Xing W, Kang Q, et al.(2015) Diagnostic value of [18F] FDG-PET and PET/CT in urinary bladder cancer: a meta-analysis. Tumour Biol. May 2015;36(5):3209-3214. PMID 25809703

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 © 2024 American Medical Association.