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Non-Genetic Urinary Biomarker for Cancer Screening, Diagnosis and Surveillance

Policy Number: MP-433

Latest Review Date: December 2023

Category: Laboratory

POLICY:

Initial Diagnosis of Urinary Bladder Cancer

The following urinary tumor markers may be considered medically necessary as an adjunct in the diagnosis of bladder cancer only in conjunction with current standard diagnostic procedures (urine cytology or cystoscopy, with or without biopsy):

  • BTA-STAT*, BTA-TRAK*;
  • NMP22*, NMP22 BLADDER CHEK*;
  • UROVYSION*;

The following urinary tumor marker is considered investigational in the diagnosis of bladder cancer:

  • IMMUNOCYT

Monitoring of Urinary Bladder Cancer

The following urinary tumor markers may be considered medically necessary as an adjunct in the monitoring of bladder cancer only in conjunction with current standard diagnostic procedures (urine cytology or cystoscopy, with or without biopsy):

  • BTA-STAT*, BTA-TRAK*;
  • IMMUNOCYT*;
  • NMP22*, NMP22 BLADDER CHEK*;
  • UROVYSION*;

Screening for Urinary Bladder Cancer

The use of urinary tumor markers is considered investigational for screening for cancer (including, but not limited to, bladder cancer and precancerous colonic polyps).

* FDA Approved indications

This policy addresses the use of non-genetic urinary tumor markers/biomarkers. For information about genetic urinary tumor markers/biomarkers refer to our genetic testing management program.

DESCRIPTION OF PROCEDURE OR SERVICE:

The diagnosis of bladder cancer is generally made by cystoscopy and biopsy. Bladder cancer has a very high frequency of recurrence and therefore follow-up cystoscopy, along with urine cytology, is done periodically to identify recurrence early. Urine biomarkers that might be used to supplement or supplant these tests have been actively investigated. Urinary biomarkers have also been suggested to have utility in identifying colonic polyps.

Urinary Bladder Cancer

Urinary bladder cancer, a relatively common form of cancer in the U.S., results in significant morbidity and mortality. Bladder cancer typically presents as a tumor confined to the superficial mucosa of the bladder. The most frequent symptom of early bladder cancer is hematuria; however, urinary tract symptoms (ie, urinary frequency, urgency, dysuria) may also occur.

Diagnosis

The criterion standard for a confirmatory diagnosis of bladder cancer is cystoscopic examination with biopsy. At initial diagnosis, approximately 70% of patients have cancers confined to the epithelium or subepithelial connective tissue. The non-muscle-invasive disease is usually treated with transurethral resection, with or without intravesical therapy, depending on the depth of invasion and tumor grade. However, a 50% to 75% incidence of recurrence has been noted in these patients, with 10% to 15% progressing to muscle invasion over a five-year period. Current follow-up protocols include flexible cystoscopy and urine cytology every three months for one to three years, every six months for an additional two to three years, and then annually thereafter, assuming no recurrence.

While urine cytology is a specific test (from 90% to 100%), its sensitivity is lower, ranging from 50% to 60% overall, and it is considered even lower for low-grade tumors. Therefore, interest has been reported in identifying tumor markers in voided urine that would provide a more sensitive and objective test for tumor recurrence.

Adjunctive testing to urine cytology has used a variety of nuclear and cytoplasmic targets, and a range of molecular pathology and traditional (e.g., immunohistochemistry) methods.

KEY POINTS:

The most recent literature update was performed through October 22, 2023.

Summary of Evidence

For individuals who are asymptomatic and at a population-level risk of colon cancer who receive urinary tests for precancerous polyps, the evidence includes a validation study. Relevant outcomes are overall survival (OS), disease-specific survival, and test accuracy and validity. The clinical data supporting a urine metabolite assay for adenomatous polyps includes a report of a training and validation set published in 2017. Current evidence does not support the diagnostic accuracy of urinary tumor markers to screen asymptomatic individuals for precancerous polyps. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. For individuals who have signs and/or symptoms of bladder cancer who receive urinary tumor marker tests in addition to cystoscopy, the evidence includes a number of diagnostic accuracy studies and meta-analyses of these studies. Relevant outcomes are OS, disease-specific survival, test accuracy and validity, and resource utilization. A meta-analysis of diagnostic accuracy studies determined that urinary tumor marker tests have a sensitivity ranging from 47% to 82% and specificity ranging from 53% to 95%. This analysis found that combining urinary tumor markers with cytology improves diagnostic accuracy, but about 10% of cancers would still be missed. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. The use of all urinary tumor markers, including the use of Immunocyt, for the diagnosis of urinary bladder cancer is considered investigational (except for the following, when used for an FDA approved indication: Bta-Stat, Bta-Trak; Nmp22, Nmp22 Bladder Chek; Urovysion)

For individuals who have a history of bladder cancer who receive urinary tumor marker tests in addition to cystoscopy, the evidence includes a number of diagnostic accuracy studies, and meta-analyses, as well as a decision curve analysis and a retrospective study examining the clinical utility of urinary tumor marker tests. Relevant outcomes are OS, disease-specific survival, test accuracy and validity, and resource utilization. The diagnostic accuracy studies found that urinary tumor marker tests have pooled sensitivity ranging from 52% to 84% and pooled specificity ranging from 71% to 91%. The decision analysis found only a small clinical benefit for use of a urinary tumor marker test and the retrospective study found that a urinary tumor marker test was not significantly associated with findings of the subsequent surveillance cystoscopy. No studies using the preferred trial design to evaluate clinical utility were identified; i.e., controlled studies prospectively evaluating health outcomes in patients managed with and without the use of urinary tests or prospective studies comparing different cystoscopy protocols used in conjunction with urinary tumor markers. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. The use of urinary tumor markers for the monitoring of urinary bladder cancer is considered investigational, unless one of the following is used for an FDA approved indication: Bta-Stat, Bta-Trak; Immunocyt; Nmp22, Nmp22 Bladder Chek; Urovysion.

For individuals who are asymptomatic and at a population-level risk of bladder cancer who receive urinary tumor marker tests, the evidence includes a systematic review and several uncontrolled prospective and retrospective studies. Relevant outcomes are OS, disease-specific survival, and test accuracy and validity. A 2010 systematic review (conducted for the U.S. Preventive Services Task Force) did not identify any randomized controlled trials, the preferred trial design to evaluate the impact of population-based screening and found only one prospective study that the Task Force rated as poor quality. A more recent retrospective study, assessing a population-based screening program in the Netherlands, reported low diagnostic yield. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. The use of all urinary tumor markers is considered investigational for screening for cancer.

In 2012, clinical input revealed a unanimous agreement that urinary tumor markers approved by the Food and Drug Administration (FDA) may be considered medically necessary as an adjunctive test in the diagnosis and monitoring of bladder cancer in conjunction with standard diagnostic procedures. This policy’s coverage determinations are supported by this information.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network

National Comprehensive Cancer Network (NCCN; v.3.2023) bladder cancer guidelines include consideration for urinary urothelial tumor markers every three months along with urine cytology for the first two years of follow-up for high-risk patients with non-muscle invasive bladder cancer (category 2B recommendation). The guidelines include the following statement: "Many of these tests have a better sensitivity for detecting bladder cancer than urinary cytology, but specificity is lower. Considering this, evaluation of urinary urothelial tumors may be considered during surveillance of high-risk non-muscle-invasive bladder cancer. However, it remains unclear whether these tests offer additional useful information for detection and management of non-muscle-invasive bladder tumors."

The NCCN colorectal cancer screening guidelines (v.3.2023) do not mention use of urinary tumor markers for detection of colon cancer in asymptomatic individuals at population-level risk of colon cancer. Colonoscopy or fecal testing are recommended for screening purposes in these individuals.

American Urological Association and Society of Urologic Oncology

The guidelines from the American Urological Association and Society of Urologic Oncology (2016; amended 2020) addressed the diagnosis and treatment of non-muscle-invasive bladder cancer, based on a systematic review completed by the Agency for Health Care Research and Quality and through additional supplementation that further addressed key questions and more recently published literature. Table 1 summarizes statements on the use of urine markers after the diagnosis of bladder cancer.

Table 1. Guidelines for Urine Tumor Markers After the Diagnosis of Bladder Cancer

Guidance Statement

SOR

LOE

“In surveillance of NMIBC, a clinician should not use urinary biomarkers in place of cystoscopic evaluation.”

Strong

B

“In a patient with a history of low-risk cancer and a normal cystoscopy, a clinician should not routinely use a urinary biomarker or cytology during surveillance.”

  

Expert opinion

“In a patient with NMIBC, a clinician may use biomarkers to assess response to intravesical BCG (UroVysion® FISH) and adjudicate equivocal cytology (UroVysion® FISH and ImmunoCyt™).”

  

Expert opinion

BCG: bacillus Calmette-Guérin; FISH: fluorescence in situ hybridization; LOE: level of evidence; NMIBC: non-muscle-invasive bladder cancer; SOR: strength of recommendation.

American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction

In 2020, the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction published a guideline on the diagnosis, evaluation, and follow-up of microhematuria. This guideline recommended the following with regard to urinary markers:

  • Clinicians should not use urine cytology or urine-based tumor markers in the initial evaluation of patients with microhematuria [Strong recommendation; Evidence level: Grade C]
  • Clinicians may obtain urine cytology for patients with persistent microhematuria after a negative workup who have irritative voiding symptoms or risk factors for carcinoma in situ [Expert opinion]

U.S. Preventive Services Task Force Recommendations

The U.S. Preventive Services Task Force concluded in (USPSTF; 2011 that there was insufficient evidence to assess the benefits and harms of screening for bladder cancer in asymptomatic adults. The recommendation was based on insufficient evidence (Grade I). In November 2021, a literature surveillance report was published that scanned for relevant literature in PubMed and PubMed databases and the Cochrane library from 2009 to present. The researchers found no relevant studies on the impact of screening for bladder cancer on morbidity and mortality, outcomes of treatment of screen-detected bladder cancer, or harms of screening for or treatment of screen-detected bladder cancer. Additionally, no studies compared the benefits or harms of treatment of screen-detected bladder cancer with no treatment.

The USPSTF (2021) recommendation for screening for colorectal cancer "does not include serum tests, urine tests, or capsule endoscopy for colorectal cancer screening because of the limited available evidence on these tests and because other effective tests are available."

KEY WORDS:

Bladder Tumor Antigen, BTA Test, FISH, Bladder Cancer Testing, ImmunoCyt, NMP-22, Tumor Marker, Bladder Cancer, UroVysion, BTA Stat, PolyDx, colonic polyp, colorectal, urothelial carcinoma, BTA stat®, BTA TRAK®, Alere NMP22®, BladderChek®, UroVysion®, Bladder EpiCheck®

APPROVED BY GOVERNING BODIES:

Table 2 lists urinary tumor marker tests approved or cleared for marketing by the FDA. The FDA approved or cleared tests are indicated as adjuncts to standard procedures for use in the initial diagnosis of bladder cancer, surveillance of bladder cancer patients, or identification of colonic polyps.

Table 2. FDA-Approved or -Cleared Urinary Tumor Marker Tests     

Test

Manufacturer

Type

Detection

Indication

BTA stat®

Polymedco

Point of care immunoassay

Human complement factor H-related protein

Qualitative detection of bladder tumor- associated antigen in the urine of persons diagnosed with bladder cancer

BTA TRAK®

Polymedco

Reference laboratory immunoassay

Human complement factor H-related protein

Quantitative detection of bladder tumor- associated antigen in the urine of persons diagnosed with bladder cancer

Alere NMP22®

Alere

Immunoassay

NMP22 protein

in vitro quantitative determination of the nuclear mitotic apparatus protein (NuMA) in stabilized voided urine. Used as adjunct to cystoscopy

Bladder Chek®

Alere

Point of care immunoassay

NMP22 protein

Adjunct to cystoscopy in patients at risk for bladder cancer

UroVysion®

Abbott Molecular

FISHa

Cell-based chromosomal abnormalities

Aid in the initial diagnosis of bladder cancer (P030052) and monitoring patients with previously diagnosed bladder cancer (K033982)

Bladder EpiCheck®

Nucleix

RT-PCR

DNA methylation biomarkers

Monitoring for tumor recurrence in conjunction with cystoscopy in patients with previously diagnosed NMIBC

FDA: U.S. Food and Drug Administration; FISH: fluorescence in situ hybridization; NMIBC: non-muscle invasive bladder cancer; IHC: immunohistochemistry; NMP: nuclear matrix protein; RT-PCR: real-time polymerase chain reaction.

aFISH is a molecular cytogenetic technology that can be used with either DNA or RNA probes to detect chromosomal abnormalities. DNA FISH probe technology involves the creation of short sequences of fluorescently labeled, single-strand DNA probes that match target sequences. The probes bind to complementary strands of DNA, allowing for identification of the location of the chromosomes targeted.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Urine-based tests are available under the auspices of CLIA. Laboratories that offer laboratory-developed tests must be licensed by CLIA for high-complexity testing. To date, FDA has chosen not to require any regulatory review of these tests.  

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP:  Special benefit consideration may apply. Refer to member’s benefit plan. 

CURRENT CODING: 

CPT Codes:

86294

Immunoassay for tumor antigen; qualitative or semiquantitative (e.g., bladder tumor antigen)

86316

Immunoassay for tumor antigen; other antigen, quantitative, each

86386

Nuclear Matrix Protein 22 (NMP22), qualitative

88120

Cytopathology, in situ hybridization (e.g., FISH), urinary tract specimen with morphometric analysis, 3-5 molecular probes, each specimen; manual

88121

Cytopathology in situ hybridization (e.g., FISH), urinary tract specimen with morphometric analysis, 3-5 molecular probes, each specimen; using computer-assisted technology

88299

Unlisted cytogenetic study

0002U

Oncology (colorectal), quantitative assessment of three urine metabolites (ascorbic acid, succinic acid and carnitine) by liquid chromatography with tandem mass spectrometry (LC-MS/MS) using multiple reaction monitoring acquisition, algorithm reported as likelihood of adenomatous polyps (PolypDX™)

REFERENCES:

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  2. Bangma CH, Loeb S, Busstra M et al. Outcomes of a bladder cancer screening program using home hematuria testing and molecular markers. Eur Urol 2013; 64(1):41-7.
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  4. Breen V, Kasabov N, Kamat AM, et al. A holistic comparative analysis of diagnostic tests for urothelial carcinoma: a study of Cxbladder Detect, UroVysion(R) FISH, NMP22(R) and cytology based on imputation of multiple datasets. BMC Med Res Methodol. 2015; 15:45.
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  8. Chou R, Buckley D, Fu R, et al. AHRQ Comparative Effectiveness Review No. 153: Emerging Approaches to Diagnosis and Treatment of Non-muscle-invasive Bladder Cancer; 2015.
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  11. D Elia C, Pycha A, Folchini DM, et al. Diagnostic predictive value of Xpert Bladder Cancer Monitor in the follow-up of patients affected by non-muscle invasive bladder cancer. J Clin Pathol. Feb 2019; 72(2): 140-144.
  12. Davis R, Jones JS, Barocas DA, et al. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol. Dec 2012; 188(6 Suppl):2473-2481.
  13. Deng L, Chang D, Foshaug RR, et al. Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps. Metabolites. Jun 22 2017; 7(3).
  14. Dimashkieh H, Wolff DJ, Smith TM et al. Evaluation of urovysion and cytology for bladder cancer detection: a study of 1835 paired urine samples with clinical and histologic correlation. Cancer Cytopathol 2013; 121(10):591-7.
  15. Eissa S, Swellam M, Shehata H, et al.  Expression of HYAL1 and surviving RNA as diagnostic molecular markers for bladder cancer.  J Urol 2010; 183(2):493-8.
  16. Fernandez CA, Milholland JM, Zwarthoff EC et al. A noninvasive multi-analyte diagnostic assay: combining protein and DNA markers to stratify bladder cancer patients. Research and Reports in Urology 2012; 4(17-26).
  17. Freidrich MG, Hellstern A, Hautmann SH et al. Clinical use of urinary markers for the detection and prognosis of bladder carcinoma: comparison of immunocytology with monoclonal antibodies against Lewis X and 486p3/12 with the BTA STAT and NMP-22 tests. J Urol 2002; 168(2):470-4.
  18. Giannopoulos A, Manousakas T, Gounari A et al. Comparative evaluation of the diagnostic performance of BTA STAT test, NMP-22, and urinary bladder cancer antigen for primary and recurrent bladder tumors. J Urol 2001; 166(2): 470-5.
  19. Grocela JA and McDougal WS.  Utility of nuclear matrix protein (NMP-22) in the detection of recurrent bladder cancer.  Urol Clin North Am 2000; 27(1):47-51.
  20. Grossfeld GD, et al.  Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy—part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up.  Urology 2001; 57(4):604-10.
  21. Grossman HB, et al.  Detection of bladder cancer using a point-of-care proteomic assay.  JAMA 2005; 293(7):810-6.
  22. Guo A, Wang X, Gao L, et al. Bladder tumour antigen (BTA stat) test compared to the urine cytology in the diagnosis of bladder cancer: A meta-analysis. Can Urol Assoc J. May 2014; 8(5-6):E347-352.
  23. Horstmann M, Patschan O, Hennenlotter J, et al.  Combinations of urine-based tumor markers in bladder cancer surveillance.  Scand J Urol Nephrol 2009; 43(6):461-6.
  24. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  25. Kamat AM, Karan JA, Grossman B et al. Prospective trial to identify optimal bladder cancer surveillance protocol: reducing costs while maximizing sensitivity. BJU Int 2011; 108(7):1119-24.
  26. Kim PH, Sukhu R, Cordon BH et al. Reflex fluorescence in situ hybridization assay for suspicious urinary cytology in bladder cancer patients with negative surveillance cystoscopy. BJU Int 2013.
  27. Ku JH, Godoy G, Amiel GE et al. Urine survivin as a diagnostic biomarker for bladder cancer: a systematic review. BJU Int 2012; 110(5):630-6.
  28. Lai Y, Ye J, Chen J, et al.  UPK3A: A promising novel urinary marker for the detection of bladder cancer.  Urology 2010 Aug; 76(2):514.e6-11.
  29. Li HX, Li M, Li CL et al. ImmunoCyt and cytokeratin 20 immunocytochemistry as adjunct markers for urine cytologic detection of bladder cancer. Ann Quant Cytol Histol 2010; 32(1):45-52.
  30. Lotan Y, Elias K, Svatek RS, et al.  Bladder cancer screening in a high risk asymptomatic population using a point of care urine based protein tumor marker.  J Urol 2009; 182(1):52-8.
  31. Mowatt G, Zhu S, Kilonzo M, et al. Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer. Health Technol Assess 2010; 14(4):1-331.
  32. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Bladder Cancer. Version 2.2022. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf.
  33. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Colorectal Cancer Screening. Version 3.2022. https://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf.
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  35. Nisman B, Yutkin V, Peretz T, et al. The follow-up of patients with non-muscle-invasive bladder cancer by urine cytology, abdominal ultrasound and urine CYFRA 21-1: A pilot study. Anticancer Res 2009; 29(10):4281-6.
  36. Parker J, Spiess PE. Current and emerging bladder cancer urinary biomarkers. Scientific World Journal 2011; 11:1103-12.
  37. Passerotti CC, Srougi M, Bomfim AC, et al. Testing for urinary hyaluronate improves detection and grading of transitional cell carcinoma. Urol Oncol 2011; 29(6):710-5.
  38. Pichler R, Fritz J, Tulchiner G, et al. Increased accuracy of a novel mRNA-based urine test for bladder cancer surveillance. BJU Int. Jan 2018; 121(1): 29-37. 
  39. Picozzi S, Ricci C, Gaeta M et al. Upper urinary tract recurrence following radical cystectomy for bladder cancer: a meta-analysis on 13,185 patients. J Urol 2012; 188(6):2046-54.
  40. Raitanen MP; Finn Bladder Group. The role of BTA stat test in follow-up of patients with bladder cancer: Results from Finn Bladder studies. World J Urol 2008; 26(1):45-50.
  41. Roobol MJ, Bangma CH, et al. Feasibility study of screening for bladder cancer with urinary molecular markers (the BLU-P project). Urol Oncol 2010 Nov-Dec, 28(6):686-90.
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  43. Shariat SF, Savage C, Chromecki TF et al. Assessing the clinical benefit of nuclear matrix protein 22 in the surveillance of patients with nonmuscle-invasive bladder cancer and negative cytology. Cancer 2011; 117(13):2893-7.
  44. Shirodkar SP and Lokeshwar VB. Potential new markers in the early detection of bladder cancer. Curr Opin Urol 2009; 19(5):488-93.
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POLICY HISTORY:

Medical Policy Group, June 2010 (3)

Medical Policy Administration Committee, July 2010

Available for comment July 2-August 16, 2010

Medical Policy Group, December 2010 (1): 2 new CPT codes added effective 1/1/2011

Medical Policy Group, June 2011; Updated Description, Key Points, & References

Medical Policy Group, July 2011 (1): Added “prior to July 1, 2010” policy statements concerning bladder cancer from policy 195

Medical Policy Group, August 2011 (1): Added CertNDx tumor marker test to investigational portion of policy statement; Key Points, Key Words and References updated related to CertNDx

Medical Policy Administration Committee, August 2011

Medical Policy Group, November 2011 (1): Added CPT 86386

Medical Policy Group, March 2012 (1): Clarification to policy statement; standard diagnostic procedures include urine cytology or cystoscopy with or without biopsy

Medical Policy Group, September 2013 (1): 2013 Update to Description, Key Points and References; no change to policy statement

Medical Policy Panel, March 2014

Medical Policy Group, March 2014 (1): 2014 Update to Description, Key Points and References; no change to policy statement

Medical Policy Panel, March 2015

Medical Policy Group, March 2015 (3): 2015 Updates to Key Points and References; no change to policy statement.

Medical Policy Panel, December 2015

Medical Policy Group, January 2016 (3): 2016 Updates to Key Points, Key Words and References. Added “Cxbladder” to the investigational policy statement for all other bladder tumor markers.

Medical Policy Panel, June 2017

Medical Policy Group, July 2017 (3): 2017 Updates to Description, Key Points, Approved by Governing Bodies & References; no change in policy statements.

Medical Policy Group, March 2018: Quarterly Coding Update, April 2018; added new CPT codes 0012M and 0013M to Current Coding.

Medical Policy Panel, June 2018

Medical Policy Group, July 2018 (3): Updates to Title, Description, Key Points, Approved by Governing Bodies, and References. Policy section - added clarifying statement to include the screening for precancerous colonic polyps as investigational. Key words added – PolypDx and colonic polyp, colorectal; Current coding – added code 0002U.  Deleted Previous Coding section containing info prior to 2011.

Medical Policy Panel, December 2018

Medical Policy Group, January 2019 (9): 2018 Updates to Approved by Governing Bodies, Key Points, Description, References. No change to policy statement.

Medical Policy Group, November 2019: 2020 Annual Coding Update. Added CPT code 0154U to Current coding section. Added key words: therascreen, FGFR3, urothelial carcinoma. Updated Key Points.

Medical Policy Panel, December 2019

Medical Policy Group, December 2019 (9): 2019 Updates to Key Points, Description, References. No change to policy statement.

Medical Policy Group, March 2020 (9): The following codes: 0012M, 0013M, 0154U, and 81479 fall under our genetic testing management program and have been removed from this policy.

Medical Policy Panel, December 2020

Medical Policy Group, December 2020 (9): 2020 Updates to Key Points, Description, References. Updated verbiage in policy statement for consistency and clarification (the terms bladder tumor markers and urinary bladder cancer tumor markers were used interchangeably). No change to policy statement intent. Remove key word: therascreen.

Medical Policy Group, January 2021 (9): Removed all information related to genetic testing, Cxbladder, and CertNDx.  This information falls under our genetic testing management program. Removed the following from policy statement: “The use of all other urinary tumor markers (including but not limited to CertNDx, Cxbladder) are considered not medically necessary and investigational in the diagnosis, monitoring, or screening for bladder cancer”. Changed title of policy to “Non-Genetic Urinary Biomarker for Cancer Screening, Diagnosis and Surveillance” from “Urinary Biomarkers for Cancer Screening, Diagnosis, and Surveillance”. Removed term ‘not medically necessary’ from remaining investigational statements. No change to policy statement intent. Removed key words: CertNDx, FGFR3, Cxbladder.

Medical Policy Panel, December 2021

Medical Policy Group, December 2021 (9): 2021 Updates to Key Points, References. No change to policy statement.

Medical Policy Panel, December 2022

Medical Policy Group, December 2022 (9): 2022 Updates to Key Points, Description, References. No change to policy statement.

Medical Policy Panel, December 2023

Medical Policy Group, December 2023 (5): Updates to Description, Key Points; Practice Guidelines and Position Statements, Key Words: BTA stat®, BTA TRAK®, Alere NMP22®, BladderChek®, UroVysion®, Bladder EpiCheck®, Benefit Application, and References. No change to Policy Statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.