Local Coverage Determination (LCD)

Lab: Bladder/Urothelial Tumor Markers

L33420

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Contractor Information

LCD Information

Document Information

LCD ID
L33420
LCD Title
Lab: Bladder/Urothelial Tumor Markers
Proposed LCD in Comment Period
N/A
Source Proposed LCD
N/A
Original Effective Date
For services performed on or after 10/01/2015
Revision Effective Date
For services performed on or after 03/04/2021
Revision Ending Date
N/A
Retirement Date
N/A
Notice Period Start Date
N/A
Notice Period End Date
N/A
AMA CPT / ADA CDT / AHA NUBC Copyright Statement

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Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein.

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Copyright © 2022, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the American Hospital Association (AHA) copyrighted materials contained within this publication may be copied without the express written consent of the AHA. AHA copyrighted materials including the UB‐04 codes and descriptions may not be removed, copied, or utilized within any software, product, service, solution or derivative work without the written consent of the AHA. If an entity wishes to utilize any AHA materials, please contact the AHA at 312‐893‐6816.

Making copies or utilizing the content of the UB‐04 Manual, including the codes and/or descriptions, for internal purposes, resale and/or to be used in any product or publication; creating any modified or derivative work of the UB‐04 Manual and/or codes and descriptions; and/or making any commercial use of UB‐04 Manual or any portion thereof, including the codes and/or descriptions, is only authorized with an express license from the American Hospital Association. The American Hospital Association (the "AHA") has not reviewed, and is not responsible for, the completeness or accuracy of any information contained in this material, nor was the AHA or any of its affiliates, involved in the preparation of this material, or the analysis of information provided in the material. The views and/or positions presented in the material do not necessarily represent the views of the AHA. CMS and its products and services are not endorsed by the AHA or any of its affiliates.

CMS National Coverage Policy

Title XVIII of the Social Security Act, §1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Title XVIII of the Social Security Act, §1862(a)(7) states Medicare will not cover any services or procedures associated with routine physical checkups.

42 CFR §411.15 Particular Services Excluded From Coverage

42 CFR §410.32 Diagnostic X-ray Tests, Diagnostic Laboratory Tests, and Other Diagnostic Tests: Conditions

42 CFR §410.33 Independent Diagnostic Testing Facility

CMS Internet-Only Manual, Pub 100-08, Medicare Program Integrity Manual, Chapter 3, §3.4.1.3 Diagnosis Code Requirements

Coverage Guidance

Coverage Indications, Limitations, and/or Medical Necessity

INDICATIONS

Gross painless hematuria is often the first manifestation of an urothelial tumor. Since the degree of hematuria bears no relation to the seriousness of the underlying disease, the microscopic finding of blood in the urine is a serious symptom until significant pathology has been excluded.

At this time, there is no published consensus from the following national organizations: National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), American Urological Association (AUA) and the International Bladder Cancer Consensus Group (IBCCG) regarding the management of persistent asymptomatic microscopic hematuria. Due to insufficient supporting data, the AUA’s 2001 best practices policy could not recommend routine use of voided urinary markers in the evaluation of patients with microscopic hematuria.3

Recommended surveillance schedules for patients with a previous negative evaluation for unexplained microscopic hematuria include annual urinalysis and voided urinary cytology until the hematuria resolves, or for up to 3 years if microscopic hematuria persists. The AUA has been silent regarding practice guidelines due to the paucity of prevalence studies on asymptomatic microscopic hematuria.

Cystoscopy in conjunction with bladder tumor markers is the standard practice to evaluate patients with symptoms suggesting bladder cancer and to monitor treated patients for recurrence or progression. Although cystoscopy is considered the “gold standard”, studies have shown that up to 20% of tumor can be missed. Urinary cytology has close to a 90%-100% specificity, but only 10%-50% sensitivity for low grade urinary cancer (UC) detection. Due to this deficit, clinicians have sought noninvasive tumor markers detectable in urine.

Upwards of 50% of patients have recurrence of bladder cancer within 5 years.

After initial diagnosis and treatment, patients with UC are frequently monitored every 3 months for the first 2 years, every 4 months for the third, year then usually twice a year for the fourth year. Annual monitoring is recommended during years 5 through 15.

Diagnostic and Surveillance Tests

  • BTA TRAK® - a quantitative determination of human complement factor H-related protein

  • Nuclear matrix protein 22 (NMP-22) – detects nuclear mitotic apparatus protein believed to be released during apoptosis; a quantitative assay, which is either positive of negative

  • NMP-22® BladderChek® – a CLIA-waved assay, point of care test with an immunochromographic qualitative format taking 20 minutes to perform

  • The UroVysion® Bladder Cancer Kit is fluorescence in situ hybridization (FISH) DNA probe technology. It is designed to detect aneuploidy for chromosomes 3, 7, 17 and loss of the 9p21 locus. This assay involves visualization of nucleic acid sequences within cells by creating short sequences of fluorescently labeled, single-strand DNA probes that match target sequences. The probes bind to complementary strands of DNA to identify the targeted chromosome(s) location. It is used to detect chromosomal abnormalities in voided urine to assist not only in bladder cancer surveillance but also in the initial identification of bladder cancer.


Scientific studies demonstrate the sensitivity of BTA and NMP-22® are superior to urinary cytology.1 Studies affirm the adjunctive value of BTA stat® and NMP-22® in suspected and known bladder cancer in conjunction with cystoscopy. However, false positive results occur more frequently in the presence of hematuria, nephrolithiasis, recent GU instrumentation, inflammation and other urological malignancies. Administration of bacillus Calmette-Guerin (BCG) within 2 years of testing decreases specificity to 28%.

The DNA probe assay has high sensitivity (81%) and specificity (96%) for high grade tumors, but lower sensitivity (36-57%) for low grade and stage tumors. The assay specificity approaches that of cytology, and can be utilized in patients recently treated with intravesical BCG. This can result in a positive UroVysion® test with a negative study for UC. This assay has also been shown to be useful in predicting tumor recurrence following BCG therapy.

At present the IBCCG has recommended that tumor markers be used in conjunction with cystoscopy. They also concluded that routine screening for bladder cancer is not cost-effective.3 The US Preventive Services Task Force concluded bladder tumor markers do not have a proven role in screening of asymptomatic patients for early detection of bladder cancer.3 NCCN, ASCO, and AUA are silent regarding the utilization of these bladder tumor markers.

Surveillance Tests

    • BTA (bladder tumor antigen) stat® - a qualitative CLIA-waved test that identifies a human complement factor H-related protein produced by several human bladder cell lines
    • The ImmunoCyt test is cleared for monitoring bladder cancer recurrence only in conjunction with cytology and cystoscopy. The assay uses fluorescent labeled antibodies to 3 markers (carcinoembryonic antigen, and mucins LDQ10 and M344) commonly found on malignant exfoliated urothelial cells. The ImmunoCyt™ assay has also been shown to be more sensitive than urine cytology.


LIMITATIONS

Cystoscopy in conjunction with bladder tumor markers is standard practice to evaluate patients with symptoms suggesting bladder cancer and to monitor treated patients for recurrence or progression. Exceptions, such as high grade bladder cancers s/p radical cystectomy, do exist which preclude cystoscopy prior to testing. Testing indications, limitations and frequency do not apply to urine cytology.

Bladder cancer tumor markers performed by any technology, immunoassay, molecular or FISH testing, are not covered for screening of all patients with hematuria. Bladder tumor markers are not expected to be performed until other diagnostic studies fail to identify the etiology of the hematuria. Urine cytology is not considered a bladder tumor marker.

All other bladder cancer marker assays, including but not limited to the following, regardless of the methodology are considered investigational and not covered by Medicare:

  • BCLA-4
  • BLCA-1
  • Hyaluronic acid
  • Hyaluronidase
  • Lewis X antigen
  • Microsatellite markers
  • Quanticyt
  • Soluble FAS TATI (tumor associated trypsin inhibitor)
  • Soluble e-cadherin
  • Survivin
  • Telomerase
  • UBC Rapid Test (urinary bladder cancer test for cytokeratins 8 and 18)
Summary of Evidence

N/A

Analysis of Evidence (Rationale for Determination)

N/A

General Information

Associated Information

Documentation Requirements

The medical record must clearly identify the number and frequency of bladder marker testing.

Medical record documentation must be legible, must be maintained in the patient’s medical record (hard copy or electronic copy), and must meet the criteria contained in this LCD and be made available to the A/B MAC upon request.

Utilization Guidelines

  • Only 1 bladder cancer test per single date of service (e.g., FISH then reflex cytology) are considered reasonable and necessary.

  • For high risk patients with persistent hematuria and a negative FISH assay following a comprehensive diagnostic (no tumor identified) workup, ONE repeat FISH testing in conjunction with cystoscopy is considered reasonable and necessary within 1 year of the original attempted diagnosis.


Follow-up after initial diagnosis/most recent occurrence and treatment

  • Maximum of 4 bladder tumor marker studies per year for years 1-2
  • Maximum of 3 bladder tumor marker studies per year for year 3
  • Maximum of 2 bladder tumor marker studies for year 4 and
  • Maximum of 1 bladder tumor marker studies follow-up annually for up to 15 years.
Sources of Information
N/A
Bibliography
  1. Polymedco, Inc. 2008. BTA stat®Test. Cortlandt, NY.
  2. Grossfeld GD, Litwin MS, Wolf JS Jr, 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.
  3. Guide to Clinical Preventive Services, U.S. Preventive Services Task Force Accessed on January 13, 2021.
  4. Lokeshwar VB, Habuchi T, Grossman HB, et al. Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers. Urology. 2005;66:35-63.
  5. Messing EM, Teot L, Korman H, et al. Performance of urine test in patients monitored for recurrence of bladder cancer: A multicenter study in the United States. J Urol. 2005;174(4 pt 1):1238-41.

Revision History Information

Revision History DateRevision History NumberRevision History ExplanationReasons for Change
03/04/2021 R16

Under CMS National Coverage Policy updated descriptions and added section headings to regulations. Moved sources 1-5 from Sources of Information to Bibliography. NMP-22®and ImmunoCyt™ was inserted where appropriate throughout the LCD. Formatting, punctuation and typographical errors were corrected throughout the LCD. Acronyms were inserted and defined where appropriate throughout the LCD.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Provider Education/Guidance
10/31/2019 R15

This LCD is being revised in order to adhere to CMS requirements per chapter 13, section 13.5.1 of the Program Integrity Manual, to remove all coding from LCDs. There has been no change in coverage with this LCD revision. Regulations regarding billing and coding were removed from the CMS National Coverage Policy section of this LCD and placed in the related Billing and Coding: Lab: Bladder/Urothelial Tumor Markers A53095 Article.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Provider Education/Guidance
08/22/2019 R14

All coding located in the Coding Information section has been moved into the related Billing and Coding: Lab: Bladder/Urothelial Tumor Markers A53095 article and removed from the LCD.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Provider Education/Guidance
01/17/2019 R13

Added "Lab" to the title of the LCD.

  • Other
08/30/2018 R12

Added the following ICD-10 codes to ICD-10 Codes that Support Medical Necessity Group 1: C7A.010, C7A.011, C7A.012, C7A.019, C7A.020, C7A.021, C7A.022, C7A.023, C7A.024, C7A.025, C7A.026, C7A.029, C7A.090, C7A.091, C7A.092, C7A.093, C7A.094, C7A.095, C7A.096, C7B.01, C7B.02, C7B.03, C7B.04, E34.0

  • Revisions Due To CPT/HCPCS Code Changes
03/08/2018 R11

Corrected numbering in the Sources of Information section.

  • Typographical Error
02/26/2018 R10 The Jurisdiction "J" Part B Contracts for Alabama (10112), Georgia (10212) and Tennessee (10312) are now being serviced by Palmetto GBA. The notice period for this LCD begins on 12/14/17 and ends on 02/25/18. Effective 02/26/18, these three contract numbers are being added to this LCD. No coverage, coding or other substantive changes (beyond the addition of the 3 Part B contract numbers) have been completed in this revision.
  • Change in Affiliated Contract Numbers
01/29/2018 R9 The Jurisdiction "J" Part A Contracts for Alabama (10111), Georgia (10211) and Tennessee (10311) are now being serviced by Palmetto GBA. The notice period for this LCD begins on 12/14/17 and ends on 01/28/18. Effective 01/29/18, these three contract numbers are being added to this LCD. No coverage, coding or other substantive changes (beyond the addition of the 3 Part A contract numbers) have been completed in this revision.
  • Change in Affiliated Contract Numbers
03/23/2017 R8 Added registered trademark to Urovysion. Under LIMITATIONS subtopic; added clarification that "testing indications, limitations and frequency do not apply to urine cytology" and Bladder cancer tumor markers performed by any technology, " immunoassay, molecular or FISH testing," are not covered for screening of all patients with hematuria.
  • Other (Clarification)
01/26/2017 R7 Response to comments for jurisdiction.
  • Creation of Uniform LCDs With Other MAC Jurisdiction
01/26/2017 R6 Policy revised as a result of comments received for JE/JF draft policies DL36678 & DL36680:

1 - Added Urothelial to the LCD title
2 - Under limitation: changed "Bladder cancer tumor markers performed by molecular assay and FISH testing are not covered for screening of all patients with hematuria"; to read "Bladder cancer tumor markers performed by any technology are not covered for screening of all patients with hematuria."
3 - added the sentence "Urine cytology is not considered a bladder tumor marker."
4 - Under ICD-10, Group 1 Codes; added asterisk to R31.21 and R31.29. Removed askterisk from Z85.51 and deleted explanation.
  • Creation of Uniform LCDs With Other MAC Jurisdiction
10/01/2016 R5 Removed reference to #6 reference from policy text
  • Typographical Error
10/01/2016 R4 Please note: The first set of changes were made in response to a reconsideration request and the second set of changes are ICD-10 updates.

1) In response to comments received by Noridian for LCD DL36678: Revised the 1st and 2nd paragraph under subtopic "Limitations" under the Coverage Indications, Limitations and/or Medical Necessity section.
  • REMOVED - Bladder cancer tumor markers performed by immunoassay are ONLY considered medically necessary as an adjunct in the diagnosis and monitoring of bladder cancer in conjunction with cystoscopy.

  • ADDED - Cystoscopy in conjunction with bladder tumor markers is standard practice to evaluate patients with symptoms suggesting bladder cancer and to monitor treated patients for recurrence or progression. Exceptions, such as high grade bladder cancers s/p radical cystectomy, do exist which preclude cystoscopy prior to testing.

  • ADDED "...and FISH testing" to the 1st sentence in the 2nd paragraph to read as follows: Bladder cancer tumor markers performed by immunoassay and FISH testing are not covered for screening of all patients with hematuria.


2) ICD-10 code changes:
  • DELETED - R31.2*
  • ADDED - R31.21
  • ADDED - R31.29
  • Reconsideration Request
  • Revisions Due To ICD-10-CM Code Changes
11/01/2015 R3 Under Annual Review inserted the last date this LCD was reviewed 1/13/2015. Under ICD-10 Codes that Support Medical Necessity added an asterisk to Z78.9 and added an explanation to the Group 1 Asterisk,"Z78.9 To be used only when repeat testing is believed to be medically reasonable and necessary, and must be listed as secondary with the primary neoplastic diagnosis."
  • Provider Education/Guidance
  • Automated Edits to Enforce Reasonable & Necessary Requirements
10/01/2015 R2 Under ICD-10 Codes That Support Medical Necessity added ICD-10 codes inadvertently omitted from the LCD:

C67.9
C7A.098
C7B.00
  • Other (ICD-10 Conversion)
10/01/2015 R1 Under Sources of Information and Basis for Decision placed 3rd bibliography in a hyperlinked url for the web site when clicked on the text.
  • Provider Education/Guidance
  • Automated Edits to Enforce Reasonable & Necessary Requirements

Associated Documents

Attachments
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Related National Coverage Documents
N/A
Public Versions
Updated On Effective Dates Status
02/25/2021 03/04/2021 - N/A Currently in Effect You are here
Some older versions have been archived. Please visit the MCD Archive Site to retrieve them.

Keywords

  • Bladder Tumor Markers

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