L32098-LCD

Automated World Health

Local Coverage Determination (LCD) for Circulating Tumor Cell Testing (L32098)

Contractor Information

Contractor Name

First Coast Service Options, Inc. opens in new window

Contractor Number 09102

Contractor Type MAC - Part B

LCD Information

Document Information

LCD ID Number L32098

LCD Title

Circulating Tumor Cell Testing

Contractor's Determination Number 0279T

Primary Geographic Jurisdiction opens in new window

Florida

Oversight Region Region IV

AMA CPT/ADA CDT Copyright Statement

CPT only copyright 2002-2011 American Medical Association. All Rights Reserved. CPT is a registered trademark of the American Medical Association. Applicable FARS/DFARS Apply to Government Use. 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. The Code on Dental Procedures and Nomenclature (Code) is published in Current Dental Terminology (CDT). Copyright © American Dental Association. All rights reserved. CDT and CDT-2010 are trademarks of the American Dental Association.

Original Determination Effective Date

For services performed on or after 10/16/2011

Original Determination Ending Date

Revision Effective Date

For services performed on or after 03/20/2012

Revision Ending Date

CMS National Coverage Policy

Language quoted from CMS National Coverage Determination (NCDs) and coverage provisions in interpretive manuals are italicized throughout the Local Coverage Determination (LCD). NCDs and coverage provisions in interpretive manuals are not subject to the LCD Review Process (42 CFR 405.860[b] and 42 CFR 426 [Subpart D]). In addition, an administrative law judge may not review an NCD. See §1869(f)(1)(A)(i) of the Social Security Act.

Unless otherwise specified, italicized text represent quotation from one or more of the following CMS sources: CMS Manual System, Pub 100-04, Medicare Claims Processing Manual, Chapter 16,Section 40 and Chapter 23,

Section 20.9.1

Indications and Limitations of Coverage and/or Medical Necessity

Circulating tumor cells (CTCs) are rare malignant cells found in the peripheral blood which originate from the primary tumor or metastatic sites. The detection of CTCs has several proposed applications, some of which have been reported in well designed observational studies (prospective and retrospective) of patients with metastatic cancers. There are also several controlled clinical trials in progress assessing the clinical utility of CTC results in the care of patients with metastatic cancers (application in clinical decision making that impacts patient outcomes). There are several methods of detecting CTCs which are in various stages of research and development. The low level of concentration of malignant epithelial cells in blood samples makes them difficult to detect though the push to improve surveillance and treatment of cancer patients makes CTC an area of research and development. The techniques that have been used to detect CTCs include direct methods (enrichment/detection) including Immunomagnetic Bead Separation, Immunohistochemistry (IHC), automated fluorescent methods, Dielectrophoresis and indirect methods (reverse-transcriptase polymerase chain reaction [RT-PCR] nucleic acid analysis).

Indications

This Medicare administrative contractor (MAC) jurisdiction 9 (J9) LCD addresses very limited coverage for one methodology, the CellSearch® assay (Veridex LLC, Warren, NJ) circulating tumor cell (CTC) assay. All other methods for CTC detection, including PCR (RT-PCR) assays, are non-covered. All assays of CTC are non-covered for all diagnoses for routine screening or surveillance (prognosis).

CTC testing per the CellSearch® assay can be covered for patients with metastatic breast, colorectal and prostate cancer when there is a signed statement by the patient and physician in the medical record that confirms a change in the chemotherapy regimen (treatment plan) can be initiated based on the assumed predictive value of the CTC result. To assist in decision making, the LCD covers up to 2 units of the test per chemotherapy regimen (defined as a complete treatment plan that specifies the dosage, the schedule, and the duration of treatment) – one pre first dose of chemotherapy and one repeat test after the first cycle of chemotherapy. Periodic testing afterward is not covered.

Repeat testing can be considered for a major change in the chemotherapy regimen when the need for additional testing for decision making addressing the new regimen is clearly documented in the medical record (the same utilization can be covered if documentation supports it – one pre first dose of chemotherapy and one repeat test after the first cycle of chemotherapy). Such repeat testing (beyond the 2 units) will be subject to prepayment medical review, and is expected to be very rare.

The chemotherapy regimen must be an evidence-based supported standard of care. CTC testing for non documented chemotherapy regimen and all other diagnoses will be denied as not reasonable and necessary. Of note, CTCs measured for patients in a clinical trial may be covered as outlined in this LCD. However, periodic testing is specifically not a covered service nor is it a covered routine cost in a clinical trial since currently it would be considered data collection per the definition in National Coverage Determination (NCD) 310.1 (Routine Cost in Clinical Trials).

The CellSearch System® was developed for the purpose of detecting CTCs in whole blood and should be identified by CPT codes 0279T and 0280T (reported with one unit). The Pathology and Laboratory section of CPT outlines many services at both the outcome and process level. Given different assay outcomes can be coded in various ways, MAC J9 is specifying these procedure codes for the CellSearch System®. No other codes are to be submitted for this service. Other methodologies for CTC or use of the CellSearch CTC for prognosis only or surveillance should be identified with the appropriate modifier; the GY modifier (item or service statutorily excluded or does not meet the definition of any Medicare benefit) (for example, if used for screening), the GA modifier (waiver of liability statement on file) (for example, if used for periodic testing), or the GZ modifier (item

or service expected to be denied as not reasonable and necessary) (for example, if used for periodic testing). The electronic equivalent of block 19 should note CTC assay and type.

The CellSearch Circulating Tumor Cell System® is described as using a combination of immunomagnetic labeling and automated digital microscopy to identify and enumerate the number of CTCs in a peripheral blood specimen. It consists of a CellTracks AutoPrep system, which isolates the CTCs, and a CellTracks Analyzer, which differentiates the tumor cells from nonspecific cells and debris. The process begins with a 7.5 mL peripheral blood specimen from the patient. Blood is collected using the Circulating Tumor Cell Collection Kit and the specimen must be promptly shipped to assure processing within 96 hours of collection. Once in the laboratory, the whole blood specimen is centrifuged and placed on the CellTracks AutoPrep system. The plasma is aspirated to waste and the remaining cellular component is mixed with buffer and ferrofluid reagent conjugated with monoclonal epithelial cell adhesion molecule (EpCAM) antibodies. The ferrofluid/antibody complex attaches specifically to epithelial cells. Magnets then attract the ferrofluid-bound cells to the side of the tube, the remaining fluid and any unlabeled cells are aspirated and the magnets are removed. The remaining cells are then resuspended in buffer. The CellSearch CTC System® uses 3 stains to help distinguish epithelial cells from contaminating leukocytes and nonspecific debris: 4’-6-diamidino-2-phenylindole (DAPI) stains the nuclei of cells and helps identify viable cells, phycoerythrin (PE)-labeled cytokeratin (CK) antibodies (CK 8, 18, and 19) recognize epithelial cells, allophycocyanin (APC)-labeled CD45 antibodies identify contaminating leukocytes. The resulting epithelial- enriched fluid is then placed in a cell presentation device (MagNest) that attracts the magnetically labeled epithelial cells to the surface of the cartridge. The cartridge is placed on the CellTracks Analyzer, a fluorescence- based microscopy system that scans the surface of the cartridge to acquire cell images to visualize DAPI-labeled nuclei, PE-labeled CK, and APC-labeled CD45. A gallery of images is reviewed by a technologist who identifies tumor cells based on the CTC phenotype showing positive DAPI and CK staining with an absence of CD45

staining. All other staining combinations represent circulating nontumor cells (e.g., leukocytes) or noncellular debris.

Limitations

All methods for CTC enrichment/detection other than the CellSearch® assay (Veridex LLC), including PCR (RT- PCR) assays, are non-covered.

All assays for CTC enrichment/detection are non-covered for all diagnoses for routine screening or surveillance (prognosis).

No further CTC testing would be expected after the transition to palliative/hospice care.

It is expected that CellSearch® assay results would be used in conjunction with all clinical information derived from diagnostic tests (i.e., imaging, laboratory tests), physical examination and complete medical history in accordance with appropriate patient management procedures in accordance with current standards of care.

Coding Information

Bill Type Codes:

Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims.

Revenue Codes:

Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory; unless specified in the policy services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes.

CPT/HCPCS Codes

0279T CELL ENUMERATION USING IMMUNOLOGIC SELECTION AND IDENTIFICATION IN FLUID SPECIMEN (EG, CIRCULATING TUMOR CELLS IN BLOOD);

0280T CELL ENUMERATION USING IMMUNOLOGIC SELECTION AND IDENTIFICATION IN FLUID SPECIMEN (EG, CIRCULATING TUMOR CELLS IN BLOOD); INTERPRETATION AND REPORT

ICD-9 Codes that Support Medical Necessity

153.0 - 153.9 opens in new window

154.0 - 154.8 opens in new window

174.0 - 174.9 opens in new window

175.0 - 175.9 opens in new window

MALIGNANT NEOPLASM OF HEPATIC FLEXURE - MALIGNANT NEOPLASM OF COLON UNSPECIFIED SITE

MALIGNANT NEOPLASM OF RECTOSIGMOID JUNCTION - MALIGNANT NEOPLASM OF OTHER SITES OF RECTUM RECTOSIGMOID JUNCTION AND ANUS

MALIGNANT NEOPLASM OF NIPPLE AND AREOLA OF FEMALE BREAST - MALIGNANT NEOPLASM OF BREAST (FEMALE) UNSPECIFIED SITE

MALIGNANT NEOPLASM OF NIPPLE AND AREOLA OF MALE BREAST - MALIGNANT NEOPLASM OF OTHER AND UNSPECIFIED SITES OF MALE BREAST

185 MALIGNANT NEOPLASM OF PROSTATE

196.0 SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF LYMPH NODES OF HEAD FACE AND NECK

198.3 SECONDARY MALIGNANT NEOPLASM OF BRAIN AND SPINAL CORD

198.5 SECONDARY MALIGNANT NEOPLASM OF BONE AND BONE MARROW

Diagnoses that Support Medical Necessity N/A

ICD-9 Codes that DO NOT Support Medical Necessity

ICD-9 Codes that DO NOT Support Medical Necessity Asterisk Explanation

Diagnoses that DO NOT Support Medical Necessity N/A

General Information

Documentations Requirements

Documentation should include the following and must be available to Medicare upon request:

• Patient history and physical;

• Office/progress notes;

• Pathology report;

• Signed statement by patient/physician as outlined in LCD, and

• Documentation which supports the medical necessity for services as outlined in this LCD.

Appendices

Utilization Guidelines It is expected that these services would be performed as indicated by current medical literature and/or standards of practice. When services are performed in excess of established parameters, they may be subject to review for medical necessity.

An example of an acceptable statement:

For patient X, with Diagnosis Y, the planned chemotherapy regimen is Z to begin on xx/xx/20xx (date).

CellSearch® assay (a measurement of Circulating Tumor Cells (CTC)) will be drawn on xx/xx/20xx prior to Rx

and repeated in x weeks one time. Based on the CTC results the planned chemotherapy regimen (treatment plan) may be changed. Medicare limits coverage to these two units of testing. Signed- patient/physician.

The protocol must be an evidence-based supported standard of care. CTC testing for non documented protocols and all other diagnoses will be denied as not reasonable and necessary. Of note, CTCs measured for patients in a clinical trial may be covered as outlined in this LCD. However, periodic testing is specifically not a covered service nor is it a covered routine cost in a clinical trial since currently it would be considered data collection per the

definition in National Coverage Determination (NCD) 310.1 (Routine Cost in Clinical Trials).

Sources of Information and Basis for Decision

Allard, W., Matera, J., Miller, M., Repollet, M., Connelly, M., Rao, C., Tibbe, A., Uhr, J., & Terstappen, L. (2004). Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clinical Cancer Research, 10, 6897-6904. doi:10.1158/1078-0432.CCR-04-0378

Budd, G., Cristofanilli, M., Ellis, M., Stopeck, A., Borden, E., Miller, M., Matera, J., Repollet, M., Doyle, G., Terstappen, L., & Hayes, D. (2006). Circulating tumor cells versus imaging - Predicting overall survival in metastatic breast cancer. Clin Cancer Res, 12(21), 6403-6409. doi:10.1158/1078-0432.CCR-05-1769

Cohen, S., Punt, C., Iannotti, N., Saidman, B., Sabbath, K., Gabrail, N., Picus, J., Morse, M., Mitchell, E., Miller, M., Doyle, G., Tissing, H., Terstappen, L., & Meropol, N. (2008). Prognostic significance of circulating tumor cells in patients with metastatic colorectal cnacer. Annals of Oncology. Retrieved from www.jco.org. doi:10.1093/annonc/mdn786

Cohen, S., Punt, C., Iannotti, N., Saidman, B., Sabbath, K., Gabrail, N., Picus, J., Morse, M., Mitchell, E., Miller, M., Doyle, G., Tissing, H., Terstappen, L., & Meropol, N. (2008). Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol, 26, 3213-3221. doi:10.1200/JCO.2007.15.8923

Cristofanilli, M., Budd, G., Ellis, M., Stopeck, A., Matera, J., Miller, M., Reuben, J., Doyle, G., Allard, W., Terstappen, L., & Hayes, D. (2004). Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med, 351, 781-791.

Cristofanilli, M., Hayes, D., Budd, G., Ellis, M., Stopeck, A., Reuben, J., Doyle, G., Matera, J., Allard, J., Miller, M., Fritsche, H., Hortobagyi, G., & Terstappen, L. (2005). Circulating tumor cells: A novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol, 23, 1420-1430. doi:10.1200/JCO.2005.08.140

Danila, D., Heller, G., Gignac, G., Gonzalez-Espinoza, R., Anand, A., Tanaka, E., Lilja, H., Schwartz, L., Larson, S., Fleisher, M., & Scher, H. (2007). Circulating tumor cell number and prognosis in progressive castration- resistant prostate cancer. Clin Cancer Res, 13(23), 7053-7058. doi:10.1158/1078-0432.CCR-07-1506

De Bono, J., Scher, H., Montgomery, R., Parker, C., Miller, M., Tissing, H., Doyle, G., Terstappen, L., Pienta, K., & Raghavan, D. (2008). Circulating tumor cells predict survival benefit from treatment in metastatic castration- resistant prostate cancer. Clin Cancer Res, 14(19), 6302-6309.doi:10.1158/1078-0432.CCR-08-0872

De Giorgi, U., Valero, V., Rohren, E., Dawood, S., Ueno, N., Miller, M., Doyle, G., Jackson, S., Andreopoulou, E., Handy, B., Reuben, J., Fritsche, H., Macapinlac, H., Hortobagyi, G., & Cristofanilli, M. (2009). Circulating tumor cells and fluorodeoxyglucose positron emission tomography/computed tomography for outcome prediction in metastatic breast cancer. J Clin Oncol. doi:10.1200/JCO.2008.19.4423

Dotan, E., Cohen, S., Alpaugh, K., & Meropol, N. (2009). Circulating tumor cells: Evolving evidence and Future challenges. The Oncologist,14, 1070-1082. doi:10.1634/theoncologist.2009-0094

Goodman, Jr., O., Fink, L., & Symanowski, J. (2009). Circulating tumor cells in patients with castration-resistant prostate cancer baseline values and correlation with prognostic factors. Cancer Epidemiol Biomarkers Prev, 18, 1904-1913. doi:10.1158/1055-9965.EPI-08-1173

Gradilone, A., Naso, G., Raimondi, C., Cortesi, E., Gandini, O., Vincenzi, B., Saltarelli, R., Chiapparino, E., Spremberg, F., Cristofanilli, M., Frati, L., Agliano, A., & Gazzaniga, P. (2011). Circulating tumor cells (CTCs) in metastatic breast cancer (MBC). Annals of Oncology, 22(1), 86-92.

Harris, L., Fritsche, H., Mennel., R., Norton, L., Ravdin, P., Taube, S., Somerfield, M., Hayes, D., & Bast Jr., R. (2007). American society of clinical oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol, 25, 5287-5312. doi:10.1200/JCO.2007.14.2364

Hayes, D., Cristofanilli, M., & Budd, G. (2006). Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res, 12(14). 4218- 4224. doi:10.1158/1078-0432.CCR-05-2821

Oldenhuis, C., Oosting, S., Gietema, J., & Vries, E. (2008). Prognostic versus predictive value of biomarkers in oncology. European Journal of Cancer, 44, 946-953. doi:10.1016/j.ejca.2008.03.006

Zhao, S., Liu, Y., Zhang, Q., Li, H., Zhang, M., Ma, W., Zhao, W., Wang, J., & Yang, M. (2011). The prognostic role of circulating tumor cells (CTCs) detected by RT-PCR in breast cancer: a meta-analysis of published literature. Breast Cancer Res Treat. doi:10.1007/s10549-011-1379-4. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/

Advisory Committee Meeting Notes This Local Coverage Determination (LCD) does not reflect the sole opinion of the contractor or Contractor Medical Director. Although the final decision rests with the contractor, this LCD was developed in cooperation with advisory groups, which includes representatives from numerous societies.

Florida Contractor Advisory Committee Meeting held on June 18, 2011.

Puerto Rico/U.S. Virgin Islands Contractor Advisory Committee Meeting held on June 23, 2011.

Start Date of Comment Period

End Date of Comment Period

Start Date of Notice Period 09/02/2011

Revision History Number 2

Revision History Explanation Revision Number:2 Start Date of Comment Period:N/A

Start Date of Notice Period:04/01/2012 Original Effective Date:03/20/2012

LCR B2012-034

March 2012 Connection

Explanation of revision: Under the ‘Indications and Limitations of Coverage and/or Medical Necessity’ and ‘Documentation requirements’ sections of the LCD, verbiage was revised for clarification of coverage. In addition, the ‘Utilization Guidelines’ section was updated with an example of an acceptable statement to include in the medical record. The effective date of this revision is based on the date of service.

Revision Number:1

Start Date of Comment Period:N/A Start Date of Notice Period:01/01/2012 Original Effective Date : 01/01/2012

LCR B2012-012

December 2011 Connection

Explanation of Revision: Annual 2012 HCPCS Update. CPT code 86849 was removed and replaced with new CPT codes 0279T and 0280T. The ‘Contractor’s Determination Number’ was changed from 86849 to 0279T. The effective date of this revision is based on date of service.

Revision Number:Original

Start Date of Comment Period:06/03/2011 Start Date of Notice Period:09/02/2011 Original Effective Date 10/16/2011

LCR B2011-095

September 2011 Connection

Reason for Change Narrative Change