L32098

 

CIRCULATING TUMOR CELL TESTING

 

01/01/2013

 

Indications and Limitations of Coverage and/or Medical Necessity

 

Indications

• This LCD addresses very limited coverage for one methodology, the CellSearch® assay (Veridex LLC, Warren, NJ) circulating tumor cell (CTC) assay.

o All other methods for CTC detection, including PCR (RT-PCR) assays, are non-covered.

o 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.

o 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.

 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:

o One pre first dose of chemotherapy.

o One repeat test after the first cycle of chemotherapy).

o 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.

o CTC testing for non-documented chemotherapy regimen and all other diagnoses will be denied as NOT reasonable and necessary.

o Of note, CTCs measured for patients in a clinical trial may be covered as outlined in this LCD.

o 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 86152 and 86153 (reported with one unit).

o The Pathology and Laboratory section of CPT outlines many services at both the outcome and process level.

o Given different assay outcomes can be coded in various ways, this LCD specifies C

PT codes 86152 and 86153 for the CellSearch System®.

o No other codes are to be submitted for this service.

o 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).

 The GZ modifier (item or service expected to be denied as not reasonable and necessary) (for example, if used for periodic testing).

o The electronic equivalent of block 19 should note CTC assay and type.

 

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.

 

 

CPT/HCPCS Codes

 

86152 CELL ENUMERATION USING IMMUNOLOGIC SELECTION AND IDENTIFICATION IN FLUID SPECIMEN (EG, CIRCULATING TUMOR CELLS IN BLOOD);

86153 CELL ENUMERATION USING IMMUNOLOGIC SELECTION AND IDENTIFICATION IN FLUID SPECIMEN (EG, CIRCULATING TUMOR CELLS IN BLOOD); PHYSICIAN INTERPRETATION AND REPORT, WHEN REQUIRED

 

 

ICD-9 Codes that Support Medical Necessity

 

153.0 MALIGNANT NEOPLASM OF HEPATIC FLEXURE

153.1 MALIGNANT NEOPLASM OF TRANSVERSE COLON

153.2 MALIGNANT NEOPLASM OF DESCENDING COLON

153.3 MALIGNANT NEOPLASM OF SIGMOID COLON

153.4 MALIGNANT NEOPLASM OF CECUM

153.5 MALIGNANT NEOPLASM OF APPENDIX VERMIFORMIS

153.6 MALIGNANT NEOPLASM OF ASCENDING COLON

153.7 MALIGNANT NEOPLASM OF SPLENIC FLEXURE

153.8 MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF LARGE INTESTINE

153.9 MALIGNANT NEOPLASM OF COLON UNSPECIFIED SITE

154.0 MALIGNANT NEOPLASM OF RECTOSIGMOID JUNCTION

154.1 MALIGNANT NEOPLASM OF RECTUM

154.2 MALIGNANT NEOPLASM OF ANAL CANAL

154.3 MALIGNANT NEOPLASM OF ANUS UNSPECIFIED SITE

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

174.0 MALIGNANT NEOPLASM OF NIPPLE AND AREOLA OF FEMALE BREAST

174.1 MALIGNANT NEOPLASM OF CENTRAL PORTION OF FEMALE BREAST

174.2 MALIGNANT NEOPLASM OF UPPER-INNER QUADRANT OF FEMALE BREAST

174.3 MALIGNANT NEOPLASM OF LOWER-INNER QUADRANT OF FEMALE BREAST

174.4 MALIGNANT NEOPLASM OF UPPER-OUTER QUADRANT OF FEMALE BREAST

174.5 MALIGNANT NEOPLASM OF LOWER-OUTER QUADRANT OF FEMALE BREAST

174.6 MALIGNANT NEOPLASM OF AXILLARY TAIL OF FEMALE BREAST

174.8 MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF FEMALE BREAST

174.9 MALIGNANT NEOPLASM OF BREAST (FEMALE) UNSPECIFIED SITE

175.0 MALIGNANT NEOPLASM OF NIPPLE AND AREOLA OF MALE BREAST

175.9 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

 

 

Documentation Requirements

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

o Patient history and physical.

o Office/progress notes.

o Pathology report.

o Signed statement by patient and physician as outlined in LCD.

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

 

 

Utilization Guidelines

• It is expected that these services would be performed as indicated by current medical literature and/or standards of practice.

o When services are performed in excess of established parameters, they may be subject to review for medical necessity.

• 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.

o 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.

o 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).

o Such repeat testing (beyond the 2 units) will be subject to prepayment medical review, and is expected to be very rare.

o 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.

o CTC testing for non-documented protocols and all other diagnoses will be denied as not reasonable and necessary.

o Of note, CTCs measured for patients in a clinical trial may be covered as outlined in this LCD.

o 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).

 

Treatment Logic

• 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).

• 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.

o 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.

o The process begins with a 7.5 mL peripheral blood specimen from the patient.

o 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.

o Once in the laboratory, the whole blood specimen is centrifuged and placed on the CellTracks AutoPrep system.

o 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.

o The ferrofluid/antibody complex attaches specifically to epithelial cells.

o 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.

o The remaining cells are then resuspended in buffer.

o 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.

o 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.

o 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.

o 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.

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

 

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 cancer. 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

 

FCSO LCD 32098, Circulating Tumor Cell Testing, 01/01/2013. The official local coverage determination (LCD) is the version on the Medicare coverage database at www.cms.gov/medicare-coverage-database/.

 

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/

 

 

AMA CPT / ADA CDT Copyright Statement

CPT codes, descriptions and other data only are copyright 2011 American Medical Association (or such other date of publication of CPT). All Rights Reserved. Applicable FARS/DFARS Clauses Apply. Current Dental Terminology, (CDT) (including procedure codes, nomenclature, descriptors and other data contained therein) is copyright by the American Dental Association. © 2002, 2004 American Dental Association. All rights reserved. Applicable FARS/DFARS apply.

 

CMS LCD L32098 CIRCULATING TUMOR CELL TESTING