Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Colorectal Cancer Screening

Policy #:11.03.12q

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract. State mandates do not automatically apply to self-funded groups; therefore, individual group benefits must be verified.

AVERAGE-RISK INDIVIDUALS

The Company recognizes recommendations from the American Cancer Society (ACS) and the United States Preventive Services Task Force (USPSTF) for colorectal cancer screening for average-risk individuals, as well as federal and state mandates for colorectal cancer screening.

Individuals at average risk are those without a history of adenomatous polyps or Colorectal Cancer (CRC) and not at increased risk for CRC due to a family history of CRC, a confirmed or suspected hereditary CRC syndrome (such as familial adenomatous polyposis or Lynch syndrome), a personal history of abdominal or pelvic radiation for a previous cancer, or a personal history of inflammatory bowel disease. In accordance with ACS, beginning at age 45, the following screening tests are covered:

Tests that find polyps and cancer:
  • Colonoscopy every 10 years
  • Computed tomographic colonography (virtual colonoscopy) every 5 years*
  • Double contrast barium enema every 5 years*
  • Flexible sigmoidoscopy every 5 years*

Tests that mainly find cancer*:
  • Fecal immunochemical test (FIT) every year*,**
  • Fecal occult blood test (FOBT) every year*,**
  • Stool DNA test (sDNA) alone or combined with FIT, (e.g., Cologuard), every three years*

* Colonoscopy is recommended if test results are positive.

** For FOBT or FIT used as a screening test, the take-home multiple method is recommended. An FOBT or FIT done during a digital rectal exam in the professional provider's office is not adequate for screening.

INCREASED-RISK OR HIGH-RISK INDIVIDUALS

The Company recognizes recommendations from the American Cancer Society and state mandates for colorectal cancer screening for increased- or high-risk individuals.

Coverage is provided for colorectal cancer screening for individuals at increased-risk or high-risk of developing colorectal cancer. Coverage will be provided for individuals at increased-risk or high-risk of developing colorectal cancer at any age and at a frequency recommended by the treating professional provider. The following conditions place the individual at increased- or high-risk:

EXPERIMENTAL/INVESTIGATIONAL

The Epi proColon™, (a test to detect methylated Septin 9 (SEPT9) gene), and the PolypDx™ test are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to, records from the physician's office, hospital, nursing home, home health agencies, therapies, other health care professionals, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, colorectal cancer screening is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in the medical policy are met.

Subject to the terms of the member's benefit contract, $0 cost share will be applied when colorectal cancer screening is performed as a preventive service at a participating provider, and there is direction from regulatory laws, such as the Affordable Care Act, to adjudicate the preventive service claim at $0 cost share.

STATE MANDATES

This policy is consistent with applicable state mandates. The laws of the state where the group benefit contract is issued determine the mandated coverage.

US FOOD AND DRUG ADMINISTRATION STATUS

The US Food and Drug Administration (FDA) has approved several noninvasive colorectal screening tests (e.g., Cologuard, Epi proColon, fecal occult blood tests, and fecal immunochemical tests), for colorectal cancer screening.

Description

Colorectal cancer (CRC) is a disease in which abnormal cell growth leads to tumor formation in the colon and/or rectum. It is the second leading cause of cancer-related death in the United States. Colorectal cancer primarily affects men and women 50 years of age and older, and risks increase with age. If detected early, colorectal cancer may be treated and cured.

Depending on the colorectal cancer screening methodologies, they may detect cancer, precancerous polyps, and other abnormalities in the colon and/or rectum. Colorectal cancer usually starts as a polyp (a growth of tissue in the inner wall of the colon and/or rectum) with no symptoms. Polyps are thought to develop into cancer over a period of several years. Polyps identified through colorectal cancer screening can be removed before they develop into cancer. Therefore, in addition to identifying existing colorectal cancer, screening also helps prevent the disease. If diagnosed in its early stages, colorectal cancer is highly curable, with a survival rate of approximately 90 percent.

In 2018, the American Cancer Society (ACS), recommended initiating screening at 45 years of age for men and women at average risk for colorectal cancer, based on the incidence of cancer above this age in the general population. Aggressive screening strategies contribute significantly to the early detection and subsequent treatment of colorectal cancer. Various methods are used to screen for colorectal cancer. The choice of method depends on the individual's risk, personal preference, and access, and should be discussed with the professional provider. For high-risk individuals, and those with a personal or family history, more frequent screening may be required, based on the recommendations of their professional provider.

In 2016, the USPSTF revised their recommendation for colorectal cancer screening to be performed beginning at 50 years of age and continuing until 75 years of age. The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the individual’s overall health and prior screening history. The USPSTF concludes with moderate certainty that the net benefit of screening for colorectal cancer in adults aged 76 to 85 years who have been previously screened is small. Adults who have never been screened for colorectal cancer are more likely to benefit. In addition, after 85 years of age, the USPSTF feels there is moderate or high certainty that colorectal cancer screening has no net benefit, or that the harms outweigh the benefits. USPSTF continues to recommend screening with either one of the stool-based tests (e.g., annual Fecal immunochemical test (FIT), annual high-sensitivity Fecal occult blood test (FOBT), or Stool DNA test (sDNA) every three years); or one of the direct visualization tests (e.g., colonoscopy every 10 years, or flexible sigmoidoscopy every 5 years combined with high-sensitivity FOBT every 3 years). Additionally, in the current recommendation, the USPSTF highlights that there is convincing evidence that colorectal cancer screening substantially reduces deaths from the disease among adults aged 50 to 75 years and that not enough adults in the United States are using this effective preventive intervention. The reasons for this gap between evidence and practice are multifaceted and will require sustained effort among clinicians, policy makers, advocates, and individuals to overcome.

The 2018 American Cancer Society Guidelines Update for CRC Screening focused on CRC screening in average-risk adults and did not address screening or surveillance in individuals at increased or high risk for developing CRC. Individuals at increased or high-risk for CRC include individuals with history of adenomatous polyps, a personal history of CRC, a family history of CRC or adenomatous polyps diagnosed in a relative before age 60 years, a personal history of inflammatory bowel disease, a confirmed or suspected hereditary CRC syndrome, or a history of abdominal or pelvic radiation for a previous cancer. Updated screening and surveillance recommendations for these groups have been developed by other organizations:
  • American College of Gastroenterology (ACG) clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes (2015)
  • Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on Colorectal Cancer (2014)
  • Colonoscopy surveillance after colorectal cancer resection: recommendations of the US Multi-Society Task Force on Colorectal Cancer (2016)
  • Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer (2012)

Identification of candidates for differential screening requires adequate collection and updating of family history information and appropriate referral for genetic counseling and testing of individuals at increased risk for hereditary syndromes.

NONINVASIVE COLORECTAL CANCER SCREENING TESTS

COLOGUARD
Cologuard uses stool DNA (sDNA) samples to test multiple biomarkers known to be associated with CRC and premalignant colorectal adenomas. The assay utilizes a novel polymerase chain reaction (PCR)-based method known as Quantitative Allele-specific Real-time Target and Signal (QuARTS) amplification to analyze the levels of methylated BMP3 and NDRG4 and to test for 7 specific variants in the KRAS gene. In addition, an analysis of the beta-actin gene (ACTB) is performed to control for variability in sDNA concentration. Finally, fecal immunochemical testing (FIT) is used to measure the hemoglobin (Hb) concentration in each stool sample. A positive Cologuard test result indicates that abnormal gene methylation, sequence variants, and/or elevated Hb were detected, while a negative result indicates that none of these were identified in the individual’s stool. Based on the available evidence, Cologuard may be considered in individuals who are at least 50 years of age and have an average risk of CRC, based on personal and family histories. Based on the available evidence, Cologuard is not appropriate for individuals with a history of CRC or colorectal adenomas, individuals with a hereditary cancer predisposition syndrome associated with CRC, or individuals with other chronic colorectal disorders (such as inflammatory bowel disease or Crohn’s disease); since these individuals do not present with average-risk for CRC.

Early studies relating to the analytical validity of the Cologuard assay included analyses of 2 additional markers that are not used in the test’s current commercially available form (i.e., methylated TFPI2 [tissue factor pathway inhibitor 2] and VIM [vimentin]). However, each of these studies used the same methods for testing, and each reports data relevant for an assessment of biomarkers included in the Cologuard assay. This preliminary data revealed that methylated NDRG4 and BMP3 were 2 of the most discriminative markers and that, while levels of all 4 methylated genes evaluated were affected by individual age, methylated TFPI2 was more significantly affected than the other 3 markers. In addition, when examining the contribution of the individual markers to test accuracy, test performance was not significantly affected when the 2 methylated TFPI2 and VIM were excluded from the panel. Specifically, the sensitivity of the multimarker sDNA test (with the 2 additional methylated genes) ranged from 78% to 89% for CRC and from 62% to 64% for advanced adenomas (AAs), compared with 82% for CRC and 62% for AAs when TFPI2 and VIM were omitted.

Based on the data from these preliminary studies, TFPI2 and VIM were removed from the multimarker sDNA test, and the performance of the final assay was examined using 2 different testing algorithms. This analysis showed that a logistic regression-based testing algorithm had a higher sensitivity than a single-marker cutoff algorithm. Consequently, the logistic regression-based testing algorithm was used in all subsequent studies and is used in the commercially available Cologuard assay. In the initial studies using this logistic regression-based algorithm, the test sensitivity was 98% for CRC, 56% for AAs, and 55% for sessile serrated adenomas (SSAs, a type of AA), at a specificity of ≥ 90%. Among individuals with any AA, test sensitivity increased with the size of the colorectal lesion and was higher in those with high-grade dysplasia (abnormal cell growth with a high risk of becoming malignant). In the largest and most recent study of analytical validity, the sensitivity and specificity of the Cologuard assay were 92.3% for CRC and 42.4% for AAs, with a specificity of 86.6%. The detection rate was 93.3% for curable-stage CRC (i.e., stages I to III) and 69.2% for AAs exhibiting high-grade dysplasia. In addition, when compared with FIT, the Cologuard assay was superior in all measures except test specificity (86.6% for Cologuard and 94.9% for FIT).

Finally, additional evidence supporting the analytical validity of Cologuard testing was reported in an FDA Summary of Safety and Effectiveness. A variety of evaluations examining the technical aspects of the Cologuard assay (including the limit of detection [LoD], the limit of quantification [LoQ], and lot-to-lot reproducibility) yielded results that met or exceeded FDA requirements. In addition, studies of cross-reactivity showed minimal cross-reactivity in the presence of partially methylated BMP3 or NDRG4, normal KRAS sequences, and other types of colorectal diseases or noncolorectal malignancies. Furthermore, an analysis of the FIT portion of the Cologuard test demonstrated that the assay would detect less common forms of Hb but would not detect animal Hb or myoglobin. A variety of potentially interfering substances (such as lotions and medications) were also evaluated and none significantly affected the results of Cologuard testing. Based on this data and the findings reported in the previously described studies, Cologuard received FDA premarket approval in August of 2014.

Studies evaluating the clinical validity of Cologuard testing are currently limited. However, since the most recent studies of analytical validity compare the results of the Cologuard assay with the current reference standard for the diagnosis of CRC (i.e., colonoscopy followed by histology), their results may also support the clinical validity of Cologuard testing. In addition, the largest of these studies calculated positive and negative predictive values (PPV and NPV, respectively), which are important measures of clinical validity. For the detection of CRC, the PPV and NPV for the Cologuard test were 3.7% and 99.9% for CRC and 23.6% and 94.7% for AAs, respectively, which were comparable to the PPV and NPV for FIT. Overall, a negative Cologuard result would reduce a individual’s chance of CRC from 1 in 154 (0.7%) to 1 in 1675 (0.06%), with a false-negative rate of 5.3%. However, according to the FDA’s documentation, an analysis of data stratified by sex revealed that the clinical sensitivity of the Cologuard assay may be higher in men than in women, and could potentially be affected by an individual's ethnicity.

Additional data regarding the clinical validity of Cologuard testing demonstrated that methylated BMP3 and NDRG4 levels normalized in 13 of 14 (93%) individuals with CRC after removal of the colorectal tumor, and that 1 Cologuard-negative individual with a sharp increase in methylated NDRG4 after surgery was subsequently found to have recurrent CRC. These findings confirmed that methylated BMP3 and NDRG4 levels are associated with CRC and suggest that it may be used for continued surveillance.

With regard to the clinical utility of Cologuard testing, it has been suggested that use of this noninvasive screening tool will increase the rate of compliance in individuals, leading to an increase in the detection of precancerous lesions and early-stage CRC, resulting in improved overall survival. Consistent with the hypothesis of increased compliance, a survey of individuals who used a different, first-generation sDNA-based assay suggested a relatively high individual acceptance rate for this form of CRC screening.

EPI PROCOLON
Epi proColon is an in vitro diagnostic (IVD) test to detect methylated Septin 9 (SEPT9) gene in ethylenediaminetetraacetic acid (EDTA) plasma derived from individual's whole-blood specimens. This test involves DNA extraction from individual's plasma, bisulfite conversion of DNA, and real-time PCR amplification of bisulfite-treated DNA for quantitation. The test comprises the Epi proColon Plasma Quick kit, Sensitive PCR kit, and Control kit.

No studies were identified that specifically stated that the Food and Drug Administration (FDA)-approved version of the Epi proColon was evaluated. However, there were 3 studies that included both analytical validity and clinical validity, and 1 clinical utility study to provide evidence for the Epi proColon 2.0 test, which uses the same kits as the FDA-approved version. Only studies that assessed the Epi proColon 2.0 test and defined methylation-positive result as ≥ 1 of 3 replicates positive, were included in support of the accuracy and performance of this test. Significant changes to the assay or data interpretation impact the test’s validity. The analytical validity of Epi proColon has been evaluated by several studies that support the test’s reproducibility, its ability to detect low levels of methylated SEPT9, and the fact that potential interfering substances do not affect test results. In addition, there is a defined assay process and the test has received FDA approval. In 3 case-control studies with mixed populations, the sensitivity for detecting CRC ranged from 68% to 95.6%, and specificity ranged from 78.8% to 84.8%. However, for high-risk/advanced adenomas, the sensitivity was very low, ranging from 14% to 22%. One additional study reported that the majority of individuals who decline colonoscopy elected to undergo the Epi proColon test for CRC rather than a stool-based test. However, there was no evidence demonstrating improved health outcomes from this test.

Epi proColon has a defined assay process approved by the FDA. However, there are discrepancies regarding the criteria for methylation-positive result as outlined in the FDA summary and presented on the manufacturer’s website. There is some evidence of clinical validity to support its use in the approved population; however, no studies have directly shown that the test results have a positive impact on health outcomes.

POLYPDX TEST™
PolypDx is purportedly the first and only urine-based test, (which detects three metabolites), for colorectal cancer prevention. There is no publicly available information regarding the makeup, (including any information regarding the biomarkers that may be part of this test), of PolypDx Test.There are no peer-reviewed published data and pertinent directions from professional/clinical guidelines for this test.
References


Aarons CB, Shanmugan S, Bleier JI. Management of malignant colon polyps: current status and controversies. World J Gastroenterol. 2014;20(43):16178-16183.

Adler A, Geiger S, Keil A, et al. Improving compliance to colorectal cancer screening using blood and stool based tests in patients refusing screening colonoscopy in Germany. BMC Gastroenterol. 2014;14:183.

Ahlquist DA, Taylor WR, Mahoney DW, et al. The stool DNA test is more accurate than the plasma septin 9 test in detecting colorectal neoplasia. Clin Gastroenterol Hepatol. 2012;10(3):272-277.e1.

American Cancer Society (ACS). Colorectal Cancer. 2018. Available at: https://www.cancer.org/health-care-professionals/american-cancer-society-prevention-early-detection-guidelines/colorectal-cancer-screening-guidelines.html. Accessed July 02nd, 2018.

Berger BM, Schroy PC, 3rd, Dinh TA. Screening for colorectal cancer using a multitarget stool DNA test: modeling the effect of the intertest interval on clinical effectiveness. Clin Colorectal Cancer. Sep 2016;15(3):e65- 74. PMID 26792032

Company Benefit Contracts.

Centers for Medicare & Medicaid Services (CMS). Decision memo for screening computed tomographic colonography (CTC) for colorectal cancer. [CMS Web site]. Available at: http://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=220&ver=14&NcaName=Screening+Computed+Tomography+Colonography+%28CTC%29+for+Colorectal+Cancer&bc=BEAAAAAAEAAA&&fromdb=true. Accessed July 02nd, 2018.

Centers for Medicare & Medicaid Services (CMS). MLN Matters. Colorectal cancer: preventable, treatable, and beatable: Medicare coverage and billing for colorectal cancer screening.[CMS Web site]. Available at: http://www.cms.hhs.gov/MLNMATTERSArticles/downloads/SE0710.pdf. Accessed July 02nd, 2018.

Centers for Medicare & Medicaid Services (CMS). National Coverage Determination (NCD). 210.3: Colorectal cancer screening tests. [CMS Web site]. 04/28/08. Available at: http://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=210.3&ncd_version=2&basket=ncd%3A210%2E3%3A2%3AColorectal+Cancer+Screening+Tests. Accessed July 02nd, 2018.

Church TR, Wandell M, Lofton-Day C, et al.; PRESEPT Clinical Study Steering Committee, Investigators and Study Team. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut. 2014;63(2):317-325.

Danese E, Minicozzi AM, Benati M, et al. Comparison of genetic and epigenetic alterations of primary tumors and matched plasma samples in patients with colorectal cancer. PloS One. 2015;10(5):e0126417.

Del Code § 3559. Colorectal Cancer Screening; 2000. [Delaware Code Web site]. 03/18/08. Available at: http://delcode.delaware.gov/sessionlaws/ga140/chp416.shtml. Accessed July 02nd, 2018.

deVos T, Tetzner R, Model F, et al. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem. 2009;55(7):1337-1346.

El Zoghbi M, Cummings LC. New era of colorectal cancer screening. World J Gastrointest Endosc. 2016;8(5):252-258.

Epigenomics AG. Epi proColon 2.0 CE: Instructions for Use (IFU). Revision 6. December 2015. Available at: http://www.epiprocolon.com/fileadmin/site_files/02_epi_procolon/e-support_lib/IFU0009_Rev_6/IFU_0009_GB_rev6_Epi_proColon_2_0_CE.pdf. Accessed July 02nd, 2018.

Epigenomics AG. The Septin9 Test. 2016b. Available at: http://www.epiprocolon.com/us/medical-professionals.html. Accessed July 02nd, 2018.

Grützmann R, Molnar B, Pilarsky C, et al. Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PloS One. 2008;3(11):e3759.

He Q, Chen HY, Bai EQ, et al. Development of a multiplex MethyLight assay for the detection of multigene methylation in human colorectal cancer. Cancer Genet Cytogenet. 2010;202(1):1-10.

Jin P, Kang Q, Wang X, et al. Performance of a second-generation methylated SEPT9 test in detecting colorectal neoplasm. JGastroenterol Hepatol. 2015;30(5):830-833.

Johnson DA, Barclay RL, Mergener K, et al. Plasma Septin9 versus fecal immunochemical testing for colorectal cancer screening: a prospective multicenter study. PloS One. 2014;9(6):e98238.

Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA. Jun 21 2016;315(23):2595-2609. PMID 27305518

Ladabaum U, Allen J, Wandell M, Ramsey S. Colorectal cancer screening with blood-based biomarkers: cost-effectiveness of methylated septin 9 DNA versus current strategies. Cancer Epidemiol Biomarkers Prev. 2013;22(9):1567-1576.

Ladabaum U, Alvarez-Osorio L, Rösch T, Brueggenjuergen B. Cost-effectiveness of colorectal cancer screening in Germany: current endoscopic and fecal testing strategies versus plasma methylated Septin 9 DNA. Endosc Int Open. 2014;2(2):E96-E104.

Lee HS, Hwang SM, Kim TS, et al. Circulating methylated septin 9 nucleic Acid in the plasma of patients with gastrointestinal cancer in the stomach and colon. Transl Oncol. 2013;6(3):290-296.

Li H, Du Y, Zhang D, et al. Identification of novel DNA methylation markers in colorectal cancer using MIRA-based microarrays. OncolRep. 2012;28(1):99-104.

Liu Y, Tham CK, Ong SY, et al. Serum methylation levels of TAC1, SEPT9 and EYA4 as diagnostic markers for early colorectal cancers: a pilot study. Biomarkers. 2013;18(5):399-405.

Lofton-Day C, Model F, Devos T, et al. DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem. 2008;54(2):414-423.

Molnár B, Tóth K, Barták BK, Tulassay Z. Plasma methylated septin 9: a colorectal cancer screening marker. Expert Rev Mol Diagn. 2015;15(2):171-184.

State of New Jersey. Department of Banking and Insurance. Individual Health Coverage. [New Jersey State Web site.]. 01/13/09. Available at: http://www.state.nj.us/dobi/division_insurance/ihcseh/bulletins/ihc0901.pdf. Accessed July 02nd, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Colorectal Cancer Screening. Version 1.2016.

Ørntoft MB, Nielsen HJ, Ørntoft TF, Andersen CL, Danish Study Group on Early Detection of Colorectal Cancer. Performance of the colorectal cancer screening marker Sept9 is influenced by age, diabetes and arthritis: a nested case-control study. BMC Cancer. 2015;15:819.

Paska AV, Hudler P. Aberrant methylation patterns in cancer: a clinical view. Biochem Med (Zagreb). 2015;25(2):161-176.

Pennsylvania (PA) General Assembly. Senate Bill 146. An act amending The Insurance Company Law of 1921, mandating health insurance coverage for colorectal cancer screening. [PA General Assembly Web site]. 03/05/2007. Available at: http://www.legis.state.pa.us/cfdocs/legis/PN/Public/btCheck.cfm?txtType=HTM&sessYr=2007&sessInd=0&billBody=S&billTyp=B&billNbr=0146&pn=0191. Accessed July 02nd, 2018.

Potter NT, Hurban P, White MN, et al. Validation of a real-time PCR-based qualitative assay for the detection of methylated SEPT9 DNA in human plasma. Clin Chem. 2014;60(9):1183-1191.

Ravegnini G, Zolezzi Moraga JM, Maffei F, et al. Simultaneous analysis of SEPT9 promoter methylation status, micronuclei frequency, and folate-related gene polymorphisms: the potential for a novel blood-based colorectal cancer biomarker. Int J Mol Sci. 2015;16(12):28486-28497.

Redwood DG, Asay ED, Blake ID, et al. Stool DNA Testing for screening detection of colorectal neoplasia in Alaska Native people. Mayo Clin Proc. Jan 2016;91(1):61-70. PMID 26520415

Riley BD, Culver JO, Skrzynia C, et al. Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns. 2012;21(2):151-161.

Song L, Li Y. SEPT9: A specific circulating biomarker for colorectal cancer. Adv Clin Chem. 2015;72:171-204.

Su XL, Wang YF, Li SJ, Zhang F, Cui HW. High methylation of the SEPT9 gene in Chinese colorectal cancer patients. Genet Mol Res. 2014;13(2):2513-2520.

Surveillance, Epidemiology, and End Results (SEER). SEER Stat Fact Sheets: Colon and Rectum Cancer. 2016. National Cancer Institute [website]. Available at: http://seer.cancer.gov/statfacts/html/colorect.html. Accessed July 02nd, 2018.

Tänzer M, Balluff B, Distler J, et al. Performance of epigenetic markers SEPT9 and ALX4 in plasma for detection of colorectal precancerous lesions. PloS One. 2010;5(2):e9061.

Teutsch SM, Bradley LA, Palomaki GE, et al.; EGAPP Working Group. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative: methods of the EGAPP Working Group. Genet Med. 2009;11(1):3-14.

Tham C, Chew M, Soong R, et al. Postoperative serum methylation levels of TAC1 and SEPT9 are independent predictors of recurrence and survival of patients with colorectal cancer. Cancer. 2014;120(20):3131-3141.

Tierling S, Schuster M, Tetzner R, Walter J. A combined HM-PCR/SNuPE method for high sensitive detection of rare DNA methylation.Epigenetics Chromatin. 2010;3(1):12.

Tóth K, Sipos F, Kalmár A, et al. Detection of methylated SEPT9 in plasma is a reliable screening method for both left- and right-sided colon cancers. PloS One. 2012;7(9):e46000.

Tóth K, Wasserkort R, Sipos F, et al. Detection of methylated septin 9 in tissue and plasma of colorectal patients with neoplasia and the relationship to the amount of circulating cell-free DNA. PloS One. 2014;9(12):e115415.

U.S. Preventive Services Task Force. Screening for colorectal cancer: summary of recommendations. [USPSTF Web site]. October 2008. Available at: http://www.uspreventiveservicestaskforce.org/uspstf/uspscolo.htm. Accessed July 02nd, 2018.

U.S. Preventive Services Task Force. Screening for colorectal cancer: Final Recommendation Statement 2016. [USPSTF Web site]. October 2008. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/colorectal-cancer-screening2. Accessed July 02nd, 2018.

U.S. Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. Jun 21 2016;315(23):2564-2575. PMID 27304597

Veenstra DL, Piper M, Haddow JE, et al. Improving the efficiency and relevance of evidence-based recommendations in the era of whole-genome sequencing: an EGAPP methods update. Genet Med. 2013;15(1):14-24.

Warren JD, Xiong W, Bunker AM, et al. Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer. BMC Med. 2011;9:133.

Warton K, Samimi G. Methylation of cell-free circulating DNA in the diagnosis of cancer. Front Mol Biosci. 2015;2:13.

Weiss G, Rösch T. Potential of a new blood test for colorectal cancer screening – the septin 9 gene biomarker. Eur Oncol. 2010:51-54.

Wu D, Zhou G, Jin P, et al. Detection of colorectal cancer using a simplified SEPT9 gene methylation assay is a reliable method for opportunistic screening. J Mol Diagn JMD. 2016. Epub ahead of print. April 28, 2016. Available at:http://jmd.amjpathol.org/article/S1525-1578(16)30026-5/abstract. Accessed July 02nd, 2018.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

MEDICALLY NECESSARY

74263, 81528, 82270


EXPERIMENTAL/INVESTIGATIONAL

THE FOLLOWING CODES ARE USED TO REPRESENT EPI PROCOLON / METHYLATION ANALYSIS OF SEPT9

81327, 81479

THE FOLLOWING CODE IS USED TO REPRESENT POLYPDX

0002U


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medical necessity as listed in the policy.


HCPCS Level II Code Number(s)


G0104 Colorectal cancer screening; flexible sigmoidoscopy

G0105 Colorectal cancer screening; colonoscopy on individual at high risk

G0106 Colorectal cancer screening; alternative to G0104, screening sigmoidoscopy, barium enema

G0120 Colorectal cancer screening; alternative to G0105, screening colonoscopy, barium enema

G0121 Colorectal cancer screening; colonoscopy on individual not meeting criteria for high risk

G0122 Colorectal cancer screening; barium enema

G0328 Colorectal cancer screening; fecal occult blood test, immunoassay, 1-3 simultaneous determinations



Revenue Code Number(s)

N/A


Misc Code

N/A:

N/A


Coding and Billing Requirements


Cross References


Policy History

Revisions from 11.03.12q:
01/01/2019Effective 01/01/2019, the following procedure code's narrative was revised in this policy due to coding updates:

81327

Revisions from 11.03.12p
10/01/2018This version of the policy is effective as of 10/01/2018.

The following procedure code has been deleted from this policy: G0464

Revisions from 11.03.12o
07/01/2018This version of the policy is effective as of 07/01/2018.

The policy has been reviewed to communicate the Company’s updated positions for the following (in accordance with American Cancer Society’s 2018 updates to the Colorectal Cancer Screening Guidelines):
  • For average-risk individuals, colorectal cancer screening is covered starting at age 45 instead of age 50.
  • A personal history of radiation to the abdomen or pelvic area to treat a prior cancer qualifies an individual as at increased- or high-risk indication.


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 01/01/2019
Version Issued Date: 01/03/2019
Version Reissued Date: N/A

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