Clinical Policy Title: Genetic testing for prostate cancer prognosis

Transcription

1 Clinical Policy Title: Genetic testing for prostate cancer prognosis Clinical Policy Number: CCP.1121 Effective Date: January 1, 2015 Initial Review Date: July 16, 2014 Most Recent Review Date: October 2, 2018 Next Review Date: October 2019 Policy contains: Prostate cancer. Inherited cancer syndromes. Risk assessment. Related policies: CCP.1012 CCP.1050 CCP.1298 Genetic testing for breast and ovarian cancer Familial polyposis gene testing Prostate-specific antigen screening ABOUT THIS POLICY: Select Health of South Carolina has developed clinical policies to assist with making coverage determinations. Select Health of South Carolina s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peerreviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by Select Health of South Carolina when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Select Health of South Carolina s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Select Health of South Carolina s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Select Health of South Carolina will update its clinical policies as necessary. Select Health of South Carolina s clinical policies are not guarantees of payment. Coverage policy Select Health of South Carolina considers the use of genetic (germline) testing for prostate cancer to be clinically proven and, therefore, medically necessary for members with any of the following clinical criteria (National Comprehensive Cancer Network, 2019 and 2018; Giri, 2018): Personal history of high-grade prostate cancer (Gleason score 7) diagnosed at any age and a strong family history defined as either: One or more first-, second-, or third-degree blood relatives on the same side of the family diagnosed with prostate cancer younger than age 60. Known germline deoxyribonucleic acid repair gene abnormalities on tumor sequencing studies. Two or more blood relatives meeting established testing or syndromic criteria for (see Appendix): Hereditary breast and ovarian cancer syndrome. Hereditary prostate cancer syndrome. 1

2 Lynch syndrome (hereditary nonpolyposis colorectal cancer). Metastatic castration-resistant prostate cancer (radiographic evidence of or biopsy-proven disease) for treatment determination. Select Health of South Carolina considers the following genetic tests to be clinically proven and, therefore, medically necessary in members with prostate cancer (Giri, 2018): Limitations: Testing for genes meeting the criteria for the corresponding cancer syndrome (see Appendix): Homeobox B13 genes for hereditary prostate cancer syndrome. Breast cancer 1 and breast cancer 2 genes for hereditary breast and ovarian cancer syndrome. Deoxyribonucleic acid mismatched repair genes for Lynch syndrome. Confirmatory germline testing for breast cancer 1 and breast cancer 2, deoxyribonucleic acid mismatched repair, homeobox B13, or ATM serine/threonine kinase genes in members with prostate tumor sequencing studies showing mutations for prostate cancer predisposition in the corresponding cancer-risk genes. Breast cancer 1 and breast cancer 2 or ATM serine/threonine kinase genes in members with metastatic castration-resistant prostate cancer. Genetic testing for a specific gene mutation is limited to once per lifetime. Genetic testing for prostate cancer is not medically necessary for persons who are not members of Select Health of South Carolina health plans. All other genetic testing for prostate cancer are not medically necessary, including but not limited to: Genetic screening in the general population. Members with no personal history of prostate cancer. Members younger than age 18 years. Genetic counseling must be accompanied with a care-coordinating, multidisciplinary team available for genetic and behavioral counseling, which includes a primary care provider and a geneticist (who is a physician or a licensed genetic counselor). If access to a genetic counselor or medical geneticist is not possible, genetic counseling may be initiated by a physician with relevant genetic expertise. For Medicare members only: Select Health of South Carolina considers the use of genetic testing for prostate cancer to be clinically proven and, therefore, medically necessary when provided in accordance with Local Coverage Article A54933 and Local Coverage Determinations L36499, L36715, L36082, and L

3 Alternative covered services: Standard diagnostic and radiographic tests for prostate cancer (e.g., prostate-specific antigen and radionuclide bone scan). Background Prostate cancer is the most common noncutaneous malignancy and the second-leading cancer cause of death in men (National Cancer Institute, 2018a). Prostate cancer is usually slow-growing, and most cases will never become symptomatic during the patients lifetimes. Efforts at early detection with prostatespecific antigen or digital rectal exam and consequent earlier treatment have not resulted in improved health or longevity, and may be harmful. Factors that may increase the risk of prostate cancer include older age (> 50 years), a family history of prostate cancer, race (e.g., African American), hormones (dihydrotestosterone), and certain dietary factors (vitamin E, folic acid, dairy, and calcium). Current strategies used to establish prostate cancer prognosis are tumor stage, Gleason grade, and prostate-specific antigen level to define risk groups. In 2014, the International Society of Urological Pathology (Epstein, 2016) revised the Gleason scoring system into five risk groups based on pathology, and the National Comprehensive Cancer Network (2018) has accepted this new system to better inform treatment decisions, yet heterogeneity within each group exists. Nomograms, molecular testing, and genetic testing may provide more individualized risk assessment information. Prostate cancer is associated with several genes and more than 100 single nucleotide polymorphisms (National Cancer Institute, 2018b). The breast cancer 1 gene, breast cancer 2 gene, deoxyribonucleic acid mismatch repair genes, and homeobox B13 confer modest to high lifetime risk of prostate cancer. Germline genetic risk markers are appealing as screening biomarkers for their accessibility at any age and their stability over time and in the setting of particular conditions. Men genetically predisposed to developing prostate cancer may benefit from targeted surveillance, and knowledge of inherited variants may differentiate indolent from aggressive disease and influence treatment decisions. Searches Select Health of South Carolina searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s Guideline Clearinghouse and other evidencebased practice centers. The Centers for Medicare & Medicaid Services. We conducted searches on August 24, Search terms were Prostate cancer, familial [Supplementary Concept] and the free text terms prostate cancer, risk stratification, and genetic tests. 3

4 We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings Evaluating the clinical value of a test for screening or diagnosis is the subject of much methodological discussion. The rationale for diagnostic testing is to provide information that history, physical examination, and any previous testing is considered insufficient to address. The diagnostic information should be useful to the clinician and to the patient in terms of improving diagnostic certainty, supporting efficacious treatment, and, ultimately, leading to a better clinical outcome. Fryback and Thornbury (1991) developed a hierarchical model for evaluating the clinical efficacy of a diagnostic test based on five levels: Technical efficacy the technical output gives accurate information concerning the item tested (feasibility). Diagnostic accuracy the information can improve the clinician s ability to diagnose disease and assess the patient s prognosis. Diagnostic impact the information can alter plans for additional diagnostic tests. Therapeutic impact the information can lead to changes in therapeutic plans for patients. Health impact the test result may be improve patient outcome. Available reviews focus on pre-clinical (laboratory) or observational research, which is still in the process of identifying optimal genetic or molecular markers to identify those men receiving active surveillance who are likely to die from, rather than with, their cancers (Yao, 2014; Guo, 2013; Li, 2013; Choudhury, 2012; Little, 2012; Batra, 2011). In other words, risk assessment for prostate cancer remains at the hypothesis-generating level (cross-sectional associations of marker concentrations with tumor volume or other intermediate/surrogate endpoints) rather than testing level (trials or cohort studies following tested patients forward in time to assess outcomes). Research confirming that any currently available tests, or those under development, actually impact therapeutic decisions or health outcomes has yet to be published or addressed in systematic reviews. Policy updates: 4

5 In 2018, we added one meta-analysis (Cui, 2017), one systematic review (Hamilton, 2017), two evidence-based guidelines from the National Comprehensive Cancer Network on prostate cancer (2018) and genetic and familial high risk assessment for breast and ovarian cancers (2019), and evidence-based and consensus recommendations from the 2017 Philadelphia Prostate Cancer Consensus Conference on genetic testing for inherited prostate cancer risk (Giri, 2018). Increasing evidence supports an inherited predisposition of prostate cancer with implications for cancer risk assessment for men and their families and targeted treatment of metastatic disease (e.g., early use of platinum chemotherapy). Higher prostate cancer risk is associated with breast cancer 1/2 mutations (linked to hereditary breast and ovarian cancer syndrome) and homeobox B13 mutations (linked to hereditary prostate cancer), and other gene mutations may be involved. Men with germline 1/2 mutations appear to have more aggressive prostate cancers (e.g., Gleason score 8), nodal involvement, and distant metastasis compared with noncarriers. Early studies and guidelines focused on breast cancer 1/2 testing, but other genes implicated in prostate cancer predisposition are now for testing available through multigene panels. Genetic testing should be analytically and clinically valid, directly impact disease management, and incorporate a tiered panel or targeted test sequence for minimal number of genes needed to establish the diagnosis. The genetic test should incorporate the genetic spectrum associated with personal and family history of prostate cancer and inherited cancer syndromes, as well as tumor sequencing results (Giri, 208). Changes to the coverage policy reflect recommendations on the expanding clinical role of genetic testing in inherited prostate cancer as a complement to current risk assessment strategies (National Comprehensive Cancer Network, 2019 and 2018; Giri, 2018). Policy ID changed from CP# to CCP Summary of clinical evidence: Citation Giri (2018) Content, Methods, Recommendations Key points: Role of genetic testing for inherited prostate cancer risk: Philadelphia Prostate Cancer Consensus Conference 2017 Evidence supports the following genetic tests for an association to prostate cancer risk: Breast cancer 1 Hereditary breast and ovarian cancer syndrome (Grade A highgrade evidence from at least one prospectively designed study or three or more large validation studies or three or more descriptive studies). Breast cancer 2 Hereditary breast and ovarian cancer syndrome (Grade A for an association to lethal/aggressive prostate cancer). Deoxyribonucleic acid mismatched repair genes Lynch syndrome (Grade B moderate grade evidence from two cohort or case-control studies). Homeobox B13 Hereditary prostate cancer syndrome (Grade A). ATM serine/threonine kinase and nibrin genes (Grade C emerging data). Tumor protein p53, checkpoint kinase 2, partner and localizer of breast cancer 2, RAD51 paralog D genes (Grade D low, insufficient). 5

6 Citation Hamilton (2017) Primary care providers' cancer genetic testingrelated knowledge, attitudes, and communication behaviors: a systematic review and research agenda Cui (2017) Breast cancer 2 mutations should be screened early and routinely as markers of poor prognosis: evidence from 8,988 patients with prostate cancer Little (2016) for the Agency for Healthcare Research and Quality Multigene panels in prostate cancer risk assessment: a systematic review Content, Methods, Recommendations Guidance: Test for genes meeting the criteria for the corresponding cancer syndrome. Confirmatory germline testing for breast cancer 1/2, deoxyribonucleic acid mismatched repair gene genes, homeobox B13, or ATM serine/threonine kinase in men with prostate tumor sequencing studies showing mutations for prostate cancer predisposition in the corresponding cancer-risk genes. Test for breast cancer 1/2 or ATM serine/threonine kinase in men with metastatic castration-resistant prostate cancer. Key points: A systematic review evaluated providers' attitudes regarding genetic testing for breast, colorectal, or prostate cancer to determine if primary care providers can play a role in helping patients receive the preventive health benefits of cancer genetic risk information. Most studies focused on genetic testing for breast cancer (23/27) and colorectal cancer risk (12/27); only one study examined testing for prostate cancer risk. Most articles addressed descriptive research questions (24/27). Many studies (24/27) documented provider knowledge, often concluding that providers' knowledge was incomplete. Providers expressed some concerns about ethical, legal, and social implications of testing. Generally favorable attitudes about the utility of clinical genetic testing, including for targeted cancer screening. Key points: Meta-analysis of 10 nonrandomized retrospective studies assessing the effect of breast cancer 2 mutation on survival (n = 525 breast cancer 2 mutation-carriers, n = 8,463 noncarriers). One study in Korea; nine in Western countries. Overall quality: fair-to-good (score 7 to 9) based on Newcastle-Ottawa Scale; no significant publication bias. No African American populations were included. Among Caucasian and Asian populations, breast cancer 2 mutation carriers exhibited lower overall survival and cancer-specific survival compared to non-carriers (pooled hazard ratios 2.53, 95% confidence interval [CI] 2.10 to 3.06, P <.001, and 2.21, 95% CI 1.64 to 2.99, P <.001, respectively); ethnicity, detection method, and sample size had no significant effect on results. Breast cancer 2 mutation-carriers were graded a higher Gleason Score (> 7), clinical stage (> T3, N1, M1), and risk level than non-carriers. Incremental value of breast cancer 2 mutation on risk stratification and impact on treatment planning are unclear. Key points: Systematic review of 21 studies of clinical validity: 18 individual panels with 2 to 35 singlenucleotide polymorphism. Overall quality: moderate. All had poor discriminative ability (overall area under receiver-operator characteristic curves, 58% to 74%; incremental gain resulting from inclusion of data, 2.5% to 11%) for predicting risk of prostate cancer and/or distinguishing between aggressive and asymptomatic/latent disease. Analytic validity insufficient evidence. 6

7 Citation Bradley (2013) for the Agency for Healthcare Research and Quality Prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer Content, Methods, Recommendations Clinical validity panels assessed would add a small and clinically unimportant improvement to factors such as age and family history in risk stratification. No evidence of clinical utility of current panels. Key points: Comparative effectiveness review of 24 diagnostic accuracy studies and 13 treatment efficacy studies. Most studies were conducted in opportunistic cohorts of men referred for procedures and were not designed to answer key clinical questions. Prostate cancer antigen 3 had a higher diagnostic accuracy than total prostate specific antigen increases, but strength of evidence was low (limited confidence in effect estimates). Strength of evidence was insufficient to conclude that prostate cancer antigen 3 testing leads to improved health outcomes. For all other outcomes and comparators, strength of evidence was insufficient. References Professional society guidelines/other: Giri VN, Knudsen KE, Kelly WK, et al. Role of genetic testing for inherited prostate cancer risk: Philadelphia Prostate Cancer Consensus Conference J Clin Oncol. 2018; 36(4): DOI: /jco National Comprehensive Cancer Network Genetic/familial high-risk assessment: breast and ovarian. Version July 30, National Comprehensive Cancer Network website. Accessed August 26, National Comprehensive Cancer Network Prostate cancer. Version August 15, National Comprehensive Cancer Network website. Accessed August 24, Peer-reviewed references: Batra J, Lose F, O'Mara T, et al. Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data. PLoS One. 2011; 6(11): e DOI: /journal.pone Bradley LA, Palomaki GE, Gutman S, Samson D, Aronson N. Comparative effectiveness review: prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer. J Urol. 2013; 190(2): DOI: /j.juro Choudhury AD, Eeles R, Freedland SJ, et al. The role of genetic markers in the management of prostate cancer. Eur Urol. 2012; 62(4): DOI: /j.eururo

8 Cui M, Gao XS, Gu X, et al. BRCA2 mutations should be screened early and routinely as markers of poor prognosis: evidence from 8,988 patients with prostate cancer. Oncotarget. 2017; 8(25): DOI: /oncotarget Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Making. 1991; 11(2): DOI: / x Genetics of Prostate Cancer (PDQ ) Health Professional Version. Updated June 13, National Cancer Institute website. Accessed August 24, 2018.(b) Guo Z, Wen J, Kan Q, et al. Lack of association between vitamin D receptor gene FokI and BsmI polymorphisms and prostate cancer risk: an updated meta-analysis involving 21,756 subjects. Tumor Biol. 2013; 34(5): DOI: /s Hamilton JG, Abdiwahab E, Edwards HM, Fang ML, Jdayani A, Breslau ES. Primary care providers' cancer genetic testing-related knowledge, attitudes, and communication behaviors: a systematic review and research agenda. J Gen Intern Med. 2017; 32(3): DOI: /s Hereditary Cancer-Related Syndromes. American Society of Clinical Oncology website. Accessed August 27, Li Q, Zhu Y. SRD5A2 V89L and A49T polymorphisms and sporadic prostate cancer risk: a meta-analysis. Mol Biol Rep. 2013; 40(5): DOI: /s x. Little J, Wilson B, Carter R, et al. Multigene panels in prostate cancer risk assessment. Evidence Report/Technology Assessment No (Prepared by the McMaster University Evidence-based Practice Center under contract No ) AHRQ Publication No. 12-E020-EF. Rockville, MD: Agency for Healthcare Research and Quality; Available from: Accessed August 26, Prostate Cancer Health Professional Version. National Cancer Institute website. Accessed August 24, 2018.(a) Yao YH, Wang H, Li BF, Tang Y. Evaluation of the TMPRSS2:ERG fusion for the detection of prostate cancer: a systematic review and meta-analysis. Tumor Biol. 2014; 35(3): DOI: /s x. Centers for Medicare & Medicaid Services National Coverage Determinations: No National Coverage Determinations identified as of the writing of this policy. 8

9 Local Coverage Determinations: A54933 BRCA1 and BRCA2 Genetic Testing (for L36499). L36499 BRCA1 and BRCA2 Genetic Testing. L36715 BRCA1 and BRCA2 Genetic Testing. L36082 MolDX: BRCA1 and BRCA2 Genetic Testing. L36813 MolDX: BRCA1 and BRCA2 Genetic Testing. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. CPT Code Description Comments PCA3/KLK3 (prostate cancer antigen Prostate specific antigen (PSA); complexed (direct measurement) Prostate specific antigen (PSA); total Prostate specific antigen (PSA); free ICD-10 Code Description Comments C61 Malignant neoplasm, prostate. Z80.42 Family history of malignant neoplasm of prostate HCPCS Level II Code S3721 Description Cancer antigen 3 (PCA3) testing. Not Covered by Medicare Comments Appendix Syndromic criteria Characteristics of hereditary breast and ovarian cancer syndrome (any): One or more female relatives diagnosed at age 45 or younger. One or more female relatives diagnosed with breast cancer before age 50 with additional family history of cancer, such as prostate cancer, melanoma, and pancreatic cancer. Breast or ovarian cancers in multiple generations on the same side of the family. A woman diagnosed with a second breast cancer or has both breast and ovarian cancers. A male relative diagnosed with breast cancer. 9

10 A history of breast, ovarian, or pancreatic cancer on the same side of the family. A history of breast, ovarian, pancreatic, or male breast cancer in a family of Ashkenazi Jewish ancestry. Characteristics of Lynch syndrome (any): Colorectal cancer younger than age 50. Colorectal cancer and other types of cancer* linked with Lynch syndrome separately or at the same time. Colorectal cancer with specific tumor features linked to Lynch syndrome at an age younger than 60. Colorectal cancer in one or more first-degree relatives with a history of another Lynch syndrome-related cancer*, with one of these cancers developing before age 50. First-degree relatives include parents, siblings, and children. Colorectal cancer in two or more first- or second-degree relatives with another Lynch syndrome-related cancer. Second-degree relatives include aunts, uncles, grandparents, grandchildren, nephews, and nieces. *Colorectal cancer, endometrial cancer, small bowel, ureter, or renal pelvis cancer; some people would also consider including ovarian cancer. Characteristics of hereditary prostate cancer syndrome (any): Three or more first-degree relatives with prostate cancer. Prostate cancer in three generations on the same side of the family. Two or more close relatives, such as a father, brother, son, grandfather, uncle, or nephew, on the same side of the family diagnosed with prostate cancer before age 55. Source: American Society of Clinical Oncology (2018). 10