Medical Policy: 02.04.57 

Original Effective Date: June 2016 

Reviewed: May 2017 

Revised: May 2017 

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy 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 will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

 

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in American men. In 2017, it is estimated that 161,360 men will be diagnosed with prostate cancer and 26,730 will die of this disease. Gene expression profile analysifs and protein biomarkers have been proposed as a means to risk-stratify patients with prostate cancer to guide treatment decisions. These tests are intended to be used either on prostate needle-biopsy tissue to guide management decisions regarding active surveillance versus therapeutic intervention, or after radical prostatectomy (RP) to guide radiotherapy use. 

 

Prolaris® (Myriad Genetics, Salt Lake City, UT) and Oncoytpe DX® Prostate Cancer Assay (Genomic Health, Redwood City, CA) are gene expression profiling tests each intended to be used in combination with accepted clinical criteria (Gleason score, prostate-specific antigen (PSA), clinical stage) to stratify needle biopsy-diagnosed localized prostate cancer according to biological aggressiveness, and direct initial patient management.

  • Prolaris® is used to directly measure tumor cell growth characteristics for stratifying the risk of disease progression in prostate cancer patients. The 46 gene expression signature test includes 31 cell cycle progression (CCP) genes and 15 housekeeper genes to generate a CCP score. The testing combines traditional risk factors (Gleason score, PSA, clinical stage) with a molecular assessment and the score helps identify those patients with less or more aggressive prostate cancer, thus assisting with individualized prostate cancer treatment/management decisions. 
  • Oncotype DX® Prostate Cancer Assay is used to quantify expression levels of 12 cancer-related and 5 reference genes to generate a Genomic Prostate Score (GPS). In the final analysis, the cell cycle progression (CCP) score or GPS is combined in proprietary algorithms with clinical risk criteria (PSA, Gleason grade, tumor stage) to generate low risk categories (i.e. reclassification) intended to reflect biological indolence or aggressiveness of individual lesions, and thus inform management decisions.

Decipher® (GenomeDx Biosciences, Vancouver, BC) is a tissue based tumor 22-biomarker gene expression profile test that is intended to guide the use of radiation after radical prostatectomy. The Decipher test classifies patient as low risk, who can delay or defer radiation after prostatectomy, or high risk, as those who would potentially benefit from early radiation. The gene expression classifier is a continuous risk score between 0 and 1, with higher risk scores indicating a greater probability of developing metastasis.

 

ProMark™ is an automated quantitative imaging method to measure 8 protein biomarkers (DERL1, PDSS2, pS6, YBX1, HSPA9, FUS, SMAD4, and CUL2) using immunofluorescence and automated quantitative images in intact biopsy tissue to risk stratify patients to active surveillance or therapeutic intervention. The assay results are combined using predefined coefficients for each marker from a logistic regression model to calculate a risk score and the risk score is continuous number between 0 and 1 which stratify the patient into a favorable or less favorable risk score.

 

Localized prostate cancers may appear very similar clinically at diagnosis. However, they often exhibit diverse risk of progression that may not be captured by clinical risk categories or prognostic tools that are based on clinical findings, including PSA titers, Gleason grade, or tumor stage. In studies of conservative management, the risk of localized disease progression based on prostate cancer-specific survival rates at 10 years may range from 15% to 20% to perhaps 27% at 20-year follow up. Among elderly men (ages > 70 years) with low risk disease, comorbidities typically supervene as a cause of death; these men will die with prostate cancer present, rather than from the cancer itself. Other very similar appearing low risk tumors may progress unexpectedly rapidly, quickly disseminating and becoming incurable.

 

In men newly diagnosed with clinically localized prostate cancer, the purpose of gene expression profiling and protein biomarkers tests is to inform decisions whether to undergo immediate therapy versus forego immediate therapy and begin active surveillance.

 

The divergent behavior of localized prostate cancers creates uncertainty whether or not to treat immediately. A patient may choose potentially curative treatment upfront. Surgery including radical prostatectomy (RP) or external beam radiotherapy (EBRT) are most commonly used to treat patients with localized prostate cancer.

 

The American Urological Association (AUA) guideline suggests patients with low risk localized prostate cancer and select patients with favorable intermediate-risk localized prostate cancer have the option of “active surveillance”, which is determined through a shared decision making process considering cancer severity (risk category), patient values and preferences, life expectancy, pre-treatment general functional and genitourinary symptoms, expected post treatment functional status, and potential for salvage treatment.  With this approach the patient will forgo immediate therapy and continue regular monitoring until signs and symptoms of disease progression are evident, at which point curative treatment is instituted.  Given the unpredictable behavior of early prostate cancer additional prognostic methods to biologically stratify this disease are being investigated to include if gene expression profiling and protein biomarkers compared with clinicopathologic risk stratification or when used with clinicopathologic risk stratification, there is improved outcomes in newly diagnosed men with clinically localized prostate cancer.

 

Clinicopathologic risk stratification is currently being used to make decisions about prostate cancer management. Clinical characteristics (e.g. stage, biopsy Gleason grade, serum PSA) and demographic characteristics (e.g. age, life expectancy) are combined to classify men according to risk. National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) provide treatment recommendations based on risk stratification. Prospective active surveillance cohorts now comprise >10,000 patients, thousands of whom have been followed for >10 years. Clinical parameters (e.g. PSA, PSA density, extent of disease on biopsy, race, T-stage) allow for stratification for risk of co-existent higher grade disease. Monitoring low risk patients on surveillance is associated with low risk of prostate cancer specific mortality. Therefore, the benefit to most patients of a biomarker to further stratify patients according to the risk of progression is modest. Per the American Urological Association (AUA)/American Society of Radiation Oncology (ASTRO) and Society Urologic Oncology (SUO) 2017 guideline for clinically localized prostate cancer states, “that tissue based genomic biomarkers have not shown a clear role in active surveillance for localized prostate cancer and are not necessary for follow up (Expert Opinion).” 

 

Initial Management Decision: Active Surveillance and Therapeutic Intervention

For individuals who have clinically localized prostate cancer who receive Prolaris, the evidence includes 1 study of analytic validity and retrospective cohort studies of clinical validity using archived samples and a decision curve analysis. No direct evidence is available to support the clinical utility of Prolaris for improving net outcomes of patients with localized prostate cancer to include when following radical prostatectomy. The indirect chain of evidence is also incomplete. Decision-curve analysis did not provide convincing evidence of meaningful improvement in net benefit in biochemical recurrence (BCR) by incorporating the cell cycle progression (CCP) score. Prolaris CCP score may have an association with BCR but disease-specific survival outcomes were not reported. A larger number of disease-specific survival events and precision estimates for discrimination measures are needed. There is insufficient evidence in the peer reviewed medical literature demonstrating Prolaris testing has a role in clinical decision making or has a beneficial effect on net health outcomes. Further studies are needed to determine the clinical utility for Prolaris gene expression profiling in the management of prostate cancer. The evidence is insufficient to determine the effects of this testing on net health outcomes and therefore, is considered investigational.  

 

In November 2015, the Food and Drug Administration’s (FDA) office of Public Health Strategy and Analysis published a document on public health evidence for FDA oversight of LDTs. FDA argued that many tests need more FDA oversight then the regulatory requirements of CLIA. CLIA standards related to laboratory operations, but do not address inaccuracies or unreliability of specific tests. Prolaris is among the 20 case studies in the document cited as needing FDA oversight. The document asserted that patients are potentially receiving inappropriate prostate cancer care because there is no evidence that results from meaningfully improve clinical outcomes.  

 

For individuals who have clinically localized prostate cancer who receive Oncotype DX Prostate, the evidence includes 2 studies of analytic validity, case-cohort and retrospective cohort studies of clinical validity using archived samples, and a decision curve analysis examining indirect evidence of clinical utility. The evidence on clinical validity for Oncotype DX Prostate has suggested the genomic prostate score (GPS) can reclassify a patient’s risk of recurrence based on a biopsy specimen. However, whether these findings support a conclusion that the GPS could predict the biological aggressiveness of a tumor or disease-specific survival, based solely on the level of pathology in a biopsy specimen is unclear. Generalizing the evidence to a true active surveillance population for which most in the study would be eligible is difficult because all of the patients had elective radical prostatectomy. Therefore, the findings do not reflect a clinical scenario of predicting risk of 10-year distant recurrence in untreated patients under active surveillance. Also, there is no direct evidence of clinical utility found for Oncotype DX Prostate in active surveillance because all patients regardless of clinical criteria elected radical prostatectomy within 6 months of diagnostic biopsy. Further studies are needed to determine the clinical utility of Oncotype DX Prostate gene expression profiling in the management of prostate cancer. There is insufficient evidence in the peer reviewed medical literature demonstrating that Oncotype DX Prostate has a clinical role in decision making or a has a beneficial effect on net health outcomes and therefore, is considered investigational.

 

For individuals who have clinically localized prostate cancer who receive the ProMark protein biomarker test, the evidence includes 1 study of analytic validity, 1 retrospective cohort study of clinical validity using archived samples, and no published studies on clinical utility were identified. There is insufficient evidence in the peer reviewed medical literature demonstrating that ProMark protein biomarker testing has a role in clinical decision making or has a beneficial effect on net health outcomes. Further studies are needed to determine the clinical utility of this test. The evidence is insufficient to determine the effects of this testing on net health outcomes and therefore, is considered investigational.  

 

Management Decision After Radical Prostatectomy

The purpose of gene expression profiling and protein biomarkers tests in patients who have prostate cancer and who have undergone radical prostatectomy is to inform management decisions. For example, the optimal timing of radiation therapy after radical prostatectomy is a debate. Adjuvant radiation therapy may maximize cancer control outcomes; however, salvage radiation therapy can maximize overtreatment and still lead to acceptable oncologic outcomes. Several analyses have shown conflicting conclusions whether adjuvant radiation therapy is favored over salvage radiation therapy (salvage radiation therapy it is typically initiated at a post-radical prostatectomy PSA level of 0.3 to 0.6 ng/mL). Clinicopathologic risk stratification is currently being used to make decisions about prostate cancer management following radical prostatectomy. Clinical characteristics (e.g. stage, biopsy Gleason grade, serum PSA, surgical margin, disease involvement) and demographic characteristics (e.g. age, life expectancy) are combined to classify men according to risk. As described previously National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) provide risk-stratification guidelines. Per the American Urological Association (AUA)/American Society of Radiation Oncology (ASTRO) and Society Urologic Oncology (SUO) 2017 guideline for clinically localized prostate cancer states, “for post-treatment follow-up, clinicians should monitor localized prostate cancer patients post therapy with PSA, even though not all PSA recurrences are associated with metastatic disease and prostate cancer specific death.” This guideline does not indicate the use of gene expression profiling or protein biomarker testing in regards to management decisions following radical prostatectomy.

 

For individuals who have high risk prostate cancer after radical prostatectomy who receive the Decipher prostate cancer classifier, the evidence includes 1 study of analytic validity, prospective and retrospective studies of clinical validity using archived samples, decision curve analyses examining indirect evidence of clinical utility, and prospective decision impact studies without pathology or clinical outcomes. The clinical validity of the Decipher genomic classifier has been evaluated in samples of patients with high risk prostate cancer undergoing different interventions following radical prostatectomy. Studies reported some incremental improvement in discrimination. However, results did not consistently demonstrate meaningful improvement in reclassification, most importantly to higher risk categories. The performance over clinicopathologic predictors did not appear consistent and meaningfully improved. Further studies are needed to determine clinical utility. There is insufficient evidence in the peer reviewed medical literature demonstrating that Decipher prostate cancer classifier has a role in clinical decision making or has a beneficial effect on health outcomes, and therefore, is considered investigational.    

 

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Prostate Cancer Version 2.2017

Molecular Testing

Several tissue based molecular assays have been developed in an effort to improve decision making in newly diagnosed men considering active surveillance and in treated men considering adjuvant therapy or treatment for recurrence. Uncertainty about the risk of disease progression can be reduced if such molecular assays can provided accurate and reproducible prognostic or predictive information beyond NCCN risk group assignment and currently available life expectancy tables and namograms. Retrospective case cohort studies have shown that these assays provide prognostic information independent of NCCN risk groups, which include likelihood of biochemical recurrence after radical management, likelihood of biochemical recurrence after radical prostatectomy or radiotherapy, and likelihood of developing metastasis after operation of salvage radiotherapy. No randomized controlled trials have studied the utility of these tests.

 

Although full assessment of their clinical utility requires prospective randomized clinical trials, which are unlikely to be done, the panel believes that men with clinically localized disease may consider the use of tumor-based molecular assays at this time. Future comparative effectiveness research may allow these tests and others like them to gain additional evidence regarding their utility for better risk stratification of men with prostate cancer.     

 

Table 1. Lists these tests in alphabetical order and provides an overview of each test, population where each test independently predicts outcomes, and supporting references (See NCCN guideline for detailed information).  Available Tissue Based Tests for Prostate Care Prognosis – includes the following:

  • Decipher
  • Oncotype DX
  • Prolaris
  • ProMark

 

American Urological Association (AUA)

In 2007, the American Urological Association issued the guideline for management of clinically localized prostate cancer which included the following:

 

Future Research Needs

The Panel has identified a number of opportunities for investment in research, clinical trials, and reporting of results that would provide the foundation for useful updates of this evidence-based guideline:

 

Determining which prostate cancers require therapy:  

  1. Markers of biological aggressiveness of prostate cancer are critical to the management of this disease with its highly variable clinical behavior in the setting of an 18% lifetime risk in the United States.
  2. These biomarkers may be constitutional, behavioral, or somatic. Valuable studies of these markers will derive from studies of patients managed with active surveillance, and it will be necessary in all other patients to factor in how treatment modulates the predictive value of these biomarkers. Additional biomarkers may prove useful to predict response to therapy.
  3. Because of the potential for significant over-detection and overtreatment of prostate cancer, integrating biomarkers of aggressiveness with early detection programs is desirable. The ideal biomarker of prostate cancer detection thus would be positive in a man with potentially aggressive disease and negative in both the man without disease and in the man with disease of very low biologic risk.
  4. An essential element for rapid validation of biomarkers of disease aggressiveness will be the validation of surrogate endpoints of disease progression. The most desirable endpoints on which to base disease aggressiveness are overall survival, metastasis-free survival, disease specific survival, and risk of disease related morbidity. Due to the time required to reach these endpoints, surrogate markers of these endpoints would accelerate the development of validated biomarkers of disease.        

In 2017, American Urological Association (AUA)/American Society of Radiation Oncology (ASTRO) and Society Urologic Oncology (SUO) issued a guideline for clinically localized prostate cancer, which states the following:

  • Active Surveillance: Tissue based genomic biomarkers have not shown a clear role in active surveillance for localized prostate cancer and are not necessary for following up. (Expert Opinion) 
  • Post-Treatment Follow-Up: Clinicians should monitor localized prostate cancer patients post therapy with PSA, even though not all PSA recurrences are associated with metastatic disease and prostate cancer specific death. (Clinical Principle)

 

Regulatory Status

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA).  Prolaris®, Oncotype DX® Prostate Cancer Assay and Decipher® gene expression profiling, and the Promark™ protein biomarker test are available under the auspices of CLIA. Laboratories that offer LDTs must be licensed by CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

 

Prior Approval:

 

Not applicable

 

Policy:

See Related Medical Policies

  • 02.04.56 Genetic and Protein Biomarkers for the Diagnosis and Cancer Risk Assessment of Prostate Cancer
  • 02.04.25 Prostate Specific Antigen Screening for Prostate Cancefr

Use of gene expression analysis and protein biomarker to guide management of prostate cancer is considered investigational in all situations. This includes but is not limited to the following:

 

Gene Expression Analysis

  • Prolaris®
  • Oncotype DX® Prostate Cancer Assay
  • Decipher®

Protein Biomarker test

  • Promark™

Based on review of the peer reviewed medical literature there is insufficient evidence demonstrating that these tests have a role in clinical decision making or have a beneficial effect on net health outcomes.  Further studies are needed to determine the clinical utility of these tests. Therefore, the use of gene expression analysis and protein biomarkers to guide management of prostate cancer is considered investigational in all situations.

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.

  • 81541 Oncology (prostate), mRNA gene expression profiling by real-time RT-PCR of 46 genes (31 content and 15 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a disease-specific mortality risk score
  • 81479 Unlisted molecular pathology procedures
  • 81599 Unlisted multianalyte assay with algorithmic analysis
  • 84999 Unlisted chemistry procedure

 

Selected References:

  • Dall'Era MA, Cooperberg MR, Chan JM, et al. Active surveillance for early-stage prostate cancer: review of the current literature. Cancer. Apr 15 2008;112(8):1650-1659. PMID 18306379
  • Brawley OW. Prostate cancer epidemiology in the United States. World J Urol. Apr 2012;30(2):195-200. PMID 22476558
  • Bangma CH, Roemeling S, Schroder FH. Overdiagnosis and overtreatment of early detected prostate cancer. World J Urol. Mar 2007;25(1):3-9. PMID 17364211
  • Johansson JE, Andren O, Andersson SO, et al. Natural history of early, localized prostate cancer. JAMA. Jun 9 2004;291(22):2713-2719. PMID 15187052
  • Ploussard G, Epstein JI, Montironi R, et al. The contemporary concept of significant versus insignificant prostate cancer. Eur Urol. Aug 2011;60(2):291-303. PMID 21601982
  • Harnden P, Naylor B, Shelley MD, et al. The clinical management of patients with a small volume of prostatic cancer on biopsy: what are the risks of progression? A systematic review and meta-analysis. Cancer. Mar 1 2008;112(5):971-981. PMID 18186496
  • Brimo F, Montironi R, Egevad L, et al. Contemporary grading for prostate cancer: implications for patient care. Eur Urol. May 2013;63(5):892-901. PMID 23092544
  • Eastham JA, Kattan MW, Fearn P, et al. Local progression among men with conservatively treated localized prostate cancer: results from the Transatlantic Prostate Group. Eur Urol. Feb 2008;53(2):347-354. PMID 17544572
  • Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. May 12 2005;352(19):1977-1984. PMID 15888698
  • Thompson IM, Jr., Goodman PJ, Tangen CM, et al. Long-term survival of participants in the prostate cancer prevention trial. N Engl J Med. Aug 15 2013;369(7):603-610. PMID 23944298
  • Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA. May 4 2005;293(17):2095-2101. PMID 15870412
  • Freedland SJ. Screening, risk assessment, and the approach to therapy in patients with prostate cancer. Cancer. Mar 15 2011;117(6):1123-1135. PMID 20960523
  • Ip S, Dahabreh IJ, Chung M, et al. An evidence review of active surveillance in men with localized prostate cancer. Evid Rep Technol Assess (Full Rep). Dec 2011;AHRQ Publication No. 12-E003-EF, Rockville, MD: Agency for Research and Quality.(204):1-341. PMID 23126653
  • Thompson I, JB T, Aus G ea. American Urological Association guideline for management of clinically localized prostate cancer 2007 update.
  • Whitson JM, Carroll PR. Active surveillance for early-stage prostate cancer: defining the triggers for intervention.J Clin Oncol. Jun 10 2010;28(17):2807-2809. PMID 20439633
  • Albertsen PC. Treatment of localized prostate cancer: when is active surveillance appropriate? Nat Rev Clin Oncol. Jul 2010;7(7):394-400. PMID 20440282
  • Wu CL, Schroeder BE, Ma XJ, et al. Development and validation of a 32-gene prognostic index for prostate cancer progression. Proc Natl Acad Sci U S A. Apr 9 2013;110(15):6121-6126. PMID 23533275
  • Spans L, Clinckemalie L, Helsen C, et al. The genomic landscape of prostate cancer. Int J Mol Sci. 2013;14(6):10822-10851. PMID 23708091
  • Schoenborn JR, Nelson P, Fang M. Genomic profiling defines subtypes of prostate cancer with the potential for therapeutic stratification. Clin Cancer Res. Aug 1 2013;19(15):4058-4066. PMID 23704282
  • Huang J, Wang JK, Sun Y. Molecular pathology of prostate cancer revealed by next-generation sequencing: opportunities for genome-based personalized therapy. Curr Opin Urol. May 2013;23(3):189-193. PMID 23385974
  • Yu YP, Song C, Tseng G, et al. Genome abnormalities precede prostate cancer and predict clinical relapse. Am J Pathol. Jun 2012;180(6):2240-2248. PMID 22569189
  • Agell L, Hernandez S, Nonell L, et al. A 12-gene expression signature is associated with aggressive histological in prostate cancer: SEC14L1 and TCEB1 genes are potential markers of progression. Am J Pathol. Nov 2012;181(5):1585-1594. PMID 23083832
  • Klein EA, Yousefi K, Haddad Z, et al. A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy. Eur Urol. Apr 2015;67(4):778-786. PMID 25466945
  • Den RB, Yousefi K, Trabulsi EJ, et al. Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy. J Clin Oncol. Mar 10 2015;33(8):944-951. PMID 25667284
  • Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Gene Expression Profiling for High-Risk Prostate Cancer Management Post-Radical Prostatectomy TEC Assessments 2015.
  • Warf MB, Reid JE, Brown KL, et al. Analytical validation of a cell cycle progression signature used as a prognostic marker in prostate cancer. J Mol Biomark Diagn. 2015;6(4).
  • Cuzick J, Stone S, Fisher G, et al. Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. Br J Cancer. Jul 28 2015;113(3):382-389. PMID 26103570
  • Cuzick J, Berney DM, Fisher G, et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer. Mar 13 2012;106(6):1095-1099. PMID 22361632
  • Pepe MS, Feng Z, Janes H, et al. Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design. J Natl Cancer Inst. Oct 15 2008;100(20):1432-1438. PMID 18840817
  • Cuzick J, Swanson GP, Fisher G, et al. Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncol. Mar 2011;12(3):245-255. PMID 21310658
  • Cooperberg MR, Simko JP, Cowan JE, et al. Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J Clin Oncol. Apr 10 2013;31(11):1428-1434. PMID 23460710
  • Bishoff JT, Freedland SJ, Gerber L, et al. Prognostic utility of the cell cycle progression score generated from biopsy in men treated with prostatectomy. J Urol. Aug 2014;192(2):409-414. PMID 24508632
  • Crawford ED, Scholz MC, Kar AJ, et al. Cell cycle progression score and treatment decisions in prostate cancer: results from an ongoing registry. Curr Med Res Opin. Jun 2014;30(6):1025-1031. PMID 24576172
  • Shore N, Concepcion R, Saltzstein D, et al. Clinical utility of a biopsy-based cell cycle gene expression assay in localized prostate cancer. Curr Med Res Opin. Apr 2014;30(4):547-553. PMID 24320750
  • Knezevic D, Goddard AD, Natraj N, et al. Analytical validation of the Oncotype DX prostate cancer assay - a clinical RT-PCR assay optimized for prostate needle biopsies. BMC Genomics. 2013;14:690. PMID 24103217
  • Klein EA, Cooperberg MR, Magi-Galluzzi C, et al. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol. Sep 2014;66(3):550-560. PMID 24836057
  • Cullen J, Rosner IL, Brand TC, et al. A Biopsy-based 17-gene Genomic Prostate Score Predicts Recurrence After Radical Prostatectomy and Adverse Surgical Pathology in a Racially Diverse Population of Men with Clinically Low- and Intermediate-risk Prostate Cancer. Eur Urol. Jul 2015;68(1):123-131. PMID 25465337
  • Badani KK, Kemeter MJ, Febbo PG. The Impact of a Biopsy Based 17-Gene Genomic Prostate Score on Treatment Recommendations in Men with Newly Diagnosed Clinically Prostate Cancer Who are Candidates For Active Surveillance. Urology Practice. 2015;2:181-189.
  • Shipitsin M, Small C, Giladi E, et al. Automated quantitative multiplex immunofluorescence in situ imaging identifies phospho-S6 and phospho-PRAS40 as predictive protein biomarkers for prostate cancer lethality. Proteome Sci. 2014;12:40. PMID 25075204
  • Blume-Jensen P, Berman DM, Rimm DL, et al. Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer. Clin Cancer Res. Jun 1 2015;21(11):2591-2600. PMID 25733599
  • Abdueva D, Wing M, Schaub B, et al. Quantitative expression profiling in formalin-fixed paraffin-embedded samples by affymetrix microarrays. J Mol Diagn. Jul 2010;12(4):409-417. PMID 20522636
  • Den RB, Feng FY, Showalter TN, et al. Genomic prostate cancer classifier predicts biochemical failure and  metastases in patients after postoperative radiation therapy. Int J Radiat Oncol Biol Phys. Aug 1 2014;89(5):1038-1046. PMID 25035207
  • Cooperberg MR, Davicioni E, Crisan A, et al. Combined value of validated clinical and genomic risk stratification tools for predicting prostate cancer mortality in a high-risk prostatectomy cohort. Eur Urol. Feb 2015;67(2):326-333. PMID 24998118
  • Ross AE, Feng FY, Ghadessi M, et al. A genomic classifier predicting metastatic disease progression in men with biochemical recurrence after prostatectomy. Prostate Cancer Prostatic Dis. Mar 2014;17(1):64-69. PMID 24145624
  • Karnes RJ, Bergstralh EJ, Davicioni E, et al. Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population. J Urol. Dec 2013;190(6):2047-2053. PMID 23770138
  • Erho N, Crisan A, Vergara IA, et al. Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One. 2013;8(6):e66855. PMID 23826159
  • Ross AE, Johnson MH, Yousefi K, et al. Tissue-based Genomics Augments Post-prostatectomy Risk Stratification in a Natural History Cohort of Intermediate- and High-Risk Men. Eur Urol. Jun 6 2015. PMID 26058959
  • Michalopoulos SN, Kella N, Payne R, et al. Influence of a genomic classifier on post-operative treatment decisions in high-risk prostate cancer patients: results from the PRO-ACT study. Curr Med Res Opin. Aug 2014;30(8):1547-1556. PMID 24803160
  • Thompson IM, Valicenti RK, Albertsen P, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. J Urol. Aug 2013;190(2):441-449. PMID 23707439
  • Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst. Nov 4 2009;101(21):1446-1452. PMID 19815849
  • Cooperberg M, Sinko J, Cowan J. et. al. Validation of Cell-Cycle Progression Gene Panel to Improve Risk Stratification in a Contemporary Prostatectomy Cohort. Journal of Clinical Oncology Volume 31 Number 11 April 10 2013
  • Shipitsin M, Small C, Choudhury S. et. al. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error. British Journal of Cancer 2014 111. 1201-1212
  • National Comprehensive Cancer Network (NCCN) Version 2.2016 Prostate Cancer
  • Prolaris Prostate Cancer Testing (Myriad Genetics).
  • Oncotype DX Prostate Cancer Assay (Genomic Health).
  • ProMark Protein Biomarker Metamark Genetics). 
  • Decipher (GenomeDX Biosciences).
  • Sanda M, Chen R, Crispino T, et. al. Clinically Localized Prostate Cancer AUA/ASTRO/SUO Guideline. April 2017
  • American Cancer Society. Key Statistics for Prostate Cancer. January 2017.
  • ECRI. Technology Trend News. Half of Laboratory-Developed Tests on FDA’s Hit List are for Cancer. Published December 2015.
  • UpToDate. Molecular Prognostic Tests for Prostate Cancer. Ashely Ross M.D., PhD, Anthony V D’Amico M.D., PhD, Stephen Freeland M.D. Topic last updated April 20, 2017.
  • Hamdy FC, Donovan JL, Lane JA, et. al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 2016 Oct 13;375(15):1415-1424. PMID 27626136
  • Sommariva S, Tarricone R, Lazzeri M, et. al. Prognostic value of the cell cycle progression score in patients with prostate cancer: a systematic review and meta-analysis. Eur Urol 2016 Jan 69(1):107-15. PMID 25481455
  • Shore ND, Kella N, Moran B, et. al. Impact of the cell cycle progression test on physician and patient treatment selection for localized prostate cancer. J Urol 2016 Mar 195(3):612-8. PMID 26403586
  • Brand TC, Zhang N, Crager MR, et. al. Patient-specific meta-analysis of 2 clinical validation studies to predict pathologic outcomes in prostate cancer using the 17 gene genomic prostate score. PMID 26723180
  • Koch MO, Cho JS, Kaimakliotis HZ, et. al. Use of the cell cycle progression (CCP) score for predicting systemic disease and response to radiation of biochemical recurrence. Cancer Biomark 2016 Jun 7;17(1):83-8. PMID 27314296
  • Klein EA, Yousefi K, Haddad Z, et. al. A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy. PMID 25466945
  • Freeland SJ, Choeumg V, Howard L, et. al. Utilization of a genomic classifier for prediction of metastasis following salvage radiation therapy after radical prostatectomy. Eur Urol 2016 Oct;70(4):588-596. PMID 26806658
  • Glass AG, Leo MC, Haddad Z, et.al. Validation of a genomic classifier for predicting post-prostatectomy recurrence in a community based health care setting. J Urol 2016 Jun;195(6):1748-53. PMID 26626216
  • Klein EA, Haddad Z, Yousefi K, et. al. Decipher genomic classifier measured on prostate biopsy predicts metastasis risk. Urology 2016 Apr 90:148-52. PMID 26809071
  • Lobo JM, Dicker AP, Buerki C, et.al. Evaluating the clinical impact of a genomic classifier in prostate cancer using individualized decision analysis. PLoS One 2015 Apr 2;10(3):e0116866. PMID 25837660
  • Nguyen PL, Shin H, Yousefi K, et. al. Impact of a genomic classifier of metastatic risk on post-prostatectomy treatment recommendations by radiation oncologists and urologists. Urology 2015 Jul;86(1):35-40. PMID 26142578
  • Badani KK, Thompson DJ, Brown G, et. al. Effect of genomic classifer test on clinical practice decision for patients with high risk prostate cancer after surgery. BJU Int 2015 Mar;115(3):419-29. PMID 24784420
  • Ross AE, Den RB, Yousefi K, et. al. Efficacy of post-operative radiation in prostatectomy cohort adjusted for clinical and genomic risk. Prostate Cancer Prostatic Dis 2016 Sep;19(3):277-82. PMID 27136742
  • Yamoah K, Johnson MH, Choeurng V, et. al. Novel biomarker signature that may predict aggressive disease in African American men with prostate cancer. J Clin Oncol 2015 Sep 1;33(25):2789-96. PMID 26195723
  • Whalen M, Hackert V, Rothberg M, et. al. Prospective correlation between likelihood of favorable pathology on the 17 gene genomic prostate score and actual pathological outcomes at radical prostatectomy. Urology Practice September 2016 Volume 3, Issue 5, Pages 379-386
  • Dall’Era M, Maddala T, Polychronopoulos L, et. al. Utility of the Oncotype DX Prostate Cancer Assay in clinical practice for treatment selection in men newly diagnosed with prostate cancer: A retrospective chart review analysis. Urology Practice November 2015 Volume 2,Issue 6,Pages 343-348

 

Policy History:

  • May 2017 - Annual Review, Policy Revised
  • June 2016 - New medical policy

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.