Latest Review Date: May 2024

Category: Laboratory

POLICY:

Analysis of proteomic patterns in serum to identify cancer is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

The analysis of proteomic patterns in serum for early detection of cancer has been proposed. Several of these proteomic tests are being studied, particularly in ovarian and prostate cancer.

Proteomics involves the use of mass spectrometry to study differences in patterns of protein expression. Proteomic patterns are patterns of proteins present within a clinical sample used as a diagnostic “fingerprint” that is proposed to provide an early diagnosis for some types of cancer.

KEY POINTS:

The most recent literature update was performed through May 2, 2024.

Summary of Evidence

While patterns of protein expression have been proposed to yield more biologically relevant and clinically useful information than assays of single proteins, many limitations in the use of proteomics exist. In contrast to genomics, in which amplification techniques like polymerase chain reaction (PCR) allow for the investigation of single cells, no technology is available at the protein level. Other issues between studies have been lack of uniform patient inclusion and exclusion criteria, small patient numbers, absence of standardized sample preparations, and limited analytical reproducibility. Data in the peer-reviewed literature are inadequate to permit scientific conclusions regarding ovarian, prostate, or other malignancies. The utility of this technology is unproven and is considered investigational.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Guidelines

NCCN guidelines for the common cancers addressed in this policy do not comment on the use of proteomics.

U.S. Preventative Services Task Force

Not applicable.

KEY WORDS:

Proteomics, ovarian cancer, OvaCheck™, Correlogic Systems, ProstaCheck, MammoCheck, NovellusDX, Vermillion

APPROVED BY GOVERNING BODIES:

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing. To date, the U.S. Food and Drug administration has chosen not to require any regulatory review of this test.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan. 

CURRENT CODING:

CPT Codes:

There is no specific code for this type of testing. One of the following codes might be used to report the test:

REFERENCES:

1. Bast RC Jr, Brewer M, Zou C, et al. Prevention and early detection of ovarian cancer: Mission impossible? Recent Results Cancer Res 2007; 174: 91-100.
2. Belluco C, Petricoin EF, Mammano E, et al. Serum proteomic analysis identifies a highly sensitive and specific discriminatory pattern in stage 1 breast cancer. Ann Surg Oncol, September 2007; 14(9): 2470-2476.
3. Conrads TP, Fusaro VA, Ross S et al. High-resolution serum proteomic features for ovarian cancer detection. Endocr Relat Cancer 2004; 11(2):163-78.
4. Conrads TP, Veenstra TD. The utility of proteomic patterns for the diagnosis of cancer. Curr Drug Targets Immune Endocr Metabol Disord 2004; 4(1): 41-50.
5. Conrads, T., Zhou, M., Petricoin, E., Liotta, L., & Veenstra, T. (2003). Cancer diagnosis using proteomic patterns. Expert Review in Molecular Diagnostics, 3(4), 411-421.
6. Cristea IM, Gaskell SJ, Whetton AD. Proteomics techniques and their application to hematology. Blood 2004; 103(10): 3624-34.
7. Diamandis EP. Analysis of serum proteomic patterns for early cancer diagnosis: drawing attention to potential problems, J Natl Cancer Inst 2004; 96(5): 353-6.
8. Dziadziuszko R and Hirsch FR. Advances in genomic and proteomic studies of non-small-cell lung cancer: clinical and translational research perspective. Clin Lung Cancer, March 2008; 9(2): 78-84.
9. Garrisi VM, Abbate I, Quaranta M, et al. SELDI-TOF serum proteomics and breast cancer: Which perspective? Expert Rev Proteomics 2008; 5(6): 779-785.
10. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
11. Leman ES, Schoen RE, Weissfeld JL, et al. Initial analyses of colon cancer-Specific antigen (CCSA)-3 and CCSA-4 as colorectal cancer-Associated serum markers. Cancer Res 2007; 67(12): 5600-5605.
12. Li J, Zhuang Z, Okamoto H et.al. Proteomic profiling distinguishes astrocytomas and identifies differential tumor markers. Neurology 2006; 66(5):733-6.
13. Lifshitz K, Ber Y, Shenhar C, et al. Cardiovascular Proteomics: A Post Hoc Analysis from a Phase II Randomized Clinical Trial Comparing GnRH Antagonist vs GnRH Agonist among Men with Advanced Prostate Cancer. J Urol. 2021;206(4):952-959.
14. Lim, L., Looi, M., Zakaria, S., Sagap, I., Rose, I., Chin, S., et al. (2016). Identification of differentially expressed proteins in the serum of colorectal cancer patients using 2D-DIGE proteomics analysis. Pathology Oncology Research, 22, 169-177.
15. Lin Y, Dynan WS, Lee JR, et al. The current state of proteomics in GI oncology. Dig Dis Sci, March 2009; 54(3): 431-457.
16. Lomnytska M and Souchelnytskyi S. Markers of breast and gynecological malignancies: The clinical approach of proteomics-based studies. Proteomics – Clinical Applications, REVIEWS 2007, Vol. 1, Issue 9, pp. 1090-1101.
17. McLerran D, Grizzle WE, Feng Z, et al. SELDI-TOF MS whole serum proteomic profiling with IMAC surface does not reliably detect prostate cancer. Clin Chem 2008; 54(1): 53-60.
18. Ornstein DK, Rayford W, Fusaro VA et al. Serum proteomic profiling can discriminate prostate cancer from benign prostates in men with total prostate specific antigen levels between 2.5 and 15.0 ng/ml. J Urol 2004; 172(4 pt 1):1302-5.
19. Petricoin EF, Ardekani AM, Hit, BE, et al. Use of proteomic patterns in serum to identify ovarian cancer, Lancet 2002; 359(9306): 572-7.
20. Shao, S., Neely, B. A., Kao, T. C., Eckhaus, J., Bourgeois, J., Brooks, J., et al. (2016). Proteomic profiling of serial pre-diagnostic serum samples for early detection of colon cancer in the U. S. military. Cancer Epidemiology Biomarkers Prevention, 2016, Epub ahead of print. Abstract retrieved February 2, 2017 from PubMed database.
21. Tanase, C., Albulescu, R., Codrici, E., Popescu, D., Mihai, S., Enciu, A., et al. (2015) Circulating biomarker panels for targeted therapy in brain tumors. Future Oncology, 11 (3), 511-524.
22. Unwin RD and Whetton AD. How will haematologists use proteomics? Blood Rev, November 2007; 21(6): 315-326.
23. Van Gorp T, Cadron I, Vergote I. The utility of proteomics in gynecologic cancers. Curr Opin Obstet Gynecol, 2011 Feb; 23(1):3-7.
24. Xu, Y., Zhuo, J., Duan, Y., Shi, B., Chen, X. Zhang, X., et al., (2014). Construction of protein profile classification model and screening of proteomic signature of acute leukemia. International Journal of Clinical Expert Pathology, 7 (9), 5569-5581.

POLICY HISTORY:

Medical Policy Group, November 2006 (4)

Medical Policy Administration Committee, November 2006

Available for comment November 18, 2006-January 2, 2007

Medical Policy Group, November 2007 (1) Update with literature search, no new references added; no change to policy statement

Medical Policy Group, March 2009 (1) Update with literature search, no new references added; no change to policy statement

Medical Policy Group, March 2010 (1) Update to Key Points and References; no change to policy statement

Medical Policy Group, July 2011 (1) Update to Key Points and References; no change to policy statement

Medical Policy Panel, July 2012

Medical Policy Group, July 2012 (1) Update with literature search, no new references added; no change to policy statement

Medical Policy Panel, August 2013

Medical Policy Group, August 2013 (1) Update with literature search, no new references added; update to Key Words with addition of mammocheck, prostacheck and novellusDX; no change to policy statement. Effective 08/29/2013: Active Policy but no longer scheduled for regular literature reviews and updates.

Medical Policy Group, November 2015: 2016 Annual Coding Update. Created Previous Coding section and moved CPT code 83788 from current coding to previous coding.

Medical Policy Group, August 2016 (3): Added Xpresys® Lung information to policy.

Medical Policy Group, June 2017 (3): Removed information related to Xpresys® Lung from Key Points, Key Words & References and placed in new medical policy # 644 Molecular Testing in the Management of Pulmonary Nodules; this policy (#176) remains retired

Medical Policy Group, June 2019 (9): Update to Key Points, Description, References. Added key word: Vermillion. No change to policy statement.

Medical Policy Group, May 2021 (9): Update to Key Points, Description, References. Policy statement updated to remove “not medically necessary,” no change to policy intent.  Removed previous coding section that includes CPT code 83788.

Medical Policy Group, October 2021 (9): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, May 2022 (9): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, May 2023 (5): Reviewed by consensus. Minor updates to Key Points and Benefit Application. No change to Policy Statement. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, May 2024 (5): Reviewed by consensus. Minor updates to Key Points and References. No change to Policy Statement. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.