Latest Review Date: August 2024

Category: Laboratory             

POLICY:

Use of tests utilizing systems pathology that include cellular and biologic features of a tumor are considered investigational, including use in predicting risk of recurrence in individuals with prostate cancer.

DESCRIPTION OF PROCEDURE OR SERVICE:

Predicting risk of recurrence in patients undergoing treatment for prostate cancer is difficult, as it is for most malignancies. Over time, risk models for patients with prostate cancer have evolved from early efforts that relied on grade, stage, and prostate-specific antigen (PSA) levels to complex multivariate models, such as “systems pathology”.

Systems pathology is an approach that combines cellular and biologic features to standard clinical parameters such as age, clinical or pathologic stage, grade, percent of cancer on biopsy cores, and prostate-specific antigen (PSA) or its derivatives. Systems pathology is proposed as a way to estimate the probability of disease progression, either prior to or following prostatectomy.

KEY POINTS:

The policy was last updated with review of literature performed August 23, 2024.

Summary of Evidence

There is a paucity of evidence demonstrating the clinical utility of the use of systems pathology testing. Studies are needed to determine which patients may benefit from this testing, as well as to determine when in the course of diagnosis and treatment the systems pathology assessment should be performed. There also should be further discussion about which outcomes are the best to be used in developing models; there can be substantial differences in models that predict PSA recurrence from those that predict metastatic disease and those that predict death. In addition, models may be needed that evaluate risk following treatments other than radical prostatectomy.

The value of using the systems pathology approach to determine risk is not known based on currently available studies. The impact on net health outcomes is not known and the clinical utility of this testing is not known. The evidence is insufficient to determine the effects of the technology on net health outcomes.

Practice Guidelines and Position Statements

No practice guidelines or position statements are identified.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Prostate Cancer, Progression Prediction, Predicting Recurrence Risk, Systems Pathology, Quantitative Nuclear Morphometry, Prostate, Aureon, Post-op Px, Prostate Px, Prostate Px+, Nadia ProsVue

APPROVED BY GOVERNING BODIES:

Iris Molecular Diagnostics offers the NADiA® ProsVue™ test, which has received FDA 510(k) clearance (k101185). NADiA® ProsVue™ is intended to be used in conjunction with Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument (k082562) and the ProsVue Software.

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:  Special benefits may apply. Refer to member’s benefit plan.

CURRENT CODING: 

CPT Codes:

There is no specific CPT code for this test. Various combinations of the following codes may be used to report this testing:

REFERENCES:

1. Cordon-Cardo C, Kotsianti A, Verbel DA, et al.  Improved prediction of prostate cancer recurrence through systems pathology.  J Clin Invest 2007; 117(7):1876-83.
2. Donovan MJ, Hamann S, Clayton M, et al.  Systems pathology approach for the prediction of prostate cancer progression after radical prostatectomy.  J Clin Oncol 2008; 26(24):3923-9.
3. Donovan MJ, Khan FM, Bayer-Zubek V et al. A systems-based modelling approach using transurethral resection of the prostate (TURP) specimens yielded incremental prognostic significance to Gleason when predicting long-term outcome in men with localized prostate cancer. BJU Int 2012; 109(2):207-13.
4. Donovan MJ, Khan FM, Fernandez G, et al.  Personalized prediction of tumor response and cancer progression on prostate needle biopsy.  J Urol 2009; 182(1):125-32.
5. Donovan MJ, Khan FM, Powell D et al. Postoperative systems models more accurately predict risk of significant disease progression than standard risk groups and a 10-year postoperative nomogram: potential impact on the receipt of adjuvant therapy after surgery. BJU Int 2012; 109(1):40-5.
6. Donovan MJ, Osman I, Khan FM. Androgen receptor expression is associated with prostate cancer-specific survival in castrate patients with metastatic disease. BJU Int 2010; 105(4):462-7.
7. Eggener SE, Vickers AJ, Serio AM, et al.  Comparison of models to predict clinical failure after radical prostatectomy.  Cancer 2009; 115(2):303-10.
8. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
9. Klein EA, Stephenson AJ, Raghavan D, et al.  Systems pathology and predicting outcome after radical prostatectomy.  J Clin Oncol 2008; 26(24):3916-7.
10. Moul JW, Chen DY, Trabulsi EJ, et al. Impact of NADiA ProsVue PSA slope on secondary treatment decisions after radical prostatectomy. Prostate Cancer Prostatic Dis. Sep 2014; 17(3):280-285.
11. Moul JW, Lilja H, Semmes OJ et al. NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy. Urology 2012; 80(6):1319-25.
12. Moul JW, Sarno MJ, McDermed JE, et al. NADiA ProsVue prostate-specific antigen slope, CAPRA-S, and prostate cancer--specific survival after radical prostatectomy. Urology. Dec 2014; 84(6):1427-1432.
13. Shariat SF, Karakiewicz PI, Margulis V, et al.  Inventory of prostate cancer predictive tools.  Curr Opin Urol 2008; 18(3):279-96.
14. Veltri RW, Miller MC, Isharwal S, et al.  Prediction of prostate-specific antigen recurrence in men with long-term follow-up post prostatectomy using quantitative nuclear morphometry.  Cancer Epidemiol Biomarkers Prev 2008; 17(1):102-10.

POLICY HISTORY:

Medical Policy Group, April 2010 (3)

Medical Policy Administration Committee May 2010

Available for comment May 7-June 21, 2010

Medical Policy Group, August 2011 (1): Update to Key Points and References; No changes to intent of policy statement (“uses” changed to “include” to improve clarity)

Medical Policy Group, December 2011 (1): 2012 Code Updates – verbiage change to code 88313

Medical Policy Group, June 2012 (3): New FDA approved Drug-Nadia ProsVue; Updated Description, Key Words, and Approved by Governing Bodies

Medical Policy Panel, March 2013

Medical Policy Group, April 2013 (3): 2013 Updates to Key Points & References; no change in policy statement

Medical Policy Panel, March 2014

Medical Policy Group, March 2014 (1): Update to Description, Key Points and References; change to Title with removal of “for predicting risk of recurrence”; no change to policy statement

Medical Policy Panel, March 2015

Medical Policy Group, March 2015 (3): Updates to Key Points and References.  No change to policy statement.

Medical Policy Group, November 2015: 2016 Annual Coding Update. Added CPT code 88345 and new CPT code 88350 to the current coding section.  Created a new previous coding section and moved CPT code 88347 from current coding to previous coding.

Medical Policy Panel, January 2016

Medical Policy Group, January 2016 (3): Updates to Key Points. No change to policy statement.  Effective January 28, 2016: Active policy but no longer scheduled for regular updates.

Medical Policy Panel, August 2019

Medical Policy Group, August 2019 (9): Updates to Key Points. No change to policy statement. Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, August 2021 (2): Updates to Key Points. Policy statement updated to remove "not medically necessary", no change in intent. Previous coding section removed. Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, July 2022 (9): Reviewed by consensus. References added. No new published peer-reviewed literature available that would alter the coverage statement in this policy. Updates to Key Points, Description.

Medical Policy Group, August 2023 (5): Updates to Key Points and Benefit Application. Policy Statement updated to replace the word “patients” with the word “individuals.” No change to policy intent. Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, August 2024 (5): Minor update to Key Points.  Reviewed by consensus. 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.