CurrentKaiser PermanentePolicy N/A

Clinical Review Criteria 4Kscore@ Test: Predicting the Risk of Aggressive Prostate Cancer

Clinical review criteria for the 4Kscore (four kallikrein marker) blood test to predict risk of high-grade/aggressive prostate cancer for Kaiser Foundation Health Plan of Washington members; includes Medicare and non-Medicare guidance, background, evidence appraisal, and code-level coverage determination.

Policy Summary

PayerKaiser Permanente

PolicyClinical Review Criteria 4Kscore@ Test: Predicting the Risk of Aggressive Prostate Cancer

Policy CodePolicy N/A

Change TypeAdministrative/coding revisions

Effective Date

Next Review Date

Key ActionIf requesting review, submit the last 6 months of clinical notes from the requesting provider and/or specialist.

POLICY UPDATE CHANGES

Removed Medicare LCD L37122 (retired 6/12/22) and LCA A57337 and added KPWA Medical Policy statement under Medicare section.

Added Medicare instructions and CPT code 81539 on 10/10/2017; subsequent removals and edits noted in revision history.

No material clinical or coverage changes identified in this update.

1CPT codes listed as not medically necessary

InsufficientEvidence for clinical utility

Coverage Summary

Scope: Clinical review criteria for the 4Kscore Test — a blood-based four kallikrein marker panel to predict risk of high-grade/aggressive prostate cancer for Kaiser Foundation Health Plan of Washington members, including Medicare and non‑Medicare guidance.

Coverage Determination and Documentation Requirements

Coverage Determination

Considered Not Medically Necessary:

Coverage Determination: 4Kscore Test (assay of four proteins: Total PSA, Free PSA, Intact PSA, and human kallikrein-2 [hK2]) reported as a probability score is considered Not Medically Necessary.

Applies to Kaiser Foundation Health Plan of Washington and Kaiser Foundation Health Plan of Washington Options, Inc. Use Non-Medicare criteria for Medicare members due to absence of active NCD/LCD guidance.

Documentation required if requesting review

Documentation required if requesting review: Provide last 6 months of clinical notes from requesting provider and/or specialist.

Not Medically Necessary / Coverage Stance

MTAC rationale for noncoverage: MTAC found fair evidence that the 4Kscore improves predictive accuracy over total PSA in mainly white men with PSA ≥3 ng/mL, but predictive accuracy alone does not demonstrate clinical benefit.

Evidence summary: The committee identified prospective and validation studies (including ProtecT and a multi‑institutional US prospective trial) and meta-analyses showing improved discrimination, but no randomized trials demonstrating that use of the 4Kscore changes management in ways that improve patient outcomes. Consequently, there is insufficient evidence of clinical utility or therapeutic impact, and the test does not meet Kaiser Permanente MTAC criteria.

- Medicare determinations: No active National Coverage Determination (NCD) — Kaiser uses its own Clinical Review Criteria for Medicare members in the absence of active NCD/LCD guidance.

- Retired Medicare guidance: LCD L37122 — retired 2022-06-12.

- Retired Local Coverage Article: A57337 — retired 2022-06-12.

Provider Actions and Billing Impact

Documentation Required

Submit clinical notes for review

If requesting review for this service, please send the last 6 months of clinical notes from the requesting provider and/or specialist.

Provide last 6 months of clinical notes.

Prior Authorization

Verify authorization requirements

Verify authorization requirements for a specific code by plan type using the Pre-authorization Code Check.

Affected code: 81539

Denial Risk

Test considered not medically necessary

Claims for the 4Kscore test (CPT 81539) are considered Not Medically Necessary and are subject to non-coverage.

CPT 81539 is subject to non-coverage

Background and Evidence

Background: The 4Kscore test measures four kallikrein protein biomarkers (total PSA, free PSA, intact PSA, and hK2) plus clinical information (age, +/- DRE) to generate a probability score for high‑grade prostate cancer; MTAC reviewed validation studies and concluded that while the test can improve predictive accuracy in certain cohorts, it lacks evidence of clinical utility.

Evidence (MTAC conclusion and key studies):

• MTAC conclusion: Fair evidence of improved predictive accuracy in mainly white men with PSA ≥3 ng/mL; insufficient evidence of clinical utility or therapeutic impact.

• Key studies: Validation and cohort analyses cited include the ProtecT study (J Natl Cancer Inst 2015), a multi‑institutional US prospective trial (Eur Urol 2015), and other validation/meta‑analyses (Voigt, Parekh, Vickers, Konety) showing improved discrimination versus PSA alone but no randomized trials demonstrating outcome benefit.

Definitions

4Kscore TestA blood-based test measuring four kallikrein markers (total PSA, free PSA, intact PSA, hK2) combined with clinical factors to produce a probability score for high-grade prostate cancer.

Revision History

03/21/2016initial

MTAC review and creation of clinical review criteria; 4Kscore test evaluated and considered Not Medically Necessary; Criteria created and MTAC review noted.

04/05/2016administrative

Criteria created; added MTAC review to the document (revision history entry).

02/07/2017administrative

Medicare is silent; MPC approved to adopt GHC criteria for Medicare members (revision history entry).

10/10/2017coding

Added Medicare instructions and CPT code 81539 to the document (revision history entry).

08/08/2018administrative

Removed OO1OM from Medicare instructions (revision history entry).

09/01/2020administrative

Added Medicare LCD L37122 and Local Coverage Article A57337; removed KPWA Medical Policy statement under Medicare section (revision history entry).

09/16/2022revisedLatest

Revision per revision history: Removed Medicare LCD L37122 (retired 6/12/22) and LCA A57337 (retired 6/12/22) and added KPWA Medical Policy statement under Medicare section.

2016-2024administrative/coding_updatesLatest

Revision history documents administrative and coding updates between 2016 and 2024, including additions and removals of Medicare instructions, codes (e.g., CPT 81539), LCDs and LCAs.