Appeal type: Experimental/Investigational
Decision: Upheld

This is a male patient who underwent a prostate biopsy due to an elevated prostate specific antigen (PSA) which revealed Gleason 7 adenocarcinoma 1 out of 12 cores. A Oncotype Dx test was performed on the biopsy specimens.

The Oncotype DX Prostate Cancer Assay is a real time polymerase chain reaction (RT-PCR) assay designed for analysis of prostate core needle biopsies.  The assay measures the expression of 17 genes to calculate a Genomic Prostate Score (GPS).  A lower GPS score more favorable biology and less aggressive disease.  This test may be utilized to counsel men regarding the best course of therapy (active surveillance vs. treatment) in newly diagnosed low or low-intermediate prostate cancer.

Two recent studies have suggested that Oncotype Dx can predict adverse pathology and unfavorable outcomes after radical prostatectomy.  In both these studies, multiple authors are either employed by the manufacturer of the test or have a financial interest.  These studies are recently published and need continued validation from a widespread clinical use.  In addition, it is difficult to ascribe clinical utility of Oncotype Dx Prostate in patients planning to undergo active surveillance as all patients in the above studies, regardless of clinical criteria, elected radical prostatectomy within 6 months of diagnostic biopsy.  Moreover, the validity of using different degrees of tumor pathology as "markers" to extrapolate the risk of progression of a tumor in vivo is unclear. 

NCCN Guidelines for prostate cancer 2018 states," 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. Retrospective case cohort studies have shown that these assays provide prognostic information independent of NCCN risk groups, which include likelihood of death with conservative management, likelihood of biochemical recurrence after radical prostatectomy or radiotherapy, and likelihood of developing metastasis after operation or salvage radiotherapy. No randomized controlled trials have studied the utility of these tests.  These molecular biomarker tests have been developed with extensive industry support, guidance, and involvement, and have been marketed under the less rigorous FDA regulatory pathway for biomarkers.  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."

An assessment by Adelaide Health Technology Assessment (Ellery, et al., 2014) concluded that "there is uncertainty about the clinical utility" of the Oncotype Dx Prostate and the Prolaris tests,"even when taking into account the highest level of evidence available" The assessment stated that it remains to be verified whether genetic expression of the unique gene panels involved are robust to heterogeneous sampling of prostate tissue at the time of biopsy.  Also, the need for tissue which has previously been fixed for histological analysis is of some concern.  The assessment observed that this is the most obvious reason for the relatively high number of patients for whom a valid test results could not be obtained.      

The carrier's denial of coverage for genetic testing for prostate cancer should be upheld.