Appeal type: Experimental/Investigational
Decision: Upheld

This is a male patient who was diagnosed with stage T1c Gleason's grade 3+4 adenocarcinoma of the prostate involving 1 out of 12 core biopsies. Prior to his biopsy he had a prostate specific antigen (PSA) of 5.0 ng/ml. A  Oncotype DX GPS test was performed. 

The scientific evidence in peer-reviewed literature does not support a result of improvement in health outcome.  The peer-reviewed literature has not confirmed that Oncotype DX Prostate Cancer Assay results in any health benefit or outcome. 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 six 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.
	
National Comprehensive Cancer Network (NCCN) guidelines for prostate cancer 2019 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"

The NCCN Guidelines for prostate cancer active surveillance includes recommendations for prostate biopsy at specific intervals.  For active surveillance and observation for individuals with clinically localized prostate cancers who are candidates for definitive treatment, follow-up should include:
 
1) 	Needle biopsy of the prostate should be repeated within 6 months of diagnosis if initial biopsy was < 10 cores or assessment discordant (eg, palpable tumor contralateral to side of positive biopsy. 
2) 	A repeat prostate biopsy should be considered if prostate exam changes or PSA increases, but neither parameter is very reliable for detecting prostate cancer progression. 
3) 	A repeat prostate biopsy should be considered as often as annually to assess for disease progression. 
4)  	Repeat prostate biopsies are not indicated when life expectancy is less than 10 years or appropriate when men are on observation." 

While Oncotype Dx may eventually have a role in making treatment decision about patients with prostate cancer, there is limited data on clinical outcomes to currently support routine use.     

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