How is Oncotype Dx (Genomic Prostate Score) used in the management of prostate cancer?

Use of Oncotype DX in Prostate Cancer Management

Oncotype DX (Genomic Prostate Score) should not be routinely used for risk stratification in prostate cancer management but may be selectively used when additional risk stratification could alter clinical decision-making. 1

Overview of Oncotype DX in Prostate Cancer

Oncotype DX Prostate is a commercially available 17-gene expression assay that:

• Generates a Genomic Prostate Score (GPS) ranging from 0 to 100 based on mRNA expression of genes across four biological pathways 1
• Requires tumor tissue from original prostate biopsy in neutral buffered formalin (prostatectomy specimens are not accepted) 1
• Has been validated on needle biopsy tissue and found to be associated with adverse pathology, biochemical recurrence, metastasis, and prostate cancer death 1
• Costs approximately $4,520 (as of 2019) 1

Clinical Applications

Appropriate Clinical Scenarios for Use

Oncotype DX may be selectively used in specific clinical scenarios:

• Patients with high-volume (multiple involved cores) Gleason score 6 (Grade Group 1) cancer who are considering active surveillance 1
• Select men with favorable intermediate-risk prostate cancer who are interested in active surveillance 1
• When the test result, considered together with routine clinical factors, might affect management decisions 1

Inappropriate Clinical Scenarios for Use

Oncotype DX is not recommended for:

• Routine risk stratification in all prostate cancer patients 1
• The majority of men with low-volume (few involved cores) Gleason score 6 cancer 1
• Men with favorable intermediate-risk prostate cancer who have already decided on definitive treatment 1

Evidence on Clinical Utility

Impact on Treatment Decisions

• A retrospective chart review showed that Oncotype DX testing was associated with a 56% relative increase in the use of active surveillance (from 43% to 67%) 2
• However, a more recent randomized controlled trial found that GPS testing reduced urologists' likelihood to prefer active surveillance, with urologists' preference for prostatectomy/radiation almost doubling in the GPS arm compared to the control arm (29.3% vs. 14.1%) 3

Predictive Value

• The GPS has been shown to be significantly associated with adverse pathology after radical prostatectomy, specifically extraprostatic extension and seminal vesicle invasion 4
• However, in the Canary Prostate Active Surveillance Study cohort, GPS was not independently associated with adverse pathology when adjusted for PSA density and diagnostic Grade Group, and showed no association with upgrading in surveillance biopsy 5

Integration with Standard Risk Assessment

• Standard risk assessment should primarily rely on clinical T stage, serum PSA, Grade Group (Gleason score), and tumor volume on biopsy 1
• Oncotype DX should be considered as a supplementary tool rather than a replacement for standard clinical parameters 1
• When used, Oncotype DX results should be interpreted in conjunction with established clinical risk factors 1

Limitations and Caveats

• There are currently no comparative data indicating whether Oncotype DX is more accurate than other genomic tests (Decipher, Prolaris, ProMark) 1
• Limited data supports the specific risk thresholds provided on the individual testing reports 1
• The ability of Oncotype DX to improve long-term outcomes (quality of life, risk of metastasis, or death) has not been prospectively evaluated 1
• The test requires as little as 5 ng of RNA from prostate needle biopsies, which can be obtained from as little as 1 mm of tumor tissue 6

Summary of Recommendations

• Use standard clinical parameters (T stage, PSA, Grade Group, tumor volume) as the primary risk stratification tools 1
• Consider Oncotype DX selectively when additional risk information might alter management decisions 1
• Do not use Oncotype DX routinely for all patients with prostate cancer 1
• When used, interpret Oncotype DX results in the context of established clinical risk factors 1