Prostate Cancer Gene Expression Testing at UCSF
A major challenge in tailoring prostate cancer care is identifying men who require immediate or aggressive treatment and those who possess prostate cancers that can safely be surveyed. Several prediction tools have been developed and tested at UCSF including the CAPRA, and CAPRA-S scores. Recently, several commercially available genetic tests taken from an individual’s prostate cancer tissue have become available that may assist urologists and patients in clinical decision making. UCSF Department of Urology has collaborated with Genomic Health, Inc and Myriad Genetics to evaluate genomic biomarkers, as well as conducted several independent studies of these markers.
Tests prior to treatment
Two biopsy based tests of prostate cancer tissue have received clinical study and are commercially available: the OncotypeDX GPS and Prolaris assays. The Oncotype DX® test was developed by Genomic Health, Inc that analyzes tissue samples obtained at the time of diagnosis from the portion of a prostate biopsy containing cancer. The Oncotype® test was developed by studying 727 genes believed to be involved in the development of prostate cancer. These were ultimately refined to a “signature” of 17 genes that are associated with a likelihood of having high grade (Gleason pattern 4) and/or high stage (pathologic T-stage 3, or cancer extending out of the prostate) if the prostate is removed and examined. In studies performed at UCSF, this 17-gene signature was a reliable and helpful tool in assessing candidates for treatment or active surveillance without re-sampling or removing the entire prostate.
This “tissue-based” test requires no additional biopsy because the specimen is taken from an individual’s existing biopsy, and can generate a result from as little as 1mm of cancerous tissue. OncotypeDX® yields a Genomic Prostate Score (GPS), on a scale of 1-100, where higher scores are more suggestive of adverse pathology. It is important to remember that a GPS score is a measurement of gene expression within prostate tumors and must be interpreted within the context of other relevant clinical factors.
The Prolaris®is a genomic test developed by Myriad Genetics that examines the expression of 31 genes involved in cell-cycle progression (CCP), an important regulatory step in the development of cancer. A study examining the Prolaris panel in prostate biopsy specimens from 582 men with prostate cancer demonstrated that the test was a very strong predictor of later clinical outcomes including disease recurrence and progression to metastasis following surgery. The Prolaris test generates a score in the range of -3 to +3 that is based on gene expression levels; higher scores corresponds to increasing probability of adverse events following treatment.
Are biopsy-based tests for me?
In a UCSF study of 395 men diagnosed with low or intermediate risk prostate cancer (based on age, PSA, clinical stage, Gleason score on biopsy), OncotypeDX® was performed at Genomic Health labs and compared with findings at surgery. This validation trial suggested that OncotypeDX® GPS was a strong and independent predictor of findings at surgery. This significant finding has led some prostate cancer experts to incorporate this tissue based test into decision making for patients considering active surveillance. Further studies are ongoing at UCSF and other institutions, and will hopefully provide insight into the value of this test in the context of men diagnosed with low risk prostate cancer.
Tests after surgical removal of the prostate
In the United States, approximately one half of men diagnosed with prostate cancer will undergo treatment with radical prostatectomy (complete surgical removal of the prostate and seminal vesicles). Of these, roughly one-third will experience recurrence of disease detected by rising prostate specific antigen (PSA). Known risk factors for recurrence after surgery include advanced stage (extension beyond prostate capsule), high grade disease, cancer at the surgical margin, and lymph node spread. For patients at high risk for recurrence, additional treatment with hormones or radiation therapy is often considered but may over-treat some who would not recur. Furthermore, some patients experience recurrence in the absence of these predictors. As a result, our ability to define which patients may benefit from additional treatment is not completely understood. Two gene-based tests of prostate cancer tissue taken from radical prostatectomy specimens aim to narrow this gap:
Prolaris®is a genomic test offered by Myriad Genetics that examines the expression of 31 genes involved in cell-cycle progression (CCP), an important regulatory step in the development of cancer. The result is a CCP score that has been studied for its ability to predict recurrence after surgery. In one UCSF-led study of 413 men treated with surgery for prostate cancer, the Prolaris® CCP score was performed at Myriad labs and shown to have significant accuracy in predicting recurrence. In addition, combining Prolaris® with existing post-surgical clinical tools (e.g. CAPRA-S [hyperlink]), led to superior predictive ability.
Decipher®is a “genomic classifier” (GC) developed by GenomeDX that was the result of large-scale analysis of prostate cancer gene expression. It tests 22 RNA biomarkers that have been identified and associated with prostate cancer aggressiveness after radical prostatectomy and is approved to evaluate the risk of metastasis after treatment. Decipher® generates a score between 0-1 in increments of 0.1. The Decipher® test was examined in a study of 545 prostate specimens of men treated with surgery at the Mayo Clinic. In this study, the results of the Decipher® GC were able to predict onset of metastasis better than other currently available tools using pathology findings, stage, grade, or PSA.
Which test is best for me?
Both Prolaris® and Decipher®are tissue-based gene expression tests that can be performed on specimen preserved after radical prostatectomy and may assist in making decisions. At present, no direct comparisons have been made between these two products. Consideration of gene expression testing should take place in careful consultation with your physician.