Genomic markers in prostate [619111]

Genomic markers in prostate
cancer

•new genomic biomarkers are being developed to refine the risk for
men with prostate cancer
•healthcare professionals look to high -impact journals and meetings to
improve their knowledge of novel trends in their
•the management of localised prostate cancer has recently been
challenged with several genomic biomarkers

BIOMARKER DEVELOPMENT
•biomarkers have to be discovered to exist, and there are numerous
discovery -level publications on various biomarkers and using various
techniques
•many markers are discovered on basic immunohistochemistry
staining platforms, and may or may not ever be pursued into a
commercially available product

Clinical utility
•the needle motion of a biomarker can also be thought of in terms of
the negative or positive predictive features
•the ideal biomarker would perform well on both ends of the scale
•but it may be clinically useful if a biomarker performs really well on one end
of the scale and weakly on the other

Clinical utility
•question relates to whether or not the endpoint of a biomarker
provides pure risk refinement versus a link to therapy
•a biomarker gives a risk of biochemical recurrence after a radical
prostatectomy
•it is often considered prognostic

COMMERCIALLY AVAILABLE BIOMARKERS
•Decipher
•Oncotype Dx
•Prolaris

COMMERCIALLY AVAILABLE BIOMARKERS
•Decipher
•a 22 -gene panel corresponding to RNAs from coding and non -protein -coding
regions of the genome
•can be tested on radical prostatectomy tissue
•likelihood of lymph node or bone metastases developing in the first 5 years after surgery

COMMERCIALLY AVAILABLE BIOMARKERS
•Decipher
•low score might indicate observation is the better plan
•a high score might indicate that early (adjuvant) radiation therapy is better
•this test is designed for the highest -risk cases where early metastatic
progression
•test result is a straightforward prognosis of the event

COMMERCIALLY AVAILABLE BIOMARKERS
•Oncotype Dx
•is a 12 cancer -related gene panel that reflects several pathways –stromal
response, cellular organisation , androgen signalling and proliferation
•test gives a direct prognosis for the finding of adverse pathology at radical
prostatectomy, such as pathologic T3 disease and/or upgrading the Gleason
4+3 or higher

COMMERCIALLY AVAILABLE BIOMARKERS
•Oncotype Dx
•test will give a unique genomic prostate score (GPS) on a scale of 0–100
•score is then translated to a percentage risk
•very low
•low
•intermediate

COMMERCIALLY AVAILABLE BIOMARKERS
•Oncotype Dx
•low GPS score of 0–10
•unfavourable pathology as <50 %
•very high GPS score in the 50 range only makes the prognosis 50 –60%

COMMERCIALLY AVAILABLE BIOMARKERS
•Oncotype Dx
•very low score –recommending active surveillance
•especially in an older patient where the mortality risk from unfavourable pathology may
be less

COMMERCIALLY AVAILABLE BIOMARKERS
•Prolaris
•is a 46 -gene panel of cell cycle progression genes that measures proliferation
as cells go into their division cycles
•general concept was developed in breast cancer
•then validated retrospectively in two large prostatectomy
•data sets and a large cohort of men placed on observation

COMMERCIALLY AVAILABLE BIOMARKERS
•Prolaris
•test can be run on biopsy or radical prostatectomy tissue, and due to the
validation datasets
•Prolaris score for a low -risk patient will report a 10 -year probability of cancer –
related mortality with only conservative management

COMMERCIALLY AVAILABLE BIOMARKERS
•Prolaris
•range of results can be as low as 1% or as high as 11%, with 4.5% being the
average
•low scores can certainly reinforce the surveillance decision –especially in
older or comorbid patients with shorter life expectancies

COMMERCIALLY AVAILABLE BIOMARKERS
•Prolaris
•intermediate -and high -risk disease, the ranges are much higher (3 –40% type
ranges), and there may be increased clinical utility
•high range of Prolaris in intermediate risk might have greater mortality

COMMERCIALLY AVAILABLE BIOMARKERS
•Prolaris
•Prolaris score can also be run on radical prostatectomy tissue and the output
will be a 10 -year biochemical recurrence risk
•be useful to make postoperative radiotherapy decision

INTERPRETING RESULTS/MAKING DECISIONS
•50% of Prolaris studies ordered in post -commercial release studies are consistent
with clinical prognostic information
•GenomeDx reports a similar metric that in their validation studies
•high -risk test score is present in 19% of the population tested
•60% are in the low risk

1. Cooperberg MR, Carroll PR, Klotz L. Active surveillance for prostate cancer: progress and promise. J Clin
Oncol 2011;29:3669 –76.
2. Oldenhuis CNAM, Oosting SF, Gietema JA, et al. Prognostic versus predictive value of biomarkers in oncology.
Eur J Cancer 2008;44:946 –53.
3. Davis JW. Novel commercially available genomic tests for prostate cancer: a roadmap to understanding their
clinical impact. BJU Int 2014;114:320 –2.
4. Den RB, Feng FY , Showalter TN, et al. Genomic prostate cancer classifier predicts biochemical failure and
metastases in patients after postoperative radiation therapy. Int J Radiat Oncol Biol Phys 2014;89:1038 –46.
5. Badani KK, Thompson DJ, Brown G, et al. Effect of a genomic classifier test on clinical practice decisions for
patients with high -risk prostate cancer after surgery. BJU Int 2015;115:419 –29