New Diagnostic Tests in the Pipeline for Prostate Cancer

[SteveH]

for Prostate Cancer


March 27, 2013—Recent advances in research have improved our understanding of prostate cancer, which is beginning to be appreciated more as a collection of different subtypes instead of a single uniform disease. Prostate cancer patients respond to the same therapeutic agent with very variable responses and this is due to the vast differences in the underlying biology of each patient’s tumor. Each prostate tumor develops its unique combination of genomic aberrations, some of which "drive" tumor development and progression, while others tag along as "passenger" alterations. For each individual patient, it is this unique combination of "driver" and "passenger" genomic alterations that will determine ultimate disease outcome.

Not all mutation combinations are lethal and a majority of prostate cancer patients don’t need any aggressive therapy (such as prostatectomy, radiation etc. that have innumerable detrimental side-effects) other than active surveillance of their disease. However, currently there is no way to distinguish clinically aggressive from indolent prostate cancer. The only FDA-approved test for prostate cancer is the serum PSA (Prostate Specific Antigen) test which is not cancer-specific and has therefore led to several negative biopsies. The PSA test has received a lot of flak lately with the United States Preventative Services Task Force (USPSTF) recommending against screening in late 2011, as data has shown that far more men were harmed by unnecessary biopsies and treatments than were saved from dying of cancer. However, for wont of more accurate diagnostic tests, many prostate cancer patients undergo unnecessary biopsies, in-effect over-treating mostly non-lethal tumors.

New research, funded in part by the Prostate Cancer Foundation, has identified several ‘biomarkers’ or genetic fingerprints that report underlying tumor biology. Combinations of these biomarkers can aid clinical management of prostate cancer by 1) allowing accurate diagnoses, 2) establishing whether a patient’s cancer is aggressive or indolent, 3) deciding if repeat biopsies are needed, 4) aiding clinical decisions on therapeutic options (drug combinations for maximal patient benefit) and 5) evaluating whether a patient’s cancer is responding to therapy or not.

Many of these biomarker-driven diagnostic/prognostic tests are ripe for clinical use and are in the final stages of clinical validation (Table below). Today the New York Times published a feature article discussing these new prostate cancer tests. These latest prostate cancer tests evaluate blood, urine or prostate biopsy specimens for the presence of either an abnormal gene activity pattern, or specific chemicals that are released by cancer cells, e.g., the test by GenProbe evaluates urine samples for the expression of the TMPRSS2-ERG gene fusion DNA and the PCA3 DNA. The abnormal TMPRSS2-ERG gene fusion is present in 50 percent of all prostate tumors, and PCA3 (prostate cancer antigen) is expressed at high levels in 95 percent of prostate cancer patients, therefore the combination of these two has a high probability of accurate diagnoses. PCF has funded the research that led to the identification of the role of both, TMPRSS2-ERG and PCA3 in prostate cancer. Testing these biomarkers in urine samples holds potential due to the non-invasiveness of urinalysis, ease of collection, and the fact that prostate cells are directly released into the urethra through prostatic ducts after a digital rectal exam (DRE) or prostate massage. The GenProbe test and several other tests that are currently in the final stages of clinical validation are described in the table below.



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Click Below For Chart

http://www.pcf.org/atf/cf/%7B7c77d6a2-5 ... 0TESTS.PDF




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The Prostate Cancer Foundation has invested over $20 million in the past twenty years in biomarker research and this funding has laid the foundation of several of these tests that are at the cusp of improving prostate cancer patient care.

“The limitations of PSA have been well documented. The technology we have used with light microscopy and traditional pathology have been used for over 100 years. By entering the world of molecular diagnostics and imaging, we are on the verge of rendering the PSA debate moot,” said urologic oncologist at Cedar-Sinai Medical Center and Medical Director of the Prostate Cancer Foundation, Dr. Stuart Holden. “The promise of the new technologies once they are validated will reduce the unnecessary biopsies and over treatment of prostate cancer through their ability to identify cancers which pose a risk, early in their natural history and at a time when they can effectively treated. PCF has been supporting better tests for a long time and directing resources to ensure they becomes a reality.”

http://www.pcf.org/site/c.leJRIROrEpH/b ... _227557192