Wednesday 3 June 2009

ASCO: Gene Test Predicts Prostate Cancer

ORLANDO, June 2 -- A set of six genes, measured in a blood test, can be used to tell whether a man has prostate cancer, a researcher said here.

In a case-control study, the six-gene panel outperformed a standard test -- age-adjusted prostate specific antigen -- in distinguishing between men with cancer and those without, according to Robert Ross, M.D., of Dana-Farber Cancer Institute in Boston.

When prostate specific antigen (PSA) levels were added to the group of genes, the performance of the test improved even more, Dr. Ross told attendees at the annual meeting of the American Society of Clinical Oncology.

The gold standard for diagnosing prostate cancer is a biopsy, he said, but 60% of biopsies in men thought to be at risk for the disease turn out to be negative.

The goal of this test is to avoid the "pain, discomfort, and anxiety" associated with biopsies, Dr. Ross said, by winnowing out the 60% of men who don't need the procedure.

Dr. Ross and his colleagues started with a set of 392 genes associated with inflammation, cancer, and the epidermal growth factor receptor, as well as some identified in other genetic studies of cancer.

In a training set of 76 healthy men and 76 with prostate cancer, six genes were significantly associated with disease. Of the six, five are less active in those with the disease and one has greater activity, the researchers found.

The finding was validated in a second cohort of 128 men with cancer and 94 without, he said.

In the second group, the six-gene test correctly detected 85.9% of the men with disease, compared with 69.5% detected by age-adjusted PSA, Dr. Ross said.

The six-gene test had a specificity of 83%, compared with 93.6% for PSA, he said.

When the researchers did both the six-gene test and measured PSA levels, the sensitivity and specificity improved -- to 87.5% and 92.6%, respectively.

The results are a "significant improvement" over the predictive value of PSA alone, Dr. Ross said.

"From a clinical hypothesis standpoint, this is great data," Dr. Ross said. But, he cautioned, "this is a case-control study (and) you'd like to see it validated prospectively."

He said his institution and several others are collaborating on a 1,000-patient prospective study -- dubbed PRECISE -- among men who meet the criteria for a biopsy, but have not yet had the test.

The goal will be to see if the test can predict the results of biopsy, he said.

Although the test is still in development, it will not be expensive, especially compared with the $2,000 it costs for a biopsy, said Karl Wassman, of Source MDx, the Boulder, Colo. company that has developed the test.

He said the blood test can be read by standard equipment, using a kit of primers and probes developed by Source MDx, so that the cost will be in the range of "a couple of hundred" dollars.

The various forms of PSA testing are "extremely valuable" in screening for prostate cancer, said Howard Sandler, M.D., of Cedars-Sinai Medical Center in Los Angeles, who was not involved in the study.
But the jury is out on whether screening and early detection have any benefit for patients, he said.

"If screening is beneficial, then better screening is important," he said, but there's no high-quality evidence that early detection is useful.

Dr. Sandler said the "weakness of this test" is that it doesn't answer the most important question about prostate cancer.

"The question is do you have clinically relevant prostate cancer or not?" he said. "Do you have potentially lethal cancer or do you have the cancer that will never kill you?"

Dr. Ross agreed that that question is important and said he and his colleagues have preliminary data that suggests it may be possible to use such a test to distinguish between types of cancer.

The study was supported by Source MDx, Dana Farber and the Harvard Cancer Center, the Gelb Center, and the Bing Sound Wong Fund.
Several researchers reported financial links with Source MDx.

Dr. Sandler reported financial links with sanofi-aventis, Genentech, Amgen, and AstraZeneca.

Primary source: Journal of Clinical Oncology
Source reference:
Ross RW, et al "Sensitivity and specificity of a whole-blood RNA transcript-based diagnostic test for the diagnosis of prostate cancer (CaP) compared with prostate-specific antigen (PSA) alone" J Clin Oncol 2009; 27(15S): Abstract 5052.

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