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Oncology Times:
doi: 10.1097/01.COT.0000381215.69568.75
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AACR Annual Meeting: Modified PSA Test Predicts Prostate Tumors with Unfavorable Characteristics in Preliminary Study

Laino, Charlene

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WASHINGTON, DC—Researchers were hopeful about a test that measures serum levels of three forms of prostate-specific antigen potentially being able to distinguish between low-risk prostate cancers that eventually will and will not require treatment.

Stage 4
Stage 4
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In a preliminary study, use of the test in combination with biopsy results proved about 70% accurate in predicting which tumors would develop unfavorable characteristics, Robert W. Veltri, PhD, Associate Professor of Urology and Oncology at Johns Hopkins University, reported here at the AACR Annual Meeting.

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The Prostate Health Index

The test—the Prostate Health Index (PHI)—is a composite score derived from measurement of total PSA, free PSA, and pro-PSA, which is a shortened molecule missing a few of the amino acids that make up the PSA protein. It's the most accurate form of PSA, Dr. Veltri.

The PHI test shows promise for safely identifying men who can undergo active surveillance rather than treatment, Dr. Veltri said. “The goal of the new test is to determine who will and who will not progress and require treatment.”

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Study Design

The federally funded study involved 71 men enrolled in the Proactive Surveillance cohort, an ongoing study of patients who choose surveillance over immediate treatment.

Serum and tissue samples were banked at the time of diagnosis, and participants underwent PSA testing and digital rectal exams every six months and follow-up biopsies annually.

By a median follow-up time of 3.7 years, 39 men had unfavorable biopsy results: a Gleason score greater than 6, Gleason pattern of 4/5, three or more biopsy cores with cancer, or any core with more than 50% cancer involvement.

Using a PHI immunoassay developed by Beckman Coulter, the researchers measured the three components of PHI in all participants' stored blood samples. They also analyzed the DNA content of their biopsy specimens.

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Combined Were Significant Predictors

Regression analysis showed that both mean PHI value and the ratio of pro-PSA to free PSA were significant predictors of subsequent conversion from favorable to unfavorable biopsy characteristics, whereas by themselves, none of the individual PSA tests were predictive.

Additionally, two parameters of biopsy DNA content predicted conversion to unfavorable results: benign adjacent excess of optical density and cancer tissue standard deviation of optical density.

Speaking about the p...
Speaking about the p...
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In multivariate analysis, all four parameters retained statistical significance for predicting which tumors would eventually have unfavorable characteristics.

By themselves, both mean PHI value and the ratio of pro-PSA to free PSA were about 62% accurate in predicting which tumors would develop unfavorable characteristics, Dr. Veltri said. “But when we combined the biopsy results and the serum Prostate Health Index, we were able to predict seven in 10 men who might progress.”

Dr. Veltri said the PHI test won't replace biopsies but will hopefully allow men to have them less frequently.

His lab is now conducting an expanded study to look for other biomarkers that may predict aggressive cancers.

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CTC Chip for Localized Cancer

Also at the meeting, researchers reported using a new microchip technology to detect circulating tumor cells in the blood of some men with localized prostate cancer.

In a proof-of-concept study, the CTC-Chip Microfluidic Technology detected CTCs in nearly half of 20 men with localized prostate cancer.

“These are patients in whom we normally cannot detect circulating tumor cells, so this could give us tremendous information about their risk,” said Sunitha Nagrath, PhD, an instructor of surgery and bioengineering at Harvard Medical School and Massachusetts General Hospital. “We think it's an indication they are more prone to metastasis,” although that remains to be proven.

CTCs also carry molecular signatures that can be used to guide targeted drug therapy, she added.

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More Sensitive than Current Tests

Currently, there is no FDA-approved technology for detecting CTCs in men with localized prostate cancer.

Technologies approved for advanced prostate cancer and a variety of other cancers are not sensitive enough for localized prostate tumors, Dr. Nagrath said.

The new CTC-Chip Microfluidic Technology can detect about five times as many CTCs per milliliter of blood as current technologies, she said.

In the new study, the CTC-chip detected circulating tumor cells in 42% of 20 patients with early-stage prostate cancer and in 64% of 30 patients with advanced prostate cancer.

Dr. Nagrath said they were able to detect circulating tumor cells nine days after surgery and three months post-surgery.

The test is not yet commercially available, but “eventually, we hope that when a patient walks in, we can take a simple blood test to differentiate patients with aggressive versus indolent disease,” she said.

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Discussion

At an AACR news conference that highlighted the study, Laura J. van't Veer, PhD, Director of Applied Genomics at the Helen Diller Family Comprehensive Cancer Center of the University of California, San Francisco, called the CTC-Chip “a new and innovative technique” for monitoring patients with early-stage disease.

Massimo Cristofanilli, MD, Chairman of the Department of Medical Oncology at Fox Chase Cancer Center, commented that a lot more work is needed before either test can be integrated into patient care.

ROBERT W. VELTRI, PH...
ROBERT W. VELTRI, PH...
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For example, he said, for the CTC-Chip, one of the issues to be worked out is when to give the test—at the time of diagnosis, at surgery, or a few weeks afterward?

© 2010 Lippincott Williams & Wilkins, Inc.

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