Postprostatectomy Test Identifies Risk for Clinical Recurrence

Emma Hitt, PhD

May 25, 2012

May 25, 2012 (Atlanta, Georgia) — A newly available diagnostic test that uses immuno-polymerase chain reaction (PCR) technology can detect serum prostate-specific antigen (PSA) at concentrations in picograms per liter in patients after radical prostatectomy to help predict risk for clinical recurrence.

Jonathan E. McDermed, PharmD, director of scientific and clinical affairs at IRIS International, in Carlsbad, California, and colleagues conducted a study using this test. The results were published in the April issue of Clinical Chemistry.

Increasing levels of PSA in prostate cancer patients who have undergone radical prostatectomy can signify a risk for biochemical recurrence. According to the researchers, this new prognostic prostate cancer system differs from standard PSA tests because it identifies risk for clinical recurrence. This can help clinicians identify patients who might be able to avoid follow-up treatment.

The test, developed using the nucleic acid detection immunoassay (NADiA) platform and sold under the name ProsVue, combines sandwich immunoassay technology with quantitative PCR to detect very low levels of serum PSA.

The sandwich assay principle uses 2 monoclonal antibodies to bind antigen between a capture antibody and a label antibody that is conjugated to a small nucleotide. After several washing steps, the samples are subjected to quantitative PCR, and the amount of PSA can be calculated using levels of amplified nucleotide.

The assay was found to be robust, with a limit of quantification above 0.65 ng/L and a linear range of 0.25 to 152 ng/L. Mean percent recovery ranged from 87.5% to 119.2% for supplemented PSA samples, and from 96.4% to 115.3% for diluted samples.

Imprecision (percent coefficient of variation), which was calculated on low (3.8 ng/L), medium (24.1 ng/L), and high (69.1 ng/L) PSA samples assayed at 2 locations, was 5.2%, 9.4%, and 10.6%, respectively.

Results were found to be similar to another commercially available test (ADVIA Centaur PSA assay, Siemens Healthcare Diagnostics), with a correlation coefficient of 0.996 and highly significant Pearson's and Spearman's rank correlations (P > .0001).

"The analytical characteristics of the assay support the use of this assay for the accurate and precise measurement of serum PSA," even at concentrations measured in nanograms per liter, Dr. McDermed and colleagues note.

According to the researchers, studies investigating the prognostic clinical utility of ProsVue PSA slope in prostatectomy patients have been completed and will be reported separately.

In an interview with Medscape Medical News here at the American Urological Association 2012 Annual Scientific Meeting, Dr. McDermed said that "by being able to measure more than 10 times below the detection limits of other assays, if there is a change in the PSA from month to month, we can measure it as a real change," not as variability inherent in the assay itself.

Geoff Metcalf, vice president of sales and business development at IRIS International, explained that this test is similar in its approach to the MammaPrint test (Agendia) for breast cancer. "It gives clinicians an idea about how well the patient will do."

"This is a major advance in the management of prostate cancer," he told Medscape Medical News. After radical prostatectomy, "most men are placed into risk categories using nomograms; with this, there are still many questions about whether patients will develop clinical recurrence," he said.

"With this test, we are able, with 92.7% accuracy, to identify patients who will not clinically recur within 8 years of radical prostatectomy," he said. "This is not biochemical recurrence, but actual clinical recurrence."

Metcalf noted that Myriad Genetics has a tissue-based test called Prolaris that is "attempting to do what ours does, but if you compare the scientific data, you will see that the 2 tests are really not in the same class."

Independent commentator David I. Lee, MD, assistant professor of surgery/urology at the Perelman School of Medicine, University of Pennsylvania, in Philadelphia, said he thinks the test is "very clinical relevant."

According to Dr. Lee, the gold-standard method of following men after radical prostatectomy for prostate cancer is monitoring PSA, which should be undetectable; if it becomes detectable, it is a sign of cancer recurrence.

"The ProsVue test, because of its very sensitive profile, may be able to detect recurrences earlier, enabling men to decide on other treatment options sooner," he told Medscape Medical News. "There is no other assay that is of any use; therefore, the ProsVue may become very useful because of its sensitivity," he added.

According to Dr. Lee, this test might be especially useful for men with higher-risk pathology, in whom an undetectable ProsVue result might lead a patient not to undergo adjuvant radiation. "Likewise, a concerning score may lead some men to start radiation or hormonal therapy earlier than otherwise contemplated," he said

The study was supported by Iris International. The authors are employed by or have received funding from the manufacturer. Dr. Lee has disclosed no relevant financial relationships.

Clin Chem. 2012;58:732-740. Abstract

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