"Watchful waiting" to monitor possible prostate cancer is valuable, but more information added to that waiting would be even better.
One company may be on its way to developing a diagnostic test of precancerous lesions of the prostate that could ultimately be used to detect high-grade prostatic intraepithelial neoplasia (PIN), a precancerous lesion often the precursor for this disease — sometimes attacking swiftly, but more usually slow-growing.
The hope is that this diagnostic could be paired with one or two drugs, perhaps in combination, being developed by two different companies to treat this condition early on, Mark Stearns, chief scientific officer for MacroArray Technologies (Philadelphia) told Diagnostics & Imaging Week.
MacroArray this week reported the identification of a urine protein called ABCA5 that can serve as a sensitive diagnostic marker for high-grade PIN, which cannot, Stearns said, be identified through such tests as the prostate specific antigen, or PSA test. Essentially, he said there is no similar test available today.
MacroArray said that men with high-grade PIN are at the highest risk for developing prostate cancer, with about 50% developing prostate cancer within three years of diagnosis and 80% developing it within eight years.
Details of the marker's identification are published in the February issue of Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR; Philadelphia).
"The assay for the ABCA protein offers a convenient and noninvasive way to detect pre-malignant high-grade PIN cells," said Stearns. "The ABCA5 assay, if successfully developed and approved for marketing by the FDA, would be the first urine diagnostic marker capable of detecting high-grade PIN and therefore represents an important scientific and medical advancement for the early detection of prostate cancer."
The way that high-grade PIN can be diagnosed today is through prostate biopsy on patients who present with an elevated serum PSA or abnormal digital rectal exam. About 5%-10% of patients who undergo a prostate biopsy will be found to have high-grade PIN only, the company said.
Today in the U.S., 1.1 million men have been diagnosed with high-grade PIN. MacroArray said that the successfully development of a non-invasive urine or blood diagnostic test for this condition could help to identify an estimated 14 million men at risk of unknowingly harboring a pre-malignant lesion, but not yet having an elevated serum PSA.
In the Clinical Cancer Research paper, Stearns and other researchers report that ABCA5 protein is over-expressed in high-grade PIN tissue and can be detected in the urine of patients with this condition; however, it is not expressed "appreciably" in prostate cancer or benign prostatic hyperplasia, the company said.
A blinded study using an ELISA test determined that ABCA5 was a highly sensitive urine marker for high-grade PIN in patients where biopsy of the prostate confirmed that condition, or greater than 98% sensitivity. The marker was found to be present at very low levels in the urine of patients where biopsy found negative high-grade PIN, or greater than 86% specificity.
GTx (Memphis, Tennessee), a biopharmaceutical company focused on developing therapies for cancer and other conditions related to men's health, supplied to MacroArray urine and serum samples from patients with high-grade PIN.
GTx is developing Acapodene (toremifen citrate), a selective estrogen receptor modulator (SERM) in two separate clinical programs in men.
The samples provided to MacrArray were from patients who are enrolled in Phase IIb and Phase III trials. GTx is conducting a pivotal Phase III trial of Acapodene 20mg for the prevention of prostate cancer in men with high-grade PIN. The trial is designed as a 36-month study but provides for an interim efficacy analysis by the first quarter of 2008.
If Acapodene achieves its efficacy endpoints in that analysis, GTx expects to file a new drug application with the FDA.
MacroArray emphasized, however, that GTx has "no commercial interest in any test which may be developed by [the company], nor does it have control over the development of such a test."
Another drug for this application is being developed by Roswell Park Cancer Institute (Buffalo, New York), an academic organization.
Stearns told D&IW that MacroArray is about two years away from submitting to the FDA any request for approval of a diagnostic test for high-grade PIN. He also said that such a test would not only be designed for screening for and detection of high-grade PIN, it also would be designed for monitoring of response following therapy.
Asked how he expected such a diagnostic to benefit men's health, Stearns said, "The clear answer is that early detection and early treatment is going to reduce the [causes] and development of prostate cancer."
Currently, the option is to get a biopsy, and then if PIN is developed, the next course of action is "watchful waiting," in other words more careful monitoring to see if the PSA rises or a cancer develops.
Stearns said, however, that the new agents being developed by GTx and Roswell Park Cancer Institute have shown "significant reduction in progression to cancer [in those] who take these compounds," and so a regimen of these drugs could be combined with watchful waiting.
MacroArray, an early-stage company, was founded in 2002 and has five employees. It is focused on diseases of the prostate.