Predictive Biosciences this week said it has started two prospective studies to assess its bladder cancer assays following a successful pilot study.
The studies, each enrolling about 1,000 subjects in at least 10 clinical trial sites, will evaluate the Lexington, Mass.-based firm's Clinical Intervention Determining Diagnostic approach, which is based on high negative predictive value, or NPV, to identify patients who do not have recurring bladder cancer.
An NPV is a metric used by clinicians to determine the probability that a patient who has tested negative for a disease is really free of it.
A pilot study on the CIDD approach was published in the November issue of the Journal of Urology.
In it, the authors said that using ELISA and zymography on urine metalloproteinase — zinc-dependent endopeptidases that regulate tumor growth, angiogenesis, and metastasis formation — they were able to distinguish patients with bladder cancer from healthy patients at a sensitivity of 80 percent and a specificity of 71 percent for metalloproteinase-9. According to the authors, these figures did not "translate well into clinical practice," as a number of false-positive and false-negative results were observed.
But by applying CIDD, the authors were able to correctly identify 42 percent of cases that were diagnosed negative by cystoscopy with a negative predictive value of 98 percent.
Cystoscopy is a standard of care after the treatment for primary lesion. Patients who have initially been diagnosed with bladder cancer and treated must receive cystoscopies at regular intervals for the rest of their lives, in order to test for recurrence.
Most non-invasive diagnostic assays, the researchers wrote, "can create ambiguity as to the desired management course. Thus there is a clear, growing need for novel clinical management approaches and assays that result in more efficient screening and treatment for recurrent disease in cancer survivors."
The CIDD incorporating NVP would more accurately identify those patients who truly are negative than cystoscopies, and thus would not have to undergo regular cystoscopies, the authors noted.
In addition, a CIDD test that also uses positive predictive value could more accurately identify "true" bladder cancer-positive patients who need "accelerated intervention," they wrote.
A test with both NPV and PPV could stratify patients into those who truly are negative for bladder cancer, as determined by a NPV value; those who are truly positive for the disease, determined by a PPV value; and those for whom neither NPV nor PPV can determine their status and thus should receive regular cystoscopies.
The study in the Journal of Urology, however, did not test their CIDD approach with a PPV. In a statement, the company also said that its assay can "identify with high confidence those patients who do not have bladder cancer," but makes no mention of developing an assay that would give a more accurate diagnosis of "true" positive cancer patients.
In a statement, John Libertino, a co-author of the study and a professor and chairman in the department of urology at Lahey Clinic Medical Center, said that though bladder cancer has a high survival rate, survivors must regularly undergo cystoscopies for the remainder of their lives. "A reliable test that can reduce the burden and associated costs of this invasive procedure would be an important improvement for both patients and physicians," he said.
Predictive Bioscience has begun both clinical trials to further its CIDD approach. One is focused on how it performs in comparison with cystoscopy for patients undergoing surveillance for urothelial bladder cancer recurrence. The other will compare CIDD with cystoscopy for patients being evaluated for the referral diagnosis of gross or microscopic hematuria, or blood in the urine.
According to the American Cancer Society, bladder cancer is the fifth-most common cancer in the US. In 2009, an estimated 71,000 Americans will be diagnosed with the disease, and approximately 14,000 will die from it.