NEW YORK (Reuters Health) – Measuring urinary levels of prostate cancer antigen 3 (PSA3) may be more accurate than PSA testing in detecting prostate cancer, but evidence is insufficient to decide if PCA3 testing improves health outcomes.
Those conclusions come from a comparative effectiveness review evaluating PCA3 testing versus other tests for the diagnosis and management of prostate cancer, published online March 29 in the Journal of Urology.
Dr. Linda A. Bradley, with Women & Infants Hospital in Providence, Rhode Island, and colleagues point out that the balance of benefit versus harm from PSA screening remains controversial, because of the test’s low specificity for prostate cancer and because some prostate tumors may never progress to symptoms. Therefore, better markers are needed.
PCA3, they continue, is highly overexpressed in prostate cancer, and in 2012 the US Food and Drug Administration approved the Progensa PCA3 assay to help with decision-making in men who have a prior negative biopsy.
The team conducted the current review to investigate the performance of PCA3 compared to other tests for two purposes: to predict a positive biopsy in men at risk for prostate cancer; and to differentiate aggressive disease requiring immediate therapy from indolent tumors that could be managed with active surveillance.
To that end, the authors identified 34 relevant observational studies.
Twenty-four studies addressed diagnostic accuracy, but comparison was only possible with total PSA. Evidence was insufficient for other comparators, ie, free PSA, PSA velocity, PSA density, complexed PSA or validated nomograms.
The authors found that PCA3 was more discriminatory than total PSA in predicting a positive biopsy, whether or not it was a repeat biopsy. At a false-positive rate of 50%, the sensitivity of PCA3 was 77% compared to 57% for total PSA.
“The possibility that PCA3 testing may be as useful in men making decisions about an initial biopsy could broaden the test’s potential use beyond decision-making about repeat biopsies,” Dr. Bradley and colleagues suggest.
Thirteen studies investigated PCA3 versus comparators in categorizing cancer risk, ie, as aggressive or insignificant. However, the team concluded that the strength of evidence in this area was insufficient to determine specificity and sensitivity of PCA3 or comparators for cancer risk classification. Similarly, the ability of PCA3 to improve health outcomes was inconclusive because of insufficient evidence.
“Newer markers like PCA3 need to be further explored in well-designed and appropriately powered and analyzed prospective trials that determine intermediate and long-term outcomes,” the investigators conclude, and add: “Long-term observational studies of health outcomes are also subject to biases. Randomized trials, though difficult and expensive, may be needed to answer these questions.”
SOURCE: Comparative Effectiveness Review: Prostate Cancer Antigen 3 Testing for the Diagnosis and Management of Prostate Cancer
J Urol 2013.
