PCA3 testing discouraged until better evidence obtained

see Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes?

The unacceptably high rate of false-positive and false-negative testing results in prostate cancer screening has led to a search for more reliable screening tests. One such assay—the prostate cancer antigen 3 (PCA3) nucleic acid amplification test—has been proposed as a tool to assist physicians in deciding whether to perform or repeat a biopsy in at-risk men. PCA3 messenger RNA (mRNA) is highly elevated in prostate cancer cells as compared with normal prostate cells. A clinical test that measures the ratio of PCA3 mRNA to prostate-specific antigen (PSA) mRNA has been approved by the US Food and Drug Administration and is commercially available from a single vendor. But the clinical effectiveness of the test remains an open question. After reviewing the available published scientific evidence, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group reports in this issue that at this time there is insufficient evidence to recommend PCA3 testing in men. The group looked specifically at evidence to support testing for patients who were deemed at risk because of an elevated PSA level or suspicious physical examination or who had previously had a negative biopsy but were being considered for re-biopsy. They found no outcome studies showing that PCA3 scores can predict the behavior of a particular tumor or can yield information related to diagnostic accuracy, prognosis, or quality of life. The authors call for studies designed to compare PCA3 testing with two other commonly used add-on tests that measure free PSA and total PSA doubling time. —Karyn Hede, News Editor

Regulatory loopholes raise concern about noninvasive prenatal tests

see Noninvasive prenatal testing: limitations and unanswered questions

The use of noninvasive prenatal testing (NIPT) has become attractive because of its high sensitivity and specificity as well as the potential to avoid invasive procedures and their associated risks. These tests evaluate circulating cell-free DNA to determine the risk of fetal aneuploidy. But many such tests being marketed to health-care providers and patients lack clinical validation and regulatory oversight, according to the review by Lutgendorf et al., who fear that neither clinicians nor the public fully appreciate the limitations and shortcomings of NIPT. The authors describe regulatory loopholes that allow companies to avoid US Food and Drug Administration oversight of lab-developed tests and suggest that patients and providers may be unwittingly participating in an unregulated public experiment in which adverse events are not being tracked. They emphasize the importance of prenatal counseling that clearly communicates the strengths and limitations of NIPT. In addition, they recommend that counselors clearly communicate with patients the possibility of false-positive and false-negative results as well as of results that don’t correlate with fetal findings. Along these lines, the American College of Medical Genetics and Genomics recently advocated changing the terminology from NIPT to NIPS (noninvasive prenatal screening) to emphasize its limitations. There remain many questions surrounding the best use of these tests and how they should be integrated into prenatal screening programs. —Karyn Hede, News Editor