Two tests designed to help identify prostate cancer in patients with negative or inconclusive results on prostate biopsy do not improve diagnosis enough to be recommended for clinical practice, says the United Kingdom (UK)’s healthcare watchdog.
In draft diagnostics guidance issued on December 17, the National Institute for Health and Care Excellence (NICE) recommends that the Progensa prostate cancer antigen 3 (PCA3) assay (Hologic GenProbe) and the Prostate Health Index (PHI) (Beckman Coulter) should not be used in the National Health Service in England.
PCA3 and PHI are both in vitro diagnostic tests for use in patients suspected of having prostate cancer who have negative or inconclusive findings on transrectal ultrasound prostate biopsy; these tests are used to determine the need for a second biopsy.
The appraisal was undertaken in the belief that the PCA3 or PHI may avoid second biopsies and associated complications by identifying patients unlikely to have a positive biopsy result and, thus, prostate cancer.
However, the draft guidance says that adding either of these tests to clinical assessment plus MRI is unlikely to improve diagnostic accuracy in clinical practice.
„Prostate biopsies are associated with discomfort and pain, as well as side effects including bleeding, problems with catheterisation and possible infections,” Carole Longson, PhD, NICE Health Technology Evaluation Centre director, commented in a statement.
„These tests would be of value if they were able to improve diagnostic certainty because it would reduce the number of prostate biopsies patients had to have, reducing patients’ anxiety,” she continued.
„However, the committee noted from the evidence that, although there were some improvements in diagnostic performance when PCA3 or PHI was added.
to clinical assessment alone, these improvements were very small.”
PCA3 Test Performed on Urine Sample
The PCA3 assay is an in vitro nucleic acid amplification test for determining levels of PCA3 RNA in urine. The urine sample is obtained after digital rectal examination, which releases prostate cells and RNA into the urinary tract.
As reported by Medscape Medical News, the PCA3 assay was approved for use in Europe in 2006, andreceived US Food and Drug Administration approval in 2012, based on a study involving 495 men at 14 clinical sites that indicated the assay had a negative predictive value for prostate cancer of 90%.
A further study conducted in 233 men with persistently elevated serum prostate-specific antigen (PSA) levels and at least one previous negative biopsy result suggested that the PCA3 assay may help reduce the number of biopsies performed in men suspected of having prostate cancer. The assay performed significantly better than serum PSA in predicting prostate biopsy outcome.
Furthermore, an analysis of 1072 men from the REDUCE (REduction by DUasteride of prostate Cancer Events) study suggested that higher PCA3 scores not only predicted a positive biopsy result but was also associated with a higher biopsy Gleason score.
Further improvements in the ability of the PCA3 assay to identify men with prostate cancer have been reported when used in combination with the TMPRSS2:ERG gene fusion, and with a panel of biomarkers.
PHI Is Blood Serum Immunoassay
In contrast, the PHI is an in vitro diagnostic multivariate index assay that combines three blood serum PSA immunoassays — PSA, free PSA, and p2PSA — into a single calculation (p2PSA/free PSA) × √total PSA.
The test is simple and inexpensive and has performed better than conventional PSA and free PSA measures in several studies for predicting overall and high-grade prostate cancer.
For the current draft NICE guidance, researchers from the External Assessment Group conducted three systematic reviews of the evidence, identifying 6 studies that reported the analytical validity and 31 that reported the clinical validity of the tests. No studies that reported the clinical validity of the tests were identified.
In addition, the group conducted a systematic review of the existing economic analyses of the PCA3 and PHI tests. Because no published economic studies met the inclusion criteria, the group designed their own de novo economic model designed to assess the cost-effectiveness of the tests.
After reviewing the available evidence, the guidance committee considered whether more research into the two assays was advisable.
Noting that any potential improvements to the tests would be small, the guidance says: „If the potential benefits of using the PCA3 assay and the PHI were realised, they were unlikely to be sufficiently large to offset the costs of the test and make a substantial difference to the number of people having a second biopsy unnecessarily.”