The clinical effectiveness and cost-effectiveness of the PROGENSA® prostate cancer antigen 3 assay and the Prostate Health Index in the diagnosis of prostate cancer: a systematic review and economic evaluation.
BACKGROUND
There is no single definitive test to identify prostate cancer in men. Biopsies are commonly used to obtain samples of prostate tissue for histopathological examination. However, this approach frequently misses cases of cancer, meaning that repeat biopsies may be necessary to obtain a diagnosis. The PROGENSA(®) prostate cancer antigen 3 (PCA3) assay (Hologic Gen-Probe, Marlborough, MA, USA) and the Prostate Health Index (phi; Beckman Coulter Inc., Brea, CA, USA) are two new tests (a urine test and a blood test, respectively) that are designed to be used to help clinicians decide whether or not to recommend a repeat biopsy.


OBJECTIVE
To evaluate the clinical effectiveness and cost-effectiveness of the PCA3 assay and the phi in the diagnosis of prostate cancer.


METHODS
Multiple publication databases and trial registers were searched in May 2014 (from 2000 to May 2014), including MEDLINE, EMBASE, The Cochrane Library, ISI Web of Science, Medion, Aggressive Research Intelligence Facility database, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number Register and World Health Organization International Clinical Trials Registry Platform.


METHODS
The assessment of clinical effectiveness involved three separate systematic reviews, namely reviews of the analytical validity, the clinical validity of these tests and the clinical utility of these tests. The assessment of cost-effectiveness comprised a systematic review of full economic evaluations and the development of a de novo economic model.


METHODS
The perspective of the evaluation was the NHS in England and Wales.


METHODS
Men suspected of having prostate cancer for whom the results of an initial prostate biopsy were negative or equivocal.


METHODS
The use of the PCA3 score or phi in combination with existing tests (including histopathology results, prostate-specific antigen level and digital rectal examination), multiparametric magnetic resonance imaging and clinical judgement.


RESULTS
In addition to documents published by the manufacturers, six studies were identified for inclusion in the analytical validity review. The review identified issues concerning the precision of the PCA3 assay measurements. It also highlighted issues relating to the storage requirements and stability of samples intended for analysis using the phi assay. Fifteen studies met the inclusion criteria for the clinical validity review. These studies reported results for 10 different clinical comparisons. There was insufficient evidence to enable the identification of appropriate test threshold values for use in a clinical setting. In addition, the implications of adding either the PCA3 assay or the phi to clinical assessment were not clear. Furthermore, the addition of the PCA3 assay or the phi to clinical assessment plus magnetic resonance imaging was not found to improve discrimination. No published papers met the inclusion criteria for either the clinical utility review or the cost-effectiveness review. The results from the cost-effectiveness analyses indicated that using either the PCA3 assay or the phi in the NHS was not cost-effective.


CONCLUSIONS
The main limitations of the systematic review of clinical validity are that the review conclusions are over-reliant on findings from one study, the descriptions of clinical assessment vary widely within reviewed studies and many of the reported results for the clinical validity outcomes do not include either standard errors or confidence intervals.


CONCLUSIONS
The clinical benefit of using the PCA3 assay or the phi in combination with existing tests, scans and clinical judgement has not yet been confirmed. The results from the cost-effectiveness analyses indicate that the use of these tests in the NHS would not be cost-effective.


BACKGROUND
This study is registered as PROSPERO CRD42014009595.


BACKGROUND
The National Institute for Health Research Health Technology Assessment programme.
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Amanda
A
Nicholson
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
James
J
Mahon
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Angela
A
Boland
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Sophie
S
Beale
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Kerry
K
Dwan
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Nigel
N
Fleeman
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Juliet
J
Hockenhull
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Yenal
Y
Dundar
D000951:Antigens, Neoplasm / Q000652:urine*; D001706:Biopsy; D003362:Cost-Benefit Analysis; D004739:England; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D021141:Nucleic Acid Amplification Techniques / Q000191:economics; D011467:Prostate / Q000002:abnormalities*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000191:economics; D013222:State Medicine; D013673:Technology Assessment, Biomedical / Q000191:economics; D016896:Treatment Outcome; D014852:Wales
D000951:Antigens, Neoplasm; C479341:prostate cancer antigen 3, human