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Archived: This report is greater than 3 years old. Findings may be used for research purposes, but should not be considered current.
We performed a comparative effectiveness review that examined the use of the prostate cancer antigen 3 (PCA3) gene in improving initial or repeat biopsy decisions in patients identified at risk for prostate cancer, or in improving decisionmaking about treatment choices (e.g., active surveillance vs. aggressive therapy) in patients with prostate cancer positive biopsies. Comparators included total prostate specific antigen (PSA) elevations, free PSA, PSA density, PSA velocity, externally validated nomograms, complexed PSA, and multivariate models.
We searched PubMed® and Embase® from January 1, 1990, to August 8 and August 15, 2011, respectively, and updated through May 15, 2012. We searched the Cochrane Database of Systematic Reviews with no date restriction and updated. A grey literature search included databases with regulatory information, clinical trial registries, abstracts/conference papers, grants and federally funded research, and manufacturer information.
Inclusion criteria required PCA3 and at least one comparator to be measured in the same cohort in one of the three clinical settings: at-risk men considering initial biopsy; at-risk men considering repeat biopsy; and men with prostate cancer making treatment decisions based on risk categorization. Data were extracted by one reviewer and audited by a second. Analyses were matched by comparing within study differences between PCA3 and a comparator. Modeling was used to smooth consensus ROC curves and to address issues relating to verification bias. Diagnostic accuracy studies were assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Strengths of evidence were judged high, moderate, low, or insufficient according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria and the AHRQ “Methods Guide for Medical Test Reviews.”
After exclusion of six studies with strong likelihood of containing duplicate data, 24 studies provided data that could be used to address diagnostic accuracy (Key Questions [KQ] 1 and 2); 13 studies addressed decisionmaking based on risk stratification criteria (KQ 3). All studies were of poor quality. Comparison of PCA3 to total PSA (tPSA) had the most available studies (22) but was subject to spectrum, verification, and sampling biases; the latter two were addressed in the analyses. We observed that: (1) PCA3 is more discriminatory for detecting cancers (i.e., at any sensitivity, the specificity is higher, or at any specificity, the sensitivity is higher) than tPSA elevations; (2) this finding appears to apply to both initial and repeat biopsies; and (3) PCA3 and tPSA are relatively independent predictors. However, strength of evidence was low. For all other diagnostic accuracy comparisons, and all intermediate and long-term health outcomes, the strength of evidence was insufficient. For treatment decisionmaking in men with positive biopsy, in all comparisons for intermediate and long-term health outcomes, the strength of evidence was found to be insufficient.
For diagnostic accuracy, there was a low strength of evidence that PCA3 had better diagnostic accuracy for positive biopsy results than tPSA elevations, but insufficient evidence that this led to improved intermediate or long-term health outcomes. For all other settings, comparators, and outcomes, there was insufficient evidence.
Bradley LA, Palomaki GE, Gutman S, et al. Comparative effectiveness review: prostate cancer antigen 3 (PCA3) testing for the diagnosis and management of prostate cancer. J Urol. 2013 Apr 1. DOI: 10.1016/j.juro.2013.02.005.