“Testing for combined urinary PCA3 and TMPRSS2:ERG (T2:ERG) RNA can improve detection of prostate cancer, according to a study published online May 18 in JAMA Oncology.
“Martin G. Sanda, M.D., from the Emory University School of Medicine in Atlanta, and colleagues conducted a multicenter diagnostic evaluation and validation in academic and community-based ambulatory urology clinics. A sample of men presenting for first-time prostate biopsy without preexisting prostate cancer were enrolled: 516 in the developmental cohort and 561 in the validation cohort. Urinary PCA3 and T2:ERG RNA were measured before prostate biopsy.”
“Incorporating scores from two urine-based biomarker assays may reduce the number of biopsies men with clinically localized prostate cancer need to undergo without greatly affecting 10-year survival rates, according to the results of a decision analysis.
“ ‘Results from recent studies have demonstrated the potential clinical utility of the urine-based PROGENSA prostate cancer antigen 3 (PCA3) assay (Gen-Probe, Inc.) to predict repeat biopsy outcomes in men with elevated serum PSA levels and previous negative biopsy findings,’ Brian T. Denton, PhD, associate professor of industrial and operations engineering at University of Michigan, and colleagues wrote. ‘A recent literature review reported current evidence suggesting that the PCA3 test is clinically useful for selecting which patients should undergo repeat biopsy. Several studies have determined that urine assessment of [T2:ERG] is also associated with biopsy outcome and may be better at discriminating between low-grade and high-grade cancers.‘ “
“Denton and colleagues performed a decision analysis using a decision tree to evaluate the clinical value of using PCA3 and T2:ERG scores to determine the need for repeat biopsy in men with clinically localized prostate cancer who had at least one prior negative biopsy. Researchers estimated the probability for cancer by using the Prostate Cancer Prevention Trial Risk Calculator.”
“In a study reported in the Journal of Clinical Oncology, Wei et al found that use of urinary prostate cancer antigen 3 (PCA3) measurement could improve avoidance of repeat prostate biopsy and detection of prostate cancer in biopsy-naive patients.
“This National Cancer Institute study involved 859 men (mean age, 62 years) from 11 centers scheduled for diagnostic prostate biopsy between December 2009 and June 2011.
“PCA3 scores were reported as a ratio of urinary PCA3 mRNA to prostate-specific antigen mRNA. Among men presenting for initial prostate biopsy, PCA score > 60 had a sensitivity of 42%, specificity of 91%, and positive predictive value of 80% (95% confidence interval [CI] = 72%–86%) for detection of any cancer. Among men presenting for repeat biopsy, PCA score < 20 had negative predictive value of 88% (95% CI = 81%–93%), with sensitivity and specificity of 76% and 52% for absence of cancer…
“The investigators concluded: ‘These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (>60) significantly increases the probability that an initial prostate biopsy will identify cancer.’ “
“The use of a prostate cancer antigen 3 (PCA3) urine test could help men avoid undergoing unnecessary repeat biopsies, and could help physicians predict which men undergoing initial biopsy will be positive for cancer.
“John T. Wei, MD, of the University of Michigan, and colleagues published the results of the National Cancer Institute Early Detection Research Network validation of PCA3 trial in the Journal of Clinical Oncology.
“According to Wei, how physicians decide to send a patient for prostate biopsy is continuing to evolve. Although in the past, an abnormal PSA test resulted in an order for a biopsy, the discovery and validation of new biomarkers is changing that precedent.
“ ‘Prostate cancer tests such as the PCA3, an FDA approved, commercially available urine assay for prostate cancer, are allowing doctors to more accurately determine if a man has prostate cancer prior to a biopsy,’ Wei told Cancer Network. ‘Based on our findings, using PCA3, many fewer men will need to undergo a repeat prostate biopsy. On the other hand, PCA3 may also indicate an elevated risk of prostate cancer in other men, prompting them to undergo a prostate biopsy when its needed.’
“In the study, Wei and colleagues evaluated 859 men scheduled for diagnostic prostate biopsy between 2009 and 2011. The researchers evaluated whether the PCA3 urine test had a high positive predictive value at initial biopsy and a high negative predictive value at repeat biopsy.”
“Researchers believe that susceptibility to common diseases stems from a combination of common genetic variants and a variety of rare genetic mutations. But this only accounts for a small proportion of potential heritable risk factors for disease. Now, new research has discovered that some genetic variants could indicate the presence of rare genetic mutations that have yet to be discovered, which may contribute to the risk of common diseases.”
Editor’s Note: While this story is about genetics as it relates to cancer risk, genetics can also provide valuable information to guide treatment. Interested readers might look into the following tests, which are just a few of several molecular/genetic tests to guide prostate cancer treatment: Oncotype DX, Prolaris, and PCA3.
Warrick JI, Tomlins SA, Carskadon SL, Young AM, et al. Mod Pathol. Sep 27, 2013.
“PCA3 is a prostate-specific non-coding RNA, with utility as a urine-based early detection biomarker. Here, we report the evaluation of tissue PCA3 expression by RNA in situ hybridization in a cohort of 41 mapped prostatectomy specimens. We compared tissue PCA3 expression with tissue level ERG expression and matched pre-prostatectomy urine PCA3 and TMPRSS2-ERG levels. Across 136 slides containing 138 foci of prostate cancer, PCA3 was expressed in 55% of cancer foci and 71% of high-grade prostatic intraepithelial neoplasia foci. Overall, the specificity of tissue PCA3 was >90% for prostate cancer and high-grade prostatic intraepithelial neoplasia combined. Tissue PCA3 cancer expression was not significantly associated with urine PCA3 expression. PCA3 and ERG positivity in cancer foci was positively associated (P<0.01). We report the first comprehensive assessment of PCA3 expression in prostatectomy specimens, and find limited correlation between tissue PCA3 and matched urine in prostate cancer.”
Lin DW, Newcomb LF, Brown EC, Brooks JD, et al. Clinical Cancer Research. Mar 20, 2013.
“Active surveillance is used to manage low risk prostate cancer. Both PCA3 and TMRPSS2-ERG are promising biomarkers that may be associated with aggressive disease. This study examines the correlation of these biomarkers with higher cancer volume and grade determined at the time of biopsy in an active surveillance cohort…”
Bradley LA, Palomaki GE, Gutman S, Samson D, Aronson N. J Urol. Mar 29, 2013.
“PURPOSE: Compare the effectiveness of PCA3 and select comparators for improving initial or repeat biopsy decision-making in men at risk of prostate cancer, or treatment choices in men with prostate cancer. MATERIALS AND METHODS: MEDLINE®, EMBASE®, Cochrane Database and grey literature were searched from January 1990 through May 2012. Included studies were matched, and measured PCA3 and comparator(s) within a cohort..”