Dataset Information

Urinary TMPRSS2:ERG and PCA3 in an active surveillance cohort: results from a baseline analysis in the Canary Prostate Active Surveillance Study.

ABSTRACT: Active surveillance is used to manage low-risk prostate cancer. Both PCA3 and TMPRSS2: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.Urine was collected after digital rectal examination prospectively as part of the multi-institutional Canary Prostate Active Surveillance Study (PASS). PCA3 and TMPRSS2:ERG levels were analyzed in urine collected at study entry. Biomarker scores were correlated to clinical and pathologic variables.In 387 men, both PCA3 and TMPRSS2:ERG scores were significantly associated with higher volume disease. For a negative repeat biopsy, and 1% to 10%, 11% to 33%, 34% or more positive cores, median PCA3, and TMPRSS2:ERG scores increased incrementally (P < 0.005). Both PCA3 and TMPRSS2:ERG scores were also significantly associated with the presence of high-grade disease. For a negative repeat biopsy, Gleason 6 and Gleason ?7 cancers, the median PCA3, and TMPRSS2:ERG scores also increased incrementally (P = 0.02 and P = 0.001, respectively). Using the marker scores as continuous variables, the ORs for a biopsy in which cancer was detected versus a negative repeat biopsy (ref) on modeling was 1.41 (95% CI: 1.07-1.85), P = 0.01 for PCA3 and 1.28 (95% CI: 1.10-1.49), P = 0.001 for TMPRSS2:ERG.For men on active surveillance, both PCA3 and TMPRSS2:ERG seem to stratify the risk of having aggressive cancer as defined by tumor volume or Gleason score.

SUBMITTER: Lin DW

PROVIDER: S-EPMC3674574 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Urinary TMPRSS2:ERG and PCA3 in an active surveillance cohort: results from a baseline analysis in the Canary Prostate Active Surveillance Study.

Lin Daniel W DW Newcomb Lisa F LF Brown Elissa C EC Brooks James D JD Carroll Peter R PR Feng Ziding Z Gleave Martin E ME Lance Raymond S RS Sanda Martin G MG Thompson Ian M IM Wei John T JT Nelson Peter S PS

Clinical cancer research : an official journal of the American Association for Cancer Research 20130320 9

<h4>Purpose</h4>Active surveillance is used to manage low-risk prostate cancer. Both PCA3 and TMPRSS2: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.<h4>Experimental design</h4>Urine was collected after digital rectal examination prospectively as part of the multi-institutional Canary Prostate Active Surveillan ...[more]

PMID: 23515404

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Project description:Importance:Potential survival benefits from treating aggressive (Gleason score, ?7) early-stage prostate cancer are undermined by harms from unnecessary prostate biopsy and overdiagnosis of indolent disease. Objective:To evaluate the a priori primary hypothesis that combined measurement of PCA3 and TMPRSS2:ERG (T2:ERG) RNA in the urine after digital rectal examination would improve specificity over measurement of prostate-specific antigen alone for detecting cancer with Gleason score of 7 or higher. As a secondary objective, to evaluate the potential effect of such urine RNA testing on health care costs. Design, Setting, and Participants:Prospective, multicenter diagnostic evaluation and validation in academic and community-based ambulatory urology clinics. Participants were a referred sample of men presenting for first-time prostate biopsy without preexisting prostate cancer: 516 eligible participants from among 748 prospective cohort participants in the developmental cohort and 561 eligible participants from 928 in the validation cohort. Interventions/Exposures:Urinary PCA3 and T2:ERG RNA measurement before prostate biopsy. Main Outcomes and Measures:Presence of prostate cancer having Gleason score of 7 or higher on prostate biopsy. Pathology testing was blinded to urine assay results. In the developmental cohort, a multiplex decision algorithm was constructed using urine RNA assays to optimize specificity while maintaining 95% sensitivity for predicting aggressive prostate cancer at initial biopsy. Findings were validated in a separate multicenter cohort via prespecified analysis, blinded per prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) criteria. Cost effects of the urinary testing strategy were evaluated by modeling observed biopsy results and previously reported treatment outcomes. Results:Among the 516 men in the developmental cohort (mean age, 62 years; range, 33-85 years) combining testing of urinary T2:ERG and PCA3 at thresholds that preserved 95% sensitivity for detecting aggressive prostate cancer improved specificity from 18% to 39%. Among the 561 men in the validation cohort (mean age, 62 years; range, 27-86 years), analysis confirmed improvement in specificity (from 17% to 33%; lower bound of 1-sided 95% CI, 0.73%; prespecified 1-sided P?=?.04), while high sensitivity (93%) was preserved for aggressive prostate cancer detection. Forty-two percent of unnecessary prostate biopsies would have been averted by using the urine assay results to select men for biopsy. Cost analysis suggested that this urinary testing algorithm to restrict prostate biopsy has greater potential cost-benefit in younger men. Conclusions and Relevance:Combined urinary testing for T2:ERG and PCA3 can avert unnecessary biopsy while retaining robust sensitivity for detecting aggressive prostate cancer with consequent potential health care cost savings.

Project description:BackgroundTMPRSS2:ERG (T2:ERG) and prostate cancer antigen 3 (PCA3) are the most advanced urine-based prostate cancer (PCa) early detection biomarkers.ObjectiveValidate logistic regression models, termed Mi-Prostate Score (MiPS), that incorporate serum prostate-specific antigen (PSA; or the multivariate Prostate Cancer Prevention Trial risk calculator version 1.0 [PCPTrc]) and urine T2:ERG and PCA3 scores for predicting PCa and high-grade PCa on biopsy.Design, setting, and participantsT2:ERG and PCA3 scores were generated using clinical-grade transcription-mediated amplification assays. Pretrained MiPS models were applied to a validation cohort of whole urine samples prospectively collected after digital rectal examination from 1244 men presenting for biopsy.Outcome measurements and statistical analysisArea under the curve (AUC) was used to compare the performance of serum PSA (or the PCPTrc) alone and MiPS models. Decision curve analysis (DCA) was used to assess clinical benefit.Results and limitationsAmong informative validation cohort samples (n=1225 [98%], 80% from patients presenting for initial biopsy), models incorporating T2:ERG had significantly greater AUC than PSA (or PCPTrc) for predicting PCa (PSA: 0.693 vs 0.585; PCPTrc: 0.718 vs 0.639; both p<0.001) or high-grade (Gleason score >6) PCa on biopsy (PSA: 0.729 vs 0.651, p<0.001; PCPTrc: 0.754 vs 0.707, p=0.006). MiPS models incorporating T2:ERG score had significantly greater AUC (all p<0.001) than models incorporating only PCA3 plus PSA (or PCPTrc or high-grade cancer PCPTrc [PCPThg]). DCA demonstrated net benefit of the MiPS_PCPTrc (or MiPS_PCPThg) model compared with the PCPTrc (or PCPThg) across relevant threshold probabilities.ConclusionsIncorporating urine T2:ERG and PCA3 scores improves the performance of serum PSA (or PCPTrc) for predicting PCa and high-grade PCa on biopsy.Patient summaryIncorporation of two prostate cancer (PCa)-specific biomarkers (TMPRSS2:ERG and PCA3) measured in the urine improved on serum prostate-specific antigen (or a multivariate risk calculator) for predicting the presence of PCa and high-grade PCa on biopsy. A combined test, Mi-Prostate Score, uses models validated in this study and is clinically available to provide individualized risk estimates.

Project description:BackgroundMany patients who are on active surveillance (AS) for prostate cancer will have surveillance prostate needle biopsies (PNBs) without any cancer evident.ObjectiveTo define the association between negative surveillance PNBs and risk of reclassification on AS.Design, setting, and participantsAll men were enrolled in the Canary Prostate Active Surveillance Study (PASS) between 2008 and 2016. Men were included if they had Gleason ≤3+4 prostate cancer and <34% core involvement ratio at diagnosis. Men were prescribed surveillance PNBs at 12 and 24 mo after diagnosis and then every 24 mo.Outcome measurements and statistical analysisReclassification was defined as an increase in Gleason grade and/or an increase in the ratio of biopsy cores to cancer to ≥34%. PNB outcomes were defined as follows: (1) no cancer on biopsy, (2) cancer without reclassification, or (3) reclassification. Kaplan-Meier and Cox proportional hazard models were performed to assess the risk of reclassification.Results and limitationsA total of 657 men met inclusion criteria. On first surveillance PNB, 214 (32%) had no cancer, 282 (43%) had cancer but no reclassification, and 161 (25%) reclassified. Among those who did not reclassify, 313 had a second PNB. On second PNB, 120 (38%) had no cancer, 139 (44%) had cancer but no reclassification, and 54 (17%) reclassified. In a multivariable analysis, significant predictors of decreased future reclassification after the first PNB were no cancer on PNB (hazard ratio [HR]=0.50, p=0.008), lower serum prostate-specific antigen, larger prostate size, and lower body mass index. A finding of no cancer on the second PNB was also associated with significantly decreased future reclassification in a multivariable analysis (HR=0.15, p=0.003), regardless of the first PNB result. The major limitation of this study is a relatively small number of patients with long-term follow-up.ConclusionsMen who have a surveillance PNB with no evidence of cancer are significantly less likely to reclassify on AS in the PASS cohort. These findings have implications for tailoring AS protocols.Patient summaryMen on active surveillance for prostate cancer who have a biopsy showing no cancer are at a decreased risk of having worse disease in the future. This may have an impact on how frequently biopsies are required to be performed in the future.

Dataset Information

Urinary TMPRSS2:ERG and PCA3 in an active surveillance cohort: results from a baseline analysis in the Canary Prostate Active Surveillance Study.

Publications

Urinary TMPRSS2:ERG and PCA3 in an active surveillance cohort: results from a baseline analysis in the Canary Prostate Active Surveillance Study.

Similar Datasets

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