MyLibrary.bib

@article{Donovan2015,
abstract = {BACKGROUND: New screening methods that can add predictive diagnostic value for aggressive (high-grade, Gleason score ⩾7) prostate cancer (PCa) are needed to reduce unnecessary biopsies for patients with non-aggressive PCa. This is particularly important for men presenting for an initial biopsy with an equivocal PSA in the 2-10 ng ml(-1) range. PCA3 and ERG are biomarkers that can add predictive value for PCa in urine; however, with a limited utility as a digital rectal exam (DRE) is required.$\backslash$n$\backslash$nMETHODS: First-catch urine samples were collected at six sites from men scheduled to undergo a prostate biopsy. Exosomal RNA was extracted, RNA copy numbers of ERG and PCA3 were measured by reverse transcription-quantitative PCR (RT-qPCR), and the EXO106 score (the sum of normalized PCA3 and ERG RNA levels) was computed. Performance was compared with standard of care (SOC; PSA, age, race or family history) parameters. Contingency table, logistic regression, receiver operating characteristics curve and box-plot analyses were performed.$\backslash$n$\backslash$nRESULTS: In this cohort (N=195), a dichotomous EXO106 score demonstrated good clinical performance in predicting biopsy result for both any cancer and high-grade disease. For high-grade disease, the negative and positive predictive values were 97.5{\%} and 34.5{\%}, respectively. The discrimination between high-grade and Gleason score ⩽6 (including benign) biopsy results by a combination of EXO106 and SOC (area under the curve (AUC)=0.803) was significantly improved compared with SOC without EXO106 (AUC=0.6723, P=0.0009). The median EXO106 score correlated (P{\textless}0.001; Spearman's rank order) with histologic grade.$\backslash$n$\backslash$nCONCLUSIONS: A novel molecular signature (EXO106 score) derived from non-DRE urine demonstrated independent, negative predictive value for the diagnosis of high-grade PCa from initial biopsy for men with 'gray zone' serum PSA levels. Its use in the biopsy decision process could result in fewer prostate biopsies for clinically insignificant disease.Prostate Cancer and Prostatic Disease advance online publication, 8 September 2015; doi:10.1038/pcan.2015.40.},
author = {Donovan, M. J. and Noerholm, M. and Bentink, S. and Belzer, S. and Skog, J. and O'Neill, V. and Cochran, J. S. and Brown, G. A.},
doi = {10.1038/pcan.2015.40},
journal = {Prostate Cancer and Prostatic Diseases},
number = {4},
pages = {370--375},
pmid = {26345389},
title = {{A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result}},
volume = {18},
year = {2015}
}
@article{Tomlins2016a,
abstract = {Background TMPRSS2:ERG (T2:ERG) and prostate cancer antigen 3 (PCA3) are the most advanced urine-based prostate cancer (PCa) early detection biomarkers. Objective Validate 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 participants T2: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 analysis Area 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 limitations Among 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 {\textless} 0.001) or high-grade (Gleason score {\textgreater}6) PCa on biopsy (PSA: 0.729 vs 0.651, p {\textless} 0.001; PCPTrc: 0.754 vs 0.707, p = 0.006). MiPS models incorporating T2:ERG score had significantly greater AUC (all p {\textless} 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. Conclusions Incorporating urine T2:ERG and PCA3 scores improves the performance of serum PSA (or PCPTrc) for predicting PCa and high-grade PCa on biopsy. Patient summary Incorporation 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.},
author = {Tomlins, Scott A and Day, John R and Lonigro, Robert J and Hovelson, Daniel H and Siddiqui, Javed and Kunju, L Priya and Dunn, Rodney L and Meyer, Sarah and Hodge, Petrea and Groskopf, Jack and Wei, John T and Chinnaiyan, Arul M},
doi = {10.1016/j.eururo.2015.04.039},
journal = {European Urology},
keywords = {Early detection,Gene fusions,PCA3,Prostate cancer,Urine biomarkers},
number = {1},
pages = {45--53},
pmid = {25985884},
title = {{Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment}},
volume = {70},
year = {2016}
}
@misc{CancerResearchUK2015,
author = {{Cancer Research UK}},
title = {{Prostate cancer incidence statistics}},
url = {http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/prostate-cancer/incidence},
urldate = {2018-02-01},
year = {2015}
}
@article{VanNeste2016,
abstract = {Background To reduce overdiagnosis and overtreatment, a test is urgently needed to detect clinically significant prostate cancer (PCa). Objective To develop a multimodal model, incorporating previously identified messenger RNA (mRNA) biomarkers and traditional risk factors that could be used to identify patients with high-grade PCa (Gleason score ≥7) on prostate biopsy. Design, setting, and participants In two prospective multicenter studies, urine was collected for mRNA profiling after digital rectal examination (DRE) and prior to prostate biopsy. The multimodal risk score was developed on a first cohort (n = 519) and subsequently validated clinically in an independent cohort (n = 386). Outcome measurements and statistical analysis The mRNA levels were measured using reverse transcription quantitative polymerase chain reaction. Logistic regression was used to model patient risk and combine risk factors. Models were compared using the area under the curve (AUC) of the receiver operating characteristic, and clinical utility was evaluated with a decision curve analysis (DCA). Results and limitations HOXC6 and DLX1 mRNA levels were shown to be good predictors for the detection of high-grade PCa. The multimodal approach reached an overall AUC of 0.90 (95{\%} confidence interval [CI], 0.85–0.95) in the validation cohort (AUC 0.86 in the training cohort), with the mRNA signature, prostate-specific antigen (PSA) density, and previous cancer-negative prostate biopsies as the strongest, most significant components, in addition to nonsignificant model contributions of PSA, age, and family history. For another model, which included DRE as an additional risk factor, an AUC of 0.86 (95{\%} CI, 0.80–0.92) was obtained (AUC 0.90 in the training cohort). Both models were successfully validated, with no significant change in AUC in the validation cohort, and DCA indicated a strong net benefit and the best reduction in unnecessary biopsies compared with other clinical decision-making tools, such as the Prostate Cancer Prevention Trial risk calculator and the PCA3 assay. Conclusions The risk score based on the mRNA liquid biopsy assay combined with traditional clinical risk factors identified men at risk of harboring high-grade PCa and resulted in a better patient risk stratification compared with current methods in clinical practice. Therefore, the risk score could reduce the number of unnecessary prostate biopsies. Patient summary This study evaluated a novel urine-based assay that could be used as a noninvasive diagnostic aid for high-grade prostate cancer (PCa). When results of this assay are combined with traditional clinical risk factors, risk stratification for high-grade PCa and biopsy decision making are improved.},
author = {{Van Neste}, Leander and Hendriks, Rianne J. and Dijkstra, Siebren and Trooskens, Geert and Cornel, Erik B. and Jannink, Sander A. and de Jong, Hans and Hessels, Daphne and Smit, Frank P. and Melchers, Willem J.G. and Leyten, Gis{\`{e}}le H.J.M. and de Reijke, Theo M. and Vergunst, Henk and Kil, Paul and Knipscheer, Ben C. and {Hulsbergen-van de Kaa}, Christina A. and Mulders, Peter F.A. and van Oort, Inge M. and {Van Criekinge}, Wim and Schalken, Jack A.},
doi = {10.1016/j.eururo.2016.04.012},
journal = {European Urology},
keywords = {Biologic markers,Logistic models,Messenger RNA,PSA,Prostate neoplasms,Urine},
number = {5},
pages = {740--748},
pmid = {27108162},
title = {{Detection of High-grade Prostate Cancer Using a Urinary Molecular Biomarker–Based Risk Score}},
volume = {70},
year = {2016}
}
@article{McKiernan2016b,
abstract = {IMPORTANCE Overdiagnosis and overtreatment of indolent prostate cancer (PCa) is a serious health issue in most developed countries. There is an unmet clinical need for noninvasive, easy to administer, diagnostic assays to help assess whether a prostate biopsy is warranted. OBJECTIVE To determine the performance of a novel urine exosome gene expression assay (the ExoDx Prostate IntelliScore urine exosome assay) plus standard of care (SOC) (ie, prostate-specific antigen [PSA] level, age, race, and family history) vs SOC alone for discriminating between Gleason score (GS)7 and GS6 and benign disease on initial biopsy. DESIGN, SETTING, AND PARTICIPANTS In training, using reverse-transcriptase polymerase chain reaction (PCR), we compared the urine exosome gene expression assay with biopsy outcomes in 499 patients with prostate-specific antigen (PSA) levels of 2 to20 ng/mL. The derived prognostic score was then validated in 1064 patients from 22 community practice and academic urology clinic sites in the United States. Eligible participants included PCa-free men, 50 years or older, scheduled for an initial or repeated prostate needle biopsy due to suspicious digital rectal examination (DRE) findings and/or PSA levels (limit range, 2.0-20.0 ng/mL)},
author = {McKiernan, James and Donovan, Michael J. and O'Neill, Vince and Bentink, Stefan and Noerholm, Mikkel and Belzer, Susan and Skog, Johan and Kattan, Michael W. and Partin, Alan and Andriole, Gerald and Brown, Gordon and Wei, John T. and Thompson, Ian M. and Carroll, Peter},
doi = {10.1001/jamaoncol.2016.0097},
journal = {JAMA Oncology},
keywords = {area under curve,biopsy,cancer diagnosis,comparative effectiveness research,exosomes,gene expression,gleason grading system for prostatic cancer,overtreatment,polymerase chain reaction,prognostic marker,prostate cancer,prostate-specific antigen,prostate-specific antigen screening,prostatic neoplasms,roc curve,unnecessary procedures,urinalysis,urine},
month = {jul},
number = {7},
pages = {882--889},
pmid = {27032035},
publisher = {American Medical Association},
title = {{A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy}},
volume = {2},
year = {2016}
}
@article{Hamdy2016,
abstract = {BackgroundThe comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. MethodsWe compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. ResultsThere were 17 prostate-cancer–specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95{\%} confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95{\%} CI, 0.4 to 2.2), and 4 in the radiotherapy group ...},
author = {Hamdy, Freddie C. and Donovan, Jenny L. and Lane, J. Athene and Mason, Malcolm and Metcalfe, Chris and Holding, Peter and Davis, Michael and Peters, Tim J. and Turner, Emma L. and Martin, Richard M. and Oxley, Jon and Robinson, Mary and Staffurth, John and Walsh, Eleanor and Bollina, Prasad and Catto, James and Doble, Andrew and Doherty, Alan and Gillatt, David and Kockelbergh, Roger and Kynaston, Howard and Paul, Alan and Powell, Philip and Prescott, Stephen and Rosario, Derek J. and Rowe, Edward and Neal, David E.},
doi = {10.1056/NEJMoa1606220},
journal = {New England Journal of Medicine},
month = {oct},
number = {15},
pages = {1415--1424},
pmid = {27626136},
publisher = {Massachusetts Medical Society},
title = {{10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer}},
volume = {375},
year = {2016}
}
@article{Selvadurai2013,
abstract = {Background: Active surveillance (AS) aims to allow men with favourable-risk, localised prostate cancer to avoid unnecessary treatment. Objective: To describe the clinical outcomes of a prospective study of AS. Design, setting, and participants: A single-centre, prospective cohort study. Eligibility criteria included histologically proven prostate adenocarcinoma, age 50-80 yr, stage T1/T2, prostate-specific antigen level (PSA) {\textless}15 ng/ml, Gleason score (GS) ≤3 + 3 (GS ≤3 + 4 if aged {\textgreater}65 yr), and percent positive biopsy cores (PPC) ≤50{\%}. Intervention: Patients were assessed by serum PSA level, and digital rectal examination at 3-mo intervals in year 1, 4-mo intervals in year 2, and at 6-mo intervals thereafter. Transrectal ultrasound-guided prostate biopsy was performed after 18-24 mo and every 2 yr thereafter. Treatment was recommended for PSA velocity (PSAV) {\textgreater}1 ng/ml per year or adverse histology, defined as GS ≥4 + 3 or PPC {\textgreater}50{\%}. Outcome measurements and statistical analysis: Outcomes described, using Kaplan-Meier methods, were rate of adverse histology on repeat biopsy, freedom from treatment, biochemical control after deferred treatment, and overall survival. Analyses using Cox regression were performed to determine predictors of deferred treatment and adverse histology. Results and limitations: The study enrolled 471 eligible patients from 2002 to 2011. Median age was 66 yr and median initial PSA value was 6.4 ng/ml. Eighty-eight percent of patients had T1 disease and 93{\%} had GS ≤3 + 3. At median follow-up of 5.7 yr, the 5-yr rate of adverse histology and treatment-free probability was 22{\%} (95{\%} confidence interval [CI], 16-29{\%}) and 70{\%} (95{\%} CI, 65-75{\%}), respectively. There were two deaths from prostate cancer. Predictors of time to adverse histology were GS 7, PSAV {\textgreater}1 ng/ml per year, low ratio of free PSA to total PSA, and PPC {\textgreater}25{\%}. Longer follow-up is needed to confirm the safety of this strategy. Conclusions: This study demonstrates satisfactory medium-term outcomes for AS in selected men with localised prostate cancer. {\textcopyright} 2013 European Association of Urology.},
author = {Selvadurai, Elizabeth D. and Singhera, Mausam and Thomas, Karen and Mohammed, Kabir and Woode-Amissah, Ruth and Horwich, Alan and Huddart, Robert A. and Dearnaley, David P. and Parker, Chris C.},
doi = {10.1016/j.eururo.2013.02.020},
journal = {European Urology},
keywords = {Active surveillance,Outcomes,Prostate cancer},
mendeley-groups = {Prostate Cancer},
month = {dec},
number = {6},
pages = {981--987},
pmid = {23473579},
title = {{Medium-term outcomes of active surveillance for localised prostate cancer}},
volume = {64},
year = {2013}
}
@article{Donovan2016,
abstract = {Background Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. Methods We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. Results The rate of questionnaire completion during follow-up was higher than 85{\%} for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. Conclusions In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).},
author = {Donovan, Jenny L. and Hamdy, Freddie C. and Lane, J. Athene and Mason, Malcolm and Metcalfe, Chris and Walsh, Eleanor and Blazeby, Jane M. and Peters, Tim J. and Holding, Peter and Bonnington, Susan and Lennon, Teresa and Bradshaw, Lynne and Cooper, Deborah and Herbert, Phillipa and Howson, Joanne and Jones, Amanda and Lyons, Norma and Salter, Elizabeth and Thompson, Pauline and Tidball, Sarah and Blaikie, Jan and Gray, Catherine and Bollina, Prasad and Catto, James and Doble, Andrew and Doherty, Alan and Gillatt, David and Kockelbergh, Roger and Kynaston, Howard and Paul, Alan and Powell, Philip and Prescott, Stephen and Rosario, Derek J. and Rowe, Edward and Davis, Michael and Turner, Emma L. and Martin, Richard M. and Neal, David E.},
doi = {10.1056/NEJMoa1606221},
journal = {New England Journal of Medicine},
mendeley-groups = {Prostate Cancer},
month = {oct},
number = {15},
pages = {1425--1437},
pmid = {27626365},
publisher = {Massachusetts Medical Society},
title = {{Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer}},
volume = {375},
year = {2016}
}