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1.
Meelan Bul Xiaoye Zhu Riccardo Valdagni Tom Pickles Yoshiyuki Kakehi Antti Rannikko Anders Bjartell Deric K. van der Schoot Erik B. Cornel Giario N. Conti Egbert R. Boevé Frédéric Staerman Jenneke J. Vis-Maters Henk Vergunst Joris J. Jaspars Petra Strölin Erik van Muilekom Fritz H. Schröder Chris H. Bangma Monique J. Roobol 《European urology》2013
Background
Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa.Objective
To update our experience in the largest worldwide prospective AS cohort.Design, setting, and participants
Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤6. PSA was measured every 3–6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification.Outcome measurements and statistical analysis
Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy–free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time.Results and limitations
In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS.Conclusions
Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized.Trial registration
The current program is registered at the Dutch Trial Register with ID NTR1718 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718). 相似文献2.
Bimal Bhindi Girish S. Kulkarni Antonio Finelli Shabbir M.H. Alibhai Robert J. Hamilton Ants Toi Theodorus H. van der Kwast Andrew Evans Karen Hersey Michael A.S. Jewett Alexandre R. Zlotta John Trachtenberg Neil E. Fleshner 《European urology》2014
Background
Active surveillance (AS) is an expectant management strategy for prostate cancer (PCa). The impact of obesity on progression is not well characterized in this population.Objective
To determine if obesity is associated with progression in men on AS for low-risk PCa.Design, setting, and participants
Men undergoing AS for low-risk PCa (no Gleason pattern ≥4, three or fewer cores involved or one-third or less of the total number of cores involved, and no core with >50% cancer involvement) were identified at our institution.Outcome measurements and statistical analysis
The outcomes were pathologic progression (defined as no longer meeting low-risk criteria on follow-up biopsy) and therapeutic progression (defined as intent to initiate active treatment). Kaplan-Meier curves and multivariable logistic regression and Cox proportional hazards models were used, with separate models for reclassification at confirmatory biopsy (first biopsy after diagnostic biopsy) and progression beyond confirmatory biopsy.Results and limitations
In this cohort of 565 men (median follow-up: 48 mo), 124 (22%) were obese (body mass index [BMI] ≥30 kg/m2). Pathologic and therapeutic progression occurred in 168 men (30%) and 172 men (30%), respectively. No association was noted between obesity and risk of progression at the confirmatory biopsy. However, beyond confirmatory biopsy, obesity was associated with a greater probability of pathologic progression (p = 0.007) and therapeutic progression (p = 0.007) in Kaplan-Meier analyses. In adjusted Cox models, each 5-unit increase in BMI was associated with an increased risk of pathologic progression (hazard ratio [HR]: 1.5; 95% confidence interval [CI], 1.1–2.1; p = 0.02) and therapeutic progression (HR: 1.4; 95% CI, 1.0–1.9; p = 0.05). The main limitation is the retrospective design, limiting the ability to assess BMI changes over time.Conclusions
Obesity was associated with a significantly increased risk of progression beyond the confirmatory biopsy. This suggests an increased risk of long-term biologic progression rather than solely misclassification.Patient summary
As opposed to immediate active treatment (surgery or radiation), active surveillance (AS) involves closely monitoring low-risk prostate cancers and only using active treatment if there are signs of progression. Our study is the first to suggest that obesity is associated with a higher risk of cancer progression while on AS. Further research is needed to determine if diet and exercise can decrease the risk of cancer progression while on AS. 相似文献3.
4.
Walz J Graefen M Chun FK Erbersdobler A Haese A Steuber T Schlomm T Huland H Karakiewicz PI 《European urology》2006,50(3):498-505
Objectives
We explored the yield of saturation biopsy and developed a nomogram predicting the probability of prostate cancer (PCa) on the basis of saturation biopsy.Materials and methods
Between 2001 and 2004, saturation biopsies (average of 24 cores) were performed in 161 men with persistently elevated prostate specific antigen (PSA) level (median, 9 ng/ml). All had at least two previously negative, eight-core biopsy sessions. PCa predictors on saturation biopsy were integrated within multivariate nomograms.Results
PCa detection was 41% (n = 66 of 161). PSA density and transition zone volume were the most significant predictors of PCa on saturation biopsy. The accuracy of the nomogram with the best performance characteristics was 72%.Conclusions
Saturation biopsy may be indicated in men with a persistent suspicion of PCa. High-risk individuals can be identified accurately with our nomogram. 相似文献5.
Rebecka Arnsrud Godtman Erik Holmberg Ali Khatami Johan Stranne Jonas Hugosson 《European urology》2013
Background
Active surveillance (AS) has emerged as a treatment strategy for reducing overtreatment of screen-detected, low-risk prostate cancer (PCa).Objective
To assess outcomes following AS of men with screen-detected PCa.Design, setting, and participants
Of the 968 men who were diagnosed with screen-detected PCa between 1995 and 2010 in the Göteborg randomised, population-based PCa screening trial, 439 were managed with AS and were included in this study. Median age at diagnosis was 65.4 yr of age, and median follow-up was 6.0 yr from diagnosis.Intervention
The study participants were followed at intervals of 3–12 mo and were recommended to switch to deferred active treatment in case of a progression in prostate-specific antigen, grade, or stage.Outcome measurements and statistical analysis
The end points—overall survival (OS), treatment-free survival, failure-free (no relapse after radical treatment) survival, and cancer-specific survival—were calculated for various risk groups (very low, low, intermediate, and high) with Kaplan-Meier estimates. A Cox proportional hazards model as well as a competing risk analysis were used to assess whether risk group or age at diagnosis was associated with failure after AS.Results and limitations
Forty-five per cent of all screen-detected PCa were managed with AS, and very low-risk and low-risk PCa constituted 60% of all screen-detected PCa. Thirty-seven per cent (162 of 439) switched from surveillance to deferred active treatment, and 39 men failed AS. The 10-yr OS, treatment-free survival, and failure-free survival were 81.1%, 45.4%, and 86.4%, respectively (Kaplan-Meier estimates). Men with low-, intermediate-, and high-risk tumours had a hazard ratio for failure of 2.1 (p = 0.09), 3.6 (p = 0.002), and 4.6 (p = 0.15), respectively, compared to very low-risk tumours (Cox regression). Only one PCa death occurred, and one patient developed metastasis (both in the intermediate-risk group). The main limitation of this study is the relatively short follow-up.Conclusions
A large proportion of men with screen-detected PCa can be managed with AS. AS appears safe for men with low-risk PCa. 相似文献6.
van den Bergh RC Roemeling S Roobol MJ Aus G Hugosson J Rannikko AS Tammela TL Bangma CH Schröder FH 《European urology》2009,55(1):1-8
Background
The incidence of small, localised, well-differentiated prostate cancer (PCa) is increasing, mainly as a result of screening. Many of these cancers will not progress, and radical therapy may lead to substantial overtreatment. Active surveillance (AS) has emerged as an alternative.Objective
To retrospectively validate the currently used criteria for eligibility for AS.Design, setting, and participants
For this cohort study, data from 616 men who were diagnosed with PCa between 1994 and 2007 at a mean age of 66.3 yr in four centres of the European Randomized Study of Screening for Prostate Cancer (ERSPC) were combined. All patients fit the criteria for AS (prostate-specific antigen [PSA] ≤10.0 ng/ml, PSA-density <0.2 ng/ml per ml, stage T1C/T2, Gleason score ≤3 + 3 = 6, and ≤2 positive biopsy cores), and initially they were managed expectantly. Median follow-up was 3.91 yr.Measurements
Disease specific-, overall-, and treatment-free survival were studied. Present PSA characteristics were assessed and also compared between men who were switching to deferred active therapy during follow-up and men remaining untreated.Results and limitations
The calculated (Kaplan-Meier) 10-yr PCa-specific survival (21 patients at risk) was 100%, which sharply contrasted with 77% overall survival. Men still alive showed favourable PSA characteristics. Although the calculated 10-yr treatment-free survival was only 43%, objective signs of progression often did not indicate the shift to radical treatment. The cohort consisted of men on AS and those on watchful waiting (WW); information on comorbidity or psychological distress was not available.Conclusions
AS seems justified in selected men with screen-detected PCa. Prospective protocol-based AS programs are necessary to optimise selection criteria and to find the appropriate trigger points for switching to active therapy. Possible negative psychological reactions with AS against improved quality of life by withholding side-effects from radical treatment should be considered. 相似文献7.
8.
Lih-Ming Wong Shabbir M.H. Alibhai Greg Trottier Narhari Timilshina Theodorus Van der Kwast Alexandre Zlotta Nathan Lawrentschuk Girish Kulkarni Robert Hamilton Sarah Ferrara David Margel John Trachtenberg Michael A. Jewett Ants Toi Andrew Evans Neil E. Fleshner Antonio Finelli 《European urology》2014
Background
Many men (21–52%) are reported to have no cancer on the second, also known as the confirmatory, biopsy (B2) for prostate cancer active surveillance (AS). If these men had a reduced risk of pathologic progression, particularly grade related, the intensity of their follow-up could be decreased.Objective
To investigate if men with no cancer on B2 are less likely to undergo subsequent pathologic progression.Design, setting, and participants
Men were identified from our tertiary care center AS prostate cancer database (1995–2012). Eligibility criteria were prostate-specific antigen (PSA) ≤10, cT2 or lower, no Gleason grade 4 or 5, three or fewer positive cores, and no core >50% involved. Only patients with three or more biopsies were selected and then dichotomized on cancer status (yes or no) at B2.Intervention
AS.Outcome measurements and statistical analysis
Pathologic progression was defined as grade (advancement in Gleason score) and/or volume (more than three positive cores, >50% core involved). Progression-free survival was compared. Predictors of progression were investigated using a Cox proportional hazards model.Results and limitations
Of the 286 patients remaining on AS after B2, 149 (52%) had no cancer and 137 (48%) had cancer. The median follow-up after B2 was 41 mo (interquartile range [IQR]: 26.5–61.9). Progression-free survival at 5 yr was 85.2% versus 67.3% for negative B2 versus cancer on B2, respectively (p = 0.002). Men with no cancer at B2 had a 53% reduction in risk of subsequent progression (hazard ratio [HR]: 0.47; 95% confidence interval [CI], 0.29–0.77; p = 0.003). Subanalysis showed prognostic indicators of volume-related progression were absence of cancer (HR: 0.36; 95% CI, 0.20–0.62; p = 0.0006) and PSA density (HR: 1.79; 95% CI, 1.12–2.89; p = 0.01). The only predictor of grade-related progression was age (HR: 1.05; 95% CI, 1.00–1.10; p = 0.04). Retrospective analysis was the major limitation of the study.Conclusions
Absence of cancer on B2 is associated with a significantly decreased risk of volume-related but not grade-related progression. This must be considered when counseling men on AS. 相似文献9.
Mark S. Soloway Cynthia T. SolowayAhmed Eldefrawy Kristell AcostaBruce Kava Murugesan Manoharan 《European urology》2010
Background
With the advent of prostate-specific antigen (PSA) screening and the increase in the number of transrectal ultrasound–guided biopsy cores, there has been a dramatic rise in the incidence of low-risk prostate cancer (LRPC). Because >97% of men with LRPC are likely to die of something other than prostate cancer, it is critical that patients give thought to whether early curative treatment is the only option at diagnosis.Objective
To identify a group of men with LRPC who may not require initial treatment and monitor them on our active surveillance (AS) protocol, to determine the percentage treated and the outcome and to analyze the quality-of-life data.Design, setting, and participants
We defined patients eligible for AS as Gleason ≤6, PSA ≤10, and two or fewer biopsy cores with ≤20% tumor in each core.Measurements
Kaplan Meier analysis was used to predict the 5-year treatment free survival. Logistic regression determined the predictors of treatment. Data on sexual function, continence, and outcome were obtained and analyzed.Results and limitations
The AS cohort consisted of 230 patients with a mean age of 63.4 yr; 86% remained on AS for a mean follow-up of 44 mo. Thirty-two of the 230 patients (14%) were treated for a mean follow-up of 33 mo. Twelve had a total prostatectomy (TP). The pathologic stage of these patients was similar to initially treated TP patients with LRPC. Fourteen underwent radiation therapy, and six underwent androgen-deprivation therapy. Fifty percent of patients had no tumor on the first rebiopsy, and only 5% of these patients were subsequently treated. PSA doubling time and clinical stage were not predictors of treatment. No patient progressed after treatment. Among the AS patients, 30% had incontinence, yet <15% were bothered by it. As measured by the Sexual Health Inventory for Men, 49% of patients had, at a minimum, moderate (≤16) erectile dysfunction.Conclusions
If guidelines for AS are narrowly defined to include only patients with Gleason 6, tumor volume ≤20% in one or two biopsy cores, and PSA levels ≤10, few patients are likely to require treatment. Progression-free survival of those treated is likely to be equivalent to patients with similar clinical findings treated at diagnosis. 相似文献10.
Roderick C.N. van den Bergh Peter C. Albertsen Chris H. Bangma Stephen J. Freedland Markus Graefen Andrew Vickers Henk G. van der Poel 《European urology》2013
Context
Delaying definitive therapy unfavourably affects outcomes in many malignancies. Diagnostic, psychological, and logistical reasons but also active surveillance (AS) strategies can lead to treatment delay, an increase in the interval between the diagnosis and treatment of prostate cancer (PCa).Objective
To review and summarise the current literature on the impact of treatment delay on PCa oncologic outcomes.Evidence acquisition
A comprehensive search of PubMed and Embase databases until 30 September 2012 was performed. Studies comparing pathologic, biochemical recurrence (BCR), and mortality outcomes between patients receiving direct and delayed curative treatment were included. Studies presenting single-arm results following AS were excluded.Evidence synthesis
Seventeen studies were included: 13 on radical prostatectomy, 3 on radiation therapy, and 1 combined both. A total of 34 517 PCa patients receiving radical local therapy between 1981 and 2009 were described. Some studies included low-risk PCa only; others included a wider spectrum of disease. Four studies found a significant effect of treatment delay on outcomes in multivariate analysis. Two included low-risk patients only, but it was unknown whether AS was applied or repeat biopsy triggered active therapy during AS. The two other studies found a negative effect on BCR rates of 2.5–9 mo delay in higher risk patients (respectively defined as any with T ≥2b, prostate-specific antigen >10, Gleason score >6, >34–50% positive cores; or D’Amico intermediate risk-group). All studies were retrospective and nonrandomised. Reasons for delay were not always clear, and time-to-event analyses may be subject to bias.Conclusions
Treatment delay of several months or even years does not appear to affect outcomes of men with low-risk PCa. Limited data suggest treatment delay may have an impact on men with non–low-risk PCa. Most AS protocols suggest a confirmatory biopsy to avoid delaying treatment in those who harbour higher risk disease that was initially misclassified. 相似文献11.
Elizabeth D. Selvadurai Mausam Singhera Karen Thomas Kabir Mohammed Ruth Woode-Amissah Alan Horwich Robert A. Huddart David P. Dearnaley Chris C. Parker 《European urology》2013
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) <15 ng/ml, Gleason score (GS) ≤3 + 3 (GS ≤3 + 4 if aged >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) >1 ng/ml per year or adverse histology, defined as GS ≥4 + 3 or PPC >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 >1 ng/ml per year, low ratio of free PSA to total PSA, and PPC >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. 相似文献12.
Pietro Pepe Antonio Garufi Giandomenico Priolo Michele Pennisi 《World journal of urology》2016,34(9):1249-1253
Purpose
The detection rate for significant prostate cancer of mMRI/TRUS fusion targeted biopsy versus saturation prostate biopsy was prospectively evaluated in men enrolled in active surveillance (AS) protocol.Methods
From May 2013 to January 2015, 40 men aged 66 years (median) with very low-risk PCa were enrolled in an AS protocol, and eligible criteria were: life expectancy greater than 10 years, cT1C, PSA below 10 ng/ml, PSA density <0.20, ≤2 unilateral positive biopsy cores, Gleason score (GS) equal to 6, greatest percentage of cancer (GPC) in a core ≤50 %. All patients underwent 3.0-Tesla pelvic mpMRI before confirmatory transperineal saturation biopsy (SPBx; median 30 cores) combined with mpMRI/TRUS fusion targeted biopsy (median 4 cores) of suspicious lesions (PI-RADS 4–5).Results
Ten out of 40 (25 %) patients were reclassified by SPBx based on upgraded GS ≥ 7; mpMRI found all the lesions predictive of significant PCa showing a false-positive rate equal to 5 %; on the contrary, mpMRI/TRUS targeted biopsy missed 3/10 (30 %) significant PCa characterised by the presence of a single positive core of GS ≥ 7 and GPC ≤ 5 %, suggesting that reduced number of targeted biopsies could miss small but significant PCa. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive value of mpMRI in diagnosing significant PCa were 95.2, 100, 93.8, 83.4, 100 %, respectively.Conclusions
Although mpMRI provided high diagnostic accuracy (about 95 %) in diagnosing clinically significant PCa, mpMRI/TRUS fusion targeted biopsy cannot replace SPBx at confirmatory biopsy of men enrolled in AS protocols.13.
Monique J. Roobol Xiaoye Zhu Fritz H. Schröder Geert J.L.H. van Leenders Ron H. van Schaik Chris H. Bangma Ewout W. Steyerberg 《European urology》2013
Background
Inconclusive test results often occur after prostate-specific antigen (PSA)–based screening for prostate cancer (PCa), leading to uncertainty on whether, how, and when to repeat testing.Objective
To develop and validate a prediction tool for the risk of PCa 4 yr after an initially negative screen.Design, setting, and participants
We analyzed data from 15 791 screen-negative men aged 55–70 yr at the initial screening round of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.Outcome measurements and statistical analysis
Follow-up and repeat screening at 4 yr showed either no PCa, low-risk PCa, or potentially high-risk PCa (defined as clinical stage >T2b and/or biopsy Gleason score ≥7 and/or PSA ≥10.0 ng/ml). A multinomial logistic regression analysis included initial screening data on age, PSA, digital rectal examination (DRE), family history, prostate volume, and having had a previous negative biopsy. The 4-yr risk predictions were validated with additional follow-up data up to 8 yr after initial screening.Results and limitations
Positive family history and, especially, PSA level predicted PCa, whereas a previous negative biopsy or a large prostate volume reduced the likelihood of future PCa. The risk of having PCa 4 yr after an initially negative screen was 3.6% (interquartile range: 1.0–4.7%). Additional 8-yr follow-up data confirmed these predictions. Although data were based on sextant biopsies and a strict protocol-based biopsy indication, we suggest that men with a low predicted 4-yr risk (eg, ≤1.0%) could be rescreened at longer intervals or not at all, depending on competing risks, while men with an elevated 4-yr risk (eg, ≥5%) might benefit from immediate retesting. These findings need to be validated externally.Conclusions
This 4-yr future risk calculator, based on age, PSA, DRE, family history, prostate volume, and previous biopsy status, may be a promising tool for reducing uncertainty, unnecessary testing, and overdiagnosis of PCa. 相似文献14.
Background
Salvage radical prostatectomy (SRP) for radiorecurrent prostate cancer (PCa) is a second local treatment with curative intent in patients with true organ-confined recurrent PCa.Objective
We evaluated preoperative prognostic risk factors to predict organ-confined, locally recurrent PCa after primary radiotherapy (RT).Design, setting, and participants
Fifty-five men with biopsy-proven, locally recurrent PCa underwent SRP and extended pelvic lymph node dissection (ePLND) after external-beam radiotherapy (EBRT) or low- or high-dose brachytherapy.Measurements
Prostate-specific antigen (PSA), clinical stage, biopsy Gleason score prior to RT and SRP, PSA nadir, time to recurrence, PSA doubling time (PSA DT), PSA prior to surgery, and pathohistology of the SRP specimen were analysed to predict organ-confined recurrent disease. Uni- and multivariate statistical analysis was performed.Results and limitations
Forty (72.7%) and 15 (27.3%) patients demonstrated organ-confined and locally advanced PCa, respectively. Eleven patients (20%) and seven patients (12.7%) had lymph node metastases and positive surgical margins (PSM), respectively. On multivariate analysis, biopsy Gleason score prior to SRP (p = 0.02), <50% positive biopsy cores (p = 0.001), PSA DT >12 mo (p = 0.001), and low-dose brachytherapy (p = 0.001) were significant predictors of organ-confined PCa with negative surgical margins (NSM). Limitations of the study are its retrospective nature and the relatively low number of patients.Conclusions
SRP is a surgically challenging but effective secondary local treatment of radiorecurrent PCa with curative intent. The identified predictive parameters will help to select patients most suitable for SRP with long-term cure and good functional outcome. 相似文献15.
Kasper Drimer Berg Ben Vainer Frederik Birkebæk Thomsen M. Andreas Røder Thomas Alexander Gerds Birgitte Grønkær Toft Klaus Brasso Peter Iversen 《European urology》2014
Background
Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed.Objective
To examine the association between ERG expression at diagnosis and the risk of progression during AS.Design, setting, and participants
This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10–12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression.Outcome measurements and statistical analysis
Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events.Results and limitations
A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression (p < 0.0001) and of the subgroups PSA progression (p < 0.0001) and histopathologic progression (p < 0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3–29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7–68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62–3.72; p < 0.0001). The main limitation of this study is its observational nature.Conclusions
In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes.Patient summary
The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression. 相似文献16.
Background
The diagnostic performance of a genetic score based on single nucleotide polymorphisms (SNPs) is unknown in the prostate-specific antigen (PSA) range of 1–3 ng/ml. A substantial proportion of men in this PSA span have prostate cancer (PCa), but biomarkers to determine who should undergo a prostate biopsy are lacking.Objective
To evaluate whether a genetic risk score identifies men in the PSA range of 1–3 ng/ml who are at higher risk for PCa.Design, setting, and participants
Men aged 50–69 yr with PSA 1–3 ng/ml and without a previous prostate biopsy were selected from the STHLM2 cohort. Of 2696 men, 49 SNPs were genotyped, and a polygenic risk score was calculated. Of these men, 860 were invited according to risk score, and 172 underwent biopsy.Outcome measurements and statistical analysis
The risk of PCa was assessed using univariate and multivariate logistic regression analysis.Results and limitations
PCa was diagnosed in 47 of 172 participants (27%), with Gleason sum 6 in 36 of 47 men (77%) and Gleason sum ≥7 in 10 of 47 men (21%); one man had intraductal cancer. The genetic score was a significant predictor of a positive biopsy (p = 0.028), even after adjusting for PSA, ratio of free to total PSA, prostate volume, age, and family history. There was an increase in the odds ratio of 1.60 (95% confidence interval, 1.05–2.45) with increasing genetic risk score. The absolute risk difference of positive biopsy was 19 percentage points, comparing the high and low genetic risk group (37% vs 18%).Conclusions
A risk score based on SNPs predicts biopsy outcome in previously unbiopsied men with PSA 1–3 ng/ml. Introducing a genetic-based risk stratification tool can increase the proportion of men being classified in line with their true risk of PCa. 相似文献17.
van Leeuwen PJ Kölble K Huland H Hambrock T Barentsz J Schröder FH 《European urology》2011,59(2):183-190
Context
We addressed the question whether the change of serum prostate-specific antigen (PSA) in men who use 5α-reductase inhibitor (5-ARI) dutasteride is sensitive for the detection of aggressive prostate cancer (PCa).Objective
The case of a man using dutasteride diagnosed with Gleason 7 transition zone cancer at biopsy indicated by a rising PSA is described. The following issues are discussed: (1) Is a rise of PSA in patients using dutasteride predictive of aggressive PCa in men with prior negative biopsies? (2) Is it safe not to biopsy men using dutasteride who do not show a rising PSA? (3) How can we avoid potentially unnecessary biopsies in men using dutasteride without a rising PSA?Evidence acquisition
We reviewed the recent literature addressing our objective that relates to two studies: the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events trial.Evidence synthesis
In men using dutasteride, the positive predictive value/detection rate of Gleason 7–10 PCa is 13.2% and 4.0% for men with and without a rising PSA, respectively. However, a substantial proportion of Gleason 7–10 cases (42.9%) would be missed if a rising PSA was used as the only biopsy indication. Currently available data do not provide selective mechanisms to diagnose these cancers.Conclusions
A rising PSA for a patient using dutasteride should be an indication for prostate biopsies. Currently, in the case of stable PSA a biopsy may still be considered. Options for a selective approach are therefore suggested in this review to avoid unnecessary biopsies and to achieve a more selective PCa detection in men on 5-ARI treatment. 相似文献18.
Monique J. Roobol Fritz H. SchröderPim van Leeuwen Tineke WoltersRoderick C.N. van den Bergh Geert J.L.H. van LeendersDaphne Hessels 《European urology》2010
Background
The performance characteristics of serum prostate-specific antigen (PSA) as a diagnostic test for prostate cancer (PCa) are poor. The performance of the PCa antigen 3 (PCA3) gene as a primary diagnostic is unknown.Objective
Assess the value of PCA3 as a first-line diagnostic test.Design, setting and participants
Participants included men aged 63–75 who were invited for rescreening in the period from September 2007 to February 2009 within the European Randomised Study of Screening for Prostate Cancer, Rotterdam section.Interventions
Lateral sextant biopsies were performed if the serum PSA value was ≥3.0 ng/ml and/or the PCA3 score was ≥10.Measurements
Measurements included distribution and correlation of PSA value and PCA3 score and their relation to the number of cases and the characteristics of PCa detected. Additional value of PCA3 was included in men with previous negative biopsy and/or PSA <3.0 ng/ml.Results and limitations
In 721 men, all biopsied, 122 PCa cases (16.9%) were detected. Correlation between PSA and PCA3 is poor (Spearman rank correlation: ρ = 0.14; p < 0.0001). A PSA ≥3.0 ng/ml misses 64.7% of the total PCa that can be detected with the sextant biopsy technique and 57.9% of serious PCa (T2a or higher and/or Gleason grade ≥4, n = 19), and 68.2% of biopsies could have been avoided; the respective data for PCA3 ≥35 are 32%, 26.3%, and 51.7%. Performance of PCA3 in men with low PSA (area under the curve [AUC]: 0.63) and/or previous negative biopsy (AUC: 0.68) is unclear but has limited reliability due to small numbers.Conclusions
PCA3 as a first-line screening test shows improvement of the performance characteristics and identification of serious disease compared with PSA in this prescreened population. 相似文献19.
Avery KN Metcalfe C Vedhara K Lane JA Davis M Neal DE Hamdy FC Donovan JL Blazeby JM 《European urology》2012,62(4):649-655
Background
Little is known about factors influencing men's decisions to undergo screening and diagnostic tests for prostate cancer (PCa).Objective
Identify predictors of attendance for prostate-specific antigen (PSA) testing and prostate biopsy.Design, setting, and participants
Literature searches and interviews with men undergoing PSA testing and prostate biopsy formed the basis of a self-report questionnaire designed to identify predictors of health behaviour, which was completed by men eligible for PSA invitation and prostate biopsy. Multitrait scaling analyses established the final questionnaire content. This revised instrument was distributed to a new cohort of men before PSA testing and biopsy invitations were received. Ethical committee approval was obtained from Trent Multicentre Research Ethics Committee (MREC/01/4/025 – 21/06/2001).Measurements
Predictors of health behaviour and attendance rates for PSA test or prostate biopsy were measured. Associations between questionnaire scores and health behaviour (PSA and prostate biopsy attendance) were examined using logistic regression.Results and limitations
The provisional 49-item health behaviour questionnaire was completed by 468 of 810 men (57.8%). Multitrait scaling refined the questionnaire to 26 items in six scales (A: health benefits, B: threats to health, C: barriers to testing, D: health intentions, E: external influences, F: current general health). A total of 1455 of 2657 men (54.8%) completed the revised instrument before invitations for PSA test or biopsy were received; 395 (43.4%) and 434 (91.6%) attended. Strong associations between men's health intentions (scale D) and PSA and biopsy attendance (odds ratio: 1.56 or 3.67, respectively; p < 0.001) were observed with modest associations between the other five scales and attendance for PSA testing. Average questionnaire response rates represent the major limitation of this study.Conclusions
Knowledge and beliefs about PCa and testing predict men's intentions and attendance for PSA testing and prostate biopsy. Understanding men's health behaviour is important for the management of patients seeking PSA testing in general practice. 相似文献20.
Guillaume Ploussard Evanguelos Xylinas Laurent Salomon Yves Allory Dimitri Vordos Andras Hoznek Claude-Clment Abbou Alexandre de la Taille 《European urology》2009,56(6):891-898