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1.
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2.
Eric A. Klein Matthew R. Cooperberg Cristina Magi-Galluzzi Jeffry P. Simko Sara M. Falzarano Tara Maddala June M. Chan Jianbo Li Janet E. Cowan Athanasios C. Tsiatis Diana B. Cherbavaz Robert J. Pelham Imelda Tenggara-Hunter Frederick L. Baehner Dejan Knezevic Phillip G. Febbo Steven Shak Michael W. Kattan Mark Lee Peter R. Carroll 《European urology》2014
3.
Jens Hansen Marco Auprich Sascha A. Ahyai Alexandre de la Taille Hendrik van Poppel Michael Marberger Arnulf Stenzl Peter F.A. Mulders Hartwig Huland Margit Fisch Clement-Claude Abbou Jack A. Schalken Yves Fradet Leonard S. Marks William Ellis Alan W. Partin Karl Pummer Markus Graefen Alexander Haese Jochen Walz Alberto Briganti Shahrokh F. Shariat Felix K. Chun 《European urology》2013
Background
Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX).Objective
To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a man's risk of harboring any PCa and high-grade PCa (HGPCa).Design, setting, and participants
Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies.Intervention
IBX (≥10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement.Outcome measurements and statistical analysis
PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model.Results and limitations
Any PCa and HGPCa were diagnosed in 46% (n = 318) and 20% (n = 137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p < 0.001). The PCA3-based IBX nomograms significantly outperformed the clinical models without PCA3 (all p < 0.001). Accuracy was increased by 4.5–7.1% related to PCA3 inclusion. When applying nomogram-derived PCa probability thresholds ≤30%, only a few patients with HGPCa (≤2%) will be missed while avoiding up to 55% of unnecessary biopsies. External validation of the PCA3-based IBX-specific nomogram is warranted.Conclusions
The internally validated PCA3-based IBX-specific nomogram outperforms a clinical prediction model without PCA3 for the prediction of any PCa, leading to the avoidance of unnecessary biopsies while missing only a few cases of HGPCa. Our findings support the concepts of a combination of novel markers with established clinical risk factors and the superiority of decision tools that are specific to a clinical scenario. 相似文献4.
Moniek M. Vedder Esther W. de Bekker-Grob Hans G. Lilja Andrew J. Vickers Geert J.L.H. van Leenders Ewout W. Steyerberg Monique J. Roobol 《European urology》2014
Background
Prostate-specific antigen (PSA) testing has limited accuracy for the early detection of prostate cancer (PCa).Objective
To assess the value added by percentage of free to total PSA (%fPSA), prostate cancer antigen 3 (PCA3), and a kallikrein panel (4k-panel) to the European Randomised Study of Screening for Prostate Cancer (ERSPC) multivariable prediction models: risk calculator (RC) 4, including transrectal ultrasound, and RC 4 plus digital rectal examination (4+DRE) for prescreened men.Design, setting, and participants
Participants were invited for rescreening between October 2007 and February 2009 within the Dutch part of the ERSPC study. Biopsies were taken in men with a PSA level ≥3.0 ng/ml or a PCA3 score ≥10. Additional analyses of the 4k-panel were done on serum samples.Outcome measurements and statistical analysis
Outcome was defined as PCa detectable by sextant biopsy. Receiver operating characteristic curve and decision curve analyses were performed to compare the predictive capabilities of %fPSA, PCA3, 4k-panel, the ERSPC RCs, and their combinations in logistic regression models.Results and limitations
PCa was detected in 119 of 708 men. The %fPSA did not perform better univariately or added to the RCs compared with the RCs alone. In 202 men with an elevated PSA, the 4k-panel discriminated better than PCA3 when modelled univariately (area under the curve [AUC]: 0.78 vs 0.62; p = 0.01). The multivariable models with PCA3 or the 4k-panel were equivalent (AUC: 0.80 for RC 4+DRE). In the total population, PCA3 discriminated better than the 4k-panel (univariate AUC: 0.63 vs 0.56; p = 0.05). There was no statistically significant difference between the multivariable model with PCA3 (AUC: 0.73) versus the model with the 4k-panel (AUC: 0.71; p = 0.18). The multivariable model with PCA3 performed better than the reference model (0.73 vs 0.70; p = 0.02). Decision curves confirmed these patterns, although numbers were small.Conclusions
Both PCA3 and, to a lesser extent, a 4k-panel have added value to the DRE-based ERSPC RC in detecting PCa in prescreened men.Patient summary
We studied the added value of novel biomarkers to previously developed risk prediction models for prostate cancer. We found that inclusion of these biomarkers resulted in an increase in predictive ability. 相似文献5.
Irene M. Shui Sara Lindström Adam S. Kibel Sonja I. Berndt Daniele Campa Travis Gerke Kathryn L. Penney Demetrius Albanes Christine Berg H. Bas Bueno-de-Mesquita Stephen Chanock E. David Crawford W. Ryan Diver Susan M. Gapstur J. Michael Gaziano Graham G. Giles Brian Henderson Robert Hoover Mattias Johansson Loic Le Marchand Jing Ma Carmen Navarro Kim Overvad Fredrick R. Schumacher Gianluca Severi Afshan Siddiq Meir Stampfer Victoria L. Stevens Ruth C. Travis Dimitrios Trichopoulos Paolo Vineis Lorelei A. Mucci Meredith Yeager Edward Giovannucci Peter Kraft 《European urology》2014
Background
Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM).Objective
To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM.Design, setting, and participants
We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred.Outcome measurements and statistical analysis
The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls.Results and limitations
Among the cases, we found that 8 of the 47 SNPs were significantly associated (p < 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p < 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only.Conclusions
Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa.Patient summary
In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction. 相似文献6.
Akash Nanda Ming-Hui Chen Brian J. Moran Michelle H. Braccioforte Daniel Dosoretz Sharon Salenius Michael Katin Rudi Ross Anthony V. D’Amico 《European urology》2014
Background
Neoadjuvant hormone therapy (NHT) use is associated with an increased risk of all-cause mortality (ACM) in men with a history of coronary artery disease (CAD)–induced congestive heart failure (CHF) or myocardial infarction (MI). However, its effect in men with no or at least a single risk factor for CAD stratified by prostate cancer (PCa) aggressiveness is unknown.Objective
To assess whether NHT use affects the risk of ACM in men with low-, intermediate-, and high-risk PCa treated with brachytherapy who have no or at least a single risk factor for CAD.Design, setting, and participants
This retrospective study cohort consisted of 5411 men with low-risk PCa (prostate-specific antigen [PSA] <10 ng/ml, Gleason score 6, and clinical stage T1–T2a); 4365 men with intermediate-risk PCa (PSA 10–20 ng/ml or Gleason score <8 or clinical stage <T3); and 1360 men with localized or locally advanced, high-risk PCa consecutively treated in a community-based, multi-institutional setting between 1991 and 2006. CAD risk factors included at least a history of diabetes mellitus, hypercholesterolemia, or hypertension. The median follow-up for men with low-, intermediate-, and high-risk PCa were 4.1, 4.4, and 4.6 yr, respectively.Interventions
Men were treated with or without a median duration of 4 mo of NHT followed by brachytherapy with or without supplemental external-beam radiation therapy (EBRT).Outcome measurements and statistical analysis
Cox regression multivariable analyses were performed to assess whether NHT use affected the risk of ACM in men with low-, intermediate-, and high-risk PCa, adjusting for age; year of brachytherapy; supplemental EBRT use; the presence of CAD risk factors; treatment propensity score; and known PCa prognostic factors, including pretreatment PSA level, biopsy Gleason score, and clinical stage.Results and limitations
NHT use was associated with a significantly increased risk of ACM in men with low-risk PCa (adjusted hazard ratio [HR]: 1.27; 95% confidence interval [CI], 1.07–1.51; p < 0.01) but not in men with intermediate-risk (adjusted HR: 1.13; 95% CI, 0.96–1.35; p = 0.15) or high-risk PCa (adjusted HR: 0.86; 95% CI, 0.66–1.13; p = 0.28). Using an interaction model for the low-risk group, NHT use was associated with a significantly increased risk of ACM in the subgroup of men with at least a single CAD risk factor (adjusted HR: 1.36; 95% CI, 1.07–1.74; p = 0.01) but not for men with no CAD risk factors (adjusted HR: 1.19; 95% CI, 0.95–1.51; p = 0.13).Conclusions
For men with no or at least a single risk factor for CAD, NHT use is associated with an increased risk of ACM in the setting of low-risk but not intermediate- or high-risk PCa. This effect is driven by the subgroup of men with at least a single risk factor for CAD. These results warrant prospective validation given the widespread use of NHT for prostate downsizing prior to brachytherapy. 相似文献7.
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8.
Gisele H.J.M. Leyten Daphne Hessels Sander A. Jannink Frank P. Smit Hans de Jong Erik B. Cornel Theo M. de Reijke Henk Vergunst Paul Kil Ben C. Knipscheer Inge M. van Oort Peter F.A. Mulders Christina A. Hulsbergen-van de Kaa Jack A. Schalken 《European urology》2014
Background
Prostate cancer antigen 3 (PCA3) and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) gene fusions are promising prostate cancer (PCa) specific biomarkers that can be measured in urine.Objective
To evaluate the diagnostic and prognostic value of Progensa PCA3 and TMPRSS2-ERG gene fusions (as individual biomarkers and as a panel) for PCa in a prospective multicentre setting.Design, setting, and participants
At six centres, post–digital rectal examination first-catch urine specimens prior to prostate biopsies were prospectively collected from 497 men. We assessed the predictive value of Progensa PCA3 and TMPRSS2-ERG (quantitative nucleic acid amplification assay to detect TMPRSS2-ERG messenger RNA [mRNA]) for PCa, Gleason score, clinical tumour stage, and PCa significance (individually and as a marker panel). This was compared with serum prostate-specific antigen and the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculator. In a subgroup (n = 61) we evaluated biomarker association with prostatectomy outcome.Outcome measurements and statistical analysis
Univariate and multivariate logistic regression analysis and receiver operating curves were used.Results and limitations
Urine samples of 443 men contained sufficient mRNA for marker analysis. PCa was diagnosed in 196 of 443 men. Both PCA3 and TMPRSS2-ERG had significant additional predictive value to the ERSPC risk calculator parameters in multivariate analysis (p < 0.001 and resp. p = 0.002). The area under the curve (AUC) increased from 0.799 (ERSPC risk calculator), to 0.833 (ERSPC risk calculator plus PCA3), to 0.842 (ERSPC risk calculator plus PCA3 plus TMPRSS2-ERG) to predict PCa. Sensitivity of PCA3 increased from 68% to 76% when combined with TMPRSS2-ERG. TMPRSS2-ERG added significant predictive value to the ERSPC risk calculator to predict biopsy Gleason score (p < 0.001) and clinical tumour stage (p = 0.023), whereas PCA3 did not.Conclusions
TMPRSS2-ERG had independent additional predictive value to PCA3 and the ERSPC risk calculator parameters for predicting PCa. TMPRSS2-ERG had prognostic value, whereas PCA3 did not. Implementing the novel urinary biomarker panel PCA3 and TMPRSS2-ERG into clinical practice would lead to a considerable reduction of the number of prostate biopsies. 相似文献9.
Roberto L. Muller Leah Gerber Daniel M. Moreira Gerald Andriole Ramiro Castro-Santamaria Stephen J. Freedland 《European urology》2012
Background
Findings of studies on the association between androgens and prostate cancer (PCa) are mixed. Androgens may affect prostate-specific antigen (PSA) levels, thereby influencing biopsy recommendations. Also, androgens may stimulate prostate growth at very low levels with no additional effects at higher levels (saturation model).Objective
To test whether androgens were associated with PCa risk in the placebo arm of a prospective study in which biopsies were performed regardless of PSA level.Design, setting, and participants
Of 8122 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, 4073 men (50.1%) received placebo. Key entry criteria were PSA 2.5–10 ng/ml and one prior negative biopsy.Intervention
Per-protocol biopsies at 2 and 4 yr; for-cause biopsies at physician discretion.Outcome measurements and statistical analysis
Multivariable logistic regression was used to test the association between baseline log-transformed testosterone and dihydrotestosterone (DHT) levels and the risk of detecting either PCa or low-grade PCa (Gleason score <6) compared with high-grade PCa (Gleason score >7). In secondary analysis, we stratified the analysis by low baseline androgen levels (testosterone <10 nmol/l; DHT <0.76 nmol/l) compared with normal baseline androgen levels.Results and limitations
Of 4073 men, 3255 (79.9%) had at least one biopsy after randomization and were analyzed. Androgen levels tested continuously or by quintiles were generally unrelated to PCa detection or grade. PCa detection was similar among men with low compared with normal baseline testosterone levels (25.5% and 25.1%; p = 0.831). In secondary analysis, higher testosterone levels at baseline were associated with higher PCa detection (odds ratio: 1.23; 95% confidence interval, 1.06–1.43; p = 0.006) only if men had low baseline testosterone (<10 nmol/l). For men with normal baseline testosterone (≥10 nmol/l), higher testosterone levels at baseline were unrelated to PCa risk (p = 0.33). No association was found for DHT and PCa (all p > 0.85).Conclusions
Baseline serum testosterone and DHT levels were unrelated to PCa detection or grade. Our findings of the lowest testosterone levels being associated with the lowest PCa risk with no further changes with higher testosterone support a saturation model but must be confirmed in future studies using an a priori defined hypothesis.ClinicalTrials.gov identifier
NCT00056407. 相似文献10.
Marco Auprich Alexander Haese Jochen Walz Karl Pummer Alexandre de la Taille Markus Graefen Theo de Reijke Margit Fisch Paul Kil Paolo Gontero Jacques Irani Felix K.-H. Chun 《European urology》2010
Background
Prior to safely adopting risk stratification tools, their performance must be tested in an external patient cohort.Objective
To assess accuracy and generalizability of previously reported, internally validated, prebiopsy prostate cancer antigen 3 (PCA3) gene-based nomograms when applied to a large, external, European cohort of men at risk of prostate cancer (PCa).Design, setting, and participants
Biopsy data, including urinary PCA3 score, were available for 621 men at risk of PCa who were participating in a European multi-institutional study.Intervention
All patients underwent a ≥10-core prostate biopsy. Biopsy indication was based on suspicious digital rectal examination, persistently elevated prostate-specific antigen level (2.5–10 ng/ml) and/or suspicious histology (atypical small acinar proliferation of the prostate, >/= two cores affected by high-grade prostatic intraepithelial neoplasia in first set of biopsies).Measurements
PCA3 scores were assessed using the Progensa assay (Gen-Probe Inc, San Diego, CA, USA). According to the previously reported nomograms, different PCA3 score codings were used. The probability of a positive biopsy was calculated using previously published logistic regression coefficients. Predicted outcomes were compared to the actual biopsy results. Accuracy was calculated using the area under the curve as a measure of discrimination; calibration was explored graphically.Results and limitations
Biopsy-confirmed PCa was detected in 255 (41.1%) men. Median PCA3 score of biopsy-negative versus biopsy-positive men was 20 versus 48 in the total cohort, 17 versus 47 at initial biopsy, and 37 versus 53 at repeat biopsy (all p ≤ 0.002). External validation of all four previously reported PCA3-based nomograms demonstrated equally high accuracy (0.73–0.75) and excellent calibration. The main limitations of the study reside in its early detection setting, referral scenario, and participation of only tertiary-care centers.Conclusions
In accordance with the original publication, previously developed PCA3-based nomograms achieved high accuracy and sufficient calibration. These novel nomograms represent robust tools and are thus generalizable to European men at risk of harboring PCa. Consequently, in presence of a PCA3 score, these nomograms may be safely used to assist clinicians when prostate biopsy is contemplated. 相似文献11.
Guillaume Ploussard Nathalie Nicolaiew Charles MarchandStéphane Terry Francis VacherotDimitri Vordos Yves AlloryClaude-Clément Abbou Laurent SalomonAlexandre de la Taille 《European urology》2014
Background
The debate on the optimal number of prostate biopsy core samples that should be taken as an initial strategy is open.Objective
To prospectively evaluate the diagnostic yield of a 21-core biopsy protocol as an initial strategy for prostate cancer (PCa) detection.Design, setting, and participants
During 10 yr, 2753 consecutive patients underwent a 21-core biopsy scheme for their first set of biopsy specimens.Intervention
All patients underwent a standardized 21-core protocol with cores mapped for location.Outcome measurements and statistical analysis
The PCa detection rate of each biopsy scheme (6, 12, or 21 cores) was compared using a McNemar test. Predictive factors of the diagnostic yield achieved by a 21-core scheme were studied using logistic regression analyses.Results and limitations
PCa detection rates using 6 sextant biopsies, 12 cores, and 21 cores were 32.5%, 40.4%, and 43.3%, respectively. The 12-core procedure improved the cancer detection rate by 19.4% (p = 0.004), and the 21-biopsy scheme improved the rate by 6.7% overall (p < 0.001). The six far lateral cores were the most efficient in terms of detection rate. The diagnostic yield of the 21-core protocol was >10% in prostates with volume >70 ml, in men with a prostate-specific antigen level < 4 ng/ml, with a prostate-specific antigen density (PSAD) <0.20 ng/ml per gram. A PSAD <0.20 ng/ml per gram was the strongest independent predictive factor of the diagnostic yield offered by the 21-core scheme (p < 0.001). The 21-core protocol significantly increased the rate of PCa eligible for active surveillance (62.5% vs 48.4%; p = 0.036) than those detected by a 12-core scheme without statistically increasing the rate of insignificant PCa (p = 0.503).Conclusions
A 21-core biopsy scheme improves significantly the PCa detection rate compared with a 12-core protocol. We identified a cut-off PSAD (0.20 ng/ml per gram) below which an extended 21-core scheme might be systematically proposed to significantly improve the overall detection rate without increasing the rate of detected insignificant PCa. 相似文献12.
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13.
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14.
Giorgio Gandaglia Maxine Sun Jim C. Hu Giacomo Novara Toni K. Choueiri Paul L. Nguyen Jonas Schiffmann Markus Graefen Shahrokh F. Shariat Firas Abdollah Alberto Briganti Francesco Montorsi Quoc-Dien Trinh Pierre I. Karakiewicz 《European urology》2014
Background
Androgen deprivation therapy (ADT) might increase the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa).Objective
To examine the impact of ADT on AKI in a large contemporary cohort of patients with nonmetastatic PCa representing the US population.Design, setting, and participants
Overall, 69 292 patients diagnosed with nonmetastatic PCa between 1995 and 2009 were abstracted from the Surveillance Epidemiology and End Results–Medicare database.Outcomes measurements and statistical analyses
Patient in both treatment arms (ADT vs no ADT) were matched using propensity-score methodology. Ten-year AKI rates were estimated. Competing-risks regression analyses tested the association between ADT and AKI, after adjusting for the risk of death during follow-up.Results and limitations
Overall, the 10-yr AKI rates were 24.9% versus 30.7% for ADT-naive patients versus those treated with ADT, respectively (p < 0.001). When patients were stratified according to the type of ADT, the 10-yr AKI rates were 31.1% versus 26.0% for men treated with gonadotropin-releasing hormone (GnRH) agonists and bilateral orchiectomy, respectively (p < 0.001). In multivariable analyses, the administration of GnRH agonists (hazard ratio [HR]: 1.24; 95% confidence interval [CI], 1.18–1.31; p < 0.001), but not bilateral orchiectomy (HR: 1.11; 95% CI, 0.96–1.29; p = 0.1), was associated with the risk of experiencing AKI. Our study is limited by its retrospective design.Conclusions
ADT is associated with an increased risk of AKI in patients with nonmetastatic PCa. In particular, the administration of GnRH agonists, but not surgical castration, may substantially increase the risk of experiencing AKI. These observations should help provide physicians with better patient selection to reduce the risk of AKI.Patient summary
The administration of gonadotropin-releasing hormone agonists, but not bilateral orchiectomy, increases the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa). These observations should help provide physicians with better patient selection to reduce the risk of AKI in PCa patients. 相似文献15.
Neill Booth Pekka Rissanen Teuvo L.J. Tammela Liisa Määttänen Kimmo Taari Anssi Auvinen 《European urology》2014
Background
Evidence of the potential impact of systematic screening for prostate cancer (PCa) on health-related quality of life (HRQoL) at a population-based level is currently scarce.Objective
This study aims to quantify the long-term HRQoL impact associated with screening for PCa.Design, setting, and participants
Postal questionnaire surveys were conducted in 1998, 2000, 2004, and 2011 among men in the Finnish PCa screening trial diagnosed with PCa (total n = 7011) and among a random subsample of the trial population (n = 2200). In 2011, for example, 1587 responses were received from men with PCa in the screening arm and 1706 from men in the control arm. In addition, from the trial subsample, 549 men in the screening arm and 539 in the control arm provided responses.Outcome measurements and statistical analysis
Health-state-value scores were compared between the intervention and control arms using three distinct HRQoL measures (15D, EQ-5D, and SF-6D), and statistical significance was assessed using t tests. In addition, differences over repeated assessments of HRQoL between groups were evaluated using generalised estimating equations.Results and limitations
In the 2011 survey, a small but statistically significant difference emerged between the trial arms among men diagnosed with PCa (mean scores, screening vs control arm: 15D: 0.872 vs 0.866, p = 0.14; EQ-5D: 0.852 vs 0.831, p = 0.03; and SF-6D: 0.763 vs 0.756, p = 0.06). Such differences in favour of the screening arm were not found among the sample of men from the trial (15D: 0.889 vs 0.892, p = 0.62; EQ-5D: 0.831 vs 0.852, p = 0.08; and SF-6D: 0.775 vs 0.777, p = 0.88). The slight advantage with screening among men with PCa was reasonably consistent across time in the longitudinal analysis and was strongest among men with early-stage disease.Conclusions
These results show some long-term HRQoL benefit from screening for men with PCa but suggest little impact overall in the trial population. 相似文献16.
Boyd R. Viers William R. Sukov Matthew T. Gettman Laureano J. Rangel Eric J. Bergstralh Igor Frank Matthew K. Tollefson R. Houston Thompson Stephen A. Boorjian R. Jeffrey Karnes 《European urology》2014
Background
The presence of a positive surgical margin (PSM) at radical prostatectomy (RP) has been linked to an increased risk of biochemical recurrence and receipt of secondary therapy; however, its association with other oncologic end points remains controversial.Objective
To evaluate the association of primary Gleason grade (GG) at the site of PSM with subsequent clinical progression and mortality among patients with Gleason score (GS) 7 prostate cancer (PCa).Design, setting, and participants
We identified 1036 patients who underwent RP between 1996 and 2002. A single uropathologist re-reviewed all specimens noted to have a PSM to record GG at the margin.Outcome measurements and statistical analysis
Survival was estimated using the Kaplan-Meier method. Cox models were used to analyze the association of margin primary GG with outcome.Results and limitations
Overall, 338 men (33%) had a PSM; of those, 242 had PSM GG3 and 96 had PSM GG4. Median postoperative follow-up was 13 yr. Compared with men with PSM GG3 or a negative SM, we noted that men with PSM GG4 had significantly worse 15-yr systemic progression-free survival (74% vs 90% vs 93%, respectively; p < 0.001) and cancer-specific survival (86% vs 96% vs 97%, respectively; p = 0.002). On multivariable analysis, the presence of PSM GG4 was associated with increased risks of systemic progression (hazard ratio [HR]: 2.77; p = 0.003) and death from PCa (HR: 3.93; p = 0.02) among men with a PSM. Limitations include the relatively small rate of disease recurrence.Conclusions
PSM primary GG4 was independently associated with adverse oncologic outcomes among men with GS7 PCa. Pending external validation, GG at the PSM may be considered for inclusion in pathologic reports and risk stratification following RP.Patient summary
Among patients with Gleason grade 7 prostate cancer and a positive surgical margin at the time of prostatectomy, we found that higher Gleason grade at the margin was associated with worse oncologic outcomes. 相似文献17.
Fritz H. Schröder Jonas Hugosson Sigrid Carlsson Teuvo Tammela Liisa Määttänen Anssi Auvinen Maciej Kwiatkowski Franz Recker Monique J. Roobol 《European urology》2012
Background
Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal.Objective
To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial.Design, setting, and participants
Data were available for 76 813 men aged 55–69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up.Intervention
Regular screening based on serum PSA measurements was offered to 36 270 men randomized to the screening arm, while no screening was provided to the 40 543 men in the control arm.Outcome measurements and statistical analysis
The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease.Results and limitations
After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p < 0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60–0.82; p = 0.001) in the intention-to-screen analysis and a 42% (p = 0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41–0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up.Conclusions
PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases.The ERSPC trial is registered under number ISRCTN49127736. 相似文献18.
Background
Although most studies found no association between alcohol intake and prostate cancer (PCa) risk, an analysis of the Prostate Cancer Prevention Trial found that high alcohol intake significantly increased PCa risk among men randomized to the 5α-reductase inhibitor (5-ARI) finasteride.Objective
Determine whether alcohol affects PCa risk among men taking the 5-ARI dutasteride.Design, settings, and participants
Reduction by Dutasteride of Prostate Cancer Events was a 4-yr, multicenter, randomized, double-blind, placebo-controlled trial to compare PCa after dutasteride administration (0.5 mg/d) with placebo. Participants had a baseline prostate-specific antigen between 2.5 and 10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined by baseline questionnaire, and participants underwent a prostate biopsy to determine PCa status at 2 yr and 4 yr of follow-up.Outcome measurements and statistical analysis
Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between alcohol intake and low-grade (Gleason <7) and high-grade (Gleason >7) PCa.Results and limitations
Of 6374 participants in our analysis, approximately 25% reported no alcohol consumption, 49% were moderate drinkers (one to seven drinks per week), and 26% were heavy drinkers (more than seven drinks per week). Alcohol intake was not associated with low- or high-grade PCa in the placebo arm and was not associated with low-grade PCa among men taking dutasteride. In contrast, men randomized to dutasteride and reporting more than seven drinks per week were 86% more likely to be diagnosed with high-grade PCa (p = 0.01). Among alcohol abstainers, dutasteride was associated with significantly reduced risk of high-grade PCa (OR: 0.59; 95% CI, 0.38–0.90), but dutasteride was no longer associated with reduced high-grade PCa among men reporting high alcohol intake (OR: 0.99; 95% CI, 0.67–1.45).Conclusions
Alcohol consumption negated a protective association between dutasteride and high-grade PCa.Patient summary
We confirmed a prior study that alcohol affects PCa prevention in patients taking 5-ARIs. Patients taking 5-ARIs may wish to eliminate alcohol intake if they are concerned about PCa. 相似文献19.
Christopher J. Weight Simon P. Kim Debra J. Jacobson Michaela E. McGree Stephen A. Boorjian R. Houston Thompson Bradley C. Leibovich R. Jeffrey Karnes Jennifer St. Sauver 《European urology》2013
Background
Lower urinary tract symptoms (LUTS) are common and have been associated with the subsequent diagnosis of prostate cancer (PCa) in population cohorts.Objective
To determine whether the association between LUTS and PCa is due to the intensity of PCa testing after LUTS diagnosis.Design, setting, and participants
We prospectively followed a representative, population-based cohort of 1922 men, aged 40–79 yr, from 1990 until 2010 with interviews, questionnaires, and abstracting of medical records for prostate outcomes. Men were excluded if they had a previous prostate biopsy or PCa diagnosis. Self-reported LUTS was defined as an American Urological Association symptom index score >7 (n = 621). Men treated for LUTS (n = 168) were identified from review of medical records and/or self report. Median follow-up was 11.8 yr (interquartile range: 10.7–12.3).Outcome measurements and statistical analysis
Associations between self-reported LUTS, or treatment for LUTS, and risk of subsequent prostate biopsy and PCa were estimated using Cox proportional hazard models.Results and limitations
Fifty-five percent of eligible men enrolled in the study. Men treated for LUTS were more likely to undergo a prostate biopsy (hazard ratio [HR]: 2.4; 95% confidence interval [CI], 1.7–3.3). Men younger than 65 yr who were treated for LUTS were more likely to be diagnosed with PCa (HR: 2.3, 95% CI, 1.5–3.5), while men aged >65 yr were not (HR: 0.89, 95% CI, 0.35–1.9). Men with self-reported LUTS were not more likely to be biopsied or diagnosed with PCa. Neither definition of LUTS was associated with subsequent intermediate- to high-risk cancer. The study is limited by lack of histologic or prostate-specific antigen level data for the cohort.Conclusions
These results indicate that a possible cause of the association between LUTS and PCa is increased diagnostic intensity among men whose LUTS come to the attention of physicians. Increased symptoms themselves were not associated with intensity of testing or diagnosis. 相似文献20.
Felix K. Chun Alexandre de la Taille Hendrik van Poppel Michael Marberger Arnulf Stenzl Peter F.A. Mulders Hartwig Huland Clement-Claude Abbou Alexander B. Stillebroer Martijn P.M.Q. van Gils Jack A. Schalken Yves Fradet Leonard S. Marks William Ellis Alan W. Partin Alexander Haese 《European urology》2009