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Daniel E. Spratt Chi Zhang Zachary S. Zumsteg Xin Pei Zhigang Zhang Michael J. Zelefsky 《European urology》2013
Background
In vitro data and early clinical results suggest that metformin has desirable antineoplastic effects and has a theoretical benefit on castration-resistant prostate cancer (CRPC).Objective
To determine whether the use of metformin would be associated with improved clinical outcomes and a reduction in the development of CRPC.Design, setting, and participants
Data from 2901 consecutive patients (157 metformin, 162 diabetic non-metformin, and 2582 nondiabetic) with localized prostate cancer treated with external-beam radiation therapy from 1992 to 2008 were collected from a single institution in the United States.Intervention
Use of metformin in localized prostate cancer.Outcome measurements and statistical analysis
Univariate and multivariate regression models utilizing k-sample, Fine and Gray, Cox regression, log-rank, and Kaplan-Meier methods to assess prostate-specific antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival (DMFS), prostate cancer–specific mortality (PCSM), overall survival (OS), and development of CRPC.Results and limitations
With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin, diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and 8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted (correcting for PSA, T stage, Gleason score, age, diabetic status, and androgen-deprivation therapy use) improvement in all outcomes compared with the diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24–3.18]; p = 0.004), DMFS (adjusted HR: 3.68 [1.78–7.62]; p < 0.001), and PCSM (HR: 5.15 [1.53–17.35]; p = 0.008). Metformin use was also independently associated with a decrease in the development of CRPC in patients experiencing biochemical failure compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83–119.89]; p = 0.01). The retrospective study design was the primary limitation of the study.Conclusions
To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-RFS, DMFS, PCSM, OS, and reduce the development of CRPC in prostate cancer patients. Further validation of metformin's potential benefits is warranted. 相似文献3.
Background
Zoledronic acid (ZOL) is a standard therapy for the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC). Although prostate-specific antigen (PSA) is an established marker for monitoring prostate cancer patients, correlations between PSA and disease outcomes during ZOL therapy are unclear.Objective
To evaluate the relationships among PSA kinetics, bone-directed therapy with ZOL, and clinical outcomes in men with bone metastases from CRPC using a ZOL phase 3 trial database.Design, setting, and participants
Exploratory analyses from a phase 3 trial in men with bone metastases from CRPC (n = 643) randomized to ZOL or placebo every 3 wk.Outcome measurements and statistical analysis
PSA levels during the first 3 mo of the study were evaluated in linear and logarithmic (log) models stratified using prognostic factors established in a ZOL phase 3 trial and a CRPC nomogram. Relative risks of SREs, bone disease progression (BDP), and death were calculated per 1 log (nanograms per milliliter) PSA increase. Baseline PSA models used the study median (PSA: 77.3 ng/ml) as the high/low cut-off point.Results and limitations
A total of 202 placebo- and 434 ZOL-treated patients were assessable. In both groups, PSA increases correlated with significantly increased risks of death, BDP, and first SRE. In the placebo and ZOL groups, associated increases in risk per 1 log (nanograms per milliliter) PSA increase were 29% (p < 0.0001) and 10% (p < 0.0074), respectively, for BDP, and 24% (p = 0.0010) and 13% (p = 0.0079), respectively, for first SRE. Limitations include the retrospective nature of these analyses and the potential confounding effects of concurrent antineoplastic therapies.Conclusions
PSA is an important prognostic tool for survival in patients with bone metastases from CRPC, and these analyses show that PSA is also prognostic for BDP and SREs regardless of bone-targeted therapy. 相似文献4.
Christopher J. Keto William J. Aronson Martha K. Terris Joseph C. Presti Christopher J. Kane Christopher L. Amling Stephen J. Freedland 《European urology》2014
Background
A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT—specifically, <0.2 ng/ml—can be used for risk stratification is untested.Objective
We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)–specific outcomes in men treated with early ADT after radical prostatectomy (RP).Design, setting, and participants
We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76%) had an undetectable nadir.Intervention
ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease.Outcome measurements and statistical analysis
PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes.Results and limitations
Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p < 0.001), metastases (HR: 3.98; p = 0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p = 0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively.Conclusions
A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials. 相似文献5.
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Florian Jentzmik Carsten Stephan Kurt Miller Mark Schrader Andreas Erbersdobler Glen Kristiansen Michael Lein Klaus Jung 《European urology》2010
Background
Sarcosine in urine was recently suggested to be a promising tool in prostate cancer (PCa) diagnostics.Objective
To reevaluate sarcosine as a potential biomarker for early PCa detection and for prediction of tumour aggressiveness.Design, setting, and participants
Sarcosine was measured in urine samples from 106 PCa patients and 33 patients with no evidence of malignancy (NEM), confirmed by 8–12 core prostate biopsies, after standardised digital rectal examination, as well as from 12 healthy men and women. The results were related to the clinicopathologic data on prostate volume, tumour stage, Gleason score, and prostate specific antigen (PSA).Measurements
Sarcosine in urine was determined by gas chromatography-mass spectrometry using a commercial amino acid assay and was normalised to urine creatinine. Nonparametric statistical tests and receiver operating characteristics (ROC) analyses were performed to assess the diagnostic performance.Results and limitations
The median sarcosine-creatinine ratio in urine was 13% lower in PCa than in NEM patients. Sarcosine values were not associated with tumour stage (pT2 vs pT3) or grade (Gleason score <7 vs ≥7). ROC analyses proved that the discrimination between PCa and NEM patients was not improved by sarcosine in comparison with total PSA, but it was significantly worse than the percent free PSA. The higher proportion of PCa than NEM patients can be considered a limitation of this study.Conclusions
Sarcosine in urine after rectal digital examination cannot be considered as a suitable marker to differentiate between patients with and without PCa. 相似文献7.
Mottet N Bellmunt J Bolla M Joniau S Mason M Matveev V Schmid HP Van der Kwast T Wiegel T Zattoni F Heidenreich A 《European urology》2011,59(4):572-583
Objectives
Our aim is to present a summary of the 2010 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC).Methods
The working panel performed a literature review of the new data emerging from 2007 to 2010. The guidelines were updated, and the levels of evidence (LEs) and/or grades of recommendation (GR) were added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews.Results
Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). Although LHRH antagonists decrease testosterone without any testosterone surge, their clinical benefit remains to be determined. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation (IAD) results in equivalent oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (CT) are of limited importance if the PSA is <2.5 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include screening for the metabolic syndrome and an analysis of PSA and testosterone levels. Treatment of castration-resistant prostate cancer (CRPC) includes second-line hormonal therapy, novel agents, and chemotherapy with docetaxel at 75 mg/m2 every 3 wk. Cabazitaxel as a second-line therapy for relapse after docetaxel might become a future option. Zoledronic acid and denusomab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.Conclusion
The knowledge in the field of advanced, metastatic, and CRPC is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or online at www.uroweb.org. 相似文献8.
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9.
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Kim N. Chi Anders Bjartell David Dearnaley Fred Saad Fritz H. Schrder Cora Sternberg Bertrand Tombal Tapio Visakorpi 《European urology》2009,56(4):594-605
Context
Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited.Objective
To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC.Evidence acquisition
Novel targeted therapies in clinical trials were identified from registries. The MEDLINE database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies.Evidence synthesis
Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression has translated into a variety of treatment approaches. Agents targeting androgen receptor (AR) activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK-ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase 3 trials for patients with CRPC.Conclusions
A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future. 相似文献11.
Background
The European Randomised Study of Screening for Prostate Cancer (ERSPC) applies a prostate-specific antigen (PSA) cut-off value ≥3.0 ng/ml as an indication for lateralised sextant biopsy.Objective
To analyse the incidence and disease-specific mortality for prostate cancer (PCa) in men with an initial PSA <3.0 ng/ml.Design, setting and participants
From November 1993 to December 1999, a total of 42 376 men identified from population registries in the Rotterdam region (55–74 yr of age) were randomised to an intervention or control arm. A total of 19 950 men were screened during the first screening round.Intervention
A PSA <3.0 ng/ml was below the biopsy threshold. PCa cases were identified at rescreens every 4 yr or as interval cancers.Measurements
Distribution of incidence, aggressiveness, and disease-specific mortality of PCa per PSA range was measured. Causes of death were evaluated by an independent committee, and follow-up was complete until 31 December 2008.Results and limitations
From 1993 to 2008, 915 PCa cases were diagnosed in 15 758 men (5.8%) with an initial PSA <3.0 ng/ml and a median age of 62.3 yr. Median overall follow-up was 11 yr. PCa incidence increased significantly with higher initial PSA levels. Aggressive PCa (clinical stage ≥T2c, Gleason score ≥8, PSA >20 ng/ml, positive lymph nodes, or metastases at diagnosis) was detected in 66 of 733 screen-detected PCa cases (9.0%) and 72 of 182 interval-detected PCa cases (39.6%). Twenty-three PCa deaths occurred in the total population (0.15%), with an increasing risk of PCa mortality in men with higher initial PSA values.Conclusions
The risk of PCa, aggressive PCa and PCa mortality in a screening population with initial PSA <3.0 ng/ml increases significantly with higher initial PSA levels. These results contribute to the risk stratification and individual management of men in PSA-based screening programmes. 相似文献12.
Martin Spahn Steven Joniau Paolo Gontero Steffen Fieuws Giansilvio Marchioro Bertrand Tombal Burkhard Kneitz Chao-Yu Hsu Katie Van Der Eeckt Pia Bader Detlef Frohneberg Alessandro Tizzani Hein Van Poppel 《European urology》2010
Background
Prostate cancer (PCa) patients with pretreatment prostate-specific antigen (PSA) >20 ng/ml have a high risk of biochemical and clinical failure and even cancer-related death after local therapy. Pretreatment predictors of outcome after radical prostatectomy (RP) in this patient group are necessary.Objective
Our aim was to assess how the use of additional high-risk factors (biopsy Gleason score [bGS] ≥8 or clinical stage 3–4) can improve prediction of treatment failure and cancer-related death after RP in patients with PSA >20.Design, setting, and participants
In a retrospective multicentre cohort study from six European centres between 1987 and 2005, 712 patients with PSA >20 ng/ml underwent RP and bilateral pelvic lymphadenectomy.Measurements
Subgroups were analysed to determine the relationship between the number of high-risk factors and histopathology, biochemical progression-free survival, clinical evidence of progressive disease, prostate cancer–specific mortality (PCSM), and overall mortality. Kaplan-Meier analysis with log-rank test and Cox multivariable analysis were applied.Results and limitations
Median follow-up was 77 mo. The number of high-risk factors was significantly associated with unfavourable histopathology. Among patients with only PSA >20 ng/ml, 33% had pT2 PCa, 57.9% had bGS <7, 54% had negative surgical margins, and 85% were lymph node negative (pN0), whereas among patients with all three high-risk factors, 4.5% had pT2 PCa, 2.3% had bGS <7, 20.5% had negative margins, and 49% were pN0 (p < 0.001). The strongest predictor of progression and mortality was bGS. PSA >20 ng/ml associated with bGS ≤7 resulted in 10-yr PCSM of 5%; when associated with bGS ≥8, PCSM was 35%. The main limitations of the study were retrospective design and varying treatment modalities.Conclusions
PCa patients with PSA >20 ng/ml have varying risk levels of disease progression and PCSM. Considering additional risk factors further stratifies this group into four subgroups that can guide the clinician in preoperative patient counselling. 相似文献13.
Background
A 23% relative risk reduction (RRR) in prostate cancer (PCa) was shown in men receiving dutasteride in the 4-yr Reduction by Dutasteride of Prostate Cancer Events study, in whom biopsies were protocol dependent.Objective
Our aim was to explore PCa risk reduction in men with benign prostatic hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study, in which biopsies were undertaken for cause.Design, setting, and participants
CombAT was a 4-yr randomized double-blind parallel group study in 4844 men ≥50 yr of age with clinically diagnosed moderate to severe BPH, International Prostate Symptom Score ≥12, prostate volume ≥30 ml, and serum prostate-specific antigen (PSA) 1.5–10 ng/ml. Men underwent annual PSA measurement and digital rectal examination (DRE), and prostate biopsies were performed for cause.Intervention
All patients took tamsulosin 0.4 mg/d, dutasteride 0.5 mg/d, or a combination of both.Measurements
The primary end point was incidence of PCa. Secondary end points included postbaseline prostate biopsy rates and Gleason score of cancers.Results and limitations
Dutasteride (alone or in combination with tamsulosin) was associated with a 40% RRR of PCa diagnosis compared with tamsulosin monotherapy (95% confidence interval, 16–57%; p = 0.002) and a 40% reduction in the likelihood of biopsy. There were similar reductions in low- and high-grade Gleason score cancers. The biopsy rate in the groups receiving dutasteride trended toward a higher diagnostic yield (combination: 29%, dutasteride: 28%, tamsulosin: 24%). One limitation was the lack of a standardized approach to PCa diagnosis and grading.Conclusions
Dutasteride, alone or in combination with tamsulosin, significantly reduced the relative risk of PCa diagnosis in men with BPH undergoing annual DRE and PSA screening. Consistent with the increased usefulness of PSA for PCa detection, men receiving dutasteride had a numerically lower biopsy rate and higher yield of PCa on biopsy.Trial registration
Clinicaltrials.gov identifier: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103). 相似文献14.
Russell Szmulewitz Supriya MohileEdwin Posadas Rangesh KunnavakkamTheodore Karrison Elizabeth ManchenWalter M. Stadler 《European urology》2009
Background
Even in castration-resistant prostate cancer (CRPC), the androgen pathway remains biologically relevant. In preclinical models, androgen therapy for CRPC leads to growth arrest, apoptosis, and tumor shrinkage.Objective
This study sought to determine the toxicity and feasibility of a testosterone therapy in early CRPC.Design, setting, and participants
Prostate cancer patients with progressive disease following androgen ablation, antiandrogen therapy, and withdrawal and no to minimal metastatic disease who were followed at the University of Chicago were randomized to treatment with three doses of transdermal testosterone.Intervention
Patients were treated with transdermal testosterone at 2.5, 5.0, or 7.5 mg/day.Measurements
Toxicity, prostate-specific antigen (PSA), imaging, quality of life (QoL), and strength were monitored. Treatment was discontinued for significant toxicity, clinical progression, or a 3-fold increase in PSA.Results and limitations
Fifteen men with a median age of 73 yr (range: 62–92) and a median PSA of 11.1 ng/ml (range: 5.2–63.6) were treated. Testosterone increased from castrate to median concentrations of 305 ng/dl, 308 ng/dl, and 297 ng/dl for dosages of 2.5 mg/day (n = 4), 5.0 mg/day (n = 5), and 7.5 mg/day (n = 5), respectively. One patient was taken off of the study at 53 wk due to grade 4 cardiac toxicity. There were no other grade 3 or 4 toxicities related to the study medication, and the grade 2 toxicities were minimal. Only one patient experienced symptomatic progression, and three (20%) patients demonstrated a decrease in PSA (largest was 43%). Median time to progression was 9 wk (range: 2–96), with no detectable difference in the three dose cohorts. There was no significant improvement in QoL, and there was a borderline statistically significant improvement in hand-grip strength with treatment. The study was limited by sample size, single arm, and variability of baseline patient characteristics.Conclusions
Testosterone is a feasible and reasonably well-tolerated therapy for men with early CRPC. A larger, randomized trial is under way to further characterize efficacy and impact on QoL measures. 相似文献15.
Giovanni Lughezzani Massimo Lazzeri Alexander Haese Thomas McNicholas Alexandre de la Taille Nicolò Maria Buffi Nicola Fossati Giuliana Lista Alessandro Larcher Alberto Abrate Alessandro Mistretta Vittorio Bini Joan Palou Redorta Markus Graefen Giorgio Guazzoni 《European urology》2014
Background
External validation of a prediction tool is mandatory to assess the tool's accuracy and generalizability within different patient cohorts.Objective
To externally validate a previously developed Prostate Health Index (PHI)–based nomogram for predicting the presence of prostate cancer (PCa) at biopsy.Design, setting, and participants
The study population consisted of 883 patients who were scheduled for a prostate biopsy at one of five European tertiary care centers. Total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and [−2]pro–prostate-specific antigen (p2PSA) levels were determined. The fPSA-to-tPSA ratio (%fPSA), p2PSA, and PHI ([p2PSA / fPSA] × √tPSA) were calculated.Intervention
Extended initial and repeat prostate biopsy.Outcome measurements and statistical analysis
Logistic regression models were fitted to test the predictors of PCa and to determine their predictive accuracy. A calibration plot was used to evaluate the extent of overestimation or underestimation between nomogram predictions and observed PCa rate. Decision curve analysis (DCA) provided an estimate of the net benefit obtained by using the PHI-based nomogram.Results and limitations
Of 833 patients, 365 (41.3%) were diagnosed with PCa at extended prostate biopsy. In accuracy analyses, PHI was the most informative predictor of PCa (0.68), outperforming tPSA (0.51) and %fPSA (0.64). The predictive accuracy of the previously developed nomogram was 75.2% (95% confidence interval, 71.4–78.1). Calibration of the nomogram was good in patients at a low to intermediate predicted probability of PCa, while calibration was suboptimal, with a tendency to overestimate the presence of PCa, in high-risk patients. Finally, DCA demonstrated that the use of the PHI-based nomogram resulted in the highest net benefit. The main limitation of the study is the fact that only Caucasian patients were included.Conclusions
At external validation, the previously developed PHI-based nomogram confirmed its ability to determine the presence of PCa at biopsy. These findings provide further evidence supporting the potential role of the nomogram in the biopsy decision pathway for European men with suspected PCa.Patient summary
In the current study, we externally validated a Prostate Health Index–based nomogram to predict the presence of prostate cancer (PCa) at biopsy. This tool may help clinicians determine the need for a prostate biopsy in European patients with suspected PCa. 相似文献16.
Hoeks CM Schouten MG Bomers JG Hoogendoorn SP Hulsbergen-van de Kaa CA Hambrock T Vergunst H Sedelaar JP Fütterer JJ Barentsz JO 《European urology》2012,62(5):902-909
Background
Patients with elevated prostate-specific antigen (PSA) and one or more previous negative transrectal ultrasound (TRUS) biopsy sessions are subject to diagnostic uncertainty due to TRUS-biopsy undersampling. Magnetic resonance (MR)–guided biopsy (MRGB) has shown high prostate cancer (PCa)–detection rates in studies with limited patient numbers.Objective
Determine the detection rate of (clinically significant) PCa for MRGB of cancer-suspicious regions (CSRs) on 3-T multiparametric MR imaging (MP-MRI) in patients with elevated PSA and one or more negative TRUS-biopsy sessions.Design, setting, and participants
Of 844 patients who underwent 3-T MP-MRI in our referral centre between March 2008 and February 2011, 438 consecutive patients with a PSA >4.0 ng/ml and one negative TRUS-biopsy session or more were included. MRGB was performed in 265 patients. Exclusion criteria were existent PCa, endorectal coil use, and MP-MRI for indications other than cancer detection.Intervention
Patients underwent MRGB of MP-MRI CSRs.Measurements
(Clinically significant) MRGB cancer-detection rates were determined. Clinically significant cancer was defined by accepted (i.a. Epstein and d’Amico) criteria based on PSA, Gleason score, stage, and tumour volume. Follow-up PSA and histopathology were collected. Sensitivity analysis was performed for patients with MP-MRI CSRs without MRGB.Results and limitations
In a total of 117 patients, cancer was detected with MRGB (n = 108) or after negative MRGB (n = 9). PCa was detected in 108 of 438 patients (25%) and in 41% (108 of 265) of MRGB patients. The majority of detected cancers (87%) were clinically significant. Clinically significant cancers were detected in seven of nine (78%) negative MRGB patients in whom PCa was detected during follow-up. Sensitivity analysis resulted in increased cancer detection (47–56%). Complications occurred in 0.2% of patients (5 of 265).Conclusions
In patients with elevated PSA and one or more negative TRUS-biopsy sessions, MRGB of MP-MRI CSRs had a PCa-detection rate of 41%. The majority of detected cancers were clinically significant (87%). 相似文献17.
Andres Jan Schrader Martin Boegemann Carsten-H. Ohlmann Thomas J. Schnoeller Laura-Maria Krabbe Turkan Hajili Florian Jentzmik Michael Stoeckle Mark Schrader Edwin Herrmann Marcus V. Cronauer 《European urology》2014
Background
Abiraterone, an androgen synthesis inhibitor, has been successfully used in the treatment of castration-resistant prostate cancer (CRPC) for 2 yr. Enzalutamide is a second-generation nonsteroidal antiandrogen that has recently been approved for the same indication.Objective
This is the first study to evaluate the effectiveness of enzalutamide after failure of abiraterone.Design, setting, and participants
Thirty-five patients were identified as having received sequential therapy with abiraterone followed by enzalutamide. All patients had undergone prior docetaxel chemotherapy, and no patient had received ketoconazole.Outcome measurements and statistical analysis
Posttreatment changes in prostate-specific antigen (PSA) were used to determine the activity of enzalutamide in patients who had received prior abiraterone.Results and limitations
The median duration of abiraterone treatment was 9.0 mo (range: 2.0–19.0 mo). Of the 35 patients, 16 (45.7%) achieved a >50% decline in PSA, and 14 (40%) had a rising PSA as the best response. The median duration of subsequent enzalutamide treatment was 4.9 mo (Kaplan-Meier estimate; 95% confidence interval [CI], 2.4–7.4). Seven of 16 CRPC patients who were initially abiraterone-sensitive (43.8%) and 3 of 19 CRPC patients who were initially abiraterone-insensitive (15.8%) showed a >50% PSA decline while taking enzalutamide. Of the 35 patients, 17 (48.6%) were primarily enzalutamide-resistant and showed a rising PSA as the best response. Median time to progression was 4.0 mo (95% CI, 2.0–6.0) for 18 of 35 patients with at least one declining PSA value while taking enzalutamide (51.4%). Of the 17 patients who were assessable radiologically, only 1 (2.9%) attained a confirmed partial response. Small sample size was the major limitation.Conclusions
Enzalutamide treatment achieved only a modest response rate in patients progressing after abiraterone. Although cross-resistance between abiraterone and enzalutamide was a common phenomenon, it was not inevitable, and a small but significant number of patients showed significant benefit from sequential treatment. 相似文献18.
Joost L. Boormans Karin G. Hermans Angelique C.J. Ziel-van der Made Geert J.H.L. van Leenders Mark F. Wildhagen Laurence Collette Fritz H. Schröder Jan Trapman Paul C.M.S. Verhagen 《European urology》2010
Background
Fusion of the androgen-regulated gene transmembrane protease, serine 2, TMPRSS2, to the v-ets erythroblastosis virus E26 oncogene homolog (avian), ERG, of the erythroblast transformation-specific (ETS) family is the most common genetic alteration in prostate cancer (PCa).Objective
To determine whether expression of androgen-regulated TMPRSS2-ERG predicts response to endocrine treatment in hormone-naïve, node-positive PCa.Design, setting, and participants
Eighty-five patients with histologically confirmed, node-positive PCa who were without treatment at the moment of lymph node dissection were analysed. RNA was isolated from the paraffin-embedded lymph node metastases and complementary DNA (cDNA) was made. The quality of cDNA was tested by polymerase chain reaction (PCR) analysis of the expression of the housekeeping gene hydroxymethylbilane synthase, HMBS (formerly PBGD). TMPRSS2-ERG expression was analysed by PCR using a forward primer in TMPRSS2 exon 1 and a reverse primer in ERG exon 4.Measurements
The primary end point was time from start of endocrine therapy to the occurrence of three consecutive rises in prostate-specific antigen (PSA) that were at least 2 wk apart and resulted in two 50% increases over the PSA nadir. Secondary end points were time to PSA nadir after start of endocrine treatment and cancer-specific and overall survival.Results and limitations
TMPRSS2-ERG was expressed in 59% of the 71 patients who could be analysed. Median duration of response to endocrine therapy was 20.9 mo versus 24.1 mo for gene fusion–positive versus gene fusion–negative patients (95% confidence intervals: 18.6–23.1 vs 18.9–29.4, p = 0.70). Furthermore, no significant differences were seen between the two groups for the secondary end points.Conclusions
Expression of TMPRSS2-ERG is frequent in lymph node metastases of patients with untreated PCa; however, expression of this androgen-regulated fusion gene did not correspond with duration of response to endocrine therapy. Our results suggest that expression of TMPRSS2-ERG is not a candidate marker to select for metastatic PCa patients who will benefit more from endocrine treatment. 相似文献19.
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20.
Carmel J. Pezaro Aurelius G. OmlinAmelia Altavilla David LorenteRoberta Ferraldeschi Diletta BianchiniDavid Dearnaley Christopher ParkerJohann S. de Bono Gerhardt Attard 《European urology》2014