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1.
K. Clint Cary Janet E. CowanMelissa Sanford Katsuto ShinoharaNannette Perez June M. ChanMaxwell V. Meng Peter R. Carroll 《European urology》2014
Background
A better understanding of the independent predictors of disease progression for prostate cancer (PCa) patients is needed to improve the selection of ideal candidates for active surveillance (AS) and refine the surveillance regimen.Objective
To examine the association of clinical and pathologic characteristics, as well as patterns of surveillance biopsy results, with the risk of progression in men on AS.Design, setting, and participants
The retrospective study consisted of men with PCa who were on AS in the prospectively maintained University of California, San Francisco, institutional database from 1996 to 2011. Strict criteria for AS were prostate-specific antigen (PSA) ≤10 ng/ml, clinical stage T1 or T2, biopsy Gleason grade 6, <33% positive cores, and <50% tumor in any single core. Men were then categorized based on results of their confirmatory surveillance biopsy.Outcome measurements and statistical analysis
Disease progression was defined as an increase in Gleason grade and/or biopsy volume beyond prespecified cut points. Serial biopsy patterns over the course of surveillance were stratified by confirmatory biopsy findings: negative, positive without progression, and positive with progression. Multivariable logistic regression models were used to evaluate predictors of progression during AS.Results and limitations
A total of 465 men met inclusion criteria (median follow-up: 51 mo). Of these men, 23% had negative confirmatory biopsies. Only 3% of the men (1 of 30) progressed by the fourth surveillance biopsy following a biopsy pattern of negative confirmatory and negative third biopsy findings. Negative confirmatory biopsy and lower PSA density (both p < 0.01) were independently associated with decreased odds of biopsy progression at 3 yr. The main limitation of this study is its observational nature.Conclusions
The patterns of surveillance biopsy results yield additional important information in AS. Negative confirmatory biopsy and PSA density are important independent predictors of progression on AS and may be used to better counsel men opting for AS. 相似文献2.
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3.
Bertrand Tombal Kurt Miller Laurent Boccon-Gibod Fritz Schröder Neal Shore E. David Crawford Judd Moul Jens-Kristian Jensen Tine Kold Olesen Bo-Eric Persson 《European urology》2010
Background
Recent data suggest prostate-specific antigen (PSA) progression may predict overall survival in prostate cancer patients.Objective
To compare the activity of degarelix and leuprolide regarding PSA recurrence-free survival.Design, setting, and participants
Phase 3, 1-yr, multicentre, randomised, open-label trial comparing the efficacy and safety of degarelix at 240 mg for 1 mo, and then 80 mg monthly (240/80 mg); degarelix at 240 mg for 1 mo, and then 160 mg monthly; and leuprolide at 7.5 mg/mo. Overall, 610 patients with histologically confirmed prostate cancer (all stages), for whom androgen deprivation therapy was indicated, were included. The primary end point of this trial has been reported previously; the protocolled and exploratory subgroup analyses reported in this paper focus on degarelix at 240/80 mg (dose approved by the US Food and Drug Administration and the European Medicine Evaluation Association for the treatment of patients with hormone-naive advanced prostate cancer).Measurements
PSA progression-free survival (two consecutive increases in PSA of 50% compared with nadir and ≥5 ng/ml on two consecutive measurements at least 2 wk apart or death) and change in PSA were reviewed. Effects of baseline disease stage (localised, locally advanced, and metastatic) and PSA level (<10, 10–20, >20–50, and >50 ng/ml) were analysed.Results and limitations
Patients receiving degarelix showed a significantly lower risk of PSA progression or death compared with leuprolide (p = 0.05). PSA recurrences occurred mainly in patients with advanced disease and exclusively in those with baseline PSA >20 ng/ml. Patients with PSA >20 ng/ml had a significantly longer time to PSA recurrence with degarelix (p = 0.04). The relatively low number of patients in each subgroup is a limitation of this study.Conclusions
These results generate the hypothesis that degarelix at 240/80 mg offers improved PSA control compared with leuprolide. PSA recurrences occurred almost exclusively in patients with metastatic prostate cancer or high baseline PSA during this 1-yr study. Further studies are warranted to confirm these findings. 相似文献4.
Massimo Lazzeri Alexander Haese Alexandre de la Taille Joan Palou Redorta Thomas McNicholas Giovanni Lughezzani Vincenzo Scattoni Vittorio Bini Massimo Freschi Amy Sussman Bijan Ghaleh Philippe Le Corvoisier Josep Alberola Bou Salvador Esquena Fernández Markus Graefen Giorgio Guazzoni 《European urology》2013
Background
Strategies to reduce prostate-specific antigen (PSA)–driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary.Objective
To test the accuracy of serum isoform [−2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)—called index tests—in discriminating between patients with and without PCa.Design, setting, and participants
This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2–10 ng/ml who were subjected to initial prostate biopsy for suspected PCa.Outcome measurements and statistical analysis
The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis.Results and limitations
Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p = 0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p < 0.001), %fPSA (0.14 vs 0.17; p < 0.001), %p2PSA (2.1 vs 1.6; p < 0.001), and PHI (48.2 vs 38; p < 0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p < 0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values.Conclusions
In patients with a tPSA range of 2–10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA.Trial registration
The study is registered at http://www.controlled-trials.com, ref. ISRCTN04707454. 相似文献5.
Peter F.A. Mulders Arturo Molina Michael Marberger Fred Saad Celestia S. Higano Kim N. Chi Jinhui Li Thian Kheoh Christopher M. Haqq Karim Fizazi 《European urology》2014
Background
Metastatic castration-resistant prostate cancer (mCRPC) is a disease that primarily affects older men. Abiraterone acetate (AA), a selective androgen biosynthesis inhibitor, in combination with low-dose prednisone (P) improved overall survival (OS) in a randomised trial in mCRPC progressing after docetaxel versus placebo (PL) plus P.Objective
To examine the efficacy and safety of AA plus P versus PL plus P in subgroups of elderly (aged ≥75 yr) (n = 331) and younger patients (<75 yr) (n = 863).Design, setting, and participants
We conducted a post hoc analysis of a randomised double-blind PL-controlled study in mCRPC patients progressing after docetaxel chemotherapy.Intervention
Patients were randomised 2:1 to AA (1000 mg) plus low-dose P (5 mg twice daily) (n = 797) or PL plus P (n = 398).Outcome measurements and statistical analysis
Primary end point was OS. Secondary end points were time to prostate-specific antigen (PSA) progression (TTPP), radiographic progression-free survival (rPFS), and PSA response rate. Treatment differences were compared using the stratified log-rank test. The Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). The key limitation was the post hoc analysis.Results and limitations
Elderly patients treated with AA plus P showed improved OS (HR: 0.64; 95% CI, 0.478–0.853; p = 0.0022), TTPP (HR: 0.76; 95% CI, 0.503–1.155; p = 0.1995), and rPFS (HR: 0.66; 95% CI, 0.506–0.859; p = 0.0019), and higher PSA response rate with relative risk (HR: 4.15; 95% CI, 2.2–8.0]; p ≤ 0.0001) compared with patients treated with PL plus P. Grade 3/4 adverse events occurred in 62% of elderly patients and in 60% of patients aged <75 yr treated with AA plus P. Incidences of hypertension and hypokalaemia, although increased in the AA plus P arm, were similar in both age subgroups and readily managed.Conclusions
AA improves OS and is well tolerated in both elderly patients and younger patients with mCRPC following docetaxel, hence providing an important treatment option for elderly patients who may not tolerate alternative therapies with greater toxicity.Trial registration
ClinicalTrials.gov, identifier NCT00638690. 相似文献6.
Fritz Schröder Chris Bangma Javier C. Angulo Antonio Alcaraz Marc Colombel Tom McNicholas Teuvo L. Tammela Indrani Nandy Ramiro Castro 《European urology》2013
Background
Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial.Objective
To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.Design, setting, and participants
Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.Intervention
The 5α-reductase inhibitor, dutasteride.Outcome measurements and statistical analysis
The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.Results and limitations
Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35–76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53–75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.Conclusions
Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.Clinical trial registry
ClinicalTrials.gov, NCT00558363. 相似文献7.
Zachary S. Zumsteg Daniel E. Spratt Isaac Pei Zhigang Zhang Yoshiya Yamada Marisa Kollmeier Michael J. Zelefsky 《European urology》2013
Background
The management of intermediate-risk prostate cancer (PCa) is controversial, in part due to the heterogeneous nature of patients falling within this classification.Objective
We propose a new risk stratification system for intermediate-risk PCa to aid in prognosis and therapeutic decision making.Design, setting, and participants
Between 1992 and 2007, 1024 patients with National Comprehensive Cancer Network intermediate-risk PCa and complete biopsy information were treated with definitive external-beam radiation therapy (EBRT) utilizing doses ≥81 Gy. Unfavorable intermediate-risk (UIR) PCa was defined as any intermediate-risk patient with a primary Gleason pattern of 4, percentage of positive biopsy cores (PPBC) ≥50%, or multiple intermediate-risk factors (IRFs; cT2b–c, prostate-specific antigen [PSA] 10–20, or Gleason score 7).Intervention
All patients received EBRT with ≥81 Gy with or without neoadjuvant and concurrent androgen-deprivation therapy (ADT).Outcome measurements and statistical analysis
Univariate and multivariate analyses were performed using a Cox proportional hazards model for PSA recurrence-free survival (PSA-RFS) and distant metastasis (DM). PCa-specific mortality (PCSM) was analyzed using a competing-risk method.Results and limitations
Median follow-up was 71 mo. Primary Gleason pattern 4 (hazard ratio [HR]: 3.26; p < 0.0001), PPBC ≥50% (HR: 2.72; p = 0.0007), and multiple IRFs (HR: 2.20; p = 0.008) all were significant predictors of increased DM in multivariate analyses. Primary Gleason pattern 4 (HR: 5.23; p < 0.0001) and PPBC ≥50% (HR: 4.08; p = 0.002) but not multiple IRFs (HR: 1.74; p = 0.21) independently predicted for increased PCSM. Patients with UIR disease had inferior PSA-RFS (HR: 2.37; p < 0.0001), DM (HR: 4.34; p = 0.0003), and PCSM (HR: 7.39; p = 0.007) compared with those with favorable intermediate-risk disease, despite being more likely to receive neoadjuvant ADT. Short follow-up and retrospective study design are the primary limitations.Conclusions
Intermediate-risk PCa is a heterogeneous collection of diseases that can be separated into favorable and unfavorable subsets. These groups likely will benefit from divergent therapeutic paradigms. 相似文献8.
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9.
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10.
Tammy Ho Leah Gerber William J. Aronson Martha K. Terris Joseph C. Presti Christopher J. Kane Christopher L. Amling Stephen J. Freedland 《European urology》2012
Background
Obesity is associated with an increased risk of biochemical recurrence (BCR) after radical prostatectomy (RP). It is unclear whether this is due to technical challenges related to operating on obese men or other biologic factors.Objective
To examine whether obesity predicts higher prostate-specific antigen (PSA) nadir (as a measure of residual PSA-producing tissue) after RP and if this accounts for the greater BCR risk in obese men.Design, setting, and participants
A retrospective analysis of 1038 RP patients from 2001 to 2010 in the multicenter US Veterans Administration–based Shared Equal Access Regional Cancer Hospital database with median follow-up of 41 mo.Intervention
All patients underwent RP.Outcome measurements and statistical analysis
We evaluated the relationship between body mass index (BMI) and ultrasensitive PSA nadir within 6 mo after RP. Adjusted proportional hazards models were used to examine the association between BMI and BCR with and without PSA nadir.Results and limitations
Mean BMI was 28.5 kg/m2. Higher BMI was associated with higher PSA nadir on both univariable (p = 0.001) and multivariable analyses (p < 0.001). Increased BMI was associated with increased BCR risk (hazard ratio [HR]: 1.06; p = 0.007). Adjusting for PSA nadir slightly attenuated, but did not eliminate, this association (HR: 1.04, p = 0.043). When stratified by PSA nadir, obesity only significantly predicted BCR in men with an undetectable nadir (p = 0.006). Unfortunately, other clinically relevant end points such as metastasis or mortality were not available.Conclusions
Obese men are more likely to have a higher PSA nadir, suggesting that either more advanced disease or technical issues confound an ideal operation. However, even after adjusting for the increased PSA nadir, obesity remained predictive of BCR, suggesting that tumors in obese men are growing faster. This provides further support for the idea that obesity is biologically associated with prostate cancer progression. 相似文献11.
Tobias Nordström Markus Aly Mark S. Clements Caroline E. Weibull Jan Adolfsson Henrik Grönberg 《European urology》2013
Background
Prostate-specific antigen (PSA) testing has increased in several countries. There is incomplete knowledge of PSA testing patterns.Objective
Determine the prevalence of PSA testing and explore patterns of PSA retesting in Stockholm County, Sweden.Design, setting, and participants
A population-based study was performed. Through registry linkages, we collected population information, data on PSA tests, pathology reports, and clinical information. The study population comprised males living in Stockholm County in 2011 (n = 1 034 129), of which 229 872 had a PSA test during the period 2003–2011.Outcome measurements and statistical analysis
We determined limited-duration-point prevalence of PSA testing and performed survival analysis on PSA retesting for men aged 40–89 yr.Results and limitations
The number of PSA tests increased from 54 239 in 2003 to 124 613 in 2011. During the 9-yr study period, 46%, 68%, and 77% of men without a prior prostate cancer (PCa) diagnosis and aged 50–59 yr, 60–69 yr, and 70–79 yr, respectively, had a PSA test. During 2010 and 2011, 25%, 40%, and 46% of men aged 50–59 yr, 60–69 yr, and 70–79 yr, respectively, had a PSA test. The prevalence of PSA testing increased from 2003 to 2011. The probability of retesting was PSA and age dependent, with a 26-mo cumulative incidence of 0.337 (95% confidence interval, 0.333–0.341) if the first PSA value was <1 ng/ml. The main limitations were (1) that PSA data prior to 2003 were not available and (2) that the study cohort was restricted to men who were alive in 2011.Conclusions
Although screening for PCa is not recommended in Sweden, PSA testing in Stockholm County was high across ages ranging from 40 to 89 yr and increased during the period 2003–2011. The probability of PSA retesting was high, regardless of the original PSA level. These results contrast with current clinical recommendations and raise calls for a change, either through structured PCa testing or more detailed guidelines on PSA testing. 相似文献12.
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13.
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.
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16.
17.
Xingkang Jiang Shimiao ZhuGuowei Feng Zhihong ZhangChangying Li Hui LiChao Wang Yong Xu 《European urology》2013
Context
The optimal initial prostate biopsy core number is still an issue with many unanswered questions and significant controversy.Objective
To compare diagnostic values of initial saturation prostate biopsy scheme and extended scheme with respect to prostate-specific antigen (PSA) levels, prostate volume (PV), and PSA density (PSAD).Evidence acquisition
Electronic databases including Medline, Web of Knowledge, and the Cochrane Library were searched through November 1, 2012. Experts were consulted, and references from relevant articles were scanned. The meta-analysis was conducted with RevMan 5.1, according to the PRISMA guidelines. Mantel-Haenszel estimates were calculated and pooled under a fixed or random effect model, with data expressed as risk difference (RD) and 95% confidence interval (CI).Evidence synthesis
We analyzed eight trials with a total of 11 997 participants who underwent transrectal ultrasound guided prostate biopsies for the first time and met inclusion criteria. Studies consisted of one paired design study, two randomized clinical trials, and five nonrandomized studies. Saturation biopsy scheme showed a significant advantage in prostate cancer (PCa) detection over an extended scheme (RD: 0.04; 95% CI, 0.01–0.08; p = 0.02). In addition, subgroup analyses found a saturation protocol to be superior to an extended protocol in the detection of PCa in men with PSA <10 ng/ml (RD: 0.04; 95% CI, 0.01–0.07; p = 0.002), PV >40 ml (RD: 0.05; 95%CI, 0.01–0.09; p = 0.02), or PSAD <0.25 ng/ml per gram (RD: 0.04; 95% CI, 0.00–0.09; p = 0.04).Conclusions
The existing evidence indicates that an initial saturation biopsy scheme is more efficient than an extended scheme for PCa detection, especially for those men with lower PSA levels, higher PV, or lower PSAD, without increasing complications and the amount of insignificant cancer. 相似文献18.
Sebastien Crouzet Xavier Rebillard Daniel Chevallier Pascal Rischmann Gilles Pasticier Gregory Garcia Olivier Rouviere Jean-Yves Chapelon Albert Gelet 《European urology》2010
Background
High-intensity focused ultrasound (HIFU) is an emerging treatment for select patients with localized prostate cancer (PCa).Objectives
To report the oncologic outcome of HIFU as a primary care option for localized prostate cancer from a multicenter database.Design, setting, and participants
Patients with localized PCa treated with curative intent and presenting at least a 2-yr follow-up from February 1993 were considered in this study. Previously irradiated patients were excluded from this analysis. In case of any residual or recurrent PCa, patients were systematically offered a second session. Kaplan-Meier analysis was performed to determine disease-free survival rates (DFSR).Measurements
Prostate-specific antigen (PSA), clinical stage, and pathologic results were measured pre- and post-HIFU.Results and limitations
A total of 803 patients from six urologic departments met the inclusion criteria. Stratification according to d’Amico's risk group was low, intermediate, and high in 40.2%, 46.3%, and 13.5% of patients, respectively. Mean follow-up was 42 ± 33 mo. Mean PSA nadir was 1.0 ± 2.8 ng/ml with 54.3% reaching a nadir of ≤0.3 ng/ml. Control biopsies were negative in 85% of cases. The overall and cancer-specific survival rates at 8 yr were 89% and 99%, respectively. The metastasis-free survival rate at 8 yr was 97%. Initial PSA value and Gleason score value significantly influence the DFSR. The 5- and 7-yr biochemical-free survival rates (Phoenix criteria) were 83–75%, 72–63%, and 68–62% (p = 0.03) and the additional treatment-free survival rates were 84–79%, 68–61%, and 52–54% (p < 0.001) for low-, intermediate-, and high-risk patients, respectively. PSA nadir was a major predictive factor for HIFU success: negative biopsies, stable PSA, and no additional therapy.Conclusions
Local control and DFSR achieved with HIFU were similar to those expected with conformal external-beam radiation therapy (EBRT). The excellent cancer-specific survival rate is also explained by the possibility to repeat HIFU and use salvage EBRT. 相似文献19.
Mario W. Kramer Roozbeh Golshani Axel S. Merseburger Judith Knapp Alfredo Garcia Joerg Hennenlotter Robert C. Duncan Mark S. Soloway Merce Jorda Marcus A. Kuczyk Arnulf Stenzl Vinata B. Lokeshwar 《European urology》2010
Background
For bladder cancer (BCa) patients undergoing bladder-sparing treatments, molecular markers may aid in accurately predicting progression to muscle invasion and recurrence. Hyaluronic acid (HA) is a glycosaminoglycan that promotes tumor metastasis. Hyaluronoglucosaminidase 1 (HYAL-1)–type hyaluronidase (HAase) promotes tumor growth, invasion, and angiogenesis. Urinary HA and HAase levels are diagnostic markers for BCa.Objective
We evaluated whether HA and HYAL-1 can predict progression to muscle invasion and recurrence among patients with non–muscle-invasive BCa.Design, setting, and participants
: Based on tissue availability, tissue microarrays were prepared from a cohort of 178 BCa specimens (144 non–muscle invasive, 34 muscle invasive). Follow-up information was available on 111 patients with non–muscle-invasive BCa (mean follow-up: 69.5 mo); 58 patients recurred and 25 progressed to muscle invasion (mean time to progress: 22.3 mo).Measurements
HA and HYAL-1 expression was evaluated by immunohistochemistry and graded for intensity and area of staining. Association of HA and HYAL-1 staining with BCa recurrence and muscle invasion was evaluated by univariate and multivariate models.Results and limitations
HA and HYAL-1 expression correlated with tumor grade, stage, and multifocality (p < 0.05). In non–muscle-invasive BCa specimens, HYAL-1 staining was higher (234.3 ± 52.2; 200.6 ± 61.4) if patients experienced progression to muscle invasion or recurrence when compared with no progression or recurrence (164.1 ± 48.2; 172.1 ± 57; p < 0.001). HA staining correlated with muscle invasion (p < 0.001). In univariate analysis, age (p = 0.014), multifocality (p = 0.023), and HYAL-1 staining (p < 0.001) correlated with muscle invasion, whereas only HYAL-1 correlated with recurrence (p = 0.013). In multivariate analysis, HYAL-1 significantly associated with muscle invasion (p < 0.001; 76.8% accuracy) and recurrence (p = 0.01; 67.8% accuracy).Conclusions
HYAL-1 is a potential prognostic marker for predicting progression to muscle invasion and recurrence. 相似文献20.
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