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1.
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2.
Luigi F. Da Pozzo Cesare Cozzarini Alberto Briganti Nazareno Suardi Andrea Salonia Roberto Bertini Andrea Gallina Marco Bianchi Gemma V. Fantini Angelo Bolognesi Ferruccio Fazio Francesco Montorsi Patrizio Rigatti 《European urology》2009
Background
Recent large, prospective, randomised studies have demonstrated that adjuvant radiotherapy (RT) is a safe and effective procedure for preventing disease recurrence in locally advanced prostate cancer (PCa) patients. However, no study has ever tested the role of adjuvant RT in node-positive patients after radical prostatectomy (RP).Objective
We hypothesised that adjuvant RT with early hormone therapy (HT) might improve long-term outcomes of patients with PCa and nodal metastases treated with RP and extended pelvic lymph node dissection (ePLND).Design, setting, and participants
This retrospective study included 250 consecutive patients with pathologic lymph node invasion. We assessed factors predicting long-term biochemical recurrence (BCR)–free and cancer-specific survival (CSS) in node-positive PCa patients treated with RP, ePLND, and adjuvant treatments between 1988 and 2002 in a tertiary academic centre.Intervention
All patients received adjuvant treatments according to the treating physician after detailed patient information: 129 patients (51.6%) were treated with a combination of RT and HT, while 121 patients (48.4%) received adjuvant HT alone.Measurements
BCR-free survival and CSS in patients with node-positive PCa.Results and limitations
Mean follow-up was 95.9 mo (median: 91.2). BCR-free survival and CSS rates at 5, 8, and 10 yr were 72%, 61%, 53% and 89%, 83%, 80%, respectively. In multivariable Cox regression models, adjuvant RT and the number of positive nodes were independent predictors of BCR-free survival (p = 0.002 and p = 0.003, respectively) as well as of CSS (p = 0.009 and p = 0.01, respectively). Moreover, there was significant gain in predictive accuracy when adjuvant RT was included in multivariable models predicting BCR-free survival and CSS (gain: 3.3% and 3%, respectively; all p < 0.001).Conclusions
Our data showed excellent long-term outcome for node-positive PCa patients treated with radical surgery plus adjuvant treatments. This study is the first to report a significant protective role for adjuvant RT in BCR-free survival and CSS of node-positive patients. 相似文献3.
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
4.
M. Minhaj Siddiqui Soroush Rais-Bahrami Hong Truong Lambros Stamatakis Srinivas Vourganti Jeffrey Nix Anthony N. Hoang Annerleim Walton-Diaz Brian Shuch Michael Weintraub Jochen Kruecker Hayet Amalou Baris Turkbey Maria J. Merino Peter L. Choyke Bradford J. Wood Peter A. Pinto 《European urology》2013
Background
Gleason scores from standard, 12-core prostate biopsies are upgraded historically in 25−33% of patients. Multiparametric prostate magnetic resonance imaging (MP-MRI) with ultrasound (US)-targeted fusion biopsy may better sample the true gland pathology.Objective
The rate of Gleason score upgrading from an MRI/US-fusion-guided prostate-biopsy platform is compared with a standard 12-core biopsy regimen alone.Design, setting, and participants
There were 582 subjects enrolled from August 2007 through August 2012 in a prospective trial comparing systematic, extended 12-core transrectal ultrasound biopsies to targeted MRI/US-fusion-guided prostate biopsies performed during the same biopsy session.Outcome measurements and statistical analysis
The highest Gleason score from each biopsy method was compared.Interventions
An MRI/US-fusion-guided platform with electromagnetic tracking was used for the performance of the fusion-guided biopsies.Results and limitations
A diagnosis of prostate cancer (PCa) was made in 315 (54%) of the patients. Addition of targeted biopsy led to Gleason upgrading in 81 (32%) cases. Targeted biopsy detected 67% more Gleason ≥4 + 3 tumors than 12-core biopsy alone and missed 36% of Gleason ≤3 + 4 tumors, thus mitigating the detection of lower-grade disease. Conversely, 12-core biopsy led to upgrading in 67 (26%) cases over targeted biopsy alone but only detected 8% more Gleason ≥4 + 3 tumors. On multivariate analysis, MP-MRI suspicion was associated with Gleason score upgrading in the targeted lesions (p < 0.001). The main limitation of this study was that definitive pathology from radical prostatectomy was not available.Conclusions
MRI/US-fusion-guided biopsy upgrades and detects PCa of higher Gleason score in 32% of patients compared with traditional 12-core biopsy alone. Targeted biopsy technique preferentially detects higher-grade PCa while missing lower-grade tumors. 相似文献5.
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6.
Context
An association between tobacco smoking and prostate cancer (PCa) incidence and mortality was suggested in an earlier meta-analysis of 24 prospective studies in which dose–response associations and risks per unit of tobacco use were not examined.Objective
We investigated the association between several measures of tobacco use and PCa mortality (primary outcome) and incidence (secondary outcome) including dose–response association.Evidence acquisition
Relevant articles from prospective studies were identified by searching the PubMed and Web of Science databases (through January 21, 2014) and reference lists of relevant articles. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects methods. We also calculated population attributable risk (PAR) for smoking and PCa mortality.Evidence synthesis
We included 51 articles in this meta-analysis (11 823 PCa deaths, 50 349 incident cases, and 4 082 606 cohort participants). Current cigarette smoking was associated with an increased risk of PCa death (RR: 1.24; 95% CI, 1.18–1.31), with little evidence for heterogeneity and publication bias. The number of cigarettes smoked per day had a dose–response association with PCa mortality (p = 0.02; RR for 20 cigarettes per day: 1.20). The PAR for cigarette smoking and PCa deaths in the United States and Europe were 6.7% and 9.5%, respectively, corresponding to >10 000 deaths/year in these two regions. Current cigarette smoking was inversely associated with incident PCa (RR: 0.90; 95% CI, 0.85–0.96), with high heterogeneity in the results. However, in studies completed in 1995 or earlier (considered as completed before the prostate-specific antigen screening era), ever smoking showed a positive association with incident PCa (RR: 1.06; 95% CI, 1.00–1.12) with little heterogeneity.Conclusions
Combined evidence from observational studies shows a modest but statistically significant association between cigarette smoking and fatal PCa. Smoking appears to be a modifiable risk factor for PCa death.Patient summary
Smoking increases the chance of prostate cancer death. Not smoking prevents this harm and many other tobacco-related diseases. 相似文献7.
Firas Abdollah Nazareno Suardi Cesare Cozzarini Andrea Gallina Umberto Capitanio Marco Bianchi Maxine Sun Nicola Fossati Niccolò Maria Passoni Claudio Fiorino Nadia Di Muzio Pierre I. Karakiewicz Patrizio Rigatti Francesco Montorsi Alberto Briganti 《European urology》2013
Background
The role of adjuvant radiotherapy (ART) after radical prostatectomy (RP) on survival of patients with prostate cancer (PCa) is still controversial.Objective
We tested the impact of ART on cancer-specific mortality (CSM) and overall mortality (OM) in PCa patients according to pathologic PCa features.Design, setting, and participants
We evaluated 1049 PCa patients treated with RP and extended pelvic lymph node dissection alone or in combination with adjuvant treatments between 1998 and 2008. All patients had positive surgical margins and/or pT3/pT4 disease with or without positive lymph nodes.Outcome measurements and statistical analysis
Cox regression analyses tested the relationship between pathologic characteristics and CSM rates. Independent predictors of survival were used to develop a novel risk score based on the number of risk factors. Finally, Cox regression models tested the relationship between ART and survival according to the number of risk factors.Results and limitations
On multivariable analyses, only pathologic Gleason score ≥8, pT3b/T4 stage, and presence of positive lymph nodes represented independent predictors of CSM (all p ≤ 0.02). The cumulative number of these pathologic findings was used to develop a risk score, which was 0, 1, 2, and 3 in 43.6%, 22.1%, 20.7%, and 13.6% of patients, respectively. In patients sharing more than two mentioned predictors of CSM (primarily having a risk score of 0 or 1), ART did not significantly improve survival (all p ≥ 0.4). Conversely, in patients with a risk score ≥2, ART was associated with lower CSM and OM rates (all p = 0.006). The observational nature of the cohort represents a limitation of the study.Conclusions
ART significantly improved survival only in patients with at least two of the following pathologic features at RP: Gleason score ≥8, pT3/pT4 disease, and positive lymph nodes. These patients represent the ideal candidates for ART after RP. 相似文献8.
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.
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.
Mani Menon Mahendra Bhandari Nilesh Gupta Zhaoli Lane James O. Peabody Craig G. Rogers Jesse Sammon Sameer A. Siddiqui Mireya Diaz 《European urology》2010
Background
There is a paucity of data on long-term oncologic outcomes for patients undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa).Objective
To evaluate oncologic outcomes in patients undergoing RARP at a high-volume tertiary center, with a focus on 5-yr biochemical recurrence–free survival (BCRFS).Design, setting, and participants
The study cohort consisted of 1384 consecutive patients with localized PCa who underwent RARP between September 2001 and May 2005 and had a median follow-up of 60.2 mo. No patient had secondary therapy until documented biochemical recurrence (BCR). BCR was defined as a serum prostate-specific antigen ≥0.2 ng/ml with a confirmatory value. BCRFS was estimated using the Kaplan-Meier method. Event–time distributions for the time to failure were compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression models were used to determine variables predictive of BCR.Intervention
All patients underwent RARP.Measurements
BCRFS rates were measured.Results and limitations
This cohort of patients had moderately aggressive PCa: 49.0% were D’Amico intermediate or high risk on biopsy; however, 60.9% had Gleason 7–10 disease, and 25.5% had ≥T3 disease on final pathology. There were 189 incidences of BCR (31 per 1,000 person years of follow-up) at a median follow-up of 60.2 mo (interquartile range [IQR]: 37.2–69.7). The actuarial BCRFS was 95.1%, 90.6%, 86.6%, and 81.0% at 1, 3, 5, and 7 yr, respectively. In the patients who recurred, median time to BCR was 20.4 mo; 65% of BCR incidences occurred within 3 yr and 86.2% within 5 yr. On multivariable analysis, the strongest predictors of BCR were pathologic Gleason grade 8–10 (hazard ratio [HR]: 5.37; 95% confidence interval [CI], 2.99–9.65; p < 0.0001) and pathologic stage T3b/T4 (HR: 2.71; 95% CI, 1.67–4.40; p < 0.0001).Conclusions
In a contemporary cohort of patients with localized PCa, RARP confers effective 5-yr biochemical control. 相似文献13.
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14.
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15.
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16.
A. Karim Kader Jielin Sun Brian H. Reck Paul J. Newcombe Seong-Tae Kim Fang-Chi Hsu Ralph B. D’Agostino Jr. Sha Tao Zheng Zhang Aubrey R. Turner Greg T. Platek Colin F. Spraggs John C. Whittaker Brian R. Lane William B. Isaacs Deborah A. Meyers Eugene R. Bleecker Frank M. Torti Jeffery M. Trent John D. McConnell S. Lilly Zheng Lynn D. Condreay Roger S. Rittmaster Jianfeng Xu 《European urology》2012
Background
Several germline single nucleotide polymorphisms (SNPs) have been consistently associated with prostate cancer (PCa) risk.Objective
To determine whether there is an improvement in PCa risk prediction by adding these SNPs to existing predictors of PCa.Design, setting, and participants
Subjects included men in the placebo arm of the randomized Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial in whom germline DNA was available. All men had an initial negative prostate biopsy and underwent study-mandated biopsies at 2 yr and 4 yr. Predictive performance of baseline clinical parameters and/or a genetic score based on 33 established PCa risk-associated SNPs was evaluated.Outcome measurements and statistical analysis
Area under the receiver operating characteristic curves (AUC) were used to compare different models with different predictors. Net reclassification improvement (NRI) and decision curve analysis (DCA) were used to assess changes in risk prediction by adding genetic markers.Results and limitations
Among 1654 men, genetic score was a significant predictor of positive biopsy, even after adjusting for known clinical variables and family history (p = 3.41 × 10−8). The AUC for the genetic score exceeded that of any other PCa predictor at 0.59. Adding the genetic score to the best clinical model improved the AUC from 0.62 to 0.66 (p < 0.001), reclassified PCa risk in 33% of men (NRI: 0.10; p = 0.002), resulted in higher net benefit from DCA, and decreased the number of biopsies needed to detect the same number of PCa instances. The benefit of adding the genetic score was greatest among men at intermediate risk (25th percentile to 75th percentile). Similar results were found for high-grade (Gleason score ≥7) PCa. A major limitation of this study was its focus on white patients only.Conclusions
Adding genetic markers to current clinical parameters may improve PCa risk prediction. The improvement is modest but may be helpful for better determining the need for repeat prostate biopsy. The clinical impact of these results requires further study. 相似文献17.
Julian Mauermann Vincent Fradet Louis Lacombe Thierry Dujardin Rabi Tiguert Bernard Tetu Yves Fradet 《European urology》2013
Background
Positive surgical margins (PSMs) increase the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), but their impact on hard clinical end points is a topic of ongoing discussion.Objective
To evaluate the influence of solitary PSMs (sPSMs) and multiple PSMs (mPSMs) on important clinical end points.Design, setting, and participants
Data from 1712 patients from the Centre Hospitalier Universitaire de Québec with pT2–4 N0 prostate cancer (PCa) and undetectable prostate-specific antigen after RP were analyzed.Intervention
RP without neoadjuvant or adjuvant treatment.Outcome measurements and statistical analysis
Kaplan-Meier analysis estimated survival functions, and Cox proportional hazards models addressed predictors of clinical end points.Results and limitations
Median follow-up was 74.9 mo. A total of 1121 patients (65.5%) were margin-negative, 281 patients (16.4%) had sPSMs, and 310 patients (18.1%) had mPSMs. A total of 280 patients (16.4%) experienced BCR, and 197 patients (11.5%) were treated with salvage radiotherapy (SRT). Sixty-eight patients (4.0%) received definitive androgen deprivation therapy, 19 patients (1.1%) developed metastatic disease, and 15 patients (0.9%) had castration-resistant PCa (CRPC). Thirteen patients (0.8%) died from PCa, and 194 patients (11.3%) died from other causes. Ten-year Kaplan-Meier estimates for BCR-free survival were 82% for margin-negative patients, 72% for patients with sPSMs, and 59% for patients with mPSMs (p < 0.0001). Time to metastatic disease, CRPC, PCa-specific mortality (PCSM), or all-cause mortality did not differ significantly among the three groups (p = 0.991, p = 0.988, p = 0.889, and p = 0.218, respectively). On multivariable analysis, sPSMs and mPSMs were associated with BCR (hazard ratio [HR]: 1.711; p = 0.001 and HR: 2.075; p < 0.0001), but sPSMs and mPSMs could not predict metastatic disease (p = 0.705 and p = 0.242), CRPC (p = 0.705 and p = 0.224), PCSM (p = 0.972 and p = 0.260), or all-cause death (p = 0.102 and p = 0.067). The major limitation was the retrospective design.Conclusions
In a cohort of patients who received early SRT in 70% of cases upon BCR, sPSMs and mPSMs predicted BCR but not long-term clinical end points. Adjuvant radiotherapy for margin-positive patients might not be justified, as only a minority of patients progressed to end points other than BCR. PCSM was exceeded 15-fold by competing risk mortality. 相似文献18.
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19.
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20.
Daniel A. Galvão Nigel Spry James Denham Dennis R. Taaffe Prue Cormie David Joseph David S. Lamb Suzanne K. Chambers Robert U. Newton 《European urology》2014