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1.
Julien Riviere Jean-Christophe Bernhard Grégoire Robert Hervé Wallerand Edouard Deti Sylvie Maurice-Tison Jean-Michel Ardiet Jean-Philippe Maire Pierre Richaud Jean-Marie Ferriere Philippe Ballanger Albert Gelet Gilles Pasticier 《European urology》2010
Background
Radiotherapy is a treatment option in the case of local failure following treatment for localised prostate cancer with high-intensity focussed ultrasound (HIFU).Objective
Our aim was to evaluate tolerance and oncologic control with salvage radiotherapy (SRT) after HIFU failure and to identify predictive factors of success.Design, setting, and participants
From March 1995 to March 2008, all patients who presented with histologically proven persistent local disease following HIFU and were treated with curative intent SRT (with or without hormonal treatment) were included in this single-centre retrospective study.Intervention
Patients underwent conformal radiotherapy. The median dose of conformal treatment was 72 Gy (65–78 Gy).Measurements
The primary outcome measure was progression-free survival (PFS) defined as no biochemical relapse (three consecutive rises in prostate-specific antigen [PSA] with a velocity >0.4 ng/ml per year or PSA >1.5 ng/ml) and no additional treatment. Predictive factors of failure were examined in univariate and multivariate analyses. Adverse events in terms of urinary and digestive toxicity, urine incontinence, and erectile dysfunction (ED) were reported.Results and limitations
The median (range) and mean (standard deviation) follow-up of the 100 patients analysed was 33 mo (5–164 mo) and 37.2 mo (23.6 mo), respectively. Eighty-three patients received SRT alone, and 17 received SRT and androgen-deprivation therapy. For the 83 patients treated with exclusive radiation therapy, PFS was 72.5% at 5 yr and 93%, 67%, and 55% for the low-, intermediate-, and high-risk groups, respectively. In the univariate analysis, PSA level prior to SRT, risk status, PSA nadir after SRT, PSA nadir after SRT >0.2 ng/ml, and time to achieve this nadir were all predictive of failure. In the multivariate analysis, PSA nadir post-SRT with a threshold at 0.2 ng/ml and time to achieve this nadir were the significant predictive factors of failure. Gastrointestinal toxicity was low; urinary toxicity grade ≤2 was 34.5%. Four were grade 3 (4.7%), one was grade 4 (1.2%), and one was grade 5 (1.2%). The incidence of severe ED (International Index of Erectile Dysfunction–5 score 5–10) was 14% pre-HIFU, and 51.9% and 82.3% pre- and post-SRT, respectively. Because our study was retrospective, results have to be interpreted cautiously.Conclusions
SRT provides satisfactory oncologic control after HIFU failure with little (or mild) additional toxicity. These results warrant further investigation. 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.
Sebastien Crouzet Jean Yves Chapelon Olivier Rouvière Florence Mege-Lechevallier Marc Colombel Hélène Tonoli-Catez Xavier Martin Albert Gelet 《European urology》2014
Background
High-intensity focused ultrasound (HIFU) is a nonsurgical therapy for selected patients with localized prostate cancer (PCa).Objective
The long-term oncologic and morbidity outcomes of primary HIFU therapy for localized PCa were evaluated in a prospective, single-arm, single-institution cohort study.Design, setting, and participants
Participants were patients treated with HIFU for localized PCa from 1997 to 2009. Excluded were patients with local recurrence following radiotherapy. A second HIFU session was systematically performed in patients with biopsy-proven local recurrence.Intervention
Whole-gland prostate ablation with transrectal HIFU.Outcome measurements and statistical analysis
Incontinence was assessed using the Ingelman-Sundberg score, and potency was assessed using the five-item version of the International Index of Erectile Function (IIEF-5) scores. Primary outcomes were survival rates (biochemical-free, cancer-specific, metastasis-free, and overall survival). Secondary outcomes were morbidity rates. Median follow-up was 6.4 yr (range: 0.2–13.9). The Kaplan-Meier method was used to determine survival estimates, and multivariate analysis was used to determine predictive factors of biochemical progression.Results and limitations
A total of 1002 patients were included. The median nadir prostate-specific antigen (PSA) was 0.14 ng/ml, with 63% of patients reaching a nadir PSA ≤0.3 ng/ml. Sixty percent of patients received one HIFU session, 38% received two sessions, and 2% received three sessions. The 8-yr biochemical-free survival rates (Phoenix definition) were 76%, 63%, and 57% for low-, intermediate-, and high-risk patients, respectively (p < 0.001). At 10 yr, the PCa-specific survival rate and metastasis-free survival rate (MFSR) were 97% and 94%, respectively. Salvage therapies included external-beam radiation therapy (EBRT) (13.8%), EBRT plus androgen-deprivation therapy (ADT) (9.7%), and ADT alone (12.1%). Severe incontinence and bladder outlet obstruction decreased with refinement in the technology, from 6.4% and 34.9% to 3.1% and 5.9%, respectively. Limitations included the fact that the study was a single-arm study without a comparison group, technological improvements, changes in surgical protocol during the study, and the use of ADT to downsize the prostate in 39% of patients.Conclusions
HIFU is a potentially effective treatment of localized PCa, with a low PCa-specific mortality rate and a high MFSR at 10 yr as well as acceptable morbidity. 相似文献4.
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.
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7.
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8.
Background
Salvage cryosurgery (SC) is a recognised option for patients who fail either primary radiation or cryosurgery.Objective
To report outcomes of patients undergoing SC.Design, setting, and participants
A consecutive series of 396 patients who had failed either primary radiotherapy or cryosurgery underwent SC between October 1994 and August 2011.Outcome measurements and statistical analysis
Demographic and clinical parameters before primary and salvage treatment were evaluated; disease-free-survival (DFS), overall-survival (OS), disease-specific-survival (DSS), and complications were assessed.Results and limitations
Sufficient follow-up data were available for 328 patients. Median age was 65.8 yr (range: 45–81 yr), median serum prostate-specific antigen (PSA) level was 8.0 ng/ml (range: 0.6–290.0 ng/ml). After primary treatment, median time to recurrence was 55 mo (range: 0.0–183.6 mo). SC was performed at a median of 67.5 mo (range: 7.0–212.7 mo) later; median pre-SC PSA level was 4.0 ng/ml (range: 0.1–112.4 ng/ml). Median PSA nadir was 0.2 ng/ml (range: 0.01–70.70 ng/ml), reached after a median of 2.6 mo (range: 2.0–67.3 mo) after SC. Median follow-up was 47.8 mo (range: 1.6–203.5 mo). Respective 5- and 10-yr DFS was 63% and 35%; OS: 74% and 45%; and DSS: 91% and 79%. In univariate analyses, time from primary treatment to SC or recurrence, PSA level before SC, and PSA nadir after SC were all significant predictors of recurrence (p ≤ 0.01). PSA before SC and time to recurrence were also predictive of DSS (p = 0.003 and p = 0.01, respectively). In multivariate analyses, only PSA nadir after SC was predictive of recurrence and DSS (p < 0.001 and p = 0.012, respectively). Complications were rare (range: 0.6–4.6%). Fifty-five patients (16.7%) underwent focal SC. Median PSA nadir after focal SC was 0.44 ng/ml (range: 0.04–20.1 ng/ml). Twenty-seven patients (49%) experienced recurrence. Respective 5- and 10-yr DFS was 47% and 42%; OS: 87% and 81%; and DSS: 100% and 83%.Conclusions
Our analysis confirms SC as an effective treatment option for patients failing primary therapy. Patients experienced excellent survival outcome and minimal associated morbidity after SC. Focal SC is an efficacious treatment for properly selected patients. 相似文献9.
Kate Tilling Hans Garmo Chris Metcalfe Lars Holmberg Freddie C. Hamdy David E. Neal Jan Adolfsson Richard M. Martin Michael Davis Katja Fall J. Athene Lane Hans-Olaf Adami Anna Bill-Axelson Jan-Eric Johansson Jenny L. Donovan 《European urology》2010
Background
Prostate-specific antigen (PSA) measurements are increasingly used to monitor men with localised prostate cancer (PCa), but there is little consensus about the method to use.Objective
To apply age-specific predictions of PSA level (developed in men without cancer) to one cohort of men with clinically identified PCa and one cohort of men with PSA-detected PCa. We hypothesise that among men with clinically identified cancer, the annual increase in PSA level would be steeper than in men with PSA-detected cancer.Design, setting, and participants
The Scandinavian Prostate Cancer Group 4 (SPCG-4) cohort consisted of 321 men assigned to the watchful waiting arm of the SPCG-4 trial. The UK cohort consisted of 320 men with PSA-detected PCa in the Prostate testing for cancer and Treatment (ProtecT) study who opted for monitoring. Multilevel models describing changes in PSA level were fitted to the two cohorts, and average PSA level at age 50, change in PSA level with age, and predicted PSA values were derived.Measurements
PSA level.Results and limitations
In the SPCG-4 cohort, mean PSA at age 50 was similar to the cancer-free cohort but with a steeper yearly increase in PSA level (16.4% vs 4.0%). In the UK cohort, mean PSA level was higher than that in the cancer-free cohort (due to a PSA biopsy threshold of 3.0 ng/ml) but with a similar yearly increase in PSA level (4.1%). Predictions were less accurate for the SPCG-4 cohort (median difference between observed and predicted PSA level: −2.0 ng/ml; interquartile range [IQR]: −7.6–0.7 ng/ml) than for the UK cohort (median difference between observed and predicted PSA level: −0.8 ng/ml; IQR: −2.1–0.1 ng/ml).Conclusions
In PSA-detected men, yearly change in PSA was similar to that in cancer-free men, whereas in men with symptomatic PCa, the yearly change in PSA level was considerably higher. Our method needs further evaluation but has promise for refining active monitoring protocols. 相似文献10.
Background
The diagnostic performance of a genetic score based on single nucleotide polymorphisms (SNPs) is unknown in the prostate-specific antigen (PSA) range of 1–3 ng/ml. A substantial proportion of men in this PSA span have prostate cancer (PCa), but biomarkers to determine who should undergo a prostate biopsy are lacking.Objective
To evaluate whether a genetic risk score identifies men in the PSA range of 1–3 ng/ml who are at higher risk for PCa.Design, setting, and participants
Men aged 50–69 yr with PSA 1–3 ng/ml and without a previous prostate biopsy were selected from the STHLM2 cohort. Of 2696 men, 49 SNPs were genotyped, and a polygenic risk score was calculated. Of these men, 860 were invited according to risk score, and 172 underwent biopsy.Outcome measurements and statistical analysis
The risk of PCa was assessed using univariate and multivariate logistic regression analysis.Results and limitations
PCa was diagnosed in 47 of 172 participants (27%), with Gleason sum 6 in 36 of 47 men (77%) and Gleason sum ≥7 in 10 of 47 men (21%); one man had intraductal cancer. The genetic score was a significant predictor of a positive biopsy (p = 0.028), even after adjusting for PSA, ratio of free to total PSA, prostate volume, age, and family history. There was an increase in the odds ratio of 1.60 (95% confidence interval, 1.05–2.45) with increasing genetic risk score. The absolute risk difference of positive biopsy was 19 percentage points, comparing the high and low genetic risk group (37% vs 18%).Conclusions
A risk score based on SNPs predicts biopsy outcome in previously unbiopsied men with PSA 1–3 ng/ml. Introducing a genetic-based risk stratification tool can increase the proportion of men being classified in line with their true risk of PCa. 相似文献11.
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12.
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13.
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14.
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15.
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16.
Flip H. Jansen Ron H.N. van Schaik Joep Kurstjens Wolfgang Horninger Helmut Klocker Jasmin Bektic Mark F. Wildhagen Monique J. Roobol Chris H. Bangma Georg Bartsch 《European urology》2010
Background
Novel markers for prostate cancer (PCa) detection are needed. Total prostate-specific antigen (tPSA) and percent free prostate-specific antigen (%fPSA = tPSA/fPSA) lack diagnostic specificity.Objective
To evaluate the use of prostate-specific antigen (PSA) isoforms p2PSA and benign prostatic hyperplasia–associated PSA (BPHA).Design, setting, and participants
Our study included 405 serum samples from the Rotterdam arm of the European Randomised Study of Screening for Prostate Cancer and 351 samples from the Urology Department of Innsbruck Medical University.Measurements
BPHA, tPSA, fPSA, and p2PSA levels were measured by Beckman-Coulter Access Immunoassay. In addition, the Beckman Coulter Prostate Health Index was calculated: phi = (p2PSA/fPSA) × √(tPSA).Results and limitations
The p2PSA and phi levels differed significantly between men with and without PCa. No difference in BPHA levels was observed. The highest PCa predictive value in both cohorts was achieved by phi with areas under the curve (AUCs) of 0.750 and 0.709, a significant increase compared to tPSA (AUC: 0.585 and 0.534) and %fPSA (AUC: 0.675 and 0.576). Also, %p2PSA (p2PSA/fPSA) showed significantly higher AUCs compared to tPSA and %fPSA (AUC: 0.716 and 0.695, respectively). At 95% and 90% sensitivity, the specificities of phi were 23% and 31% compared to 10% and 8% for tPSA, respectively. In both cohorts, multivariate analysis showed a significant increase in PCa predictive value after addition of p2PSA to a model consisting of tPSA and fPSA (increase in AUC from 0.675 to 0.755 and from 0.581 to 0.697, respectively). Additionally, the specificity at 95% sensitivity increased from 8% to 24% and 7% to 23%, respectively. Furthermore, %p2PSA, phi, and the model consisting of tPSA and fPSA with or without the addition of p2PSA missed the least of the tumours with a biopsy or pathologic Gleason score ≥7 at 95% and 90% sensitivity.Conclusions
This study shows significant increases in PCa predictive value and specificity of phi and %p2PSA compared to tPSA and %fPSA. p2PSA has limited additional value in identifying aggressive PCa (Gleason score ≥7). 相似文献17.
Eric Barret Youness Ahallal Rafael Sanchez-Salas Marc Galiano Jean-Marc Cosset Pierre Validire Petr Macek Matthieu Durand Dominique Prapotnich François Rozet Xavier Cathelineau 《European urology》2013
Background
Focal therapy (FT) for prostate cancer (PCa) seems to be part of a natural evolution in the quest to improve the management of early organ-confined disease.Objective
To assess the morbidity of the initial experience of FT in a tertiary referral center for PCa management.Design, setting, and participants
From 2009 to 2011, a total of 1213 patients with clinically localized PCa were treated at our institution. Of these patients, 547 were considered to have indolent disease according to the D’Amico criteria for low-risk disease plus unilateral disease with a maximum of three positive biopsies. A total of 106 patients underwent FT using high-intensity focused ultrasonography (HIFU), brachytherapy, cryotherapy, or vascular-targeted photodynamic therapy (VTP).Outcome measurements and statistical analysis
Complications were prospectively recorded and graded according to the Clavien-Dindo scale. Data were prospectively collected and retrospectively analyzed.Results and limitations
This study included 106 patients, median age 66.5 yr (interquartile range [IQR]): 61–73), who had a prostate hemiablation; 50 patients (47%) had cryotherapy, 23 patients (22%) had VTP, 21 patients (20%) received HIFU, and 12 patients (11%) had brachytherapy. The median prostate-specific antigen (PSA) level was 6.1 ng/ml (IQR: 5–8.1), all the patients had a biopsy Gleason score of 6, and the median prostate weight was 43 g (IQR: 33–55). The median International Prostate Symptom Score was 6 (IQR: 3–10), and the median International Index of Erectile Function score was 20 (IQR: 15–23). After treatment, the median PSA at 3, 6, and 12 mo was 3.1 2.9, and 2.7 ng/ml (IQR: 2–5.1, 1.1–4.7, and 1–4.4), respectively. Thirteen percent of the patients experienced treatment-related complications. There were 11 minor medical complications (10 grade 1 complications and 1 grade 2 complication), 2 grade 3 complications, and no grade 4 or higher complications.Conclusions
FT for a highly selected population with PCa is feasible and had an acceptable morbidity with <2% major complications. 相似文献18.
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19.
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20.
Fernando Calais da Silva Fernando Manuel Calais da Silva Frederico Gonçalves Américo Santos Jan Kliment Peter Whelan Tim Oliver Nicos Antoniou Spiro Pastidis Anton Marques Queimadelos Chris Robertson 《European urology》2014