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1.
Christopher C. Parker Sarah Pascoe Aleš Chodacki Joe M. O'Sullivan Josep R. Germá Charles Gillies O’Bryan-Tear Trond Haider Peter Hoskin 《European urology》2013
Background
Patients with castration-resistant prostate cancer (CRPC) and bone metastases have an unmet clinical need for effective treatments that improve quality of life and survival with a favorable safety profile.Objective
To prospectively evaluate the efficacy and safety of three different doses of radium chloride (Ra 223) in patients with CRPC and bone metastases.Design, setting, and participants
In this phase 2 double-blind multicenter study, 122 patients were randomized to receive three injections of Ra 223 at 6-wk intervals, at doses of 25 kBq/kg (n = 41), 50 kBq/kg (n = 39), or 80 kBq/kg (n = 42). The study compared the proportion of patients in each dose group who had a confirmed decrease of ≥50% in baseline prostate-specific antigen (PSA) levels.Outcome measurements and statistical analysis
Efficacy was evaluated using blood samples to measure PSA and other tumor markers, recorded skeletal-related events, and pain assessments. Safety was evaluated using adverse events (AEs), physical examination, and clinical laboratory tests. The Jonckheere-Terpstra test assessed trends between groups.Results and limitations
The study met its primary end point with a statistically significant dose–response relationship in confirmed ≥50% PSA declines for no patients (0%) in the 25-kBq/kg dose group, two patients (6%) in the 50-kBq/kg dose group, and five patients (13%) in the 80-kBq/kg dose group (p = 0.0297). A ≥50% decrease in bone alkaline phosphatase levels was identified in six patients (16%), 24 patients (67%), and 25 patients (66%) in the 25-, 50-, and 80-kBq/kg dose groups, respectively (p < 0.0001). The most common treatment-related AEs (≥10%) occurring up to week 24 across all dose groups were diarrhea (21%), nausea (16%), and anemia (14%). No difference in incidence of hematologic events was seen among dose groups. Potential limitations include small patient numbers and differences among dose groups at baseline.Conclusions
Ra 223 had a dose-dependent effect on serum markers of CRPC activity, suggesting that control of bone disease with Ra 223 may affect cancer-related outcomes. Ra 223 was well tolerated at all doses.Trial registration
ClinicalTrials.gov: NCT00337155. 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.
Michael T. Schweizer Xian C. ZhouHao Wang Sunakshi BassiMichael A. Carducci Mario A. EisenbergerEmmanuel S. Antonarakis 《European urology》2014
Background
Taxanes may partly mediate their effect in castration-resistant prostate cancer (CRPC) through disruption of androgen-receptor trafficking along microtubules. This raises the possibility of cross-resistance between androgen-directed agents and docetaxel.Objective
To evaluate docetaxel efficacy after abiraterone treatment in CRPC patients.Design, setting, and participants
This was a single-institution, retrospective analysis in CRPC patients (N = 119) who either received abiraterone before docetaxel (AD) (n = 24) or did not receive abiraterone before docetaxel (docetaxel-only; n = 95). Men initiated docetaxel between December 2007 (the date abiraterone was first used at our center) and May 2013.Outcome measurements and statistical analysis
The primary efficacy end points were prostate-specific antigen progression-free survival (PSA-PFS) and clinical/radiographic progression-free survival (PFS) on docetaxel. Differences between groups were assessed using univariate and multivariable analyses.Results and limitations
Men in the AD group had a significantly higher risk for progression than those in the docetaxel-only group. Median PSA-PFS was 4.1 mo in the AD group and 6.7 mo in the docetaxel-only group (p = 0.002). Median PFS was also shorter in the AD group (4.4 mo vs 7.6 mo; p = 0.003). In multivariable analysis, prior abiraterone treatment remained an independent predictor of shorter PSA-PFS (hazard ratio [HR]: 3.48; 95% confidence interval [CI], 1.36–8.94; p = 0.01) and PFS (HR: 3.62; 95% CI, 1.41–9.27; p = 0.008). PSA declines ≥50% were less frequent in the AD group (38% vs 63%; p = 0.02). The small size and retrospective nature of this study may have introduced bias.Conclusions
Men receiving abiraterone before docetaxel were more likely to progress on docetaxel and less likely to achieve a PSA response than abiraterone-naïve patients. Cross-resistance between abiraterone and docetaxel may explain these findings; however, larger, more definitive studies are still needed to confirm this.Patient summary
We examined the efficacy of docetaxel in castration-resistant prostate cancer patients who either did or did not receive prior abiraterone. We found that men receiving abiraterone before docetaxel were less likely to achieve a PSA response and were more likely to progress sooner on docetaxel than abiraterone-untreated patients. This may be due to cross-resistance. 相似文献4.
Daniel E. Spratt Chi Zhang Zachary S. Zumsteg Xin Pei Zhigang Zhang Michael J. Zelefsky 《European urology》2013
Background
In vitro data and early clinical results suggest that metformin has desirable antineoplastic effects and has a theoretical benefit on castration-resistant prostate cancer (CRPC).Objective
To determine whether the use of metformin would be associated with improved clinical outcomes and a reduction in the development of CRPC.Design, setting, and participants
Data from 2901 consecutive patients (157 metformin, 162 diabetic non-metformin, and 2582 nondiabetic) with localized prostate cancer treated with external-beam radiation therapy from 1992 to 2008 were collected from a single institution in the United States.Intervention
Use of metformin in localized prostate cancer.Outcome measurements and statistical analysis
Univariate and multivariate regression models utilizing k-sample, Fine and Gray, Cox regression, log-rank, and Kaplan-Meier methods to assess prostate-specific antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival (DMFS), prostate cancer–specific mortality (PCSM), overall survival (OS), and development of CRPC.Results and limitations
With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin, diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and 8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted (correcting for PSA, T stage, Gleason score, age, diabetic status, and androgen-deprivation therapy use) improvement in all outcomes compared with the diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24–3.18]; p = 0.004), DMFS (adjusted HR: 3.68 [1.78–7.62]; p < 0.001), and PCSM (HR: 5.15 [1.53–17.35]; p = 0.008). Metformin use was also independently associated with a decrease in the development of CRPC in patients experiencing biochemical failure compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83–119.89]; p = 0.01). The retrospective study design was the primary limitation of the study.Conclusions
To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-RFS, DMFS, PCSM, OS, and reduce the development of CRPC in prostate cancer patients. Further validation of metformin's potential benefits is warranted. 相似文献5.
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6.
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7.
Carmel J. Pezaro Aurelius G. OmlinAmelia Altavilla David LorenteRoberta Ferraldeschi Diletta BianchiniDavid Dearnaley Christopher ParkerJohann S. de Bono Gerhardt Attard 《European urology》2014
Background
Cabazitaxel, abiraterone, and enzalutamide are survival-prolonging treatments in men with castration-resistant prostate cancer (CRPC) progressing following docetaxel chemotherapy. The sequential activity of these agents has not been studied and treatment sequencing remains a key dilemma for clinicians.Objective
To describe the antitumour activity of cabazitaxel after docetaxel and next-generation endocrine agents.Design, setting, and participants
We report on a cohort of 59 men with progressing CRPC treated with cabazitaxel, 37 of whom had received prior abiraterone and 9 of whom had received prior enzalutamide.Outcome measurements and statistical analysis
Changes in prostate-specific antigen (PSA) level were used to determine activity on abiraterone, enzalutamide, and cabazitaxel treatment. Radiologic tumour regressions according to Response Evaluation Criteria in Solid Tumors (RECIST) and symptomatic benefit were evaluated for cabazitaxel therapy.Results and limitations
The post–endocrine-therapy patients received abiraterone (n = 32), sequential abiraterone and enzalutamide (n = 5) or enzalutamide (n = 4). These patients received a median of 7 mo of abiraterone and 11 mo of enzalutamide. A median of six cabazitaxel cycles (range: 1–10 cycles) were delivered, with ≥50% PSA declines in 16 of 41 (39%) patients, soft tissue radiologic responses in 3 of 22 (14%) evaluable patients, and symptomatic benefit in 9 of 37 evaluable patients (24%). Median overall survival and progression-free survival were 15.8 and 4.6 mo, respectively. Antitumor activity on cabazitaxel was less favourable in the abiraterone- and enzalutamide-naïve cohort (n = 18), likely reflecting biologic differences in this cohort. These data were obtained from a retrospective analysis.Conclusions
This is the first report of cabazitaxel activity in CRPC progressing after treatment with docetaxel and abiraterone or enzalutamide. We demonstrate significant cabazitaxel activity in this setting.Patient summary
We looked at the antitumour activity of the chemotherapy drug cabazitaxel in men previously treated with docetaxel chemotherapy and the hormonal drugs abiraterone and enzalutamide. Cabazitaxel appeared active when given after abiraterone and enzalutamide. We can reassure men that cabazitaxel can be used after these novel endocrine treatments. 相似文献8.
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9.
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10.
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11.
Laurence Klotz Kurt Miller E. David Crawford Neal Shore Bertrand Tombal Cathrina Karup Anders Malmberg Bo-Eric Persson 《European urology》2014
Background
Studies comparing the gonadotropin-releasing hormone antagonist, degarelix, with luteinising hormone-releasing hormone (LHRH) agonists indicate differences in outcomes.Objective
To assess differences in efficacy and safety outcomes in a pooled analysis of trials comparing degarelix with LHRH agonists.Design, setting, and participants
Data were pooled from five prospective, phase 3 or 3b randomised trials (n = 1925) of degarelix and leuprolide or goserelin in men requiring androgen deprivation therapy for the treatment of prostate cancer. Patients received either 3 mo (n = 467) or 12 mo (n = 1458) of treatment.Intervention
Men were randomised to receive degarelix (n = 1266), leuprolide (n = 201), or goserelin (n = 458).Outcome measurements and statistical analysis
Unadjusted Kaplan-Meier analyses were supported by the Cox proportional hazards model, adjusted for disease-related baseline factors, to estimate hazard ratios (HRs) of efficacy and safety outcomes. The Fisher exact test compared crude incidences of adverse events.Results and limitations
Prostate-specific antigen (PSA) progression-free survival (PFS) was improved in the degarelix group (HR: 0.71; p = 0.017). For patients with baseline PSA levels >20 ng/ml, the HR for PSA PFS was 0.74 (p = 0.052). Overall survival (OS) was higher in the degarelix group (HR: 0.47; p = 0.023). OS was particularly improved with degarelix in patients with baseline testosterone levels >2 ng/ml (HR: 0.36; p = 0.006). In terms of disease-related adverse events, there were, overall, fewer joint-related signs and symptoms, musculoskeletal events, and urinary tract events in the degarelix group.Conclusions
These data indicate clinical benefits with degarelix, including a significant improvement in PSA PFS and OS, as well as reduced incidence of joint, musculoskeletal, and urinary tract adverse events, compared with LHRH agonists. 相似文献12.
Rana R. McKay Xun Lin Julia J. Perkins Daniel Y.C. Heng Ronit Simantov Toni K. Choueiri 《European urology》2014
Background
Bone metastases (BMs) are frequently present in patients with metastatic renal cell carcinoma (mRCC) and cause significant morbidity.Objective
The purpose of this analysis was to assess the impact of BMs and bisphosphonate therapy (BT) on outcomes in mRCC.Design, setting, and participants
We conducted a pooled analysis of patients with mRCC treated from 2003 to 2011 in phase 2 and 3 trials.Outcome measurements and statistical analysis
Statistical analyses were performed using Cox regression and the Kaplan-Meier method.Results and limitations
We identified 2749 patients treated with sunitinib (n = 1059), sorafenib (n = 355), axitinib (n = 359), temsirolimus (n = 208), temsirolimus plus interferon-α (IFN-α) (n = 208), or IFN-α (n = 560), with 28% (n = 781) having BMs. A total of 285 patients (10.4%) received BT. The presence of BMs in patients was associated with shorter overall survival (OS) when compared with patients without BMs (13.2 vs 20.2 mo, respectively; p < 0.0001) and shorter progression-free survival (PFS) (5.1 vs 6.7 mo, respectively; p < 0.0008). When stratified by risk groups, the presence of BMs was associated with shorter OS in all risk groups. The use of BT in patients with BMs was not associated with improved OS compared with patients who did not receive BT (13.3 vs 13.1 mo, respectively; p = 0.3801) or improved PFS (5.1 vs 4.9 mo, respectively; p = 0.1785). Bisphosphonate users with BMs did not have a decreased rate of skeletal-related events (SREs) compared with nonusers (8.6% vs 5.8%, respectively; p = 0.191). In addition, BT was associated with increased rates of hypocalcemia, renal insufficiency, and osteonecrosis of the jaw (p < 0.0001). Data were analyzed retrospectively.Conclusions
We confirm that the presence of BMs is associated with shorter survival in mRCC. BT did not affect survival or SRE prevention and was associated with increased toxicity.Patient summary
In this analysis, we demonstrate that bone metastases are associated with shorter survival in patients with metastatic renal cell carcinoma. In addition, we call into question the utility of bisphosphonate therapy in this population. 相似文献13.
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14.
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15.
Kasper Drimer Berg Ben Vainer Frederik Birkebæk Thomsen M. Andreas Røder Thomas Alexander Gerds Birgitte Grønkær Toft Klaus Brasso Peter Iversen 《European urology》2014
Background
Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed.Objective
To examine the association between ERG expression at diagnosis and the risk of progression during AS.Design, setting, and participants
This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10–12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression.Outcome measurements and statistical analysis
Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events.Results and limitations
A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression (p < 0.0001) and of the subgroups PSA progression (p < 0.0001) and histopathologic progression (p < 0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3–29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7–68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62–3.72; p < 0.0001). The main limitation of this study is its observational nature.Conclusions
In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes.Patient summary
The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression. 相似文献16.
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17.
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18.
Francesco Porpiglia Ivano MorraMarco Lucci Chiarissi Matteo ManfrediFabrizio Mele Susanna GrandeFrancesca Ragni Massimiliano PoggioCristian Fiori 《European urology》2013
Background
The advantages of robot-assisted radical prostatectomy (RARP) over laparoscopic radical prostatectomy (LRP) have rarely been investigated in randomised controlled trials.Objective
To compare RARP and LRP in terms of the functional, perioperative, and oncologic outcomes. The main end point of the study was changes in continence 3 mo after surgery.Design, setting, and participants
From January 2010 to January 2011, 120 patients with organ-confined prostate cancer were enrolled and randomly assigned (using a randomisation plan) to one of two groups based on surgical approach: the RARP group and the LRP group.Intervention
All RARP and LRP interventions were performed with the same technique by the same single surgeon.Outcome measurements and statistical analysis
The demographic, perioperative, and pathologic results, such as the complications and prostate-specific antigen (PSA) measurements, were recorded and compared. Continence was evaluated at the time of catheter removal and 48 h later, and continence and potency were evaluated after 1, 3, 6, and 12 mo. The student t test, Mann-Whitney test, χ2 test, Pearson χ2 test, and multiple regression analysis were used for statistics.Results and limitations
The two groups (RARP: n = 60; LRP: n = 60) were comparable in terms of demographic data. No differences were recorded in terms of perioperative and pathologic results, complication rate, or PSA measurements. The continence rate was higher in the RARP group at every time point: Continence after 3 mo was 80% in the RARP group and 61.6% in the LRP group (p = 0.044), and after 1 yr, the continence rate was 95.0% and 83.3%, respectively (p = 0.042). Among preoperative potent patients treated with nerve-sparing techniques, the rate of erection recovery was 80.0% and 54.2%, respectively (p = 0.020). The limitations included the small number of patients.Conclusions
RARP provided better functional results in terms of the recovery of continence and potency. Further studies are needed to confirm our results. 相似文献19.
Objective
Our study aimed to determine whether the displacement and morphology of a fragment in femur fracture with Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association/32-B/32-C (AO/OTA/32-B/32-C) classification affect the outcomes following closed reduction and internal fixation with an interlocking nail.Design
This was a retrospective study.Setting
The study was conducted at a Level III trauma centre.Patients
A total of 50 consecutive patients presenting femoral shaft fracture with AO/OTA-type 32-B/32-C were included in the present study.Interventions
Patients were divided into two groups according to the displacement of the fragments. In the large displacement group, patients were further subgrouped according to whether a reversed morphology of the fragment was present.Outcomes measurement
The radiographic union score of femur (RUSF), the mean union time and the re-operation rate were assessed.Results
The union rate of small- and large-gap groups at 12 months postoperatively was 75.9% and 21.1%, respectively (p = 0.000). The mean union time of those union cases in these two groups was 7.8 and 13.0 months, respectively (p = 0.000). The union rate of the non-reversed and reversed groups at 12 months postoperatively was 30% and 11.1%, respectively (p = 0.179). The mean RUSF at 12 months in the non-reversed and reversed groups was 8.8 and 8.3, respectively (p = 0.590). However, we found that patients presenting a reversed fragment had an increased risk of more than one re-operation (p = 0.030).Conclusions
A fragmentary displacement of >1 cm in AO/OTA-type 32-B/32-C femoral shaft fracture after nailing affected bone healing. Among the large-gap group patients, an unreduced reverse fragment presented a negative prognostic factor for re-operation.Level of evidence
Prognostic level III. 相似文献20.
Xingkang Jiang Shimiao ZhuGuowei Feng Zhihong ZhangChangying Li Hui LiChao Wang Yong Xu 《European urology》2013