共查询到20条相似文献，搜索用时 546 毫秒
1.
Wei Shen Tan Anesh Panchal Laura Buckley Adam J. Devall Laurence S. Loubière Ann M. Pope Mark R. Feneley Jo Cresswell Rami Issa Hugh Mostafid Sanjeev Madaan Rupesh Bhatt John McGrath Vijay Sangar T.R. Leyshon Griffiths Toby Page Dominic Hodgson Shibendra N. Datta John D. Kelly 《European urology》2019,75(1):63-71
Background
There is no effective intravesical second-line therapy for non–muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails.Objective
To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG.Design, settings, and participants
Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]).Intervention
Patients were randomly assigned (1:1) to RITE (60 min, 40 mg mitomycin-C, 42 ± 2 °C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre.Outcome measurements and statistical analysis
Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat.Results and limitations
A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84–2.10, p = 0.23) or in 3-mo CR rate in CIS patients (n = 71; RITE: 30% vs control: 47%, p = 0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n = 33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22–1.17, p = 0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n = 71; HR 2.06, 95% CI 1.17–3.62, p = 0.01; treatment-subgroup interaction p = 0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable.Conclusions
DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies.Patient summary
This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated. 相似文献2.
Daniel J. Canter Julia Reid Maria Latsis Margaret Variano Shams Halat Saradha Rajamani Kristen E. Gurtner Zaina Sangale Michael Brawer Steven Stone Stephen Bardot 《European urology》2019,75(3):515-522
Background
Better prostate cancer risk stratification is necessary to inform medical management, especially for African American (AA) men, for whom outcomes are particularly uncertain.Objective
To evaluate the utility of both a cell cycle progression (CCP) score and a clinical cell-cycle risk (CCR) score to predict clinical outcomes in a large cohort of men with prostate cancer highly enriched in an AA patient population.Design, setting, and participants
Patients were diagnosed with clinically localized adenocarcinoma of the prostate and treated at The Ochsner Clinic (New Orleans, LA, USA) from January 2006 to December 2011. CCP scores were derived from archival formalin-fixed, paraffin-embedded biopsy tissue. CCR scores were calculated as the combination of molecular (CCP score) and clinical (Cancer of the Prostate Risk Assessment [CAPRA] score) components.Intervention
Active treatment (radical prostatectomy, radiation therapy alone, or radiation and hormone therapy) or watchful waiting.Outcome measurements and statistical analysis
The primary outcome was progression to metastatic disease. Association with outcomes was evaluated via Cox proportional hazards survival analysis and likelihood ratio tests.Results and limitations
The final cohort included 767 men, of whom 281 (36.6%) were AA. After accounting for ancestry, treatment, and CAPRA in multivariable analysis, the CCP score remained a significant predictor of metastatic disease (hazard ratio [HR] 2.04; p < 0.001), and there was no interaction with ancestry (p = 0.20) or treatment (p = 0.09). The CCR score was highly prognostic (HR 3.86; p < 0.001), and as with the CCP score, there was no interaction with ancestry (p = 0.24) or treatment (p = 0.32). Limitations include the retrospective study design and the use of self-reported ancestry information.Conclusions
A CCR score provided significant prognostic information regardless of ancestry. The findings demonstrate that AA men in this study cohort appear to have similar prostate cancer outcomes to non-AA patients after accounting for all available molecular and clinicopathologic variables.Patient summary
In this study we evaluated the ability of a combined molecular and clinical score to predict the progression of localized prostate cancer. We found that the combined molecular and clinical score predicted progression to metastasis regardless of patient ancestry or treatment. This suggests that the combined molecular and clinical score may be a valuable tool for determining the risk of metastasis in men with newly diagnosed prostate cancer in order to make appropriate treatment decisions. 相似文献3.
John D. Kelly Wei Shen Tan Nuria Porta Hugh Mostafid Robert Huddart Andrew Protheroe Richard Bogle Jane Blazeby Alison Palmer Jo Cresswell Mark Johnson Richard Brough Sanjeev Madaan Stephen Andrews Clare Cruickshank Stephanie Burnett Lauren Maynard Emma Hall 《European urology》2019,75(4):593-601
Background
Non–muscle-invasive bladder cancer (NMIBC) has a significant risk of recurrence despite adjuvant intravesical therapy.Objective
To determine whether celecoxib, a cyclo-oxygenase 2 inhibitor, reduces the risk of recurrence in NMIBC patients receiving standard treatment.Design, setting, and participants
BOXIT (CRUK/07/004, ISRCTN84681538) is a double-blinded, phase III, randomised controlled trial. Patients aged ≥18 yr with intermediate- or high-risk NMIBC were accrued across 51 UK centres between 1 November 2007 and 23 July 2012.Intervention
Patients were randomised (1:1) to celecoxib 200 mg twice daily or placebo for 2 yr. Patients with intermediate-risk NMIBC were recommended to receive six weekly mitomycin C instillations; high-risk NMIBC cases received six weekly bacillus Calmette-Guérin and maintenance therapy.Outcome measurements and statistical analysis
The primary endpoint was time to disease recurrence. Analysis was by intention to treat.Results and limitations
A total of 472 patients were randomised (236:236). With median follow-up of 44 mo (interquartile range: 36–57), 3-yr recurrence-free rate (95% confidence interval) was as follows: celecoxib 68% (61–74%) versus placebo 64% (57–70%; hazard ratio [HR] 0.82 [0.60–1.12], p = 0.2). There was no difference in high-risk (HR 0.77 [0.52–1.15], p = 0.2) or intermediate-risk (HR 0.90 [0.55–1.48], p = 0.7) NMIBC. Subgroup analysis suggested that time to recurrence was longer in pT1 NMIBC patients treated with celecoxib compared with those receiving placebo (HR 0.53 [0.30–0.94], interaction test p = 0.04). The 3-yr progression rates in high-risk patients were low: 10% (6.5–17%) and 9.7% (6.0–15%) in celecoxib and placebo arms, respectively. Incidence of serious cardiovascular events was higher in celecoxib (5.2%) than in placebo (1.7%) group (difference +3.4% [–0.3% to 7.2%], p = 0.07).Conclusions
BOXIT did not show that celecoxib reduces the risk of recurrence in intermediate- or high-risk NMIBC, although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib.Patient summary
Celecoxib was not shown to reduce the risk of recurrence in intermediate- or high-risk non–muscle-invasive bladder cancer (NMIBC), although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib. 相似文献4.
Kerri Beckmann Hans Garmo Jan Adolfsson Cecilia Bosco Eva Johansson David Robinson Lars Holmberg Par Stattin Mieke Van Hemelrijck 《European urology》2019,75(4):676-683
Background
Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.Objective
To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.Design, setting, and participants
Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).Outcome measures and statistical methods
Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.Results and limitations
Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20–1.44).Conclusions
Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.Patient summary
Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy. 相似文献5.
Vincenzo Ficarra Gianluca Giannarini Alessandro Crestani Vito Palumbo Marta Rossanese Claudio Valotto Antonino Inferrera Vito Pansadoro 《European urology》2019,75(2):294-299
Background
Ureteroileal anastomotic stricture (UAS) after ileal conduit diversion occurs in a non-negligible proportion of patients undergoing radical cystectomy (RC). Surgical techniques aimed at preventing this potential complication are sought.Objective
To describe our surgical technique of retrosigmoid ileal conduit, and to assess perioperative outcomes and postoperative complications with a focus on UAS rate.Design, setting, and participants
A prospective single-centre, single-surgeon cohort of 67 consecutive patients undergoing open RC with ileal conduit urinary diversion between July 2013 and April 2017 was analysed. A study group of 30 patients receiving retrosigmoid ileal conduit was compared with a control group of 37 patients receiving standard Wallace ileal conduit.Surgical procedure
Retrosigmoid versus Wallace ileal conduit diversion after open RC.Measurements
Operative room (OR) time, estimated blood loss (EBL), transfusion rate, and 90-d postoperative complications were recorded and compared between the two groups. In particular, rate of UAS, defined as upper collecting system dilatation requiring endourological or surgical management, was assessed and compared.Results and limitations
The two groups were comparable with regard to all demographic, clinical, and pathological variables. No differences were observed in terms of OR time (p = 0.35), EBL (p = 0.12), and transfusion rate (p = 0.81). Ninety-day postoperative complications were observed in 11 (36.7%) patients who underwent a retrosigmoid ileal conduit and 20 (54.1%) patients who received a traditional ileal conduit (p = 0.32). Major complications (grade 3–4) were observed in three (10%) cases in the former group and in 12 (32.4%) cases in the latter group (p = 0.08). Mean (standard deviation) follow-up time was 10.8 ± 4.0 mo in the study group and 27.5 ± 9.5 mo in the control group (p < 0.001). No single case of UAS was observed in the study group, whereas six (16.2%) cases of UAS occurred in the control group (p = 0.02). The main limitation is a nonrandomised comparison of a relatively small cohort with short-term follow-up.Conclusions
In our study, we observed a significantly reduced rate of UAS and no increase in postoperative complications with the retrosigmoid ileal conduit diversion compared with standard Wallace ileal conduit diversion after open RC.Patient summary
We describe our surgical technique of retrosigmoid ileal conduit as urinary diversion after open radical cystectomy. Compared with traditional techniques, our technique for ileal conduit was found to be safe and reduce the risk of ureteric strictures. 相似文献6.
Jacob A. Burns Adam B. Weiner William J. Catalona Eric V. Li Edward M. Schaeffer Stephen B. Hanauer Scott Strong James Burns Maha H.A. Hussain Shilajit D. Kundu 《European urology》2019,75(5):846-852
Background
There are limited data examining the risk of prostate cancer (PCa) in patients with inflammatory bowel disease (IBD).Objective
To compare the incidence of PCa between men with and those without IBD.Design, setting, and participants
This was a retrospective, matched-cohort study involving a single academic medical center and conducted from 1996 to 2017. Male patients with IBD (cases = 1033) were randomly matched 1:9 by age and race to men without IBD (controls = 9306). All patients had undergone at least one prostate-specific antigen (PSA) screening test.Outcome measurements and statistical analysis
Kaplan-Meier and multivariable Cox proportional hazard models, stratified by age and race, evaluated the relationship between IBD and the incidence of any PCa and clinically significant PCa (Gleason grade group ≥2). A mixed-effect regression model assessed the association of IBD with PSA level.Results and limitations
PCa incidence at 10 yr was 4.4% among men with IBD and 0.65% among controls (hazard ratio [HR] 4.84 [3.34–7.02] [3.19–6.69], p < 0.001). Clinically significant PCa incidence at 10 yr was 2.4% for men with IBD and 0.42% for controls (HR 4.04 [2.52–6.48], p < 0.001). After approximately age 60, PSA values were higher among patients with IBD (fixed-effect interaction of age and patient group: p = 0.004). Results are limited by the retrospective nature of the analysis and lack of external validity.Conclusions
Men with IBD had higher rates of clinically significant PCa when compared with age- and race-matched controls.Patient summary
This study of over 10 000 men treated at a large medical center suggests that men with inflammatory bowel disease may be at a higher risk of prostate cancer than the general population. 相似文献7.
Henry D. Mitcheson Suvajit Samanta Karen Muldowney Cathy A. Pinto Beatriz de A. Rocha Stuart Green Nathan Bennett Paul N. Mudd Tara L. Frenkl 《European urology》2019,75(2):274-282
Background
Antimuscarinics have shown modest efficacy with unwanted side effects in patients with overactive bladder (OAB). Efficacy of vibegron, a new β3-adrenergic receptor agonist, for OAB is unknown.Objective
To evaluate the efficacy of once-daily oral vibegron in OAB patients (primary), and its safety, tolerability, and efficacy when administered alone or concomitantly with tolterodine (secondary).Design, setting, and participants
International, phase IIb, randomized, double-blind, placebo- and active comparator–controlled, two-part superiority trial (2011–2013) in OAB-wet or OAB-dry patients aged 18–75 yr (NCT01314872).Interventions
Part 1: once-daily oral vibegron monotherapy (3 [V3], 15 [V15], 50 [V50], or 100 [V100] mg), tolterodine extended release 4 mg (TER4), or placebo for 8 wk, or combination V50/TER4 for 4 wk and then V50 for 4 wk; part 2: V100/TER4, V100, TER4, or placebo for 4 wk.Outcome measurements and statistical analysis
Average daily micturitions at week 8 of part 1 (primary); urge incontinence episodes, total incontinence episodes, and urgency episodes (secondary).Results and limitations
Overall, 1395 patients were randomized. From baseline to week 8, V50 and V100 significantly decreased average daily micturitions (least square mean difference [95% confidence interval], ?0.64 [?1.11, ?0.18]; p = 0.007 and ?0.91 [?1.37, ?0.44]; p < 0.001, respectively) and the number of urge incontinence episodes (?0.72 [?1.11, ?0.33] and ?0.71 [?1.10, ?0.32], respectively; both p < 0.001) versus placebo. All vibegron doses were well tolerated. The incidence of dry mouth was higher with TER4 than with vibegron monotherapy. Results are limited by the relatively short treatment duration.Conclusions
Once-daily V50 and V100 improved OAB symptoms; vibegron was well tolerated as monotherapy and concomitantly with tolterodine. Further development is warranted.Patient summary
Antimuscarinics, commonly used to treat overactive bladder, produce modest efficacy and unwanted side effects. In this study, a different type of drug (vibegron) was efficacious and safe, alone or with an antimuscarinic (tolterodine). 相似文献8.
Liselotte M.S. Boevé Maarten C.C.M. Hulshof André N. Vis Aeilko H. Zwinderman Jos W.R. Twisk Wim P.J. Witjes Karl P.J. Delaere R. Jeroen A. van Moorselaar Paul C.M.S. Verhagen George van Andel 《European urology》2019,75(3):410-418
Background
The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue.Objective
To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT.Design, setting, and participants
The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20 ng/ml and primary bone mPCa on bone scan between 2004 and 2014.Intervention
Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group).Outcome measurements and statistical analysis
Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect.Results and limitations
Median PSA level was 142 ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4–49.6) in the radiotherapy group and 43 mo (95% CI: 32.6–53.4) in the control group (p = 0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70–1.14; p = 0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8–18.2), compared with 12 mo (95% CI: 10.6–13.4) in the control group. The crude HR (0.78; 95% CI: 0.63–0.97) was statistically significant (p = 0.02).Conclusions
The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings.Patient summary
This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings.Twitter summary
Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival. 相似文献9.
Paolo Capogrosso Emily A. Vertosick Nicole E. Benfante James A. Eastham Peter J. Scardino Andrew J. Vickers John P. Mulhall 《European urology》2019,75(2):221-228
Background
The last decade has seen several advances in radical prostatectomy (RP) technique and post-RP care that are relevant to erectile function (EF) recovery.Objective
We examined whether these practice changes have led to observed improvements in EF rates over time.Design, setting, and participants
We identified 2364 patients treated with either open or minimally-invasive RP at a single academic center in 2008–2015. To mitigate confounding by the surgical learning curve, only patients treated by surgeons who performed at least 100 procedures were considered.Intervention
EF before and after RP was assessed by the International Index of Erectile Function 6 (IIEF-6), with recovery defined as IIEF-6 ≥24.Outcome measurements and statistical analysis
We analyzed EF recovery rates of patients treated with bilateral nerve-sparing surgery and free from adjuvant/salvage treatment at the time of EF assessment. Local polynomial regression analyses explored changes in the outcomes over time. Linear and logistic regression analyses were used to estimate the influence of year of surgery on baseline variables and EF recovery.Results and limitations
We observed a significant decrease over time of the EF recovery rates at both 12 and 24 mo post-RP (all p = 0.01). However, patient's age at surgery increased over time (mean increase of 0.5 per year; p < 0.01), with a resultant increase in risk of comorbidity (odds ratio [OR] = 1.1, 95% confidence interval [CI]: 1.02–1.15; p = 0.008) and thus decrease in baseline IIEF-6 score (0.35 points per year; p = 0.0003). After accounting for baseline and pathological characteristics, urinary function, and type of surgery in a multivariable analysis, year of surgery was not associated with EF recovery (12 mo: OR = 0.97, 95% CI: 0.91–1.03, p = 0.4; 24 mo: OR = 0.97, 95% CI: 0.91–1.03, p = 0.3).Conclusions
Findings from a high-volume center suggest that, despite the advancements in surgical and postoperative care, EF outcomes after RP have not improved over the last decade. Additional strategies are required to improve EF recovery after RP.Patient summary
The probability of regaining potency after surgery for prostate cancer did not improve over the last decade; more efforts are needed to improve patient's care after radical prostatectomy. 相似文献10.
J. Caño-Velasco F. Herranz-Amo G. Barbas-Bernardos L. Polanco-Pujol E. Lledó-García C. Hernández-Fernández 《Actas urologicas espa?olas》2019,43(1):18-25
Introduction and objectives
The onset of second primary tumours should be considered in high-risk prostate cancer patients in the natural course of the disease. Our aim was to evaluate the influence of primary treatment with curative intent for these patients on the development of second primary tumours.Material and methods
A retrospective study of 286 patients diagnosed between 1996 and 2008, treated by radical prostatectomy (n = 145) or radiotherapy and androgen blockade (n = 141). The homogeneity of both series was analysed using the Chi-squared test for the qualitative variables, and the Student's t-test for the quantitative variables. A multivariate Cox regression analysis was performed to assess whether the type of primary treatment influenced the development of second tumours.Results
The median age was 66 years, and the median follow-up was 117.5 months. At the end of follow-up, 60 patients (21%) had developed a second primary tumour. In the prostatectomy group it was located in the pelvis in 13 (9%) cases, and those treated with radiotherapy and hormonotherapy in 8 (5.7%) cases (P = .29). The most common organ sites were: colo-rectal in 17 (28.3%) patients, the lung in 11 (18.3%), and the bladder in 6 (10%) patients. In the multivariable analysis, the risk of a second tumour doubled for those treated with radiotherapy and hormonotherapy (HR = 2.41, 95%CI: 1.31-4.34, P = .005) compared to the patients treated by prostatectomy. Age and rescue radiotherapy did not behave as independent predictive factors.Conclusions
The onset of a second primary tumour was related with the primary treatment given; thus the risk for those treated with radiotherapy and androgen deprivation therapy more than doubled. 相似文献11.
Todd M. Morgan Rohit Mehra Placede Tiemeny J. Stuart Wolf Shulin Wu Zaina Sangale Michael Brawer Steven Stone Chin-Lee Wu Adam S. Feldman 《European urology》2018,73(5):763-769
Background
There is a critical need for improved prognostic discrimination in patients with renal cell carcinoma (RCC) given the increasing awareness that some patients may be managed with active surveillance, while others with higher-risk disease might benefit from adjuvant therapy following surgery.Objective
To determine whether a multigene proliferation signature predicts long-term oncologic outcomes in surgically resected RCC.Design, setting, and participants
The cell cycle proliferation (CCP) score was determined after radical nephrectomy for localized clear cell, papillary, or chromophobe RCC in 565 patients.Outcome measurements and statistical analysis
The primary end point was disease-specific mortality (DSM), and disease recurrence was a secondary end point. Association with outcomes was evaluated by Cox proportional hazards survival analysis. The CCP score was compared with the Karakiewicz nomogram, and a composite (R-CCP) score was developed.Results and limitations
A total of 68 patients (12%) recurred and 32 (6%) died of disease within 5 yr of nephrectomy. The CCP score was an independent predictor of recurrence (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.07–2.09) and DSM (HR 2.49, 95% CI 1.53–4.04) after adjusting for clinical variables using the baseline nomogram. The composite R-CCP score gave a Harrell's concordance index of 0.87 and stratified patients into low- (n = 338) and high-risk (n = 202) categories with 99% and 84% cancer-specific survival probabilities, respectively (p < 0.001).Conclusions
The CCP score is a significant, independent predictor of long-term oncologic outcomes in patients who have undergone nephrectomy for RCC. Combining the molecular classifier with baseline clinical variables allows for accurate, patient-specific risk assessment for use in guiding clinical management.Patient summary
In this study, we sought to understand how well gene expression information from individual kidney tumors can predict cancer recurrence and death following surgical removal. We found that the combination of the gene expression test and clinical characteristics provides an accurate prognostic assessment to help inform clinical decisions. 相似文献12.
H. Ballentine Carter Brian Helfand Mufaddal Mamawala Yishuo Wu Patricia Landis Hongjie Yu Kathleen Wiley Rong Na Zhuqing Shi Jacqueline Petkewicz Sameep Shah Richard J. Fantus Kristian Novakovic Charles B. Brendler S. Lilly Zheng William B. Isaacs Jianfeng Xu 《European urology》2019,75(5):743-749
Background
Mutations in DNA repair genes are associated with aggressive prostate cancer (PCa).Objective
To assess whether germline mutations are associated with grade reclassification (GR) in patients undergoing active surveillance (AS).Design, setting, and participants
Two independent cohorts of PCa patients undergoing AS; 882 and 329 patients from Johns Hopkins and North Shore, respectively.Outcome measurements and statistical analysis
Germline DNA was sequenced for DNA repair genes, including BRCA1/2 and ATM (three-gene panel). Pathogenicity of mutations was defined according to the American College of Medical Genetics guidelines. Association of mutation carrier status and GR was evaluated by a competing risk analysis.Results and limitations
Of 1211, 289 patients experienced GR; 11 of 26 with mutations in a three-gene panel and 278 of 1185 noncarriers; adjusted hazard ratio (HR) = 1.96 (95% confidence interval [CI] = 1.004–3.84, p = 0.04). Reclassification occurred in six of 11 carriers of BRCA2 mutations and 283 of 1200 noncarriers; adjusted HR = 2.74 (95% CI = 1.26–5.96, p = 0.01). The carrier rates of pathogenic mutations in the three-gene panel, and BRCA2 alone, were significantly higher in those reclassified (3.8% and 2.1%, respectively) than in those not reclassified (1.6% and 0.5%, respectively; p = 0.04 and 0.03, respectively). Carrier rates for BRCA2 were greater for those reclassified from Gleason score (GS) 3 + 3 at diagnosis to GS ≥4 + 3 (4.1% vs 0.7%, p = 0.01) versus GS 3 + 4 (2.1% vs 0.6%; p = 0.03). Results are limited by the small number of mutation carriers and an intermediate end point.Conclusions
Mutation status of BRCA1/2 and ATM is associated with GR among men undergoing AS.Patient summary
Men on active surveillance with inherited mutations in BRCA1/2 and ATM are more likely to harbor aggressive prostate cancer. 相似文献13.
P.A. Gondim Teixeira A. Chanson J.-L. Verhaeghe S. Lecocq M. Louis G. Hossu A. Blum 《Diagnostic and interventional imaging》2019,100(1):47-55
Purpose
To evaluate the impact of hormonal therapy on MRI characteristics of desmoid-type fibromatosis on T1-weighted, T2-weighted fat-saturated and post-contrast sequences.Materials and methods
Nineteen patients with histologically-proven desmoid-type fibromatosis were prospectively followed up on MR imaging. Eight patients underwent hormonal therapy and 11 were only surveyed. Change in tumor size during follow-up was analyzed according to RECIST. Signal intensity on T1-weighted, T2-weighted fat-saturated and T1-weighted fat-saturated post-contrast images was graded from 0 to 5 using adjacent normal muscle as reference. Findings were compared with tumor growth and treatment option.Results
There were seven men and 12 women with a mean age of 42.2 ± 16.4 (SD) years (range: 18 - 64 years) yielding twenty-six follow-up periods: eight of tumor progression and 18 of tumor stability/regression (some tumors exhibited more than one behavior type). Hormonal therapy was associated with tumor stability or regression (P = 0.0207). There was a significant reduction in enhancement among treated patients with stable/regressing disease (P = 0.049). The mean variation in enhancement grade was ?1.3 ± 1.2 in these patients. All successfully treated patients presented a reduction in enhancement. Lesions with marked low enhancement or very low signal on T2-weighted images were rare in progressing lesions (0% and 13%).Conclusion
Hormonal therapy has an impact on desmoid-type fibromatosis signal characteristics reducing lesion enhancement. 相似文献14.
Jürgen E. Gschwend Matthias M. Heck Jan Lehmann Herbert Rübben Peter Albers Johannes M. Wolff Detlef Frohneberg Patrick de Geeter Axel Heidenreich Tilman Kälble Michael Stöckle Thomas Schnöller Arnulf Stenzl Markus Müller Michael Truss Stephan Roth Uwe-Bernd Liehr Joachim Leißner Margitta Retz 《European urology》2019,75(4):604-611
Background
The extent of lymph node dissection (LND) in bladder cancer (BCa) patients at the time of radical cystectomy may affect oncologic outcome.Objective
To evaluate whether extended versus limited LND prolongs recurrence-free survival (RFS).Design, setting, and participants
Prospective, multicenter, phase-III trial patients with locally resectable T1G3 or muscle-invasive urothelial BCa (T2-T4aM0).Intervention
Randomization to limited (obturator, and internal and external iliac nodes) versus extended LND (in addition, deep obturator, common iliac, presacral, paracaval, interaortocaval, and para-aortal nodes up to the inferior mesenteric artery).Outcome measurements and statistical analysis
The primary endpoint was RFS. Secondary endpoints included cancer-specific survival (CSS), overall survival (OS), and complications. The trial was designed to show 15% advantage of 5-yr RFS by extended LND.Results and limitations
In total, 401 patients were randomized from February 2006 to August 2010 (203 limited, 198 extended). The median number of dissected nodes was 19 in the limited and 31 in the extended arm. Extended LND failed to show superiority over limited LND with regard to RFS (5-yr RFS 65% vs 59%; hazard ratio [HR] = 0.84 [95% confidence interval 0.58–1.22]; p = 0.36), CSS (5-yr CSS 76% vs 65%; HR = 0.70; p = 0.10), and OS (5-yr OS 59% vs 50%; HR = 0.78; p = 0.12). Clavien grade ≥3 lymphoceles were more frequently reported in the extended LND group within 90 d after surgery. Inclusion of T1G3 tumors may have contributed to the negative study result.Conclusions
Extended LND failed to show a significant advantage over limited LND in RFS, CSS, and OS. A larger trial is required to determine whether extended compared with limited LND leads to a small, but clinically relevant, survival difference (ClinicalTrials.gov NCT01215071).Patient summary
In this study, we investigated the outcome in bladder cancer patients undergoing cystectomy based on the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce the rate of tumor recurrence in the expected range. 相似文献15.
Farrukh Aslam Khalid Muhammad Younas Mehrose Muhammad Saleem Muhammad Amin Yousaf Abdul Malik Mujahid Saif Ur Rehman Sania Ahmad Moazzam Nazeer Tarar 《Burns : journal of the International Society for Burn Injuries》2019,45(1):69-75
The treatment of keloid and hypertrophic scar is challenging with no universally accepted mode for permanent ablation. Conventional therapies yield unpredictable results, significant complications and require elaborate hardware.
Objective
The objective was to establish the safety and efficacy of intralesional 5-fluorouracil (5-FU) for the treatment of keloids and hypertrophic scars.Study design
Randomized controlled trial (RCT).Place and duration
It was conducted at the Jinnah Burn and Reconstructive Surgery Center/Allama Iqbal Medical College, Lahore, Pakistan from May 2012 to March 2013.Subjects and methods
We included 120 patients divided in two groups. The group A patients received intralesional triamcinolone acetonide (TAC) and the group B patients received both 5-FU and TAC. 8 injections at a week interval were given and patients were evaluated at the start of treatment and then at 4th and at 8th week during the treatment and then 4 weeks after the end of treatment. Patents were assessed for mean reduction in scar height, efficacy and complications.Results
Total of 108 patients completed the study. The mean reduction in the scar height in group B (5-FU + TAC) 1.144 + .4717 was markedly better than that of group A (TAC alone) 1.894 + 1.0751 (t = 4.781, p = .000). The efficacy (defined previously as >50% reduction in initial scar height) was superior in group B 44 (77.2%) than that of group A 25 (49.0% (X2 = 9.260, p = .002). Recurrence was seen in 39.2% (20) of patients of the group A while in only 17.5% (10) of the cases of group B (P = 0.012). Mean follow up was of 22 months.Conclusion
5-FU + TAC is safe, easy to administer and effective treatment for problematic scars and has the lower rate of recurrence on larger follow up. 相似文献16.
Francisco Campos-Rodriguez Nuria Reyes-Nuñez Carlos Queipo-Corona Angeles Sanchez-Armengol Bernabe Jurado-Gamez Jose Cordero-Guevara Maria F. Troncoso Araceli Abad-Fernandez Julian Caballero-Rodriguez Mercedes Martin-Romero Ana Encabo-Motiño Lirios Sacristan-Bou Javier Navarro-Esteva Maria Somoza-Gonzalez Juan F. Masa Maria A. Sanchez-Quiroga Beatriz Jara-Chinarro Belen Orosa-Bertol Andrea Crespo Sedano 《Archivos de bronconeumologia》2019,55(4):201-207
Objectives
Although an association between uric acid (UA) levels and obstructive sleep apnea (OSA) has been reported, the effect of continuous positive airway pressure (CPAP) on this measure is yet unclear. We aimed to investigate the effect of CPAP therapy on serum UA levels in patients with OSA.Methods
We conducted a multicenter, open-label, randomized controlled trial in 307 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 15) in 19 Spanish Sleep Units. Women were randomized to CPAP (n = 151) or conservative treatment (n = 156) for 12 weeks. Changes in serum UA measures were assessed on an intention-to-treat basis. Additional analyses were conducted in the subgroup of women with CPAP adherence ≥4 h/night and those with UA levels ≥6 mg/dl.Results
Women had a mean (SD) age of 57.1 (10.1) years, median (first–third quartile) body mass index of 33.7 (29.0–38.5) mg/kg2 and AHI of 32.0 (22.6–48.5). The average serum UA measure was 5.11 (1.26) mg/dl, and 80 (26.1%) participants had UA ≥ 6 mg/dl. Compared with the control group, the CPAP group did not achieve any reduction in UA levels (non-adjusted intergroup difference ?0.03 mg/dl, 95%CI ?0.20 to 0.13; p = 0.702) after 12 weeks of follow-up. These results did not change when the analysis was restricted to women with CPAP adherence ≥4 h/night, or the subgroup of women with hyperuricemia.Conclusions
Twelve weeks of CPAP therapy does not reduce UA levels compared to conservative treatment in women with moderate-to-severe OSA. 相似文献17.
Olivier Wegelin Leonie Exterkate Marloes van der Leest Jean A. Kummer Willem Vreuls Peter C. de Bruin J.L.H.Ruud Bosch Jelle O. Barentsz Diederik M. Somford Harm H.E. van Melick 《European urology》2019,75(4):582-590
Background
Guidelines advise multiparametric magnetic resonance imaging (mpMRI) before repeat biopsy in patients with negative systematic biopsy (SB) and a suspicion of prostate cancer (PCa), enabling MRI targeted biopsy (TB). No consensus exists regarding which of the three available techniques of TB should be preferred.Objective
To compare detection rates of overall PCa and clinically significant PCa (csPCa) for the three MRI-based TB techniques.Design, setting, and participants
Multicenter randomised controlled trial, including 665 men with prior negative SB and a persistent suspicion of PCa, conducted between 2014 and 2017 in two nonacademic teaching hospitals and an academic hospital.Intervention
All patients underwent 3-T mpMRI evaluated with Prostate Imaging Reporting and Data System (PIRADS) version 2. If imaging demonstrated PIRADS ≥3 lesions, patients were randomised 1:1:1 for one TB technique: MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), cognitive registration TRUS TB (COG-TB), or in-bore MRI TB (MRI-TB).Outcome measurements and statistical analysis
Primary (overall PCa detection) and secondary (csPCa detection [Gleason score ≥3 + 4]) outcomes were compared using Pearson chi-square test.Results and limitations
On mpMRI, 234/665 (35%) patients had PIRADS ≥3 lesions and underwent TB. There were no significant differences in the detection rates of overall PCa (FUS-TB 49%, COG-TB 44%, MRI-TB 55%, p = 0.4). PCa detection rate differences were ?5% between FUS-TB and MRI-TB (p = 0.5, 95% confidence interval [CI] ?21% to 11%), 6% between FUS-TB and COG-TB (p = 0.5, 95% CI ?10% to 21%), and ?11% between COG-TB and MRI-TB (p = 0.17, 95% CI ?26% to 5%). There were no significant differences in the detection rates of csPCa (FUS-TB 34%, COG-TB 33%, MRI-TB 33%, p > 0.9). Differences in csPCa detection rates were 2% between FUS-TB and MRI-TB (p = 0.8, 95% CI ?13% to 16%), 1% between FUS-TB and COG-TB (p > 0.9, 95% CI ?14% to 16%), and 1% between COG-TB and MRI-TB (p > 0.9, 95% CI ?14% to 16%). The main study limitation was a low rate of PIRADS ≥3 lesions on mpMRI, causing underpowering for primary outcome.Conclusions
We found no significant differences in the detection rates of (cs)PCa among the three MRI-based TB techniques.Patient summary
In this study, we compared the detection rates of (aggressive) prostate cancer among men with prior negative biopsies and a persistent suspicion of cancer using three different techniques of targeted biopsy based on magnetic resonance imaging. We found no significant differences in the detection rates of (aggressive) prostate cancer among the three techniques. 相似文献18.
Nicola Fossati Nazareno Suardi Giorgio Gandaglia Carlo A. Bravi Matteo Soligo R. Jeffrey Karnes Shahrokh Shariat Antonino Battaglia Wouter Everaerts Steven Joniau Hendrik Van Poppel Nieroshan Rajarubendra Inderbir S. Gill Alessandro Larcher Alexander Mottrie Maximilian Schmautz Axel Heidenreich Almut Kalz Alberto Briganti 《European urology》2019,75(1):176-183
Background
Salvage lymph node dissection (SLND) represents a possible treatment option for prostate cancer patients affected by nodal recurrence after local treatment. However, SLND may be associated with intra- and postoperative complications, and the oncological benefit may be limited to specific groups of patients.Objective
To identify the optimal candidates for SLND based on preoperative characteristics.Design, setting, and participants
The study included 654 patients who experienced prostate-specific antigen (PSA) rise and nodal recurrence after radical prostatectomy (RP) and underwent SLND at nine tertiary referral centers. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga-labeled prostate-specific membrane antigen ligand.Intervention
SLND.Outcome measurements and statistical analysis
The study outcome was early clinical recurrence (eCR) developed within 1 yr after SLND. Multivariable Cox regression analysis was used to develop a predictive model. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model.Results and limitations
Median follow-up was 30 (interquartile range, 16–50) mo among patients without clinical recurrence (CR), and 334 patients developed CR after SLND. In particular, eCR at 1 yr after SLND was observed in 150 patients, with a Kaplan-Meier probability of eCR equal to 25%. The development of eCR was significantly associated with an increased risk of cancer-specific mortality at 3 yr, being 20% versus 1.4% in patients with and without eCR, respectively (p < 0.0001). At multivariable analysis, Gleason grade group 5 (hazard ratio [HR]: 2.04; p < 0.0001), time from RP to PSA rising (HR: 0.99; p = 0.025), hormonal therapy administration at PSA rising after RP (HR: 1.47; p = 0.0005), retroperitoneal uptake at PET/CT scan (HR: 1.24; p = 0.038), three or more positive spots at PET/CT scan (HR: 1.26; p = 0.019), and PSA level at SLND (HR: 1.05; p < 0.0001) were significant predictors of CR after SLND. The coefficients of the predictive model were used to develop a risk calculator for eCR at 1 yr after SLND. The discrimination of the model (Harrel's C index) was 0.75. At decision-curve analysis, the net benefit of the model was higher than the “treat-all” option at all the threshold probabilities.Conclusions
We reported the largest available series of patients treated with SLND. Roughly 25% of men developed eCR after surgery. We developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach.Patient summary
The risk of early recurrence after salvage lymph node dissection (SLND) was approximately 25%. In this study, we developed a novel tool to predict the risk of early failure after SLND. This tool will be useful to identify patients who would benefit the most from SLND from other patients who should be spared from surgery. 相似文献19.
Sami Hamid Ian A. Donaldson Yipeng Hu Rachael Rodell Barbara Villarini Ester Bonmati Pamela Tranter Shonit Punwani Harbir S. Sidhu Sarah Willis Jan van der Meulen David Hawkes Neil McCartan Ingrid Potyka Norman R. Williams Chris Brew-Graves Alex Freeman Caroline M. Moore Hashim U. Ahmed 《European urology》2019,75(5):733-740
Background
Multiparametric magnetic resonance imaging (mpMRI)-targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the overdetection of insignificant cancers. It is unknown whether visual-registration targeting is sufficient or augmentation with image-fusion software is needed.Objective
To assess concordance between the two methods.Design, setting, and participants
We conducted a blinded, within-person randomised, paired validating clinical trial. From 2014 to 2016, 141 men who had undergone a prior (positive or negative) transrectal ultrasound biopsy and had a discrete lesion on mpMRI (score 3–5) requiring targeted transperineal biopsy were enrolled at a UK academic hospital; 129 underwent both biopsy strategies and completed the study.Intervention
The order of performing biopsies using visual registration and a computer-assisted MRI/ultrasound image-fusion system (SmartTarget) on each patient was randomised. The equipment was reset between biopsy strategies to mitigate incorporation bias.Outcome measurements and statistical analysis
The proportion of clinically significant prostate cancer (primary outcome: Gleason pattern ≥3 + 4 = 7, maximum cancer core length ≥4 mm; secondary outcome: Gleason pattern ≥4 + 3 = 7, maximum cancer core length ≥6 mm) detected by each method was compared using McNemar's test of paired proportions.Results and limitations
The two strategies combined detected 93 clinically significant prostate cancers (72% of the cohort). Each strategy detected 80/93 (86%) of these cancers; each strategy identified 13 cases missed by the other. Three patients experienced adverse events related to biopsy (urinary retention, urinary tract infection, nausea, and vomiting). No difference in urinary symptoms, erectile function, or quality of life between baseline and follow-up (median 10.5 wk) was observed. The key limitations were lack of parallel-group randomisation and a limit on the number of targeted cores.Conclusions
Visual-registration and image-fusion targeting strategies combined had the highest detection rate for clinically significant cancers. Targeted prostate biopsy should be performed using both strategies together.Patient summary
We compared two prostate cancer biopsy strategies: visual registration and image fusion. A combination of the two strategies found the most clinically important cancers and should be used together whenever targeted biopsy is being performed. 相似文献20.