共查询到20条相似文献，搜索用时 47 毫秒
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Su-Min Lee Sidath H. Liyanage Wahyu Wulaningsih Konrad Wolfe Thomas Carr Choudhry Younis Mieke Van Hemelrijck Rick Popert Peter Acher 《Urologic oncology》2017,35(11):664.e11-664.e18
Purpose
To develop and internally validate a nomogram using biparametric magnetic resonance imaging (B-MRI)–derived variables for the prediction of prostate cancer at transperineal sector-guided prostate biopsy (TPSB).Subjects/patients and methods
Consecutive patients referred to our institution with raised prostate-specific antigen (PSA), abnormal prostate examination, or persistent suspicion of prostate cancer after previous transrectal biopsy between July 2012 and November 2015 were reviewed from a prospective database.All patients underwent prebiopsy B-MRI with T2-weighted and diffusion-weighted imaging sequences, followed by 24 to 40 core TPSB with additional targeted cores using cognitive registration.Univariable and multivariable logistic regression analysis was used to determine predictors of prostate cancer outcomes. Multivariable coefficients were used to construct 2 MRI-based nomograms to predict any and significant (Gleason 4 or maximum cancer core length ≥6 mm) prostate cancer at TPSB. Bootstrap resamples were used for internal validation. Accuracy was assessed by calculating the concordance index.Results
In total, 615 men were included in the study. Prostate cancer was diagnosed in 317 (51.5%) men with significant cancer diagnosed in 237 (38.5%) men.Age, Prostate Imaging Reporting and Data System (PI-RADS) score, PSA, PSA density, and primary biopsy were predictors of prostate cancer at TPSB on univariable analysis (P<0.0001). PSA showed strong correlation with PSA density and was excluded. The remaining variables were all independent predictors of prostate cancer on multivariable analysis (P<0.0001) and used to generate the nomograms.Both nomograms showed good discrimination for prostate cancer, with a concordance index of 87% for any cancer and 92% for significant disease. Using a nomogram-derived probability threshold of<15%, 111 (18.0%) biopsies can be saved, at the expense of 3 missed significant prostate cancers.Conclusions
These internally validated MR-based nomograms were able to accurately predict TPSB outcomes for prostate cancer, especially significant disease. Our findings support the combination of prebiopsy MRI results and clinical factors as part of the biopsy decision-making process. 相似文献3.
Akhil Muthigi Abhinav Sidana Arvin K. George Michael Kongnyuy Mahir Maruf Subin Valayil Bradford J. Wood Peter A. Pinto 《Urologic oncology》2017,35(1):32.e1-32.e7
Introduction and objective
Multiparametric magnetic resonance imaging (MRI) and magnetic resonance (MR) -targeted biopsy have a growing role in the screening and evaluation of prostate cancer. We aim to evaluate the current knowledge, attitude, and practice patterns of urologists regarding this new technique.Methods
An anonymous online questionnaire was designed to collect information on urologists’ beliefs and use of prostate multiparametric MRI and MR-targeted biopsy. The survey was sent to members of the Society of Urologic Oncology, the Endourological Society, and European Association of Urology. Multivariate logistic regression analysis was performed to determine predictors for use of prostate MRI and MR-targeted biopsy.Results
A total of 302 responses were received (Endourological Society: 175, European Association of Urology: 23, and Society of Urologic Oncology: 104). Most respondents (83.6%) believe MR-targeted biopsy to be moderately to extremely beneficial in the evaluation of prostate cancer. Overall, 85.7% of responders use prostate MRI in their practice, and 63.0% use MR-targeted biopsy. The 2 most common settings for use of MR-targeted biopsy include patients with history of prior negative biopsy result (96.3%) and monitoring patients on active surveillance (72.5%). In those who do not use MR-targeted biopsy, the principal reasons were lack of necessary infrastructure (64.1%) and prohibitive costs (48.1%). On multivariate logistic regression analysis, practice in an academic setting (1.86 [1.02–3.40], P = 0.043) and performing greater than 25 radical prostatectomies per year (2.32 [1.18–4.56], P = 0.015) remained independent predictors for using MR-targeted biopsy.Conclusions
Most respondents of our survey look favorably on use of prostate MRI and MR-targeted biopsy in clinical practice. Over time, reduction in fixed costs and easier access to equipment may lead to further dissemination of this novel and potentially transformative technology. 相似文献4.
Cetin Boran Engin Kandirali Serdar Yanik Hilal Ahsen Emre Ulukaradağ Fahri Yilmaz 《Urologic oncology》2017,35(8):533.e1-533.e8
Objectives
Somatic mutations can be present in clonally expanded cell populations in nonmalignant tissues, which are detectable at tissue-level resolution. Some of the mutational changes may arise due to smoking. We aimed to find out changes in carcinogenic gene expressions related to smoking in nonmalignant prostate gland epithelia.Materials and methods
The patients who came to the Department of Urology at Abant Izzet Baysal University Medical Faculty from December 2006 to December 2009 for prostate biopsy were questioned for cigarette smoking. The patients were divided into 2 groups, namely, smokers and nonsmokers. Paraffin sections were stained immunohistochemically with p53, PTEN, p16INK4a, MSH2, CHK2, RB, and E-cadherin.Results
Smoking was the main independent factor that had an effect on the immunohistochemical expressions for p53, p16, and PTEN (P = 0.007, P = 0.036, P = 0.015, respectively). Age and inflammation had no statistically significant effects on gene expressions. No difference was found between smokers and nonsmokers for immunohistochemical expressions of E-cadherin, MSH2, RB, and CHK2.Conclusions
Smoking-related carcinogens can alter the expressions of some suppressor genes in a prostate tissue, and these alterations can be determined immunohistochemically. Alterations in these genes in prostate gland epithelia could possibly increase the risk for prostate carcinoma. 相似文献5.
Brian F. Dinerman Francesca Khani Ron Golan Adrien N. Bernstein Michael F. Cosiano Daniel J. Margolis Jim C. Hu 《Urologic oncology》2017,35(12):673.e9-673.e14
Purpose
The degree to which intraductal carcinoma of the prostate (IDC-P) affects clinical course remains poorly understood owing to small sample sizes from single-center studies. We sought to determine prognostic factors and outcomes associated with IDC-P in radical prostatectomy (RP) specimens.Materials and methods
This is a retrospective study of RP during 2004 to 2013 using Surveillance, Epidemiology, and End Results to compare IDC-P with non-IDC-P. The effect of IDC-P on overall and disease-specific survival was assessed using Cox regression with a median follow-up of 4.8 years (interquartile range [IQR]: 2.6–7.0 y; P = 0.01). Median prostate-specific antigen at diagnosis in IDC-P vs. non-IDC-P was similar (P = 0.23) at 6.2 (IQR: 4.6–13.0) vs. 6.1 ng/ml (IQR: 4.6–9.8).Results
We identified 159,777 RP from 2004 to 2013, and 242 (0.002%) had IDC-P pathologic features. IDC-P was associated with a greater likelihood of extraprostatic stage, pT3/T4, 45.9% vs. 21.6% (P<0.001), higher grade, GS≥ 7, 79.3% vs. 62.7% (P<0.001), lymph node metastases, 5.8% vs. 2.4% (P<0.001), and positive surgical margins, 25.6% vs. 19.5% (P = 0.02). IDC-P was associated with a 3-fold increase in prostate cancer-specific mortality relative to non-IDC-P (hazard ratio = 3.0, 95% CI: 1.5–5.7; P<0.01). Limitations include retrospective design and potential underreporting of IDC-P that leads to underestimation of the true effect size.Conclusions
The significance of IDC-P features has been recently recognized by the World Health Organization and it is associated with high-grade, extraprostatic features, and worse prostate cancer-specific mortality. Understanding its prognostic significance better guides adjuvant therapies and clinical trials. 相似文献6.
Ben Yi Tew Sumanta K. Pal Miaoling He Tommy Tong Huiqing Wu JoAnn Hsu Xueli Liu Susan L. Neuhausen Jeremy O. Jones 《Urologic oncology》2017,35(3):112.e13-112.e18
Purpose
Increasing evidence has demonstrated that men taking the anticoagulant warfarin have a lower risk of developing prostate cancer. This phenomenon is not observed in other cancers. We sought to determine if the target of warfarin, vitamin K epoxide reductase (VKOR), is expressed in benign and cancerous prostate tissues and if a functional single nucleotide polymorphism (SNP) in the VKOR gene is associated with prostate cancer risk.Materials and methods
The expression of VKOR was quantified by immunohistochemistry in an institutional series of 54 radical prostatectomy samples and metastatic biopsies, as well as in 40 other cancers and matched benign tissues on a tissue microarray. Genotyping of SNP rs2359612 was performed in a prospective series of 57 patients.Results
VKOR is highly expressed in benign human prostate epithelial cells but is not expressed or expressed at very low levels in cancerous cells. This expression pattern is unique to prostate cancer. Additionally, the proportion of the carrier C allele of rs2359612 in the patients with prostate cancer was significantly higher than in the population, suggesting an association between this allele and the risk of having a diagnosis of prostate cancer.Conclusions
The expression of VKOR in benign prostate epithelial cells, along with the association between a functional VKOR SNP and prostate cancer risk, suggests a possible role for VKOR in mediating the effect of warfarin on prostate cancer risk. Larger multi-institutional cohort studies are warranted, as are molecular studies on the role of VKOR in prostate cancer development. 相似文献7.
Line Victoria Moen Håkon Ramberg Sen Zhao Helene Hartvedt Grytli Anita Sveen Viktor Berge Rolf I. Skotheim Kristin Austlid Taskén Bjørn Steen Skålhegg 《Urologic oncology》2017,35(3):111.e1-111.e8
Background
Today overtreatment of indolent prostate cancers and undertreatment of aggressive prostate cancer are a major concern for patients, their families, and the health care system. New biomarkers distinguishing indolent and aggressive prostate cancer are needed to improve precision medicine. In prostate cancer, protein kinase A (PKA) is known to activate the androgen receptor and published data indicate that PKA subunits can act as predictive markers for response to radiation and chemotherapy. We have previously shown that the catalytic subunit, Cβ2, of PKA is up-regulated in prostate cancer and we would in this study investigate the potential of Cβ2 to become a prognostic biomarker in prostate cancer.Methods
Data were sampled from a total of 241 patients from 3 independent cohorts. We measured and compared Cβ2 messenger RNA (mRNA) levels in prostate tumor and nontumor samples (n = 22), and exon levels in a cohort of 50 tumor samples, as well as acquiring mRNA data from the publicly available database The cancer genome atlas (n = 169).Results
Cβ2 mRNA was up-regulated in prostate cancer in all 3 cohorts, measured by 3 different methods. Furthermore, the relative Cβ2 mRNA expression levels were lower in prostate cancer samples with Gleason score 8 to 10 compared with samples with Gleason score<8 (P = 0.004). Finally, low expression of Cβ2 mRNA in prostate cancer biopsies correlated with poor survival (hazard ratio = 0.20; 95% CI: 0.048–0.86; P = 0.031), adjusted for risk group and age.Conclusions
We suggest that Cβ2 mRNA expression may be used as a biomarker together with established prognostic markers to more precisely predict aggressiveness in patients diagnosed with prostate cancer. 相似文献8.
Objective
We aim to highlight the progression from the early definition of nononcologic outcomes in prostate cancer (PC) to measurement and use of preferences to ensure appropriate treatment decisions in men with localized disease.Methods
We review the assessment of nononcologic outcomes after PC treatment and ways to use the outcomes to augment patient care.Results
PC treatments may have similar oncologic efficacy in men with certain clinical features, but they differ in their nononcologic outcomes. Tools to assess these outcomes have been developed and are useful in areas from treatment reimbursement to shared decision-making.Conclusions
The ability to measure and make useful data on nononcologic outcomes evolved substantially over the past 20 years. Current work suggests that individual preference assessment for nononcologic outcomes is a promising means of matching patients with appropriate treatment. 相似文献9.
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David B. Samadi Dov Sebrow Adele R. Hobbs Adrien N. Bernstein Jonathan Brajtbord Hugh J. Lavery Seyed Behzad Jazayeri 《Urologic oncology》2017,35(1):30.e17-30.e24
Background
To define the pathologic and functional outcomes of men 50 years of age and younger with prostate cancer in a contemporary robotic cohort, this study was designed.Methods
Patients undergoing robotic-assisted laparoscopic prostatectomy from April 2002 to April 2012 (n = 2,495) formed the base population for the current analyses. The patients were dichotomized according to their age≤50 (n = 271) and>50-year-old (n = 2,224). Clinicopathological and health-related quality-of-life outcomes were recorded and analyzed for differences. Propensity score matching was used when assessing urinary and sexual function outcome.Results
Baseline prostate-specific antigen and clinical stage were similar between men older than 50 years and those younger. Younger patients had less severe disease (D?Amico risk and Gleason scores) and smaller prostates. Young men had higher rates of erectile function at all time points, including baseline (94% vs. 83% at 12 mo, P <0.01). Continence was similar at all time points except for 6 months, where younger patients experienced a faster return than older patients and then remained constant, while older patients continued to improve (96% vs. 89%, P<0.01). After matching process, the difference in erectile function at 6-month follow-up was lost.Conclusion
Most men aged 50 years and younger who received robotic-assisted laparoscopic prostatectomy had clinically significant prostate cancer. Although histopathologic and short-term oncologic outcomes were nearly identical when compared to older patients, younger men had a more rapid and superior return of erectile function. 相似文献11.
Tarun Jindal Naveen Kachroo Jesse Sammon Deepansh Dalela Akshay Sood Malte W. Vetterlein Patrick Karabon Wooju Jeong Mani Menon Quoc-Dien Trinh Firas Abdollah 《Urologic oncology》2017,35(7):460.e9-460.e20
Objective
Black men are more prone to harbor prostate cancer. They are more likely to succumb to this tumor than their White counterparts and may benefit from early detection and treatment. In this study, we assess the nationwide and regional disparity in prostate-specific antigen (PSA) screening for prostate cancer between Black men and non-Hispanic Whites (NHWs).Methods
A total of 247,079 (weighted 55,185,102) men, aged 40 to 99 years, who responded to the 2012 and 2014 behavioral risk factor surveillance system surveys were used for our analysis. End points consisted of self-reported PSA screening and self-reported nonrecommended PSA screening within 12 months of the interview. The latter was defined as screening in men with <10-year life expectancy. Available sociodemographic variables were used to predict these end points. The independent predictors from multivariate models were used to calculate the adjusted prevalence of PSA screening and nonrecommended PSA screening on a nationwide and regional level. These numbers were calculated for Blacks and NHWs separately and were compared between the 2 groups.Results
Prevalence of PSA screening was 30.7% in NHWs vs. 28.1% in Blacks (P<0.001). On a region-based analysis, New England, Middle Atlantic, South Atlantic, East North Central, East South Central, West South Central, and Mountain showed a significantly higher rate of PSA screening in NHWs as compared to Blacks (all P<0.001). Middle Atlantic had a significantly higher prevalence of nonrecommended screening in NHWs as compared to Blacks, whereas South Atlantic, West South Central, and Pacific had a significantly higher prevalence of nonrecommended screening in Blacks as compared to NHWs (all P<0.001). Overall, 43 states performed screening more frequently to NHWs, whereas only 8 states performed it more frequently to Black men. The nonrecommended screening was performed more frequently to NHWs in 19 states, whereas 24 states performed it more frequently to Black men.Conclusion
Our study demonstrates that on a regional-level (and state-level), there are significant racial differences in overall and nonrecommended PSA screening across the United States. Further research is necessary to identify the reasons for the differences and help overcoming it. 相似文献12.
Massimo Valerio Taimur Tariq Shah Paras Shah Neil Mccartan Mark Emberton Manit Arya Hashim Uddin Ahmed 《Urologic oncology》2017,35(4):150.e1-150.e7
Objectives
The use of software-based magnetic resonance-transrectal ultrasound fusion to deliver focal therapy may increase the precision of treatment. This is a prospective development study assessing the feasibility of Magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion focal cryotherapy.Methods and materials
Consecutive patients undergoing focal cryotherapy were included in an academic registry (December 2013–June 2014). MRI-TRUS fusion focal cryotherapy was offered to men with visible clinically significant prostate cancer (Galil SeedNet system). Eligibility was determined by multiparametric MRI (mpMRI), and transperineal template mapping or targeted biopsies. A rigid fusion platform (Biojet) was used with the operator ensuring the ice ball covered at least the lesion. Adverse events were scored using the NCICTC V4. Genitourinary toxicity was assessed using patient-reported outcome measures (IPSS, IIEF-15, and UCLA-EPIC). Early contrast-enhanced MRI and mpMRI at 6 to 12 months were used to assess extent of lesion ablation.Results
Of 23 patients scheduled, 5 did not have image fusion owing to surgeon preference. Overall, 18 patients undergoing image-fusion cryotherapy had median age of 68 (interquartile range [IQR]: 65–73) years and median preoperative prostate-specific antigen = 9.54 (5.65–16) ng/ml. In all, 13 (72.2%) and 5 (27.8%) patients had intermediate and high-risk cancer, respectively. In total, 10 adverse events were reported with one of these as serious (grade 3) because of admission for hematuria requiring wash out only. There was no difference in the IIEF-15 between baseline and study end (P = 0.24). The IPSS remained stable (P = 0.12), whereas the UCLA-EPIC tended to improve (P = 0.065). The prostate-specific antigen level significantly decreased at 1.8 (1.04–2.93) ng/ml (P<0.001). Both early and late mpMRI showed no residual disease in the treated area. In 2 men, radiological progression of known contralateral disease was observed; both underwent focal high intensity focused ultrasound.Conclusion
MRI-TRUS fusion focal cryotherapy is feasible in most patients and seems to accurately guide ablation demonstrated by posttreatment imaging. Additional studies are needed to determine efficacy using postcryotherapy biopsy. 相似文献13.
Background and objective
Erectile dysfunction is one of the complications occurring after radical prostatectomy (RP), and recovery of erectile function is quantitatively related to the preservation of the neurovascular bundles (NVB).We evaluated the significance of NVB area on functional outcomes after RP.Materials and methods
Preoperative magnetic resonance imaging was performed on 141 patients who underwent bilateral, nerve-sparing, robot-assisted RP for clinically localized prostate cancer (clinically T2N0M0 on magnetic resonance imaging) and were evaluated at least 12 months after surgery. NVB area was measured as a region of interest that coincided with the outline of the maximum area of the posterolateral region of the prostate on T2-weighted axial imaging. Factors associated with functional outcomes were evaluated using logistic regression analysis.Results
Of 141 patients, 36 patients (25.5%) had no preoperative potency (group 1), 66 patients (46.8%) recovered potency (group 2), and 39 patients (27.7%) did not recover potency (group 3). Although the mean age of the entire cohort was 65.4 years, the mean age of group 1 was greater than groups 2 and 3 (P = 0.001). The NVB area of group 2 was larger than those of groups 1 and 3 (P = 0.001). Potency evaluations involved 105 patients (74.5%; groups 2 and 3), and patients with pre-existing erectile dysfunction were excluded. The median time to potency recovery was 3.0 months after surgery. The multivariable analysis revealed that the NVB area was the only significant factor predictive of potency recovery.Conclusions
The NVB area in the posterolateral region of the prostate is an independent factor for predicting potency recovery. The degree of postoperative erectile function can be predicted based on the preoperative NVB area. 相似文献14.
Ejaculatory frequency and the risk of aggressive prostate cancer: Findings from a case-control study
Nathan P. Papa Robert J. MacInnis Dallas R. English Damien Bolton Ian D. Davis Nathan Lawrentschuk Jeremy L. Millar John Pedersen Gianluca Severi Melissa C. Southey John L. Hopper Graham G. Giles 《Urologic oncology》2017,35(8):530.e7-530.e13
Objectives
Recent literature reports inverse associations with ejaculator frequency and prostate cancer (PC). We sought to explore the relationship between ejaculatory frequency from ages 20 to 50 and subsequent development of aggressive PC.Material and methods
We conducted a case-control study sampling 2,141 men from private urology practices in Victoria, Australia. Cases were defined as men with high grade or high stage PC and controls being biopsy negative men. Ejaculation frequency recalled at age decades 20, 30, and 40 second was assessed by questionnaire. Unconditional multivariable logistic regression models were used to generate odds ratios (ORs).Results
An inverse association with ejaculatory frequency at age 30 to 39 was observed (OR per 5-unit increase per week = 0.83, 95% CI: 0.72–0.96) but not at ages 20 to 29 (OR = 1.01, 95% CI: 0.89–1.14) or ages 40 to 49 (OR = 0.95, 95% CI: 0.81–1.12). This result differed between men with new sexual partners after age 30 (OR = 0.77, P = 0.009) and those with no new partners (OR = 0.97, P = 0.8) though the test for a difference between these estimates was not significant (P = 0.11).Conclusion
We found only weak evidence of an inverse association between ejaculatory frequency in the fourth decade of life and advanced PC, which was not significantly modified by number of new sexual partners. No relationship was found for ejaculatory frequency in the third and fifth decades of life. 相似文献15.
Martijn G. Schouten Marloes van der Leest Morgan Pokorny Martijn Hoogenboom Jelle O. Barentsz Les C. Thompson Jurgen J. Fütterer 《European urology》2017,71(6):896-903
Background
Knowledge of significant prostate (sPCa) locations being missed with magnetic resonance (MR)- and transrectal ultrasound (TRUS)-guided biopsy (Bx) may help to improve these techniques.Objective
To identify the location of sPCa lesions being missed with MR- and TRUS-Bx.Design, setting, and participants
In a referral center, 223 consecutive Bx-naive men with elevated prostate specific antigen level and/or abnormal digital rectal examination were included. Histopathologically-proven cancer locations, Gleason score, and tumor length were determined.Intervention
All patients underwent multi-parametric MRI and 12-core systematic TRUS-Bx. MR-Bx was performed in all patients with suspicion of PCa on multi-parametric MRI (n = 142).Outcome measurements and statistical analysis
Cancer locations were compared between MR- and TRUS-Bx. Proportions were expressed as percentages, and the corresponding 95% confidence intervals were calculated.Results and limitations
In total, 191 lesions were found in 108 patients with sPCa. From these lesion 74% (141/191) were defined as sPCa on either MR- or TRUS-Bx. MR-Bx detected 74% (105/141) of these lesions and 61% (86/141) with TRUS-Bx. TRUS-Bx detected more lesions compared with MR-Bx (140 vs 109). However, these lesions were often low risk (39%). Significant lesions missed with MR-Bx most often had involvement of dorsolateral (58%) and apical (37%) segments and missed segments with TRUS-Bx were located anteriorly (79%), anterior midprostate (50%), and anterior apex (23%).Conclusions
Both techniques have difficulties in detecting apical lesions. MR-Bx most often missed cancer with involvement of the dorsolateral part (58%) and TRUS-Bx with involvement of the anterior part (79%).Patient summary
Both biopsy techniques miss cancer in specific locations within the prostate. Identification of these lesions may help to improve these techniques. 相似文献16.
Franklin D. Gaylis Jae E. Choi Zachary Hamilton Paul Dato Edward Cohen Renee Calabrese Hilary Prime Aaron Rosenbaum Andrew Karim Kader 《Urologic oncology》2017,35(11):663.e1-663.e7
Objective
The benefits of prostate-specific antigen (PSA)–based prostate cancer screening are controversial. We sought to determine the change in prostate cancer presentation coinciding with the release of the United States Preventative Services Task Force recommendations against screening in a high-volume community-based urology practice.Methods
Characteristics of men presenting for an elevated PSA at a community urology practice from August 2011 to August 2015 were queried from a prospectively collected database. A retrospective analysis of presenting PSA, Gleason grade at biopsy, and prostatectomy as well as clinical and pathologic stage was performed. Kruskal-Wallis rank sum and chi-square tests were used for analysis.Results
Referrals for elevated PSA decreased from 933 in year 1 to 816 by year 4 (12.5% decrease) with a concomitant reduction in biopsies performed in newly referred men from 461 to 356 (22.8% decrease, P = 0.02). The proportion of men presenting with PSAs>10 increased from 28.1% to 36.8% (P = 0.009). First-time biopsy-positivity rate increased from 48.4% to 62.4% with a rise in the proportion having Gleason≥7 from 51.6% to 69.7% (P = 0.0001). Of the 578 men who underwent radical prostatectomy, there was a 19.4% increase in Gleason≥7 tumors (P = 0.01).Conclusions
Our findings demonstrate a decrease in elevated PSA referrals, increase in PSA at the time of referral, decrease in detection of low-risk disease, and increase in detection of intermediate-/high-risk disease in a high-volume, multisite, community-based urology practice, coinciding with the United States Preventative Services Task Force recommendations against PSA screening. 相似文献17.
Arya Amini David Raben E. David Crawford Thomas W. Flaig Elizabeth R. Kessler Elaine T. Lam Paul Maroni Thomas J. Pugh 《Urologic oncology》2017,35(6):438-446
Purpose
To evaluate usage trends and identify factors associated with proton beam therapy (PBT) compared to alternative forms of external beam radiation therapy (RT) (EBRT) for localized prostate cancer.Patients and Methods
The National Cancer Database was queried for men with localized (N0, M0) prostate cancer diagnosed between 2004 and 2013, treated with EBRT, with available data on EBRT modality (photon vs. PBT). Binary multiple logistic regression identified variables associated with EBRT modality.Results
In total, 143,702 patients were evaluated with relatively few men receiving PBT (5,709 [4.0%]). Significant differences in patient and clinical characteristics were identified between those men treated with PBT compared to those treated with photon (odds ratio [OR]; 95% CI). Patients treated with PBT were generally younger (OR = 0.73; CI: 0.67–0.82), National Comprehensive Cancer Network low-risk compared to intermediate (0.71; 0.65–0.78) or high (0.44; 0.38–0.5) risk, white vs. black race (0.66; 0.58–0.77), with less comorbidity (Charlson-Deyo 0 vs. 2+; 0.70; 0.50–0.98), live in higher income counties (1.55; 1.36–1.78), and live in metropolitan areas compared to urban (0.21; 0.18–0.23) or rural (0.14; 0.10–0.19) areas. Most patients treated with PBT travelled more than 100 miles to the treatment facility. Annual PBT utilization significantly increased in both total number and percentage of EBRT over time (2.7%–5.6%; P<0.001). PBT utilization increased mostly in men classified as National Comprehensive Cancer Network low-risk (4%–10.2%).Conclusion
PBT for men with localized prostate cancer significantly increased in the United States from 2004 to 2013. Significant demographic and prognostic differences between those men treated with photons and protons were identified. 相似文献18.
Josef Mang Konstanze Merkle Martina Heller Julia Schüler Yanis Tolstov Jielin Li Markus Hohenfellner Stefan Duensing 《Urologic oncology》2017,35(1):32.e9-32.e16
Background
Taxanes are routinely used to treat men with advanced prostate cancer, yet their molecular mode of action is poorly characterized. Taxanes stabilize microtubules and may hence interfere with a plethora of cellular processes, most notably mitosis. However, prostate cancer is typically a slowly growing tumor suggesting that additional processes play a role in the response to taxanes.Methods
Here, we analyzed the potential effect of taxanes on microtubuli-dependent intracellular transport and signaling processes, specifically, nuclear translocation of the androgen receptor and modulation of the RAS-RAF-MEK-ERK signaling cascade.Results
We show that the androgen-driven nuclear translocation of the androgen receptor remains virtually undisturbed by docetaxel in prostate cancer cells. However, we found a striking down-regulation of activated ERK1/2 together with enhanced cytotoxicity in both docetaxel or cabazitaxel-treated cells that was comparable to direct MEK kinase inhibition. Remarkably, MEK inhibition alone was less effective in inducing cytotoxicity than taxanes indicating that a down-regulation of activated ERK1/2 may be necessary but is not sufficient for taxane-induced antitumoral effects. In line with this notion, we show in a xenograft mouse model that prostate cancer cells that are resistant to docetaxel overexpress activated ERK1/2. Taken together, our findings underscore that the modulation of ERK1/2 activation, in concert with other mechanisms, plays an important role in taxane-induced antineoplastic effects on prostate cancer cells.Conclusions
These results suggest at least partially nonoverlapping effects of docetaxel and androgen deprivation therapy and hence help to understand recent clinical findings. A further elucidation of the mode of action of docetaxel would have important implications to optimize current treatment strategies and biomarker development for men with metastatic prostate cancer. 相似文献19.
Background
There is increasing evidence that androgen deprivation therapy (ADT) may be associated with depression. Existing studies have shown conflicting results.Methods
PubMed, Web of Science, Embase, and PsycINFO were queried on April 5, 2017. Eligible studies were in English and reported depression among individuals with prostate cancer exposed to a course of ADT vs. a lesser-exposed group (e.g., any-ADT vs. no ADT and continuous ADT vs. intermittent ADT). We used the MOOSE statement guidelines and the Cochrane Review Group’s data extraction template. Study quality was evaluated by Newcastle-Ottawa Scale criteria. We conducted a random-effects meta-analysis to calculate summary statistic risk ratios (RRs) and 95% CIs. Heterogeneity was quantified using the I2 statistic and prespecified subgroup analysis. Small study effects were evaluated using Begg and Egger statistics.Results
A total of 1,128 studies were initially identified and evaluated. A meta-analysis of 18 studies among 168,756 individuals found that ADT use conferred a 41% increased risk of depression (RR = 1.41; 95% CI: 1.18–1.70; P<0.001). We found a consistent strong statistically significant association when limiting our analysis to studies in localized disease (RR = 1.85; 95% CI: 1.20–2.85; P = 0.005) and those using a clinical diagnosis of depression (RR = 1.19; 95% CI: 1.08–1.32; P = 0.001). We did not find an association for continuous ADT with depression risk compared to intermittent ADT (RR = 1.00; 95% CI: 0.50–1.99; P = 0.992). There was no statistically significant evidence of small study effects. Statistically significant heterogeneity in the full analysis (I2 = 80%; 95% CI: 69–87; P<0.001) resolved when examining studies using a clinical diagnosis of depression (I2 = 16%; 95% CI: 0–60; P = 0.310).Conclusion
The currently available evidence suggests that ADT in the treatment of prostate cancer is associated with an increased risk of depression. 相似文献20.
Daniel N. Costa Fernando U. Kay Ivan Pedrosa Lauren Kolski Yair Lotan Claus G. Roehrborn Brad Hornberger Yin Xi Franto Francis Neil M. Rofsky 《Urologic oncology》2017,35(4):149.e15-149.e21