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3.0 T multiparametric prostate MRI using pelvic phased-array coil: Utility for tumor detection
prior to biopsy
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Andrew B. Rosenkrantz , Thais C. Mussi , Michael S. Borofsky , Stephen S. Scionti , Michael
Grasso , Samir S. Taneja
Objective To evaluate the role of multiparametric magnetic resonance imaging (MRI) performed in men
without a biopsy-proven diagnosis of prostate cancer using follow-up biopsy as the reference standard.
Materials and methods Forty-two patients without biopsy-proven cancer and who underwent MRI were
included. In all patients, MRI was performed at 3T using a pelvic phased-array coil and included T2weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging. Thirteen had
undergone no previous biopsy, and 29 had undergone at least 1 previous negative biopsy. All patients
underwent prostate biopsy following MRI. Two fellowship-trained radiologists in consensus reviewed all
cases and categorized each lobe as positive or negative for tumor. These interpretations were correlated
with findings on post-MRI biopsy. Results Follow-up biopsy was positive in 23 lobes in 15 patients (36% of
study cohort). On a per-patient basis, MRI had a sensitivity of 100%, specificity of 74%, positive predictive
value (PPV) of 68%, and negative predictive value (NPV) of 100%. On a per-lobe basis, MRI had a
sensitivity of 65%, specificity of 84%, PPV of 60%, and NPV of 86%. There was a nearly significant
association between Gleason score and tumor detection on MRI (P = 0.072). Conclusions In our sample,
MRI had 100% sensitivity in predicting the presence of tumor on subsequent biopsy on a per-patient basis,
suggesting a possible role for MRI in selecting patients with an elevated prostatic specific antigen (PSA) to
undergo prostate biopsy. However, MRI had weaker specificity for prediction of a subsequent positive
biopsy, as well as weaker sensitivity for tumor on a per-lobe basis, indicating that in patients with a positive
MRI result, tissue sampling remains necessary for confirmation of the diagnosis as well as for treatment
planning.
A Hybrid Radioactive and Fluorescent Tracer for Sentinel Node Biopsy in Penile Carcinoma
as a Potential Replacement for Blue Dye
27 Nov 2013 04:55 am
Indocyanine green-99mTc-nanocolloid allows for both preoperative sentinel node (SN) imaging and imageguided SN biopsy in penile carcinoma patients. This hybrid approach combines the beneficial properties of
both modalities and improves optical SN identification compared with blue dye. Background:Sentinel node
(SN) biopsy in penile cancer is typically performed using a combination of radiocolloid and blue dye.
Recently, the hybrid radioactive and fluorescent tracer indocyanine green (ICG)-99mTc-nanocolloid was
developed to combine the beneficial properties of both radio guidance and fluorescence
imaging.Objective:To explore the added value of SN biopsy using ICG-99mTc-nanocolloid in patients with
penile carcinoma.Design, setting, and participants:Sixty-five patients with penile squamous cell carcinoma
were prospectively included (January 2011 to December 2012). Preoperative SN mapping was performed
using lymphoscintigraphy and single-proton emission computed tomography supplemented with computed
tomography (SPECT/CT) after peritumoural injection of ICG-99mTc-nanocolloid. During surgery, SNs were
initially approached using a gamma probe, followed by patent blue dye and/or fluorescence imaging. A
portable gamma camera was used to confirm excision of all SNs.Surgical procedure:Patients underwent SN
biopsy of the cN0 groin and treatment of the primary tumour.Outcome measurements and statistical
analysis:The number and location of preoperatively identified SNs were documented. Intraoperative SN
identification rates using radio- and/or fluorescence guidance were assessed and compared with blue dye.
Statistical evaluation was performed using a two-sample test for equality of proportions with continuity
correction.Results and limitations:Preoperative imaging after injection of ICG-99mTc-nanocolloid enabled
SN identification in all patients (a total of 183 SNs dispersed over 119 groins). Intraoperatively, all SNs
identified by preoperative mapping were localised using combined radio-guided, fluorescence-guided, and
blue dye guidance. Fluorescence imaging enabled visualisation of 96.8% of SNs, while only 55.7% was
stained by blue dye (p
A Multinational, Multi-institutional Study Comparing Positive Surgical Margin Rates Among
22393 Open, Laparoscopic, and Robot-assisted Radical Prostatectomy Patients
25 Nov 2013 04:45 am
Background:Positive surgical margins (PSMs) are a known risk factor for biochemical recurrence in patients
with prostate cancer (PCa) and are potentially affected by surgical technique and volume.Objective:To
investigate whether radical prostatectomy (RP) modality and volume affect PSM rates.Design, setting, and
participants:Fourteen institutions in Europe, the United States, and Australia were invited to participate in
this study, all of which retrospectively provided margins data on 9778 open RP, 4918 laparoscopic RP, and
7697 robotic RP patients operated on between January 2000 and October 2011.Outcome measurements
and statistical analyses:The outcome measure was PSM rate. Multivariable logistic regression analyses and
propensity score methods identified odds ratios for risk of a PSM for one modality compared with another,
after adjustment for age, preoperative prostate-specific antigen, postoperative Gleason score, pathologic
stage, and year of surgery. Classic adjustment using standard covariates was also implemented to compare
PSM rates based on center volume for each minimally invasive surgical cohort.Results and limitations:Open
RP patients had higher-risk PCa at time of surgery on average and were operated on earlier in the study
time period on average, compared with minimally invasive cohorts. Crude margin rates were lowest for
robotic RP (13.8%), intermediate for laparoscopic RP (16.3%), and highest for open RP (22.8%); significant
differences persisted, although were ameliorated, after statistical adjustments. Lower-volume centers had
increased risks of PSM compared with the highest-volume center for both laparoscopic RP and robotic RP.
The study is limited by its nonrandomized nature; missing data across covariates, especially year of surgery
in many of the open cohort cases; lack of standardized histologic processing and central pathology review;
and lack of information regarding potential confounders such as patient comorbidity, nerve-sparing status,
lymph node status, tumor volume, and individual surgeon caseload.Conclusions:This multinational, multiinstitutional study of 22 393 patients after RP suggests that PSM rates might be lower after minimally
invasive techniques than after open RP and that PSM rates are affected by center volume in laparoscopic
and robotic cases.Patient summary:In this study, we compared the effectiveness of different types of
surgery for prostate cancer by looking at the rates of cancer cells left at the margins of what was removed in
the operations. We compared open, keyhole, and robotic surgery from many centers across the globe and
found that robotic and keyhole operations appeared to have lower margin rates than open surgeries. How
many cases a center and surgeon do seems to affect this rate for both robotic and keyhole procedures.In
this multi-institutional, multinational study, positive surgical margin rates appear lower after minimally
invasive radical prostatectomy than with the open approach. Case volume is likely to affect margin rates for
laparoscopic and robotic techniques.
A Plea for Higher-quality Data for GreenLight Laser Technology in the Context of Surgical
Benign Prostatic Obstruction Trials: The GOLIATH Study—Fact or Fiction in the Era of
Evidence-based Urology?
03 Dec 2013 04:45 am
A cross-sectional investigation of fatigue in advanced renal cell carcinoma treatment:
Results from the FAMOUS study
09 Dec 2013 01:56 am
Publication date: Available online 7 December 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): P.J. Goebell , A. Münch , L. Müller , H.J. Hurtz , M. Koska , S. Busies , N. Marschner
Objective With an increasing choice of new treatment options, the management of side effects to maintain a
chosen treatment if likely to be effective on the tumor remains important. The perception of side effects
however varies between the physician and the patient, leading to possible wrong assumptions on tolerability
that result in dose modifications, which may ultimately affect effectiveness. The aim was to assess fatigue in
patients with advanced or metastatic renal cell carcinoma (RCC) by comparing the evaluation of the
physician to the one provided by their respective patient. In addition, we aimed to assess possible
influences of fatigue on parameters of quality of life. Methods Patients receiving systemic treatment for
advanced RCC and their physicians were questioned independently regarding incidence and severity of
fatigue and its effect on quality of life. Results Both physicians and patients completed 98 matching
questionnaires. Patients were treated with sunitinib, sorafenib, bevacizumab combined with interferon
alpha, temsirolimus, everolimus, or interferon alpha alone. Incidence and severity of fatigue was differently
assessed by patients and physicians, with fatigue being more severe when reported by the patient. The
severity of fatigue increased with progressing treatment lines. Quality of life was significantly lower in
patients experiencing fatigue compared with patients without fatigue. Emotional, functional, and physical
well-being were all affected by fatigue, the latter being the most affected subscale. Social well-being was
least affected. Conclusion Fatigue is a complex and cumulative condition of patients treated for advanced
RCC, and it considerably affects patient's quality of life. As many of its underlying causes may be treated,
the divergent perception of occurrence and severity of fatigue should be integrated in treatment concepts.
The active role of the patient in helping to manage ailments through assessment should be implemented
when optimizing treatment of RCC.
Activated 5′flanking region of NANOGP8 in a self-renewal environment is associated with
increased sphere formation and tumor growth of prostate cancer cells
07 Dec 2013 06:33 am
INTRODUCTION NANOGP8 is a retrogene which encodes a full-length protein similar to the NANOG1
gene. The expression of NANOGP8 has been documented in several cancers and is related to cell
proliferation and tumor development. However, the regulation of NANOGP8 expression has not been
investigated. Therefore, the role of NANOGP8 in cell proliferation has not been completely understood.
METHODS We evaluate the expression of NANOG1 and NANOGP8 in prostate cancer cell lines and
primary cultures of prostate tissues. We investigate clonogenicity, sphere formation, and xenograft tumor
growth of prostate cancer cells with an activated 5′flanking region of NANOGP8. We examine the role of
NANOGP8 in cell cycle progression. RESULTS In the prostate cells the NANOG RNA was transcribed from
NANOGP8 and not from NANOG1. Cells with the activated 5′flanking region of NANOGP8 exhibited
enhanced clonogenicity, sphere formation, and xenograft tumor growth. The sphere culture and tumor
initiation mouse mode promoted the activation of the 5′flanking region of NANOGP8. Forced expression of
NANOGP8 increased the entry into the cell cycle. DISCUSSION In prostate cells NANOGP8 is a
predominant molecule of NANOG. The activation of 5′flanking sequence of NANOGP8 could play a role in
the regulation of the stem-like properties of cancer stem cells and prostate tumor initiation and
development. The microenvironment favoring cancer stem cells could promote the activation of the
5′flanking region of NANOGP8. © 2013 Wiley Periodicals, Inc.
Androgen Deprivation Therapy and Cardiovascular Harm: Are All Men Created Equal?
21 Nov 2013 05:05 am
Assessing the Response to Targeted Therapies in Renal Cell Carcinoma: Technical
Insights and Practical Considerations
28 Nov 2013 04:35 am
Context:The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in
new challenges for assessing response to therapy, and conventional response criteria using computed
tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis
without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may
occur long before there is any reduction in tumour size.Objective:To perform a systematic review of
conventional and novel imaging methods for the assessment of response to targeted agents in RCC and to
discuss their use from a clinical perspective.Evidence acquisition:Relevant databases covering the period
January 2006 to April 2013 were searched for studies reporting on the use of anatomic and functional
imaging techniques to predict response to targeted therapy in RCC. Inclusion criteria were randomised
trials, nonrandomised controlled studies, retrospective case series, and cohort studies. Reviews, animal
and preclinical studies, case reports, and commentaries were excluded. A narrative synthesis of the
evidence is presented.Evidence synthesis:A total of 331 abstracts and 76 full-text articles were assessed;
34 studies met the inclusion criteria. Current methods of response assessment in RCC include anatomic
methods—based on various criteria including Choi, size and attenuation CT, and morphology, attenuation,
size, and structure—and functional techniques including dynamic contrast-enhanced (DCE) CT, DCEmagnetic resonance imaging, DCE-ultrasonography, positron emission tomography, and approaches
utilising radiolabelled monoclonal antibodies.Conclusions:Functional imaging techniques are promising
surrogate biomarkers of response in RCC and may be more appropriate than anatomic CT-based methods.
By enabling quantification of tumour vascularisation, functional techniques can directly and rapidly detect
the biologic effects of antiangiogenic therapies compared with the indirect detection of belated effects on
tumour size by anatomic methods. However, larger prospective studies are needed to validate early results
and standardise techniques.Available evidence supports the use of functional imaging techniques to predict
response to targeted therapy in renal cell carcinoma. Following further validation and standardisation, these
techniques will ultimately allow tailoring of treatment to patients who are most likely to benefit from therapy.
Beyond the androgen receptor: New approaches to treating metastatic prostate cancer.
Report of the 2013 Prouts Neck Prostate Cancer Meeting
19 Nov 2013 06:24 am
INTRODUCTION The Prouts Neck Meetings on Prostate Cancer began in 1985 through the efforts of the
Organ Systems Branch of the National Cancer Institute to stimulate new research and focused around
specific questions in prostate tumorigenesis and therapy. METHODS These meetings were think tanks,
composed of around 75 individuals, and divided equally between young investigators and senior
investigators. Over the years, many new concepts related to prostate cancer resulted from these meetings
and the prostate cancer community has sorely missed them since the last one in 2007. RESULTS We
report here the first of a new series of meetings. The 2013 meeting focused on defining how the field of
treatment for metastatic prostate cancer needs to evolve to impact survival and was entitled: “Beyond AR:
New Approaches to Treating Metastatic Prostate Cancer.” As castrate resistant prostate cancers escape
second generation anti-androgen agents, three phenotypes/genotypes of CRPC appear to be increasing in
prevalence and remain resistant to treatment: NeuroEndocrine Prostate Cancer, Persistent AR—Dependent
Prostate Cancer, and Androgen Receptor Pathway Independent Prostate Cancer. DISCUSSION It is clear
that new treatment paradigms need to be developed for this diverse group of diseases. The Prouts Neck
2013 Meeting on Prostate Cancer helped to frame the current state of the field and jumpstart ideas for new
avenues of treatment. Prostate © 2013 Wiley Periodicals, Inc.
Biomarkers of renal cell carcinoma
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Tin C. Ngo , Christopher G. Wood , Jose A. Karam
The incidence of renal cell carcinoma (RCC) has increased steadily in past few decades and is partially
attributable to the increased utilization of cross-sectional imaging. Many of these carcinomas are small
incidental discoveries, although a subset leads to locally advanced or distant disease. Although its
molecular pathophysiology is not completely understood, knowledge of hereditary RCCs has shed light on
some of the pathways involved. More recently, the rapid advances in genomics, proteomics, and
metabolomics have allowed for a deeper and more nuanced understanding of the genetic aberrations that
lead up to and result from the transformation of a renal tubular epithelial cell into a carcinoma. These
discoveries have allowed for the development of novel therapeutics that target these pathways. They have
also led to the development of diagnostic, prognostic, and predictive biomarkers that could radically change
the way RCC is diagnosed and treated. Although some of the current investigations are nascent and it
remains to be seen which biomarkers will become clinically available, many candidate biomarkers show
promise and require external validation. Ultimately, biomarkers may allow for cost-effective screening of
high-risk patients, the identification of aggressive cancers among small renal masses, the identification of
high-risk patients, the detection of recurrences postoperatively with minimal imaging, and the ability to
choose appropriate targeted therapies for patients with metastatic disease.
Boldine induces cell cycle arrest and apoptosis in T24 human bladder cancer cell line via
regulation of ERK, AKT, and GSK-3β
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Daniéli Gerhardt , Gabriela Bertola , Fabrícia Dietrich , Fabrício Figueiró , Alfeu Zanotto-Filho ,
José Cláudio Moreira Fonseca , Fernanda Bueno Morrone , Carlos Henrique Barrios , Ana Maria O.
Battastini , Christianne G. Salbego
Objective Bladder cancer is one of the most prevalent genitourinary malignancies. Despite active
chemotherapy regimens, patients with bladder cancer suffer from a high rate of tumor recurrence. Thus,
new approaches and agents to improve quality of life and survival still need to be developed. The objective
of the present study was to evaluate the effect and underlying mechanisms of boldine, an aporphine
alkaloid of Peumus boldus, on bladder cancer proliferation and cell death. Methods Sulforhodamine B
assay, Tetrazolium reduction assay, Flow Cytometry Analysis, Ecto-5’-nucleotidase activity and Western
blot assay were performed. Results The results showed that boldine was able to reduce cell viability and
cell proliferation in T24 cells. In addition, boldine arrests the cell cycle at G2/M-phase and cause cell death
by apoptosis. Boldine-induced inhibition of cell growth and cell cycle arrest appears to be linked to
inactivation of extracellular signal–regulated kinase protein (ERK). Additionally, the efficacy of boldine in
apoptosis-induced in T24 cells is correlated with modulation of AKT (inactivation) and glycogen synthase
kinase-3β (GSK-3β) (activation) proteins. Conclusions The present findings may, in part, explain the
therapeutic effects of boldine for treatment of urinary bladder cancer.
Clinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma
treated with sunitinib and sorafenib after progression on cytokines
09 Dec 2013 01:56 am
Publication date: Available online 7 December 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Alexandr Poprach , Tomas Pavlik , Bohuslav Melichar , Katerina Kubackova , Zbynek Bortlicek ,
Marek Svoboda , Radek Lakomy , Rostislav Vyzula , Igor Kiss , Ladislav Dusek , Tomas Buchler
Objectives The aim of this retrospective study was to analyze prognostic factors in patients with metastatic
renal cell carcinoma treated with tyrosine kinase inhibitors (TKIs) sunitinib or sorafenib after progression on
cytokine therapy. Materials and methods A national database of patients treated with targeted agents was
used as the data source. A total of 319 patients treated with sunitinib ( n = 181) or sorafenib ( n = 138) after
progression on cytokine therapy were analyzed. Results Prognostic factors significantly associated with
poor overall survival in a multivariable Cox model included the time from diagnosis to the start of treatment
with TKIs<1 year, increased neutrophil counts, increased lactate dehydrogenase, and Eastern Oncology
Cooperative Group performance status 2 or higher. The parameters showing statistically significant
association with progression-free survival included time from diagnosis to the beginning of treatment with
TKI<1 year, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance
status 2 or higher. We have also validated the International Metastatic Renal Cell Carcinoma Database
Consortium prognostic model in our cohort of patients. Conclusion We demonstrate that the International
Database Consortium prognostic model performs well for European patients treated with TKIs, including
sunitinib or sorafenib, after progression on cytokines and suggest that a reduction from original 6 down to 4
parameters is possible.
Clinical prognostic factors associated with outcome in patients with renal cell cancer with
prior tyrosine kinase inhibitors or immunotherapy treated with everolimus
09 Dec 2013 01:56 am
Publication date: Available online 7 December 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Robert J. Amato , Amber Flaherty , Yufeng Zhang , Fangqian Ouyang , Virginia Mohlere
Background The mTOR inhibitor, everolimus, is approved for the treatment of metastatic renal cell
carcinoma (RCC). However, prognostic models are needed to determine the patients who would most
benefit from this therapy. We have developed a model based on clinical parameters and patient
stratification into risk groups to predict patients with RCC who will derive the most benefit from treatment
with everolimus. Methods We assessed retrospective data on 57 patients with RCC who received
everolimus after previous treatment with immunotherapy or tyrosine kinase inhibitors to identify prognostic
factors for progression-free survival (PFS) and overall survival (OS). In the original phase II study, patients
received 10 mg of everolimus daily without interruption and were assessed every other week for the first 8
weeks on therapy and every 4 weeks thereafter. Kaplan-Meier analysis was used to calculate OS and PFS.
Univariate and multivariate analyses were constructed using the Cox proportional hazards model and a
stepwise procedure to validate the data. Results We grouped patients according to risk: 0 prognostic factors
indicated favorable risk, 1 to 2 factors intermediate risk, and≥3 factors poor risk. We found notable
differences in median OS (29.6 mo for favorable risk, 14.3 mo for intermediate risk, and 7.2 mo for poor
risk). Three risk factors (prior radiation treatment, no lung metastasis present at the start of treatment, and
lymphocytes<25 cells/µl) in the multivariate analysis were found to be associated with PFS, and 4 risk
factors were found to be associated with OS (bone metastasis at start of treatment, LDH>1.5×upper limit
of normal, alkaline phosphatase>120 U/l, and lymphocytes<25 cells/µl). Conclusions Our prognostic
model includes 3 readily available clinical parameters for PFS and 4 readily available clinical parameters for
OS to help stratify patients into poor, intermediate, and favorable prognosis groups for the treatment of
everolimus in clear cell RCC. These intriguing results warrant further study in a larger patient population to
validate the findings.
Cognitive problems in patients on androgen deprivation therapy: A qualitative pilot study
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Lisa M. Wu , Michael A. Diefenbach , Wayne A. Gordon , Joshua B. Cantor , Monique M.
Cherrier
Objectives Androgen deprivation therapy (ADT; also known as hormone therapy) is a well-established
treatment for prostate cancer patients with rising prostate-specific antigen levels after localized treatment,
and for those with metastatic disease. The neurological impact of ADT has been likened to that of aging and
is therefore theorized to impair cognitive functioning in prostate cancer patients. We briefly summarize the
research that has examined cognitive functioning of ADT patients primarily through neuropsychological
assessment. A qualitative pilot study is presented with the aim of describing ADT patients' experiences of
cognitive changes since starting ADT. Materials and methods Semistructured telephone interviews were
undertaken with 11 community-dwelling prostate cancer patients undergoing ADT following definitive
localized treatment. Participants were recruited via online prostate cancer support forums. Content analyses
were conducted to establish relevant themes, which in this case were the cognitive domains of impairment.
Results Eight of the 11 participants reported impairments in the domains of concentration, information
processing, verbal fluency, visual information processing/visuospatial function, memory, and executive
dysfunction. Neurobehavioral problems, including neurofatigue and apathy were also reported. Conclusions
The interviews illustrate the potential negative effects of ADT on cognitive and neurobehavioral functions,
and their impact on patients' work and in their daily lives. We describe how the field of cognitive
rehabilitation offers promising tools to assist ADT patients with cognitive problems.
Comparative Efficacy and Safety of Medical Treatments for the Management of Overactive
Bladder: A Systematic Literature Review and Mixed Treatment Comparison
19 Nov 2013 04:45 am
mg has efficacy similar to most antimuscarinics and is associated with a significantly lower probability of dry
mouth. mg had similar efficacy to most antimuscarinics and lower incidence of dry mouth, the most
common adverse event reported with antimuscarinics and one of the main causes of discontinuation of
treatment. Despite being a powerful tool for evidence-based health care evaluation, the Bayesian MTC
method has limitations. Further head-to-head comparisons between mirabegron and antimuscarinics should
be conducted to confirm our results.Based on this systematic literature review and mixed treatment
comparison, mirabegron 50 mg had an incidence of dry mouth similar to placebo and significantly lower
than all included antimuscarinics.Conclusions:Mirabegron 50 mg in improving micturition frequency and
frequency of UUI. Mirabegron 50 mg that was more efficacious than mirabegron 50 mg was as efficacious
as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the
exception of solifenacin 10 mg versus antimuscarinics in patients with OAB.Evidence acquisition:A
systematic literature search was performed on published peer-reviewed articles from 2000 to 2013. This
review included randomised controlled trials (RCTs) studying changes in symptoms (micturition frequency,
incontinence, and urgency urinary incontinence [UUI] episodes) and incidence of the most frequently
reported adverse events (dry mouth, constipation) associated with current OAB medications. The following
drugs were considered in addition to mirabegron: darifenacin, tolterodine immediate release (IR) and
extended release (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed
treatment comparisons (MTCs) were performed for efficacy (micturition, incontinence, UUI) and tolerability
(dry mouth, constipation, blurred vision).Evidence synthesis:Overall, 44 RCTs involving 27 309 patients
were included. The MTCs showed that mirabegron 50 Context:Overactive bladder (OAB) treatment
guidelines recommend antimuscarinics as first-line pharmacologic therapy. Mirabegron is a first-in-class β3adrenoceptor agonist licensed for the treatment of OAB and has shown to be well tolerated and effective in
the treatment of OAB symptoms.Objective:To assess the relative efficacy and tolerability of OAB
medications, specifically mirabegron 50
Comparison of prostate volume measured by transrectal ultrasound and magnetic
resonance imaging: Is transrectal ultrasound suitable to determine which patients should
undergo active surveillance?
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Brian E. Weiss , Alan J. Wein , S. Bruce Malkowicz , Thomas J. Guzzo
Objectives To compare prostate volume obtained by transrectal ultrasound (TRUS) and endorectal MRI
(eMRI) to assess the reliability of TRUS in determining prostate-specific antigen (PSA) density. Materials
and methods Data for 2,410 patients diagnosed with localized prostate cancer (CaP) and treated with
radical retropubic prostatectomy (RRP) at the University of Pennsylvania Health System between 1991 and
2005 was reviewed. Of these patients, 756 had both a preoperative TRUS and eMRI of the prostate
performed. Prostate size was estimated using the prolate ellipsoid formula (height × width × length × π/6);
maximal height or antero-posterior (A-P) diameter was determined using a midsagittal view for TRUS and
an axial view for eMRI. Pearson's correlation, linear regression, and paired t- test were performed to
compare prostate volumes estimated via both imaging modalities. Results Average prostate size measured
with TRUS and eMRI correlated significantly with one another ( R = 0.801; P < 0.0001), demonstrating a
strong linear relationship (y = 0.891x + 2.622, R 2 = 0.642). Comparison of PSA density also demonstrated
a strong linear relationship (y = 0.811x + 0.053, R 2 = 0.765). Average prostate volume differed by 1.7 ml
(TRUS relative to eMRI), which was statistically significant based on a paired t -test ( P < 0.001). Upon
stratification of patients into three groups based on average TRUS volume (≤30, >30–60, and >60 ml),
significant correlation (0.318, 0.564, 0.650) and difference between volumes (−2.1, 4.0, 5.1 ml; P <
0.0001, P < 0.0001, P < 0.05 TRUS relative to eMRI) was maintained. Conclusions Prostate volume
estimations with TRUS and eMRI are highly correlated. It is therefore, reasonable to conclude that in the
hands of an experienced sonographer, TRUS is not only an efficient and economical examination, but also
an accurate and reproducible modality to estimate prostate size.
Contents
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Cutting for stone in augmented bladders: What is the risk of recurrence and is it impacted
by treatment modality? - Accepted Manuscript
06 Dec 2013 12:00 am
Abstract: Introduction: Bladder stones are common after bladder augmentation, often resulting in numerous
procedures for recurrence. We sought to determine whether surgical technique and stone fragmentation
were significant predictors of bladder stone recurrence after augmentation. Materials and Methods: We
conducted a retrospective review of 107 patients treated for first bladder stones at our institution. Patient
demographics, details of surgeries, stone therapy and recurrence were reviewed. Kaplan-Meier survival and
Cox proportional hazards analysis were used to determine predictors of time to first stone recurrence.
Results: Of 107 patients, 55.1% were female and 79.4% had neuropathic bladder. Patients were
augmented at a median 8.0 years old (range 2.4-22.8) and followed for a median 12.4 years (range 1.8-34).
Segments used for augmentation included ileum (72.9%), sigmoid (16.8%), cecum/ileocecum (9.4%) and
other (ureter, stomach/ileum) (1.8%). Bladder neck procedures were performed in 63.6%, catheterizable
channels in 75.7%. First stone surgery occurred at a median 3.1 years post-augmentation (range 5 months21.8 years). Endoscopy was used in 66.4%, open cystolithotomy in 33.6%. Overall, 47.7% were
fragmented. Bladder stones recurred in 47.7% patients (median recurrence time 9.5 years, range 3 months14.7 years). Recurrence risk was highest in the first 2 years (12.1% per patient per year, p=0.03).
Recurrence risk did not change with technique (endoscopic vs. open) or fragmentation, even after
controlling for surgical and clinical variables. Conclusions: Bladder stones recurred in almost half of patients
at 9 years independent of treatment technique and patient characteristics. As a high-risk group, annual KUB
films and RBUS are recommended.
Defining prostate cancer risk before prostate biopsy
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Raj P. Pal , Neil U. Maitra , J. Kilian Mellon , Masood A. Khan
Prostate cancer is the most commonly diagnosed cancer in men. At present, patients are selected for
prostate biopsy on the basis of age, serum prostate specific antigen (PSA), and prostatic digital rectal
examination (DRE) findings. However, due to limitations in the use of PSA and DRE, many patients
undergo unnecessary prostate biopsy. A further problem arises as many patients are diagnosed and treated
for indolent disease. This review of the literature highlights the strengths and weaknesses of existing
methods of prebiopsy risk stratification and evaluates promising serum, urine, and radiologic prostate
cancer biomarkers, which may improve risk stratification for prostate biopsy in the future.
Differences in prostate cancer grade, stage, and location in radical prostatectomy
specimens from United States and Japan
20 Nov 2013 01:10 pm
BACKGROUND To compared prostate cancer at radical prostatectomy between men in the United States
(US) and Japan in the modern era. METHODS Three hundred seventy consecutive totally embedded RP
cases (159 US; 211 Japan) from 2010 to 2012 were reviewed. RESULTS US men were significantly
younger (mean age 58.8 years) than Japanese men (mean age 64.6 years; P < 0.00001). Japanese patients
presented with higher PSA levels (mean = 10.9 ng/ml) compared to US patients (mean = 5.8 ng/ml,
P < 0.00001) and higher clinical stage (P = 0.003). Japanese tumors were: higher grade; larger; more
advanced stage; with increased lymphovascular invasion; and more commonly TZ in location (P < 0.00001).
In multivariate analysis, independent predictors of high tumor volume were PSA level, clinical stage, TZ
location, Gleason grade, and country of origin (Japan). Independent predictors of TZ location were clinical
stage, tumor volume, and country of origin (Japan). CONCLUSION A major factor for larger, higher grade
and stage tumors in Japanese patients is the lower prevalence of screening for prostate cancer in Japan.
Another contributing factor may be their TZ location, where they are not palpable until advanced and where
they are difficult to sample on needle biopsy possibly leading to a delay in diagnosis. The finding of a
difference in zonality of prostate cancer between US and Japanese cases is novel and may reflect
differences in biology rather than different health care practice between the groups. If this data is confirmed,
consideration should be given to TZ sampling as part of routine needle biopsies in Japanese men. Prostate
© 2013 Wiley Periodicals, Inc.
Do Erectile Dysfunction and Cardiovascular Disease Have the Same Mechanism?
20 Nov 2013 04:45 am
Does genotyping of risk-associated single nucleotide polymorphisms improve patient
selection for prostate biopsy when combined with a prostate cancer risk calculator?
22 Nov 2013 05:32 am
BACKGROUND Genome-wide association studies have identified single nucleotide polymorphisms (SNPs)
associated with higher risk of prostate cancer (PCa). This study aimed to evaluate whether published SNPs
improve the performance of a clinical risk-calculator in predicting prostate biopsy result. METHODS Three
hundred forty-six patients with a previous prostate biopsy (191 positive, 155 negative) were enrolled. After
literature search, nine SNPs were selected for their statistically significant association with increased PCa
risk. Allelic odds ratios were computed and a new logistic regression model was built integrating the clinical
risk score (i.e., prior biopsy results, PSA level, prostate volume, transrectal ultrasound, and digital rectal
examination) and a multilocus genetic risk score (MGRS). Areas under the receiver operating characteristic
(ROC) curves (AUC) of the clinical score alone versus the integrated clinic-genetic model were compared.
The added value of the MGRS was assessed using the Integrated Discrimination Improvement (IDI) and
Net Reclassification Improvement (NRI) statistics. RESULTS Predictive performance of the integrated
clinico-genetic model (AUC = 0.781) was slightly higher than predictive performance of the clinical score
alone (AUC = 0.770). The prediction of PCa was significantly improved with an IDI of 0.015 (P-value = 0.035)
and a continuous NRI of 0.403 (P-value < 0.001). CONCLUSIONS The predictive performance of the clinical
model was only slightly improved by adding MGRS questioning the real clinical added value with regards to
the cost of genetic testing and performance of current inexpensive clinical risk-calculators. Prostate © 2013
Wiley Periodicals, Inc.
Dual inhibition by S6K1 and Elf4E is essential for controlling cellular growth and invasion in
bladder cancer☆,☆☆?>
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Jong Kyou Kwon , Soon-Ja Kim , Jung Hoon Kim , Kyung Mee Lee , In Ho Chang
Purpose We investigated how dual inhibition of the molecular mechanism of mammalian target of
rapamycin (mTOR) downstream of S6K1 and the eukaryotic initiation factor 4E (eIF4E) can lead to
suppression of proliferation and progression of urothelial carcinoma. Materials and methods We
characterized the molecular mechanism of the mTOR pathway in the T24 and 5637 urothelial carcinoma
cell lines by interfering with different molecular components using rapamycin and short interfering (siRNA)
technology (S6K1 or elF4E) and analyzed the effects on molecular activation status, cell growth,
proliferation, and invasion. Results A high concentration of rapamycin (10 μM) blocked both S6K1 and
elF4E phosphorylation and inhibited cell proliferation in T24 and 5637 cells. The inhibition of both S6K1 and
elF4E phosphorylation by rapamycin reduced cell viability and proliferation more than transfection of siRNA
against S6K1 or elF4E in 5637 and T24 cells. Cells silenced for S6K1 or elF4E expression exhibited
significantly reduced cell migration and invasion compared with those of the control but inhibition of both
S6K1 and elF4E phosphorylation by rapamycin reduced cell migration and invasion more than siRNA
transfection against S6K1 or elF4E in 5637 and T24 cells. Conclusion These findings suggest that both the
mTOR pathway downstream of eukaryotic initiation factor 4E and S6K1 can be successfully inhibited,
therefore, the recurrence of bladder cancer can be prevented by high-dose rapamycin only, suggesting that
4E-BP1 might be still under mTORC1.
Editorial Board
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Editorial Comment - Uncorrected Proof
06 Dec 2013 12:00 am
The authors reviewed the risk factors associated with symptomatic VTE in a large population of patients
who underwent RP plus pelvic lymph node dissection at a single institution during 23 years. They identified
several factors associated with VTE on multivariate analysis, of which many were previously identified in
other series. However, the association between VTE and nonO blood type (OR 1.87) is a novel and
interesting finding that has not been previously studied in the RP population. Furthermore, a similar
association between nonO blood type and VTE of similar magnitude (HR 1.85) was recently reported in the
radical cystectomy population. The authors suggest that increased vWF in men with nonO blood type may
increase the risk of thrombosis. Although studies have not shown benefit to routine heparin prophylaxis al
after RP plus pelvic lymph node dissection (reference 24 in article), high risk populations such as men with
nonO blood type may warrant special consideration.
Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the
bladder: A critical analysis of 1,994 patients
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Anirban P. Mitra , Eila C. Skinner , Anne K. Schuckman , David I. Quinn , Tanya B. Dorff ,
Siamak Daneshmand
Objective The oncological basis behind the observation that females experience worse outcomes following
radical cystectomy for urothelial carcinoma of the bladder (UCB) is unclear. This study was aimed at
examining the sole effect of gender on postcystectomy UCB outcomes and identifying potential factors that
may explain the poor prognosis in females using a balanced case-control approach. Materials and methods
A review of 2,567 patients with UCB who underwent radical cystectomy identified 414 females (“cases”)
who were matched 1:1 for demographic, tumor, and treatment characteristics with 414 male counterparts
(“controls”). Cases were also compared with an independent male UCB cohort ( n = 1,166). Differences
between females vs. matched control and independent male patients with UCB were analyzed. Recurrencefree survival, cancer-specific survival, and overall survival were compared by univariable and multivariable
Cox regression models. Results Median follow-up for cases, controls, and independent control cohort was
12.2, 8.6, and 13.5 years, respectively. Females were matched to male controls for tumor and nodal stages
( P = 1.00), lymphovascular invasion and surgical margin status, age, prior intravesical treatment, and
neoadjuvant and adjuvant chemotherapy administration ( P = 0.61–1.00). Cases were also balanced with
controls for grade, p53 status, nodal yield, American Society of Anesthesiologists score, presence of
hydronephrosis, and times to diagnosis and cystectomy ( P ≥0.14). When thus matched, outcomes between
females and males were not different ( P ≥0.34). However, when compared with an independent unmatched
male control cohort, females had significantly poorer outcomes ( P ≤0.006). In this comparison, females
presented with higher tumor ( P &lt;0.001) and nodal ( P = 0.049) stages and a lesser proportion received
precystectomy intravesical therapy ( P = 0.032). Conclusions Females have similar UCB outcomes to males
when matched for demographic, clinicopathologic, and management characteristics. However, they present
with more advanced tumors, thus explaining the observation of poor outcomes.
Effects of Nonlinear Aerobic Training on Erectile Dysfunction and Cardiovascular Function
Following Radical Prostatectomy for Clinically Localized Prostate Cancer
22 Nov 2013 04:45 am
0.406). There were no significant between-group differences in any erectile function subscale (p = min per
session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as
measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes
were brachial artery flow–mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid
profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤21)
decreased by 20% in the AT group and by 24% in the UC group (difference: p 25 per group) after RP. AT
consisted of five walking sessions per week at 55–100% of peak oxygen uptake (VO2peak) for 30–60 =
Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a
randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC)
on ED prevalence in 50 men (n>0.05). Significant between-group differences were observed for changes in
FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or
PROs . In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute
period following RP.Trial registration:Clinicaltrials.gov identifier NCT00620932.This proof-of-concept trial
demonstrated that aerobic training following a novel nonlinear prescription approach incorporating highintensity training is safe and feasible and improves cardiovascular function but not erectile dysfunction in
men with localized prostate cancer in the acute period following radical prostatectomy.
Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castrationresistant prostate cancer: Implications for prior therapy in clinical trials
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Gregory R. Pond , Andrew J. Armstrong , Matthew D. Galsky , Brian A. Wood , Lance Leopold ,
Guru Sonpavde
Objectives Abiraterone acetate (AA) is a CYP17 inhibitor of androgen synthesis approved for use following
docetaxel for metastatic castration-resistant prostate cancer (mCRPC); evaluation in the pre-docetaxel
setting is ongoing. Given that the reported efficacy of AA is lower following docetaxel vs. pre-docetaxel, the
potential exists for cross resistance given docetaxel's partly androgen receptor targeting activity. The
efficacy of docetaxel following ketoconazole (KC), a weaker and nonspecific inhibitor of CYP17, may
provide some insights into this potential interaction. We retrospectively evaluated the efficacy of every 3week docetaxel with prednisone (DP) in mCRPC previously exposed to KC compared to KC-naive patients.
Materials and methods A randomized phase II trial of men with mCRPC treated with DP + AT-101 (bcl-2
inhibitor) vs. DP plus placebo was analyzed. Both arms were combined for analysis as no significant
differences were seen. Overall survival (OS), progression-free survival (PFS), objective response (ORR),
pain, and prostate-specific antigen (PSA) response rates were estimated with and without prior KC. Cox
proportional hazards regression models were used to estimate the effect of covariates on OS. Results Of
220 evaluable men, 40 (18.2%) received prior KC. The median OS with DP-based therapy of KC-naive
patients (18.3 months, 95% CI: 15.0, 24.5) and post-KC patients (17.0 months, 95% CI: 9.9, 20.4) was not
statistically different ( P = 0.20). After controlling for prognostic classifications, analyses demonstrated
consistent trends for worsening of OS after KC, with (hazard ratios (HRs) 1.33–1.46. Similar unfavorable
trends were observed for ORR, PSA declines, and PFS. Conclusions In this hypothesis-generating
analysis, patients treated with docetaxel-based chemotherapy following prior KC had numerically and
consistently worse outcomes than patients not exposed to prior KC. Although the estimated differences did
not attain statistical significance, evaluation of outcomes with docetaxel in particular, and all classes of
novel and emerging agents following AA, is of clinical importance, given its more potent androgen synthesis
inhibition compared with KC. Drug development should take into account the potential impact of previous
therapy.
Epidemiological Studies Are Important to Trigger Health Care Decisions
29 Nov 2013 04:35 am
Essential elements of personalized medicine
09 Dec 2013 01:56 am
Publication date: Available online 7 December 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Wylie Burke , Susan Brown Trinidad , Nancy A. Press
Objectives Genomic information has been promoted as the basis for “personalized” health care. We
considered the benefits provided by genomic testing in context of the concept of personalized medicine.
Materials and Methods We evaluated current and potential uses of genomic testing in health care, using
prostate cancer as an example, and considered their implications for individualizing or otherwise improving
health care. Results and Conclusions Personalized medicine is most accurately seen as a comprehensive
effort to tailor health care to the individual, spanning multiple dimensions. While genomic tests will offer
many potential opportunities to improve the delivery of care, including the potential for genomic research to
offer opportunities to improve prostate cancer screening and treatment, such advances do not in
themselves constitute a paradigm shift in the delivery of health care. Rather, personalized medicine is
based on a partnership between clinician and patient that utilizes shared decision making to determine the
best health care options among the available choices, weighing the patient’s personal values and
preferences together with clinical findings. This approach is particularly important for difficult clinical
decisions involving uncertainty and trade-offs, such as those involved in prostate cancer screening and
management. The delivery of personalized medicine also requires adequate health care access and
assurance that basic health needs have been met. Substantial research investment will be needed to
identify how genomic tests can contribute to this effort.
European Association of Urology Guidelines on Priapism
16 Nov 2013 05:25 am
Context:Priapism is defined as a penile erection that persists beyond or is unrelated to sexual interest or
stimulation. It can be classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent or
intermittent).Objective:To provide guidelines on the diagnosis and treatment of priapism.Evidence
acquisition:Systematic literature search on the epidemiology, diagnosis, and treatment of priapism. Articles
h unrelated to sexual stimulation. It is more common in patients with sickle cell disease. This article
represents the shortened EAU priapism guidelines, based on a systematic literature review. Cases of
priapism are classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent). Treatment for
ischaemic priapism must be prompt in order to avoid the risk of permanent erectile dysfunction. This is not
the case for arterial priapism.This paper summarises the first publication of the European Association of
Urology guidelines on priapism. The guidelines aim to present the most recent scientific information and
provide recommendations on diagnosis and treatment of the three forms of priapism: ischaemic, arterial,
and stuttering. h, including decompression of the corpora cavernosa by aspiration and intracavernous
injection of sympathomimetic drugs (e.g. phenylephrine). Surgical treatment is recommended for failed
conservative management, although the best procedure is unclear. Immediate implantation of a prosthesis
should be considered for long-lasting priapism. Arterial priapism is not an emergency. Selective
embolization is the suggested treatment modality and has high success rates. Stuttering priapism is poorly
understood and the main therapeutic goal is the prevention of future episodes. This may be achieved
pharmacologically, but data on efficacy are limited.Conclusions:These guidelines summarise current
information on priapism. The extended version are available on the European Association of Urology
Website (www.uroweb.org/guidelines/).Patient summary:Priapism is a persistent, often painful, penile
erection lasting more than 4 with highest evidence available were selected to form the basis of these
recommendations.Evidence synthesis:Ischaemic priapism is usually idiopathic and the most common form.
Arterial priapism usually occurs after blunt perineal trauma. History is the mainstay of diagnosis and helps
determine the pathogenesis. Laboratory testing is used to support clinical findings. Ischaemic priapism is an
emergency condition. Intervention should start within 4–6
Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer
progression
06 Dec 2013 12:54 am
INTRODUCTION Prostate cancer is the second leading cause of cancer-related death among men in North
America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive
cancers, which may lead to death. The current methods of detection include digital rectal examination and
the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately
discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic
factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in
aggressive prostate cancer. METHODS In the current study, we assessed the diagnostic and prognostic
potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray
consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy.
RESULTS Using quantitative digital imaging software, we found that ACAT1 expression was significantly
greater in cancerous cores compared to adjacent benign cores (P < 0.0001), in Gleason score (GS) ≥8
cancers versus GS≤6 cancers (P < 0.0001), GS≥8 cancers versus GS7 cancers (P = 0.001), as well as
pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate
(HR, 1.81, CI = 1.13–2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01–2.81, P = 0.0431)
including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence
analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG
positive cases did not display any differences. DISCUSSION Taken together, these findings indicate that
ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in
differentiating indolent and aggressive forms of cancer. Prostate © 2013 Wiley Periodicals, Inc.
Exercise as Treatment for Androgen Deprivation Therapy–Associated Physical Dysfunction:
Ready for Prime Time?
30 Nov 2013 04:45 am
Expression of molecular markers associated with the mammalian target of rapamycin
pathway in nonmetastatic renal cell carcinoma: Effect on prognostic outcomes following
radical nephrectomy
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Masatomo Nishikawa , Hideaki Miyake , Ken-ichi Harada , Masato Fujisawa
Objectives To evaluate the expression of multiple molecular markers involved in mammalian target of
rapamycin (mTOR) signaling pathway in renal cell carcinoma (RCC) to determine the prognostic
significance of these markers following radical nephrectomy. Material and methods The expression levels of
5 markers, including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase, and p-4E-binding
protein 1 (4E-BP1), were measured in radical nephrectomy specimens from 137 patients with nonmetastatic
RCC by immunohistochemical staining. Results During the follow-up period of this series (median, 63.5
mo), disease recurrence occurred in 59 of the 137 patients (43.0%), with a 5-year recurrence-free survival
rate of 58.3%. On Univariate analysis, expression levels of p-mTOR and p-4E-BP1, in addition to the Creactive protein level, pathological stage, and microvascular invasion, were identified as significant
predictors for disease recurrence. Of these factors, the expression of p-4E-BP1, C-reactive protein level,
and pathological T stage appeared to be independently related to recurrence-free survival on multivariate
analysis. Moreover, significant differences were observed in recurrence-free survival according to the
positive numbers of these 3 independent factors; that is, disease recurrence developed in 5 of 42 patients
with negative results for any risk factor (11.9%), 23 of 50 patients with positive results for a single risk factor
(46.0%), and 31 of 45 patients with positive results for 2 or 3 risk factors (68.8%). Conclusions The
combined evaluation of the expression levels of potential markers in the mTOR signaling pathway,
particularly p-4E-BP1, in RCC specimens with conventional prognostic parameters would contribute to the
accurate prediction of disease recurrence following radical nephrectomy for nonmetastatic RCC.
Fluorescence-enhanced Robotic Radical Prostatectomy Using Real-time
Lymphangiography and Tissue Marking with Percutaneous Injection of Unconjugated
Indocyanine Green: The Initial Clinical Experience in 50 Patients
21 Nov 2013 05:05 am
min postinjection and had 100% sensitivity, 75.4% specificity, 14.6% positive predictive value, and 100%
negative predictive value for the detection of nodal metastasis.Conclusions:FERRP is safe, feasible, and
allows for reliable prostate tissue marking and identification of sentinel lymphatic drainage in the majority of
patients. ICG sentinel nodes are highly sensitive but relatively nonspecific for the detection of nodal
metastasis.Percutaneous, robotic-guided injection of unconjugated indocyanine green is a simple and
reproducible means of performing pelvic lymphangiography. The real-time technique is highly sensitive and
avoids ionizing radiation or the need for adjunctive procedures. min postinjection. Sentinel nodes were
identified in 76% of patients at a mean time of 30 mg/ml ICG solution were injected into each lobe of the
prostate using a robotically guided percutaneous needle. After ICG was allowed to travel through the pelvic
lymphatics, lymphadenectomy was performed from the endopelvic fascia to the aortic bifurcation.Outcome
measurements and statistical analysis:Parameters describing the time course of tissue fluorescence and
pelvic lymphangiography were systematically recorded. Lymphatic packets containing fluorescent nodes
were considered sentinel.Results and limitations:Percutaneous, robotic-guided ICG injection proved
superior to cystoscope or transrectal delivery. Tissue marking was achieved in all patients, positively
identifying the prostate with uniform fluorescence relative to the obturator nerve, seminal vesicles, vas
deferens, and neurovascular pedicles at a mean time of 10 ml of a 2.5 Background:Pilot studies have
demonstrated the utility of indocyanine green (ICG) sentinel lymphadenectomy for prostate cancer. Prior
work has used ICG with radiocontrast agents injected at a separate procedure and relied on assistantcontrolled fluorescence systems, making the technique costly and cumbersome.Objective:To describe the
initial optimization and feasibility of fluorescence-enhanced robotic radical prostatectomy (FERRP) using
real-time injection of ICG for tissue marking and identification of sentinel lymphatic drainage visualized by a
fully integrated surgeon-controlled system.Design, setting, and participants:Patients with clinically localized
prostate cancer at a tertiary referral center were offered FERRP. Ten patients participated in a pilot arm in
which ICG dosing and injection technique were optimized. Fifty consecutive patients then underwent
FERRP.Surgical procedure:After development of the space of Retzius, 0.4
Gender-specific Differences in Clinicopathologic Outcomes Following Radical Cystectomy:
An International Multi-institutional Study of More Than 8000 Patients
05 Dec 2013 04:45 am
0.05).Conclusions:We found female gender to be associated with a higher risk of CSM following RC.
However, these findings do not appear to be explained by gender differences in pathologic stage, nodal
status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.We found
female gender to be associated with a higher risk of cancer-specific mortality following radical cystectomy.
However, these findings do not appear to be explained by gender differences in pathologic stage, nodal
status, or lymphovascular invasion. 0.033) and had higher rates of pathologic stage T3/T4 disease (p =
Background:The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder
(UCB) is insufficiently understood.Objective:To assess gender-specific differences in pathologic factors and
survival of UCB patients treated with radical cystectomy (RC).Design, setting, and participants:Data from
8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012
were analyzed.Outcome measurements and statistical analysis:Multivariable competing-risk regression
analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancerspecific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and
lymphovascular invasion (LVI).Results and limitations:Female patients were older at the time of RC (p
Genetic analysis of the principal genes related to prostate cancer: A review
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Maria Jesus Alvarez-Cubero , Maria Saiz , Luis Javier Martinez-Gonzalez , Juan Carlos Alvarez ,
Jose Antonio Lorente , Jose Manuel Cozar
Prostate cancer is one of the most common leading causes of cancer death in men. Attributable to many
genetic linkage and genome-wide association studies (GWAS) around the world, several high-penetrance
genetic variants have been identified. Many polymorphisms in genes, such as ELAC2 (locus HPC2), RNase
L (locus hereditary prostate cancer 1 gene [HPC1]), and MSR1 have been recognized as important genetic
factors that confer an increased risk of developing prostate cancer in many populations. A review of the
literature was then performed analyzing the roles of these and other genes in prostate cancer. Our main
challenge is optimizing the role of these genes in prostate cancer development, even trying to use these
genes as general biomarkers. The principal aim of this review is to determine the most important variants in
the principal genes related to prostate cancer and examine the differences among populations. The concept
of individualized or personalized targeted cancer therapy has gained significant attention throughout
oncology. In prostate cancer, the creation of a personalized panel of single-nucleotide polymorphisms
(SNP) biomarkers may be important for the early and accurate detection of this cancer. As a result, the
need for a good biomarker is required to detect prostate cancer earlier and to provide tools to follow
patients during the early stages of the cancer. At present, prostate cancer continues to have an unclear
etiology, which is a combination of genetic and numerous environmental factors. Among genetic factors, no
variants of the RNase L, ELAC2, or MSR1 genes have been detected with similar expression patterns in
different populations all around the world.
Geographical and Temporal Trends in Bladder Cancer Occurrence: So What?
03 Dec 2013 04:45 am
Health-related quality of life for men with prostate cancer—an evaluation of outcomes 12–
24 months after treatment
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Stephen A. Brassell , Sally I. Elsamanoudi , Jennifer Cullen , Molly E. Williams , David G.
McLeod
Objective To determine the health-related quality of life (HRQoL) impact of prostate cancer interventions at
2 years post-treatment, and between the 12- and 24-month interval, to better characterize this measure.
Materials and methods Patients treated at the Center for Prostate Disease Research between June 2003
and February 2010 were offered enrollment into a HRQoL study that entailed a baseline evaluation before
prostate biopsy and at 3, 6, 9, 12, 18, 24, and 30 months thereafter. The instruments used were the
Expanded Prostate Cancer Index Composite (EPIC), EPIC Demographic, and Medical Outcomes Study
Short-Form 36 (SF-36). A Student's t- test and ANOVA were used to examine the association between
HRQoL scores, patient demographic, and disease features. Multivariable regression models were used to
analyze change over time. Estimates of risk, corresponding confidence intervals, and P values are
presented for these longitudinal findings. Results The study group was comprised of 595 patients. African
Americans (AA) had slightly lower baseline raw scores in all EPIC and SF-36 HRQoL domains, but on
bivariate analysis, there was no statistical difference in change of scores over time. Radical prostatectomy
(RP) led to the greatest decline in urinary function. Bowel function significantly worsened with the addition of
hormone therapy (HT) to external beam radiation therapy (EBRT). Sexual bother and function had a
marked decline in all active treatment options. Despite these changes, there were no differences in overall
satisfaction. SF-36 domains were not affected by RP, whereas EBRT and EBRT + HT had universal impact.
For the 12- to 24-month interval, specifically, patients who underwent EBRT fared worse over this time
period, showing continued worsening of urinary bother, hormonal function, physical role, physical
component summary, and overall satisfaction. Patients who underwent RP did not show any further decline
in the 12- to 24-month interval, but instead showed improvement. Conclusions Because of the protracted
nature of recovery after surgery, delayed onset of effects from radiation, potential interval decline secondary
to age-related symptoms, and longevity of patients with prostate cancer, determination of long-term HRQoL
outcomes is integral. Counseling with regard to these outcomes should be balanced with oncologic
expectations from treatment.
Implications for human papillomavirus in penile cancer
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Amber Flaherty , Timothy Kim , Anna Giuliano , Anthony Magliocco , Tariq S. Hakky , Lance C.
Pagliaro , Philippe E. Spiess
Human papillomavirus infection (HPV) has been implicated in penile cancer, and although the annual
incidence is estimated to be 1,570 in the United States, there are areas of the world in which the incidence
is as much as 20-fold higher. Ample data in the literature support testing and vaccination against HPVrelated cervical cancer, but for men and penile cancer, these data are lacking. However, some preliminary
data would suggest that HPV not only plays an important role in a significant subset of patients with penile
cancer but also may be a target for penile cancer prevention as well via initiation of a vaccination program
in high-risk male populations.
Improving Outcome of Surgical Procedures Is Not Possible Without Adequate Quality
Measurement
08 Dec 2013 05:05 am
Outcome measurement allows for acknowledging differences in quality and must be used as a basis for
quality assessment, regardless of what procedure is to be assessed and improved. As urologists, we should
actively take the lead to guide this necessary and inevitable process.
In-hospital death and hospital-acquired complications among patients undergoing partial
cystectomy for bladder cancer in the United States
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Max Kates , Michael A. Gorin , Christopher M. Deibert , Phillip M. Pierorazio , Mark P.
Schoenberg , James M. McKiernan , Trinity J. Bivalacqua
Background Partial cystectomy (PC) is a therapeutic option for select patients with bladder cancer, but its
associated perioperative risks and costs are unknown. We estimated annual rates of PC in a nationally
representative sample of hospitals, and analyzed whether hospital volume affects postoperative outcomes
and costs in patients undergoing PC. Methods From the Nationwide Inpatient Sample, we selected a
weighted cohort of patients with bladder cancer who underwent PC between 2002 and 2008. Differences in
length of stay, charges, and clinical outcomes were calculated based on operative volume, and univariate
and multivariate regression models were fitted to predict in-hospital mortality (IHM) and hospital-acquired
conditions. Results A total of 10,780 patients with bladder cancer who underwent PC were identified with an
annual rate between 1457 and 1628 cases. IHM rates were 1.8%, constituting 195 patients (between 9 and
46 annually). A total of 417 patients (3.9%) experienced a “never event” complication, which Medicare no
longer reimburses. The mean annual hospital volume of patients who died was 1.7 cases/y compared with
2.4 cases/y among those without fatal complications. No cases of IHM were identified among hospitals
performing at least 5 partial cystectomies/y. In a multivariate regression model increased hospital volume
was independently associated with decreased mortality (odds ratio = 0.70, 95% confidence interval; 0.60–
0.80). Conclusions Approximately 1 in 25 patients undergoing PC experience a hospital-acquired
complication, and nearly 1 in 50 die as a result of the operation. For each additional case a hospital
performs annually, the risk of IHM decreases by 30%.
Indications for and anatomical extent of pelvic lymph node dissection for prostate cancer:
Practice patterns of uro-oncologists in North America
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Karim A. Touijer , Youness Ahallal , Bertrand D. Guillonneau
Purpose To investigate the prevailing practice of uro-oncologists regarding the indications for and extent of
pelvic lymph node dissection (PLND) for prostate cancer. Materials and methods A 9-question survey was
sent as a hyperlink by electronic mail to all members of the Society of Urologic Oncology. Participants were
asked about their surgical volume, indications for PLND, which nodal packets are dissected as delineated
on anatomical schema, and type of surgical approach. Results Of 340 members, 183 urologists (58%)
completed the survey. Of these, 43% were ≥10 years out of fellowship and 62% performed &gt;50 radical
prostatectomies per year. Of the surveyed surgeons, 45% performed PLND on all patients undergoing
radical prostatectomy. The remainder used various risk-stratification schemas. A total of 32 different
indications for PLND were reported, the most common being “intermediate risk” according to the American
Urological Association's risk classification. As to extent of PLND, 15% perform a PLND limited to the
external iliac, while 30% include the external iliac, obturator fossa, and hypogastric lymph nodes. Among
surgeons using both open and robotic approaches, 19% reported that the indication for and extent of
lymphadenectomy performed differ based on the surgical approach used. Conclusions The results of this
survey provide insight into the practice patterns of uro-oncologists regarding PLND and highlight the lack of
uniformity in determining when and how a PLND should be performed. Collaborative efforts are needed to
develop guidelines on this issue and are a necessary step toward standardization of reporting the outcomes
of surgical clinical trials.
Kenneth Hubert Slatter
05 Dec 2013 04:22 pm
Kenneth Hubert Slatter was the first consultant neurologist to be appointed in Liverpool at Walton Hospital
in 1960. He was born in Droylsden near Manchester, but his father, a bank manager, died...
Long-term oncological outcomes of men undergoing radical prostatectomy with
preoperative prostate-specific antigen <2.5 ng/ml and 2.5–4 ng/ml
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Peter Qi , Matvey Tsivian , Michael R. Abern , Lionel L. Bañez , Ping Tang , Judd W. Moul ,
Thomas J. Polascik
Objectives Prostate-specific antigen (PSA) screening has increased the detection of small, organ-confined
tumors, and studies suggest that these patients may have favorable outcomes following radical
prostatectomy (RP). To date, there are limited data available on the outcomes of patients diagnosed with
low PSA (≤4 ng/ml) who underwent RP. This study aimed to evaluate long-term oncological outcomes of
patients undergoing RP with preoperative PSA &lt;2.5 and 2.5–4 ng/ml compared with PSA 4.1–10 ng/ml.
Materials and methods Data were analyzed from 3,621 men who underwent RP between 1988 and 2010 at
our institution. Patients were stratified into 3 PSA groups: &lt;2.5 ng/ml ( n = 280), 2.5–4 ng/ml ( n = 563),
and 4.1–10 ng/ml ( n = 2,778). Patient and disease characteristics were compared. Overall, biochemical
disease-free (bDFS), and PCa-specific survivals were analyzed and compared between the groups.
Multivariable analyses were conducted using proportional hazards model. Results Compared with the 4.1–
10 ng/ml PSA group, Gleason score &gt;7, extracapsular extension, and non-organ-confined disease were
less common in patients with PSA ≤4 ng/ml (all P &lt; 0.001). The incidence of organ-confined disease was
similar between the PSA &lt; 2.5 and 2.5–4 ng/ml groups while perineural invasion ( P = 0.050) and
Gleason score ≥7 ( P = 0.026) were more common in the 2.5–4 ng/ml PSA group. Estimated 10-year overall
and PCa-specific survivals were comparable across all PSA groups, whereas bDFS was significantly lower
in PSA 4.1–10 group ( P &lt; 0.001). bDFS was not statistically different between PSA &lt;2.5 and 2.5–4
groups ( P = 0.300). 10-year bDFS were 59.0%, 70.1%, and 76.4% in PSA 4.1–10, 2.5–4, and &lt;2.5,
respectively. For the PSA ≤ 4 ng/ml groups, age, race, margin status, pathologic stage, but not PSA were
independent predictors of bDFS, whereas age, pathologic Gleason, and biochemical recurrence were
associated with overall survival. Conclusions Long-term oncological outcomes (overall, bDFS, PCa-specific
survivals) of patients presenting with low PSA (≤4 ng/ml) were excellent in this study. Compared with PSA
4.1–10 ng/ml, patients presenting with PSA ≤4 ng/ml had better bDFS outcomes. However, there was no
difference in long-term outcomes between PSA &lt;2.5 and 2.5–4 ng/ml.
Low Androgen-Induced Penile Mal-development Involves Altered Gene Expression for
Biomarkers for Smooth Muscle Differentiation and a Key Enzyme Regulating Cavernous
Smooth Muscle Cell Tone - Accepted Manuscript
06 Dec 2013 12:00 am
Abstract: Purpose:: To determine effects of low androgens in the neonatal period on biomarkers for smooth
muscle cell differentiation, Myh11 and Acta2, and Pde5A expression in the penis. Materials and Methods::
One-day-old pups were treated daily with gonadotropin releasing hormone antagonist antide (GnRH-A),
with or without dihydrotestosterone (DHT), for 1-6 days. Tissues were collected at age day 7 and adulthood
(120-day-old). Penises were examined using quantitative RT-PCR (Q-RT-PCR), Western blot, and
immunohistochemistry. Testes were assayed for intra-testicular testosterone and steroidogenic enzymes
(Cyp17ą1, StAR). Results:: GnRH-A exposure suppressed the neonatal testicular testosterone surge by 7080%. Q-RT-PCR data revealed 80-90% reductions in Cyp17ą1 and StAR protein and 40-60% reductions in
Myh11 and ACTA2, as a result of GnRH-A exposure, compared to controls. DHT co-administration
mitigated the above decreases. Western blot analyses confirmed Myh11 decrease at the protein level.
Immunohistochemistry of Acta2 confirmed cavernous smooth muscle (CSM) cell loss at the tissue level.
Additionally, GnRH-A exposure decreased Pde5a expression, and DHT co-administration mitigated the
decrease. Comparison of data between two parts of the penis body, corpora cavernosa (CC) and corpus
spongiosum (CS), showed that GnRH-A-induced decreases in Myh11, Acta2, and Pde5a expression
occurred only in CC, implying the latter as the target site for a low androgen action. Conclusion:: Low
androgens in the neonatal period, as evidenced by GnRH-A-induced suppression of the neonatal
testosterone surge and reduced steroidogenesis, altered gene expression of biomarkers for smooth muscle
cell differentiation, leading to loss of CSM cells and, consequently, penile mal-development.
Low flows after Tubularized Incised Plate (TIP) urethroplasty: increased fibrogenesis,
elastin fibers loss or none of the above? - Accepted Manuscript
06 Dec 2013 12:00 am
Abstract: Introduction:: Low flows rates are common after TIP urethroplasty but their etiology remains
unclear and may related to low urethral compliance, maybe due to abnormal collagen concentrations and/or
less elastic fibers in the healed urethral plate. We also hypothesized that inserting a preputial mucosal graft
over the dorsal raw area after the midline incision (TIPG) may avoid scarring and improve urethral
compliance. Methods:: Adult rabbits were submitted to TIP and TIPG operations according to a previously
described protocol. Tissular concentrations of collagens I/III/IV/VI/VIII/XIII were measured.
Histomorphometry was used to quantify elastic fibers in the urethra. TIP, TIPG and normal rabbits’ urethras
(controls) were compared. Results:: The mRNA concentrations for collagens I, II and XIII were similar
between controls and operated rabbits. The proportions between collagen I and III were, respectively, 1.05,
1.21 and 0.87, in controls, TIP and TIPG animals. mRNA concentrations for collagen IV and for collagens
VI/VIII tended to be higher and lower, respectively, in the operated urethras, despite showing statistical
significance only for collagen VIII in TIPG animals versus controls (p=0.02). The operated animals did not
show a lower number of elastic fibers in the urethral tissues, as compared to controls. Conclusion:: Elastic
fiber number and distribution was similar between TIP and controls, suggesting that lower concentrations of
elastic fibers are not the explanation for low urethral compliances after TIP. The raw area determined by the
dorsal urethral incision regenerated after TIP, while cicatrization with fibrosis occurred in correspondence to
the grafted areas after TIPG surgery.
Masthead
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Might Men Diagnosed with Metastatic Prostate Cancer Benefit from Definitive Treatment of
the Primary Tumor? A SEER-Based Study
20 Nov 2013 04:45 am
Definitive treatment of the primary tumor, either through surgery or radiation therapy, suggests a survival
benefit in men diagnosed with metastatic prostate cancer. These results, using a large population-based
cancer database, should serve as a foundation for future prospective trials. 129). The 5-yr OS and
predicted DSS were each significantly higher in patients undergoing RP (67.4% and 75.8%, respectively) or
BT (52.6 and 61.3%, respectively) compared with NSR patients (22.5% and 48.7%, respectively) (p = 245),
and BT (n = 7811), RP (n = Background:Few data exist regarding the impact on survival of definitive
treatment of the prostate in men diagnosed with metastatic prostate cancer (mPCa).Objective:To evaluate
the survival of men diagnosed with mPCa based on definitive treatment of the prostate.Design, setting, and
participants:Men with documented stage IV (M1a–c) PCa at diagnosis identified using Surveillance
Epidemiology and End Results (SEER) (2004–2010) and divided based on definitive treatment of the
prostate (radical prostatectomy [RP] or brachytherapy [BT]) or no surgery or radiation therapy
(NSR).Outcome measurements and statistical analysis:Kaplan-Meier methods were used to calculate
overall survival (OS). Multivariable competing risks regression analysis was used to calculate diseasespecific survival (DSS) probability and identify factors associated with cause-specific mortality
(CSM).Results and limitations:A total of 8185 patients were identified: NSR (n
Mixed High and Low Grade Bladder Tumors- Are They Clinically High or Low Grade
Tumors? - Accepted Manuscript
06 Dec 2013 12:00 am
Abstract: Purpose: The pathological grade of bladder cancer has an immense impact on patient
management and prognosis. While most bladder tumors show pure high or low grade patterns, some
tumors show a mixed pattern. We aimed to explore the incidence and the clinical significance of this
phenomenon. Materials and Methods: Between June 1998 and December 2008, 642 patients (mean age of
67.5 years) underwent transurethral resection of non-muscle invasive bladder tumors, including 156, and
454 patients with low grade (LG) and high grade (HG), respectively. In 32 patients (5%), mixed grade (MG)
tumors were found defined as LG tumors with ≤10% HG component. All patients were followed for a median
period of 60 months post-operatively. Results: The mean age, the proportion of men and the proportions of
stages Ta/T1 of patients with MG tumors were all in the middle between the HG and LG groups. The 5-year
recurrence-free survival was similar for all tumor types (56.9%, 63.8%, 66.4% for HG, LG and MG
respectively, p=0.252). The 5-year progression-free survival was significantly lower (p<0.0001) in patients
with HG (73.9%), but similar for patients with LG and MG tumors (99% and 96.9%, p=0.167). Similarly,
disease specific survival was significantly worse for patients with HG tumor (p<0.0001), but similar for
patients with LG and MG (p=0.679). Conclusions: MG tumors are found in about 5% of the non-muscle
invasive tumors. They represent a group of patients with unique clinical features. The clinical course of
patients with MG tumors parallels that of patients with LG tumors.
Moniliformediquinone induces in vitro and in vivo antitumor activity through glutathioneinvolved DNA damage response and mitochondrial stress in human hormone-refractory
prostate cancers - Accepted Manuscript
06 Dec 2013 12:00 am
Abstract: Purpose:: Hormone-refractory metastatic prostate cancer (HRMPC) is a major obstacle in clinical
treatment. Discovery and development of anti-HRMPC are the key focus in this study. Materials and
methods:: Several pharmacological and biochemical assays were used to characterize the apoptotic
signaling pathways of moniliformediquinone in HRMPC. Results:: Moniliformediquinone, a natural product,
induced cell-cycle arrest at S-phase and subsequent apoptosis in both PC-3 and DU-145, two HRMPC cell
lines. Further examination showed that moniliformediquinone induced DNA damage response associated
with the activation of Chk1, Chk2, c-Jun and JNK. The activation of mitochondrial apoptosis pathways also
occurred, including loss of mitochondrial membrane potential, cytochrome c release and activation of
caspase-9 and caspase-3. Both N-acetyl cysteine (NAC, an antioxidant and a glutathione precursor) and
trolox (an antioxidant) completely abolished moniliformediquinone-induced generation of reactive oxygen
species; however, NAC but not trolox blocked moniliformediquinone-mediated apoptosis and related
signaling cascades. Further identification showed that moniliformediquinone, by itself, did not conjugate
glutathione but significantly decreased the levels of cellular glutathione. The in vivo study also showed that
moniliformediquinone completely inhibited tumor growth with no weight loss. Conclusions:: The data
suggest that moniliformediquinone is a potential anticancer agent against HRMPC through the decrease of
cellular glutathione levels, leading to DNA damage response and an arrest of cell cycle at S phase. The
mitochondrial stress also occurs to moniliformediquinone action through loss of mitochondrial membrane
potential and cytochrome c release, which in turn induce the activation of caspase cascades and apoptotic
cell death.
Morbidity and costs of salvage vs. primary radical prostatectomy in older men
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Sandip M. Prasad , Xiangmei Gu , Keith J. Kowalczyk , Stuart R. Lipsitz , Paul L. Nguyen , Jim C.
Hu
Objectives Salvage radical prostatectomy (RP) is performed with curative intent following post-radiotherapy
recurrence for prostate cancer. While single-center salvage RP outcomes appear promising, little is known
about outcomes in the community setting in elderly men. We sought to evaluate utilization, outcomes, and
costs of salvage RP vs. primary RP in older men. Materials and methods Surveillance, Epidemiology and
End Results-Medicare linked data from 1992 to 2007 was used to identify 18,317 men aged 65 years or
older who underwent RP from 2002 to 2007. Propensity score analyses were used to compare outcomes
and costs for primary vs. salvage RP. Results Salvage RP was rare, accounting for 0.5% of RP. Men
undergoing salvage vs. primary RP were older, white, and less likely to undergo CT, bone scan and
prostate biopsy preoperatively ( P &lt; 0.05 for all). In adjusted analyses, salvage vs. primary RP was
associated with increased 30-day complications (60.1% vs. 22.7%, P &lt; 0.01), lengths of stay (mean 7 vs.
3 days, P &lt; 0.01), and hospital readmissions within 30 days (30.4% vs. 5.7%, P &lt; 0.01). The odds of
death within 90 days were higher for salvage vs. primary RP (OR 26.7, 95% CI 12.9–55.1, P &lt; 0.01). The
median expenditure for salvage RP within 6 months postoperatively was almost twice that for primary RP
(US$30,881 vs. US$12,431, P &lt; 0.01). Conclusions Metastatic workup was performed less frequently
before salvage vs. primary RP, and morbidity and mortality for salvage RP was high relative to primary RP.
Given the morbidity and high cost of salvage RP, guidelines for patient selection and selective referral may
optimize outcomes, especially in older men.
Optimal timing of early versus delayed adjuvant radiotherapy following radical
prostatectomy for locally advanced prostate cancer11Funding: This work was supported by
a Department of Defense Prostate Cancer Physician Training Award (W81XWH-08-1-0283)
presented to Dr. Hu.
09 Dec 2013 01:56 am
Publication date: Available online 7 December 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Keith J. Kowalczyk , Xiangmei Gu , Paul L. Nguyen , Stuart R. Lipsitz , Quoc-Dien Trinh , John H.
Lynch , Sean P. Collins , Jim C. Hu
Objectives Although post–radical prostatectomy (RP) adjuvant radiation therapy (ART) benefits disease that
is staged as pT3 or higher, the optimal ART timing remains unknown. Our objective is to characterize the
outcomes and optimal timing of early vs. delayed ART. Materials and methods From the Surveillance,
Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963 men with pT3N0
disease receiving early (&lt;4 mo after RP, n = 419) vs. delayed (4–12 mo after RP, n = 544) ART after RP.
Utilizing propensity score methods, we compared overall mortality, prostate cancer–specific mortality
(PCSM), bone-related events (BRE), salvage hormonal therapy utilization, and intervention for urethral
stricture. We then used the maximal statistic approach to determine at what time post-RP ART had the
most significant effect on outcomes of interest in men with pT3N0 disease. Results When compared with
delayed ART in men with pT3 disease, early ART was associated with improved PCSM (0.47 vs. 1.02
events per 100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59 events per 100
person-years; P = 0.001). Delaying ART beyond 5 months is associated with worse PCSM (hazard ratio
[HR] 2.3; P = 0.020), beyond 3 months is associated with more BRE (HR 1.6; P = 0.025), and beyond 4
months is associated higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after 9
months was associated with fewer urethral strictures (HR 0.6; P = 0.042). Conclusion Initiating ART less
than 5 months after RP for pT3 is associated with improved PCSM. Early ART is also associated with fewer
BRE and less use of salvage hormonal therapy if administered earlier than 3 and 4 months after RP,
respectively. However, ART administered later than 9 months after RP is associated with fewer urethral
strictures. Our population-based findings complement randomized trials designed with fixed ART timing.
Outcomes after radical prostatectomy for patients with clinical stages T1-T2 prostate cancer
with pathologically positive lymph nodes in the prostate-specific antigen era
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Ryan P. Dorin , Gary Lieskovsky , Adrian S. Fairey , Jie Cai , Siamak Daneshmand
Objectives To evaluate the outcomes of radical prostatectomy (RP) and pelvic lymph node dissection
(PLND) for clinically organ confined prostate cancer (CaP) with regional lymph node metastases (pN1)
treated in the era of prostate-specific antigen (PSA) screening. Materials and methods A single institution
cohort of 2,487 men with cT1-T2 CaP treated with open radical prostatectomy and pelvic lymph node
dissection between 1988 and 2008 were analyzed. Kaplan-Meier and Cox proportional regression models
were used to analyze overall survival (OS), clinical recurrence-free survival (cRFS), and biochemical
recurrence-free survival (bRFS). Results Overall, 150 out of 2,487 patients (6%) had pN1 disease, with a
median follow-up of 10.4 years. The predicted 10-year OS, cRFS, and bRFS rates for patients with pN0 and
pN1 were 86% and 74% (Log rank P &lt; 0.001), 97% and 84% (Log rank P &lt; 0.001), and 88% and 57%
(Log rank P &lt; 0.001), respectively. In the subset of pN1 patients treated with surgery only ( n = 49), the
predicted 10-year OS, cRFS, and bRFS rates were 81%, 80%, and 59%, respectively. Exploratory
univariate regression analysis showed that age ( P = 0.003), total number of lymph nodes identified ( P =
0.040), and total number of positive lymph nodes identified ( P = 0.004) were associated with OS. Total
number of positive lymph nodes (LNs) identified was also significantly associated with cRFS ( P = 0.05).
Conclusions The incidence of pN1 in patients with cT1-T2 CaP treated with surgery in the era of PSA
screening was low. RP and PLND demonstrated therapeutic efficacy in a subset of pN1 patients treated
with surgery alone.
Outcomes in patients with metastatic renal cell cancer treated with individualized sunitinib
therapy: Correlation with dynamic microbubble ultrasound data and review of the literature
09 Dec 2013 01:56 am
Publication date: Available online 7 December 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Georg A. Bjarnason , Bishoy Khalil , John M. Hudson , Ross Williams , Laurent M. Milot , Mostafa
Atri , Alex Kiss , Peter N. Burns
Background Increased sunitinib exposure (area under the curve) is associated with better outcome in
metastatic renal cell cancer. Recommendations for dose modification do not take this into account. A
treatment strategy, based on individual patient toxicity, was developed to maximize dose and minimize time
without therapy for patients who could not tolerate the standard sunitinib schedule of 50 mg given for 28
days with a 14-day break (50 mg, 28/14). Methods A single-center retrospective review was conducted on
patients with metastatic renal cell cancer treated from October 2005 to March 2010. Dose/schedule
modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and gastrointestinal) at≤grade
2. DSM-1 was 50 mg, 14 days on/7 days off with individualized increases in days on treatment. DSM-2 was
50 mg, 7 days on/7 days off with individualized increase in days on treatment. DSM-3 was 37.5 mg with
individualized 7-day breaks. DSM-4 was 25 mg with individualized 7-day breaks. Multivariable analysis was
performed for outcome as a function of patient and treatment variables. Results Overall, 172 patients were
included in the analysis. Most patients had clear cell histology (79.1%) with sunitinib given as a first-line
therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a progression-free survival (PFS) (10.9–
11.9 mo) and overall survival (OS) (23.4–24.5 mo) that was significantly better than the PFS (5.3 mo; P
&lt;0.001) and OS (14.4 mo; P = 0.03 and 0.003) for the standard schedule (50 mg, 28/14). DCE-US in a
subset of patients showed that maximum antiangiogenic activity was achieved after 14 days on therapy.
Conclusions Individualized sunitinib scheduling based on toxicity may improve PFS and OS. This
hypothesis is supported by several other respective data that are reviewed. A confirmatory prospective trial
is ongoing.
Overactive Bladder and Mental Health Symptoms in Recently Deployed Women Veterans Accepted Manuscript
06 Dec 2013 12:00 am
Abstract: Purpose: Our objectives were to estimate the prevalence of current overactive bladder (OAB)
symptoms in recently-deployed women veterans, and to determine if OAB symptoms were associated with
problems commonly reported after deployment, including mental health symptoms and prior sexual assault.
Materials and Methods: Baseline data were analyzed from a nationwide cohort study of urogenital
symptoms in women veterans. Women returning from Iraq or Afghanistan deployment in the prior two years
and ending military service were eligible. Self-reported data were collected by computer-assisted telephone
interview. OAB and mental health conditions were identified using standardized definitions and validated
urinary and mental health instruments. Associations between OAB and depression, post-traumatic stress
disorder (PTSD), anxiety and sexual assault were assessed in separate logistic regression models using
propensity scores to adjust for confounding. Results: The 1702 participants had mean (SD) age of 31.1
(8.4) years and were racially/ethnically diverse. Three hundred seventy-five (22%, 95% CI (20.1%, 24.1%))
reported OAB. Mental health outcomes included PTSD (19%), anxiety (21%), depression (10%), and prior
sexual assault (27%); all were associated with OAB (adjusted OR [95% CI] = 2.7 [2.0, 3.6], 2.7 [2.0, 3.5],
2.5 [1.5, 4.3], and 1.4 [1.1, 1.9] respectively). Conclusions: OAB symptoms occurred in 22% of recentlydeployed women veterans and were associated with self-reported mental health symptoms and traumatic
events, including prior sexual assault. Screening and evaluation for bothersome urinary symptoms and
mental health problems in women veterans presenting for primary and urologic care after deployment
appears warranted.
PCA3 sensitivity and specificity for prostate cancer detection in patients with abnormal PSA
and/or suspicious digital rectal examination. First Latin American experience
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Christian G. Ramos , Raul Valdevenito , Ivonne Vergara , Patricio Anabalon , Catherine Sanchez
, Juan Fulla
Introduction Prostate Cancer Gene 3 (PCA3) is a recently described and highly specific urinary marker for
prostate cancer (CaP). Its introduction in clinical practice to supplement low specificity of prostate specific
antigen (PSA) can improve CaP diagnosis and follow-up. However, before its introduction, it is necessary to
validate the method of PCA3 detection in distinct geographic populations. Objectives Our aim was to
describe for the first time in Latin America, the application of the PROGENSA PCA3 assay for PCA3
detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate
biopsy. Materials and methods Sixty-four Chilean patients (mean age, 64 years) with indication of prostate
biopsy because of elevated PSA and/or suspicious digital rectal examination (DRE) were prospectively
recruited. PCA3 scores were assessed from urine samples obtained after DRE, before biopsy, and
compared with PSA levels and biopsy outcome. Results The median PSA value and mean PCA3 score
were 5.8 ng/ml and 31.7, respectively. Using a cutoff PCA3 score of 35, the sensitivity and specificity for
detecting CaP were 52% and 87%, respectively. The receiver operating characteristic (ROC) curve analysis
showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA, for the same group of patients. In
patients with previous negative biopsy, PCA3 specificity increased by 2.2%. Conclusions This is the first
report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those
reported in other populations in the literature, demonstrating the reproducibility of the test. PCA3 score was
highly specific and we specially recommend its use in patients with persistent elevated PSA and prior
negative biopsies.
Pathologic T0 Following Radical Cystectomy with or without Neoadjuvant Chemotherapy: A
Useful Surrogate - Accepted Manuscript
02 Dec 2013 12:00 am
Abstract: Purpose:: Several large randomized controlled trials have provided evidence that neoadjuvant
chemotherapy (NC) improves outcomes in patients with muscle-invasive urothelial bladder cancer (MIBC)
who undergo radical cystectomy (RC). We sought to analyze the study design, methods and observations
in these trials to identify patient subgroups that appeared most likely to benefit and discover distinguishing
features from those groups that did not obtain improved outcomes. Materials and Methods:: We analyzed
the initial and updated methods and results of the four main prospective trials of NC (SWOG, MRC, and
Nordic I and II) and subsequent meta-analyses that have been the basis for advocating the use of NC in all
patients with MIBC who undergo RC. Results:: The group that demonstrated the greatest apparent benefit
were those patients who were free of cancer at the time of RC (pT0). These patients had markedly
improved overall and disease-specific survivals compared to those with residual disease. However, these
improvements occurred regardless of whether downstaging from MIBC to pT0 was seen with transurethral
resection (TUR) alone (control group) or with TUR+NC. Thus, the major benefit from NC appeared to be the
greater number of patients achieving pT0 in the chemotherapy group. In focusing on this, we explored
limitations in these studies which may have influenced these outcomes. We also considered the potential
for overtreatment of patients not likely to benefit from chemotherapy regimens. Finally, we employed risk
stratification techniques to offer a decision tree model in the selection of patients for NC that conceivably
could maximize oncologic outcomes and minimize overtreatment. Conclusions:: In the four main NC trials
and their subsequent meta-analyses, pT0 patients in each group experienced similar survival, far exceeding
those in both groups that did not achieve pT0 status. The benefit from NC appeared to be the larger number
of patients than in the TUR-only group that were downstaged to pT0, suggesting that variables other than
NC may have influenced outcomes. Therefore, employing strategies to selectively administer NC to certain
at-risk patients has the potential to maintain improved bladder cancer outcomes while reducing
overtreatment and its associated toxicities.
Pathological characteristics and prognostic effect of peritumoral capsule penetration in renal
cell carcinoma after tumor enucleation
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Andrea Minervini , Maria Rosaria Raspollini , Agostino Tuccio , Claudio Di Cristofano ,
Giampaolo Siena , Matteo Salvi , Gianni Vittori , Arcangelo Sebastianelli , Alberto Lapini , Sergio Serni ,
Marco Carini
Objective To evaluate the pathological characteristics of peritumoral capsule (PC) and the prognostic effect
of capsule penetration on tumor recurrence in patients treated with tumor enucleation for clinically
intracapsular renal cell carcinomas (RCCs). Methods and materials PC status was analyzed in 304
consecutive patients with single intracapsular RCC. Degree and side of capsule penetration if present were
evaluated. Mean (median, range) follow-up was 49 months (46, 25–69). Local recurrence rate, progressionfree survival (PFS), and cancer-specific survival were the main outcomes. Statistical analyses included the
Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression models. Results
Overall, 51% of RCCs had intact PC and free from neoplastic invasion (PC−), 34.9% had capsular
penetration on the parenchymal side (PCK), and 14.1% had tumor invasion on the perirenal fat tissue side
(PCF). None of the patients had positive surgical margins. The 5-year PFS rates for tumors PC−, PCK, and
PCF were 97.5%, 96.7%, and 77.1%, respectively ( P &lt;0.0001). The multivariate Cox model showed PCF
to be the sole significant independent predictor of PFS, whereas patients who had PCK did not present a
significant increased risk in developing recurrence. Conclusions Tumor enucleation is an oncologically safe
nephron-sparing surgery technique. PCF is a significant and independent predictor of tumor recurrence in
patients with clinically intracapsular RCCs scheduled for nephron-sparing surgery. PCK does not predict the
risk of recurrence.
Periprostatic adipose tissue from obese prostate cancer patients promotes tumor and
endothelial cell proliferation: A functional and MR imaging pilot study
25 Nov 2013 10:13 am
BACKGROUND Obesity, particularly visceral adiposity, confers a worse prognosis for prostate cancer
(PCa) patients, and increasing periprostatic adipose (PPA) tissue thickness or density is positively
associated with more aggressive disease. However, the cellular mechanism of this activity remains unclear.
Therefore, in this pilot study, we assessed the functional activity of PPA tissue secretions and established a
biochemical profile of PPA as compared to subcutaneous adipose (SQA) tissues from lean, overweight and
obese PCa patients. METHODS Adipose tissues were collected from PCa patients undergoing surgical
prostate removal. Tissues were analyzed by histologic and magnetic resonance (MR) techniques. Explant
tissue culture secretions were used in proliferation assays on PCa and endothelial cells. RESULTS PPA
secretions obtained from obese patients were significantly more pro-proliferative in both PCa and
endothelial cells as compared to PPA obtained from lean or overweight men and SQA tissues. Consistent
with this, PPA microvessel density was increased, and the T2 relaxation time was decreased, compared to
SQA tissues, and we observed a modest, inverse correlation between the T2 and tumor stage. Moreover,
the ratio of unsaturated to saturated fatty acids, obtained using MR spectroscopy, showed a modest,
inverse correlation with Gleason score. CONCLUSIONS These pilot data show that PPA stimulates PCa
cell proliferation and angiogenesis and that obesity intensifies this activity, thus generating a mechanistic
hypothesis to explain the worse prognosis observed in obese PCa patients. Our pilot study also shows that
MR technology may be useful in further elucidating the relationship between obesity and PCa progression.
Prostate © 2013 Wiley Periodicals, Inc.
Pirin down-regulates the EAF2/U19 protein and alleviates its growth inhibition in prostate
cancer cells
23 Nov 2013 03:30 am
BACKGROUND The tumor suppressor ELL associated factor 2 (EAF2/U19) has been reported to induce
apoptosis of LNCaP cells and suppress AT6.1 xenograft prostate tumor growth. EAF2/U19 expression level
is down-regulated in advanced human prostate cancer. EAF2/U19 is also a putative transcription factor with
a transactivation domain and capability of sequence-specific DNA binding. Identification of binding partners
and regulators of EAF2/U19 is essential to understand its function in regulating apoptosis/survival of
prostate cancer cells. METHODS Through a yeast two-hybrid screening system, we identified Pirin as a
binding partner of EAF2. We further determined the interaction between epitope-tagged EAF2/U19 and
Pirin by co-immunoprecipitation in mammalian cells. The effect of Pirin on EAF2/U19 inhibition of LNCaP
growth was assayed by colony formation. RESULTS Pirin co-immunoprecipitated with EAF2/U19 and the
overexpressed Pirin decreased the expression level of EAF2/U19 protein in prostate cancer cell lines
LNCaP and PC3. Furthermore, overexpression of EAF2/U19 suppressed LNCaP colony formation, and coexpression of Pirin significantly blocked the growth inhibition induced by EAF2/U19 overexpression.
CONCLUSION Pirin is a newly identified binding partner of EAF2/U19 capable of down-regulating
EAF2/U19 protein and alleviating its inhibition of prostate cancer cell survival/proliferation. Pirin may play an
important role involved in EAF2/U19 function as an androgen-responsive gene and tumor repressor.
Prostate © 2013 Wiley Periodicals, Inc.
Practice patterns and resource utilization for infants with bladder exstrophy: a national
perspective - Accepted Manuscript
02 Dec 2013 12:00 am
Abstract: Purpose:: Substantial variability exists in bladder exstrophy (BE) care, and little is known about
costs associated with BE. We aim to define the care patterns and first-year cost for BE patients at select
free-standing children’s hospitals in the United States. Materials and Methods:: The Pediatric Health
Information System (PHIS) database was used to identify BE patients born between 1/99 and 12/10 whose
primary closure occurred in the first 120 days of life (DOL). Demographic, surgical, postoperative, and cost
data for all encounters were assessed. A multivariable linear regression was used to examine the
association between patient, surgeon, and hospital characteristics and costs. Results:: Of the 381 patients
who underwent primary closure within the first 120 DOL, 279 (73%) had this done within 3 DOL. 119 (31%)
patients received pelvic osteotomies, including 51/279 (18%) of those closed within DOL 3, 38/67 (56%) of
those closed between DOL 4-30 and 30/35 (86%) of those closed between DOL 31-120 (p=0.0017). The
median inflation-adjusted first-year cost (US$) per patient was $66,577 [IQR: 45,335-102,398]. The
presence of non-renal comorbidity and primary closure after 30 DOL were associated with 24% and 53%
increased first-year costs, respectively. Increasing post-closure length of stay (LOS) was associated with
increased costs. Conclusions:: At select freestanding U.S. children’s hospitals, the majority of bladder
closures occur within the first 3 DOL. Most, but not all, patients closed after the neonatal period underwent
osteotomy. The presence of non-renal comorbidity and increasing postoperative LOS were associated with
increased costs.
Precision medicine for metastatic renal cell carcinoma11Disclosures: Guru Sonpavde, MD:
Research support from Novartis, Pfizer, and speaker or advisory board for Novartis, Pfizer,
and GSK. Toni K. Choueiri, MD: Research support from Pfizer. Advisory board: Pfizer,
Novartis, Aveo, GSK, Bayer/Onyx, and Genentech. No speakers bureau.
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Guru Sonpavde , Toni K. Choueiri
Objectives This review provides a broad overview of emerging data that provide hope that rational precision
medicine for metastatic renal cell carcinoma (RCC) may be possible. Methods PubMed and major
conferences were searched for studies reporting potential predictive biomarkers for the therapy of
metastatic RCC. Results The availability of multiple new agents for the therapy of advanced RCC poses
new challenges in terms of optimal selection of patients for the appropriate drug. Prognostic stratification
based on routine histopathologic, clinical and laboratory factors have been utilized to broadly select
individuals based, i.e. high-dose interleukin (IL)-2 or vascular endothelial growth factor (VEGF) inhibitors for
good and intermediate risk patients and temsirolimus for poor risk patients. While multiple candidate
predictive molecular biomarkers suggest that rational selection of patients for high-dose interleukin (IL)-2,
and VEGF and mammalian target of rapamycin (mTOR) inhibitors may be possible, none have been
validated for use in the clinic. Tumor heterogeneity and standardization of tissue collection and analysis are
massive challenges that need to be addressed. Predictive molecules derived from tumor tissue, plasma and
host tissue may all be predictive for therapeutic benefit. Moreover, gene expression may be modulated by
multiple factors including epigenetics, transcription factors and post-transcriptional and post-translational
modifications. Indeed, study of the interaction of molecular factors from all of these sources with
environmental and clinical factors may be necessary to develop a unified profile composed of a panel of
factors predictive of benefit from specific agents (i.e. sustained response, limited toxicity and overall a
positive benefit/risk ratio). Conclusions Conducting clinical trials with 1) prospective incorporation of
promising candidate predictive molecular biomarkers, 2) novel biomarkers endpoints, and 3) mandatory
biopsies of metastatic sites at different time points on therapy, are potential important steps in developing
the concept of “the right medication for the right patient”.
Preoperative estimated glomerular filtration rate predicts overall mortality in patients
undergoing radical prostatectomy
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Matthew K. Tollefson , Stephen A. Boorjian , Matthew T. Gettman , Laureano J. Rangel , Eric J.
Bergstralh , R. Jeffrey Karnes
Background Assessment of overall health is a critical component in the evaluation of patients presenting
with clinically localized prostate cancer. Estimated glomerular filtration rate (eGFR) has been associated
with increased risk of cardiovascular and overall mortality. Therefore, the objective of our study was to
evaluate the impact of baseline renal function on oncologic outcomes and overall survival following radical
prostatectomy. Materials and methods We identified 10,099 patients who underwent radical prostatectomy
at our institution from 1990 to 2004 with a preoperative serum creatinine available for analysis. eGFR was
calculated by the chronic kidney disease-epidemiology formula (CKD-EPI) and reported as ml/min per 1.73
m2. Patients were then classified according to their eGFR: &lt;30, 30–59, 60–89, 90–119, and 120–150
ml/min/1.73 m2. Multivariate Cox proportional hazard regression models were used to analyze the impact of
eGFR on postoperative outcomes. Results At the time of surgery, 25 patients (0.1%) had an eGFR &lt;30
ml/min/1.73 m2, 2,398 (23.7%) between 30 and 60, 7,097 (70.3%) between 60 and 90, and 605 (6.0%)
patients had an eGFR &gt;90. eGFR was not associated with oncologic outcomes, including biochemical
recurrence, systemic progression or cancer-specific survival ( P &gt; 0.05 for all). However, eGFR was
strongly associated with all-cause mortality and non-prostate cancer death. On multivariate analysis, after
controlling for age, BMI, prostate-specific antigen doubling time (PSA), Gleason score, and clinical stage,
eGFR remains a statistically significant predictor of all-cause mortality. Conclusions Assessment of eGFR is
an important metric in the overall evaluation of patient health and should be considered in combination with
patient age and other medical comorbidities when selecting the initial treatment of prostate cancer. While
prostate cancer-specific outcomes do not appear to be impacted by renal function, overall survival is
decreased in those with lower and higher than normal eGFR.
Presence of positive surgical margin in patients with organ-confined prostate cancer equals
to extracapsular extension negative surgical margin. A plea for TNM staging system
reclassification
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Firas Abdollah , Maxine Sun , Nazareno Suardi , Andrea Gallina , Umberto Capitanio , Marco
Bianchi , Manuela Tutolo , Nicola Fossati , Fabio Castiglione , Massimo Freschi , Pierre Karakiewicz ,
Patrizio Rigatti , Francesco Montorsi , Alberto Briganti
Background To test the hypothesis that patients with pT2 and positive surgical margins (SM) have a similar
biochemical-recurrence (BCR) risk to patients with pT3a, and negative SM. Moreover, we examined the
effect of incorporating positive SM as a higher stage on the discrimination accuracy of the current TNM
staging system. Materials and methods We evaluated 1,503 prostate cancer patients treated with radical
prostatectomy, between 1998 and 2010. Only individuals with pT2N0 or pT3aN0, without neoadjuvant
and/or adjuvant therapy, were included. Cox regression analyses tested the relationship between SM status
(negative [R0] vs. positive [R1]) and BCR rate, after stratification according to T stage. Predictive accuracy
of the current T stage and of a novel T stage, which consider positive SM as a higher stage, was quantified
with Harrell's concordance index. Results Positive SM rate was 20.3%. The 5-year BCR rates were 96%,
82%, 78%, and 62% for patients with, respectively, pT2R0, pT2R1, pT3aR0, and pT3a1 (all P ≤ 0.03). In
multivariable analyses, the BCR rate was 3.6-, 2.5-, and 6.0-fold higher (all P &lt; 0.001) in patients with,
respectively, pT2R1, pT3aR0, and pT3aR1 stage relative to patients with pT2R0 stage. The maximum
univariable (14.1%) and multivariable (6.9%) discrimination accuracy gains were observed, when tumor
stage was stratified into pT2R0 vs. pT2R1/pT3R0 vs. pT3R1. Conclusions The presence of positive SM at
radical prostatectomy (RP) specimen substantially increases the BCR risk. Patients with pT2R1 have
similar BCR risk to patients with pT3aR0. Considering these patients as 1 category substantially improves
the discrimination accuracy of the current TNM staging system.
Primary spermatic cord tumors: Disease characteristics, prognostic factors, and treatment
outcomes
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Dayron Rodríguez , Glen W. Barrisford , Alejandro Sanchez , Mark A. Preston , Evgeniy I.
Kreydin , Aria F. Olumi
Introduction Experience with management of spermatic cord tumors (SCTs) is uncommon. We utilized a
large population-based cancer registry to characterize the demographic, pathological, treatment
characteristics, and outcomes of SCTs. Material and methods The Surveillance, Epidemiology, and End
Results database (1973–2007) was queried. Results From the database, 362 patients were identified with
SCT. The annual incidence of SCT was 0.3 cases per million and did not change over time. The most
common histologic types were liposarcoma (46%), leiomyosarcoma (20%), histiocytoma (13%), and
rhabdomyosarcoma (9%). The median age of diagnosis for rhabdomyosarcomas was (26.3 y), whereas for
other SCTs, it was (64.7 y) ( P &lt;0.001). On multivariate analysis, a worse outcome was observed with
undifferentiated tumor grade, distant disease, positive lymph nodes, and leiomyosarcoma or histiocytoma
cell histology. Conclusion We describe the largest cohort of SCT studied to date. Liposarcoma was most
common, while leiomyosarcoma and histiocytoma histologic subtypes were observed to be the most
aggressive. Multivariate analysis revealed that tumor grade, stage, histologic type, and lymph node
involvement were independently predictive of prognosis.
Prognostic significance of primary Gleason pattern in Japanese men with Gleason score 7
prostate cancer treated with radical prostatectomy
09 Dec 2013 01:56 am
Publication date: November 2013
Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8
Author(s): Hideaki Miyake , Mototsugu Muramaki , Junya Furukawa , Hirokazu Tanaka , Taka-aki Inoue ,
Masato Fujisawa
Objectives To evaluate the significance of the primary Gleason pattern in patients with Gleason score (GS)
7 prostate cancer treated with radical prostatectomy. Materials and methods This study included 959
consecutive Japanese men who underwent radical prostatectomy without neoadjuvant therapies and were
subsequently diagnosed as having GS 7 prostate cancer based on the modified International Society of
Urological Pathology (ISUP) 2005 Gleason grading system. Results Of these 959 patients, 666 (69.4%) and
293 (30.6%) had GS 3+4 and GS 4+3 tumors, respectively. There were significant differences in the
prostate-specific antigen (PSA) level, biopsy GS, pathologic T stage, lymphatic invasion, microvenous
invasion, and perineural invasion between these 2 groups. During the mean observation of 48.9 months,
biochemical recurrence occurred in 211 patients (22.0%), and there was a significant difference in the
biochemical recurrence-free survival between patients with GS 3+4 tumors and those with GS 4+3 tumors.
Of several factors examined, biochemical recurrence-free survival was significantly associated with the PSA
level, biopsy Gleason score, capsular penetration, seminal vesicle invasion, surgical margin status,
lymphatic invasion, microvenous invasion, perineural invasion, and primary Gleason pattern, among which
the PSA level, capsular penetration, seminal vesicle invasion, and surgical margin status, but not primary
Gleason pattern, appeared to be independent predictors of biochemical recurrence. Conclusions Despite
the lack of an independent significance, primary Gleason pattern based on the modified ISUP 2005
Gleason grading system is shown to be significantly associated with the biochemical outcome of Japanese
men with GS 7 prostate cancer.
Prostate angiogenesis in development and inflammation
30 Nov 2013 02:39 pm
BACKGROUND Prostatic inflammation is an important factor in development and progression of
BPH/LUTS. This study was performed to characterize the normal development and vascular anatomy of the
mouse prostate and then examine, for the first time, the effects of prostatic inflammation on the prostate
vasculature. METHODS Adult mice were perfused with India ink to visualize the prostatic vascular anatomy.
Immunostaining was performed on the E16.5 UGS and the P5, P20, and adult prostate to characterize
vascular development. Uropathogenic E. coli 1677 was instilled transurethrally into adult male mice to
induce prostate inflammation. RT-PCR and BrdU labeling was performed to assay anigogenic factor
expression and endothelial proliferation, respectively. RESULTS An artery on the ventral surface of the
bladder trifurcates near the bladder neck to supply the prostate lobes and seminal vesicle. Development of
the prostatic vascular system is associated with endothelial proliferation and robust expression of proangiogenic factors Pecam1, Tie1, Tek, Angpt1, Angpt2, Fgf2, Vegfa, Vegfc, and Figf. Bacterial-induced
prostatic inflammation induced endothelial cell proliferation and increased vascular density but surprisingly
decreased pro-angiogenic factor expression. CONCLUSIONS The striking decrease in pro-angiogenic
factor mRNA expression associated with endothelial proliferation and increased vascular density during
inflammation suggests that endothelial response to injury is not a recapitulation of normal development and
may be initiated and regulated by different regulatory mechanisms. Prostate © 2013 Wiley Periodicals, Inc.
Prostate-specific antigen growth rate constant after first-line cytotoxic chemotherapy in
metastatic castration-resistant prostate cancer: A monoinstitutional experience
09 Dec 2013 01:56 am
Publication date: Available online 13 November 2013
Source:Urologic Oncology: Seminars and Original Investigations
Author(s): Giuseppe Colloca , Antonella Venturino , Gianfranco Addamo , Riccardo Ratti , Zaira Coccorullo ,
Graziano Caltabiano , Giorgio Viale , Domenico Guarneri
Objective Validation in clinical practice, after first-line chemotherapy (CT) of metastatic castration-resistant
prostate cancer (PC), of prostate-specific antigen growth rate constant logarithm (PSA-G), calculated by a
formula developed by Stein et al. in comparison with PSA decrease (PSA-D), calculated as recommended
by PCWG2. Patients and methods This study is a retrospective monoinstitutional assessment of PSA-G
and PSA-D after 12 weeks from the beginning of first-line cytotoxic CT in 49 patients with metastatic
castration-resistant PC treated from 2006 to 2011, and whose pre-CT PSA and post-CT PSA
determinations have been measured at specific time points. The 12-week PSA was measured at 80 to 91
days from the beginning of CT. Results PSA-G exhibited a significant correlation with overall survival by
Mann-Whitney U test and by linear regression, whereas PSA-D did only at the first test. After multivariate
analysis, PSA-G was the only posttreatment measure to predict overall survival. Conclusion PSA-G
appears a reliable surrogate end point after first-line cytotoxic CT outside of clinical trials. A cutoff value of
PSA-G post-CT higher than−2.4 could be considered suggestive for moving to another treatment.
Re: Aflibercept versus Placebo in Combination with Docetaxel and Prednisone for
Treatment of Men with Metastatic Castration-Resistant Prostate Cancer (VENICE): A Phase
3, Double-Blind Randomised Trial - Uncorrected Proof
04 Dec 2013 12:00 am
I. F. Tannock, K. Fizazi, S. Ivanov, C. T. Karlsson, A. Fléchon, I. Skoneczna, F. Orlandi, G. Gravis, V.
Matveev, S. Bavbek, T. Gil, L. Viana, O. Arén, O. Karyakin, T. Elliott, A. Birtle, E. Magherini, L. Hatteville, D.
Petrylak, B. Tombal and M. Rosenthal; VENICE Investigators
Re: Age-Related Prevalence of Low Testosterone in Men with Spinal Cord Injury Uncorrected Proof
04 Dec 2013 12:00 am
W. A. Bauman, M. F. Fountaine and A. M. Spungen James J. Peters VA Medical Center, Bronx, New York
Re: Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer - Uncorrected
Proof
04 Dec 2013 12:00 am
C. Parker, S. Nilsson, D. Heinrich, S. I. Helle, J. M. O’Sullivan, S. D. Fosså, A. Chodacki, P. Wiechno, J.
Logue, M. Seke, A. Widmark, D. C. Johannessen, P. Hoskin, D. Bottomley, N. D. James, A. Solberg, I.
Syndikus, J. Kliment, S. Wedel, S. Boehmer, M. Dall’Oglio, L. Franzén, R. Coleman, N. J. Vogelzang, C. G.
O’Bryan-Tear, K. Staudacher, J. Garcia-Vargas, M. Shan, Ø. S. Bruland and O. Sartor; ALSYMPCA
Investigators
Re: American Geriatrics Society Identifies Five Things that Healthcare Providers and
Patients Should Question - Uncorrected Proof
02 Dec 2013 12:00 am
AGS Choosing Wisely Workgroup American Geriatrics Society, New York, New York
Re: Autonomic Nervous Control of the Urinary Bladder - Uncorrected Proof
04 Dec 2013 12:00 am
P. Ochodnicky, B. Uvelius, K. E. Andersson and M. C. Michel Department of Pharmacology and
Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Re: Clomiphene Citrate in the Management of Male Infertility - Uncorrected Proof
02 Dec 2013 12:00 am
L. W. Roth, A. R. Ryan and R. B. Meacham Department of Obstetrics and Gynecology, University of
Colorado at Denver School of Medicine, Aurora, Colorado
Re: Coenzyme Q10 and Male Infertility: A Meta-Analysis - Uncorrected Proof
02 Dec 2013 12:00 am
R. Lafuente, M. González-Comadrán, I. Solà, G. López, M. Brassesco, R. Carreras and M. A. Checa
Andrology Laboratory, Centro de Infertilidad y Reproducción Humana, Clínica Corachan, Asociación
Nacional de Clínicas de Reproducción Asistida, Barcelona, Spain
Re: Determinants of Testosterone Recovery after Bariatric Surgery: Is it Only a Matter of
Reduction of Body Mass Index? - Uncorrected Proof
02 Dec 2013 12:00 am
M. Luconi, J. Samavat, G. Seghieri, G. Iannuzzi, M. Lucchese, C. Rotella, G. Forti, M. Maggi and E.
Mannucci Department of Clinical Physiopathology, Endocrinology Unit, University of Florence, Florence,
Italy
Re: Docetaxel and Atrasentan versus Docetaxel and Placebo for Men with Advanced
Castration-Resistant Prostate Cancer (SWOG S0421): A Randomised Phase 3 Trial Uncorrected Proof
02 Dec 2013 12:00 am
D. I. Quinn, C. M. Tangen, M. Hussain, P. N. Lara, Jr., A. Goldkorn, C. M. Moinpour, M. G. Garzotto, P. C.
Mack, M. A. Carducci, J. P. Monk, P. W. Twardowski, P. J. Van Veldhuizen, N. Agarwal, C. S. Higano, N. J.
Vogelzang and I. M. Thompson, Jr.
Re: Effects of PRM Rehabilitation on PFM Function and Morphology in Older Women Uncorrected Proof
02 Dec 2013 12:00 am
S. J. Madill, S. Pontbriand-Drolet, A. Tang and C. Dumoulin School of Physical Therapy, University of
Saskatchewan, Saskatoon, Saskatchewan, Canada
Re: High-Intensity Diode Laser in Combination with Bipolar Transurethral Resection of the
Prostate: A New Strategy for the Treatment of Large Prostate (>80 ml) - Uncorrected Proof
02 Dec 2013 12:00 am
C. H. Chen, P. H. Chiang, W. C. Lee, Y. C. Chuang, C. H. Kang, C. C. Hsu, W. C. Lee, Y. T. Chen and Y.
T. Cheng Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University
College of Medicine, Kaohsiung, Taiwan
Re: Improving BPH Symptoms and Sexual Dysfunctions with a Saw Palmetto Preparation?
Results from a Pilot Trial - Uncorrected Proof
02 Dec 2013 12:00 am
A. Suter, R. Saller, E. Riedi and M. Heinrich Medical Department, A. Vogel Bioforce AG, Roggwil,
Switzerland
Re: Increased Intra-Abdominal Fat Predicts Perioperative Complications Following
Minimally Invasive Partial Nephrectomy - Uncorrected Proof
02 Dec 2013 12:00 am
M. A. Gorin, J. K. Mullins, P. M. Pierorazio, G. Jayram and M. E. Allaf James Buchanan Brady Urological
Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland
Re: Increases in Consumer Cost Sharing Redirect Patient Volumes and Reduce Hospital
Prices for Orthopedic Surgery - Uncorrected Proof
02 Dec 2013 12:00 am
J. C. Robinson and T. T. Brown Berkeley Center for Health Technology, School of Public Health, University
of California, Berkeley, California
Re: Inhibition of Bladder Overactivity by a Combination of Tibial Neuromodulation and
Tramadol Treatment in Cats - Uncorrected Proof
02 Dec 2013 12:00 am
F. Zhang, A. D. Mally, P. D. Ogagan, B. Shen, J. Wang, J. R. Roppolo, W. C. de Groat and C. Tai
Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania
Re: Inhibitors of 5α-Reductase-Related Side Effects in Patients Seeking Medical Care for
Sexual Dysfunction - Uncorrected Proof
02 Dec 2013 12:00 am
G. Corona, G. Rastrelli, E. Maseroli, G. Balercia, A. Sforza, G. Forti, E. Mannucci and M. Maggi Sexual
Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence,
Italy
Re: Inhibitory Control Task is Decreased in Vascular Incontinence Patients - Uncorrected
Proof
02 Dec 2013 12:00 am
H. Haruta, R. Sakakibara, T. Ogata, J. Panicker, C. J. Fowler, F. Tateno, M. Kishi, Y. Tsuyusaki, T.
Uchiyama and T. Yamamoto Departments of Neurology and Internal Medicine, Sakura Medical Center,
Sakura, Japan
Re: Intravesical Bacille Calmette-Guérin (BCG) in Immunologically Compromised Patients
with Bladder Cancer - Uncorrected Proof
02 Dec 2013 12:00 am
H. W. Herr and G. Dalbagni Department of Urology, Memorial Sloan-Kettering Cancer Center, New York,
New York
Re: Kenneth G. Nepple, Andrew J. Stephenson, Dorina Kallogjeri, et al. Mortality After
Prostate Cancer Treatment with Radical Prostatectomy, External-Beam Radiation Therapy,
or Brachytherapy in Men Without Comorbidity. Eur Urol 2013;64:372–8
30 Nov 2013 04:45 am
Re: Loss of β1-Integrin from Urothelium Results in Overactive Bladder and Incontinence in
Mice: A Mechanosensory Rather than Structural Phenotype - Uncorrected Proof
04 Dec 2013 12:00 am
K. Kanasaki, W. Yu, M. von Bodungen, J. D. Larigakis, M. Kanasaki, F. Ayala de la Pena, R. Kalluri and W.
G. Hill Division of Matrix Biology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Re: Management and Outcomes of Penile Fracture: 10 Years' Experience from a Tertiary
Care Center - Uncorrected Proof
02 Dec 2013 12:00 am
A. Ozorak, M. B. Hoşcan, T. Oksay, A. Güzel and A. Koşar Department of Urology, Faculty of Medicine,
Süleyman Demirel University, Isparta, Turkey
Re: Novel Anti-Biofilm Mechanism for Wireless Capsule Endoscopy in the Urinary Tract:
Preliminary Study in a Sheep Model - Uncorrected Proof
02 Dec 2013 12:00 am
A. Neheman, C. Schulman and O. Yossepowitch Urology Department, Meir Medical Center, Kfar-Saba,
Israel
Re: Novel Tumor Subgroups of Urothelial Carcinoma of the Bladder Defined by Integrated
Genomic Analysis - Uncorrected Proof
04 Dec 2013 12:00 am
C. D. Hurst, F. M. Platt, C. F. Taylor and M. A. Knowles Cancer Research UK Centre, Leeds Institute of
Molecular Medicine, St. James’s University Hospital, Leeds, United Kingdom
Re: PS3-36: Testosterone Replacement Therapy Patterns for Aging Males in a Managed
Care Setting - Uncorrected Proof
04 Dec 2013 12:00 am
J. An, T. C. Cheetham and S. Van Den Eeden Kaiser Permanente Southern California, Pasadena,
California
Re: Pathological Response to Neoadjuvant Chemotherapy for Muscle-Invasive
Micropapillary Bladder Cancer - Uncorrected Proof
04 Dec 2013 12:00 am
J. J. Meeks, J. M. Taylor, K. Matsushita, H. W. Herr, S. M. Donat, B. H. Bochner and G. Dalbagni
Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, New York
Re: Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial Uncorrected Proof
04 Dec 2013 12:00 am
T. M. Brasky, A. K. Darke, X. Song, C. M. Tangen, P. J. Goodman, I. M. Thompson, F. L. Meyskens, Jr., G.
E. Goodman, L. M. Minasian, H. L. Parnes, E. A. Klein and A. R. Kristal
Re: Randomised, Multicentre, Placebo-Controlled, Double-Blind Crossover Study
Investigating the Effect of Solifenacin and Oxybutynin in Elderly People with Mild Cognitive
Impairment: The SENIOR Study - Uncorrected Proof
04 Dec 2013 12:00 am
A. Wagg, M. Dale, R. Tretter, B. Stow and G. Compion University of Alberta, Edmonton, Alberta, Canada
Re: Solifenacin plus Tamsulosin Combination Treatment in Men with Lower Urinary Tract
Symptoms and Bladder Outlet Obstruction: A Randomized Controlled Trial - Uncorrected
Proof
02 Dec 2013 12:00 am
S. A. Kaplan, W. He, W. D. Koltun, J. Cummings, T. Schneider and A. Fakhoury Weill Medical College of
Cornell University, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York
Re: Sperm Banking is of Key Importance in Patients with Prostate Cancer - Uncorrected
Proof
02 Dec 2013 12:00 am
A. Salonia, P. Capogrosso, F. Castiglione, A. Russo, A. Gallina, M. Ferrari, M. C. Clementi, G. Castagna, A.
Briganti, F. Cantiello, R. Damiano and F. Montorsi Department of Urology, University Vita--Salute San
Raffaele, Milan, Italy
Re: Testosterone Therapy during Exercise Rehabilitation in Male Patients with Chronic
Heart Failure Who Have Low Testosterone Status: A Double-Blind Randomized Controlled
Feasibility Study - Uncorrected Proof
02 Dec 2013 12:00 am
M. Stout, G. A. Tew, H. Doll, I. Zwierska, N. Woodroofe, K. S. Channer and J. M. Saxton Department of
Cardiology, University Hospital of South Manchester, Wythenshawe, Manchester, United Kingdom
Re: The Association between Urinary and Fecal Incontinence and Social Isolation in Older
Women - Uncorrected Proof
02 Dec 2013 12:00 am
S. O. Yip, M. A, Dick, A. M. McPencow, D. K. Martin, M. M. Ciarleglio and E. A. Erekson Section of
Urogynecology and Pelvic Reconstructive Surgery, Department of Obstetrics, Gynecology and
Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut
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