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1.  Poor survival of females with bladder cancer is limited to those aged 70 years or over: a population-wide linkage study, New South Wales, Australia 
Cancer Medicine  2015;4(8):1145-1152.
Although men are diagnosed with bladder cancer (BC) with a rate three times higher than women, women experience poorer survival. The cause of this gender difference is not clear. The aim of this study was to investigate the discrepancy in survival from BC by gender and explore potential explanations for the difference using a population-wide linkage study. Using the New South Wales (NSW) Central Cancer Registry, all invasive BC cases diagnosed between 2001 and 2009 were identified. Records were linked to the NSW Admitted Patient Data Collection (APDC), to retrieve treatment details, and to the Registry of Births Deaths and Marriages and Australian Bureau of Statistics to obtain death details. A total of 5377 new cases of BC were identified. No differences were identified in the proportions of patients presenting at different stages between genders. However, disease-specific survival (DSS) was worse for females compared to males with localized and regional disease (P < 0.05). This difference was only apparent in individuals aged ≥70 years and no difference was identified in those younger. Multivariable Cox-regression analysis of the cohort of individuals aged ≥70 years revealed that stage, age, comorbidity, and sex remained independent variables (P < 0.05) predicting DSS. In a population wide analysis, females aged 70 years or more suffer worse DSS compared to males. The differences are not accounted for by stage at presentation or comorbidity and are independent of age. BC in postmenopausal females may be biologically more aggressive.
PMCID: PMC4559025  PMID: 25914165
Age; bladder cancer; gender; sex; survival
2.  Men under the age of 55 years with screen detected prostate cancer do not have less significant disease compared to older men in a population of patients in Australia 
BMC Urology  2015;15:124.
The American Urological Association (AUA) changed their Prostate-Specific Antigen (PSA) screening guidelines in 2013 to not recommend testing in men under 55 years of age without significant risk factors (such as a family history of prostate cancer or African ethnicity). The AUA argues that the rates of 'insignificant' prostate cancer (PC) in men under 55 are so high that the potential harms of PSA-testing in this population (over diagnosis and overtreatment) outweigh the benefits (early detection and treatment). Our study aims to identify and compare the rates of insignificant and high-risk PC in men diagnosed with PC ≤55 years and >55 years in two centres in Sydney, Australia.
Men with an abnormal screening PSA or DRE and diagnosed with PC by prostate biopsy were included in this study. A consecutive series of men were accrued from two major urology centres between the years 2006 and 2014. The analysis was divided into two parts, the first compared PC biopsy characteristics between men aged ≤55 years and those >55 years. The second analysis compared the prostatectomy pathological characteristics between the two groups. Differences were analysed by Chi squared and significance set at p < 0.05.
A total of 598 prostate biopsies and 723 prostatectomy matched subjects were included. On prostate biopsies, 14.0 % of men ≤55 years and 11.9 % of men >55 years had insignificant PC (X2 = 0.32, df = 1, p = 0.57), whilst 24.7 % of men ≤55 years and 25.1 % of men >55 years had high-risk PC (X2 = 0.007, df = 1, p = 0.93). On prostatectomy specimens, 9.1 % of men ≤55 years and 6.5 % of men >55 years had insignificant PC (X2 = 1.25, df = 1, p = 0.26), whilst 20.0 % of men ≤55 years and 24.0 % of men >55 years had high-risk PC (X2 = 0.83, df = 1, p = 0.36).
We found no significant difference in the rates of insignificant and high-risk PC between men ≤55 years and >55 years, in either the prostate biopsies or prostatectomy specimens. Further trials need to be performed with comparable sample sizes and controlling of risk factors to assess the utility of PSA screening in younger men.
PMCID: PMC4696233  PMID: 26715039
Insignificant; Prostate Cancer; PSA testing; Prostatectomy; Biopsy
3.  Relationship between Lifestyle and Health Factors and Severe Lower Urinary Tract Symptoms (LUTS) in 106,435 Middle-Aged and Older Australian Men: Population-Based Study 
PLoS ONE  2014;9(10):e109278.
Despite growing interest in prevention of lower urinary tract symptoms (LUTS) through better understanding of modifiable risk factors, large-scale population-based evidence is limited.
To describe risk factors associated with severe LUTS in the 45 and Up Study, a large cohort study.
Design, Setting, and Participants
A cross-sectional analysis of questionnaire data from 106,435 men aged ≥45 years, living in New South Wales, Australia.
Outcome Measures and Statistical Analysis
LUTS were measured by a modified version of the International Prostate Symptom Score (m-IPSS). The strength of association between severe LUTS and socio-demographic, lifestyle and health-related factors was estimated, using logistic regression to calculate odds ratios, adjusted for a range of confounding factors.
Overall, 18.3% reported moderate, and 3.6% severe, LUTS. Severe LUTS were more common among men reporting previous prostate cancer (7.6%), total prostatectomy (4.9%) or having part of the prostate removed (8.2%). After excluding men with prostate cancer or prostate surgery, the prevalence of moderate-severe LUTS in the cohort (n = 95,089) ranged from 10.6% to 35.4% for ages 45–49 to ≥80; the age-related increase was steeper for storage than voiding symptoms. The adjusted odds of severe LUTS decreased with increasing education (tertiary qualification versus no school certificate, odds ratio (OR = 0.78 (0.68–0.89))) and increasing physical activity (high versus low, OR = 0.83 (0.76–0.91)). Odds were elevated among current smokers versus never-smokers (OR = 1.64 (1.43–1.88)), obese versus healthy-weight men (OR = 1.27 (1.14–1.41)) and for comorbid conditions (e.g., heart disease versus no heart disease, OR = 1.36 (1.24–1.49)), and particularly for severe versus no physical functional limitation (OR = 5.17 (4.51–5.93)).
LUTS was associated with a number of factors, including modifiable risk factors, suggesting potential targets for prevention.
PMCID: PMC4198085  PMID: 25333345
4.  Relationships between perioperative physical activity and urinary incontinence after radical prostatectomy: an observational study 
BMC Urology  2013;13:67.
Higher physical activity levels are continence-protective in non-prostate cancer populations. Primary aims of this study were to investigate changes in physical activity levels over the perioperative period in patients having radical prostatectomy, and relationships between perioperative physical activity levels and post-prostatectomy urinary incontinence.
A prospective analysis of patients having radical prostatectomy and receiving perioperative physiotherapy including pelvic floor muscle training and physical activity prescription (n = 33). Physical activity levels were measured using the International Physical Activity Questionnaire and/or the SenseWear Pro3 Armband at four timepoints: before preoperative physiotherapy, the week before surgery, and 3 and 6 weeks postoperatively. Urinary incontinence was measured at 3 and 6 weeks postoperatively using a 24-hour pad test and the International Consultation on Incontinence Questionnaire – Urinary Incontinence Short Form (ICIQ).
Physical activity levels changed significantly over the perioperative period (p < 0.001). At 6 weeks postoperatively, physical activity levels did not differ significantly from baseline (p = 0.181), but remained significantly lower than the week before surgery (p = 0.002). There was no significant interaction effect between preoperative physical activity category and time on the 24-hour pad test (p = 0.726) or ICIQ (p = 0.608). Nor were there any significant correlations between physical activity levels and the 24-hour pad test and ICIQ at 3 or 6 weeks postoperatively.
This study provides novel data on perioperative physical activity levels for patients having radical prostatectomy. There was no relationship between perioperative physical activity levels and post-prostatectomy urinary incontinence, although participants had high overall preoperative physical activity levels and low overall urinary incontinence.
PMCID: PMC4219599  PMID: 24289104
Prostatectomy; Urinary incontinence; Exercise; Pelvic floor muscle training
5.  The COMPASs Study: Community Preferences for Prostate cAncer Screening. Protocol for a quantitative preference study 
BMJ Open  2012;2(1):e000587.
Prostate cancer screening using prostate-specific antigen (PSA) testing remains controversial. Trade-offs between the potential benefits and downsides of screening must be weighed by men deciding whether to participate in prostate cancer screening; little is known about benefit:harm trade-offs men are willing to accept.
The Community Preferences for Prostate Cancer Screening (COMPASs) Study examines Australian men's preferences for prostate cancer screening using PSA testing. The aims are to (1) determine which factors influence men's decision to participate in prostate cancer screening or not and (2) determine the extent of trade-offs between benefits and harms that men are willing to accept in making these decisions. Quantitative methods will be used to assess men's preferences for PSA screening. Using data on the quantitative outcomes of PSA testing from the published literature, a discrete choice study will be designed to quantitatively assess men's preferences. A web-based survey will be conducted in approximately 1000 community respondents aged 40–69 years, stratified by family history of prostate cancer, to assess men's preferences for PSA testing. A mixed logit model will be used; model results will be expressed as parameter estimates (β) and the odds of choosing screening over no screening. Trade-offs between attributes will also be calculated.
Ethics and Dissemination
The COMPASs study has been approved by the University of Sydney, Human Research Ethics committee (Protocol number 13186). The results will be published in internal reports, in peer-reviewed scientific journals as well as via conference presentations.
Article summary
Article focus
To assess men's preferences for prostate cancer screening and determine the relative importance of various factors that influence men's decision to participate in prostate cancer screening or not.
To determine the extent of trade-offs between benefits and harms that men are willing to accept in making decisions about participation in screening.
Key messages
Prostate cancer screening may offer some benefit in terms of a reduction in prostate cancer-specific mortality. However, there is also evidence of substantial harms: screened men have a higher likelihood of being diagnosed as having prostate cancer, including the diagnosis of cancers that would not have become clinically apparent within the man's lifetime, meaning more men experiencing the attendant harms of diagnosis and treatment such as unnecessary biopsies from false-positive prostate-specific antigen tests or impotence and/or incontinence from treatments.
Trade-offs between the potential benefits and downsides of screening must be weighed by men deciding whether to participate in prostate cancer screening; little is known about benefit:harm trade-offs men are willing to make.
This study will use best practice quantitative methods for preference elicitation (discrete choice experiments) to assess men's preferences for prostate-specific antigen screening and the trade-offs they are willing to make decision whether to participate in screening.
Strengths and limitations of this study
The strengths of the study are that it is the first study to use discrete choice methods to examine men's preferences for prostate cancer screening, and the benefit:harm trade-offs men may be willing to make; it will consider the influence of age and family history on preferences in a large cohort of men, broadly representative of the Australian population aged 40 to 69 years.
The limitation is that it is conducted in one country, Australia, and thus its generalisability may be limited by the prevailing screening environment.
PMCID: PMC3253419  PMID: 22226686
6.  Projecting prevalence by stage of care for prostate cancer and estimating future health service needs: protocol for a modelling study 
BMJ Open  2011;1(1):e000104.
Current strategies for the management of prostate cancer are inadequate in Australia. We will, in this study, estimate current service needs and project the future needs for prostate cancer patients in Australia.
Methods and analysis
First, we will project the future prevalence of prostate cancer for 2010–2018 using data for 1972–2008 from the New South Wales (NSW) Central Cancer Registry. These projections, based on modelled incidence and survival estimates, will be estimated using PIAMOD (Prevalence, Incidence, Analysis MODel) software. Then the total prevalence will be decomposed into five stages of care: initial care, continued monitoring, recurrence, last year of life and long-term survivor. Finally, data from the NSW Prostate Cancer Care and Outcomes Study, including data on patterns of treatment and associated quality of life, will be used to estimate the type and amount of services that will be needed by prostate cancer patients in each stage of care. In addition, Central Cancer Registry episode data will be used to estimate transition rates from localised or locally advanced prostate cancer to metastatic disease. Medicare and Pharmaceutical Benefits data, linked with Prostate Cancer Care and Outcomes Study data, will be used to complement the Cancer Registry episode data. The methods developed will be applied Australia-wide to obtain national estimates of the future prevalence of prostate cancer for different stages of clinical care.
Ethics and dissemination
This study was approved by the NSW Population and Health Services Research Ethics Committee. Results of the study will be disseminated widely to different interest groups and organisations through a report, conference presentations and peer-reviewed articles.
Article summary
Article focus
To describe the statistical models we will develop to obtain estimates of the future prevalence of prostate cancer in Australia for each stage of clinical care.
To describe how the methods developed will be used to determine:
i. How many prostate cancer patients will need medical attention in the near future, and
ii. What types of services they will need.
Key messages
This study will provide the first Australian estimates of current health service needs and projections of future needs for prostate cancer patients.
This information will be essential for ensuring that men with prostate cancer have adequate access to the different types of care they will require as they move through the disease trajectory.
Strengths and limitations of this study
Breakdown of prevalence according to health service needs by patient subgroup
Development and testing of validated statistical methods for use in other settings
Multiple population-based data sources: cancer registry, a patterns of care study and Medicare and Pharmaceutical Benefits data.
PIAMOD software has substantial data demands (requiring detailed specially-formatted input data including externally modelled survival estimates)
Numerous decisions are required regarding the best statistical models for incidence and survival
Several assumptions are needed regarding the future trends in incidence and survival.
PMCID: PMC3191396  PMID: 22021763
Organisation of health services; epidemiology; public health; statistics & research methods; urological tumours; health service research
7.  Discrepancy between radiological and pathological size of renal masses 
BMC Urology  2011;11:2.
Tumor size is a critical variable in staging for renal cell carcinoma. Clinicians rely on radiological estimates of pathological tumor size to guide patient counseling regarding prognosis, choice of treatment strategy and entry into clinical trials. If there is a discrepancy between radiological and pathological measurements of renal tumor size, this could have implications for clinical practice. Our study aimed to compare the radiological size of solid renal tumors on computed tomography (CT) to the pathological size in an Australian population.
We identified 157 patients in the Westmead Renal Tumor Database, for whom data was available for both radiological tumor size on CT and pathological tumor size. The paired Student's t-test was used to compare the mean radiological tumor size and the mean pathological tumor size. Statistical significance was defined as P < 0.05. We also identified all cases in which post-operative down-staging or up-staging occurred due to discrepancy between radiological and pathological tumor sizes. Additionally, we examined the relationship between Fuhrman grade and radiological tumor size and pathological T stage.
Overall, the mean radiological tumor size on CT was 58.3 mm and the mean pathological size was 55.2 mm. On average, CT overestimated pathological size by 3.1 mm (P = 0.012). CT overestimated pathological tumor size in 92 (58.6%) patients, underestimated in 44 (28.0%) patients and equaled pathological size in 21 (31.4%) patients. Among the 122 patients with pT1 or pT2 tumors, there was a discrepancy between clinical and pathological staging in 35 (29%) patients. Of these, 21 (17%) patients were down-staged post-operatively and 14 (11.5%) were up-staged. Fuhrman grade correlated positively with radiological tumor size (P = 0.039) and pathological tumor stage (P = 0.003).
There was a statistically significant but small difference (3.1 mm) between mean radiological and mean pathological tumor size, but this is of uncertain clinical significance. For some patients, the difference leads to a discrepancy between clinical and pathological staging, which may have implications for pre-operative patient counseling regarding prognosis and management.
PMCID: PMC3056852  PMID: 21342488
8.  Cytosolic Phospholipase A2-α: A Potential Therapeutic Target for Prostate Cancer 
Cytosolic Phospholipase A2-α (cPLA2-α) provides intracellular arachidonic acid to supply both cyclooxygenase and lipoxygenase pathways. We aim to determine the expression and activation of cPLA2-α in prostate cancer (PC) cell line and tissue and the effect of targeting cPLA2-α in-vitro and in-vivo.
Experimental Design
The expression of cPLA2-α was determined in PC cells by RT-PCR, Western blot and immunocytochemistry. Growth inhibition, apoptosis and cPLA2-α activity were determined after inhibition with cPLA2-α siRNA or inhibitor (Wyeth-1). cPLA2-α inhibitor or vehicle was also administered to PC xenograft mouse models. Finally the expression of phospho-cPLA2-α was determined by immunohistochemistry in human normal, androgen sensitive and insensitive PC specimens.
cPLA2-α is present in all PC cells lines, but increased in androgen insensitive cells. Inhibition with siRNA or Wyeth-1 results in significant reductions in PC cell numbers, as a result of reduced proliferation as well as increased apoptosis and this was also associated with a reduction in cPLA2-α activity. Expression of cyclin D1 and phosphorylation of Akt were also observed to decrease. Wyeth-1 inhibited PC3 xenograft growth by approximately 33% and again, also reduced cyclin D1. Immunohistochemistry of human prostate tissue revealed that phospho-cPLA2-α is increased when hormone refractory is reached.
cPLA2-α expression and activation is increased in the androgen insensitive cancer cell line and tissue. Inhibition of cPLA2-α results in cells and xenograft tumor growth inhibition and serves as a potentially effective therapy for hormone refractory PC.
PMCID: PMC2605658  PMID: 19088022
prostate cancer; cPLA2-α; eicosanoids; angiogenesis

Results 1-8 (8)