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1.  The COMPASs Study: Community Preferences for Prostate cAncer Screening. Protocol for a quantitative preference study 
BMJ Open  2012;2(1):e000587.
Background
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.
Methods/Design
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.
doi:10.1136/bmjopen-2011-000587
PMCID: PMC3253419  PMID: 22226686
2.  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.
Introduction
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
Strengths
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.
Limitations
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.
doi:10.1136/bmjopen-2011-000104
PMCID: PMC3191396  PMID: 22021763
Organisation of health services; epidemiology; public health; statistics & research methods; urological tumours; health service research
3.  Discrepancy between radiological and pathological size of renal masses 
BMC Urology  2011;11:2.
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1186/1471-2490-11-2
PMCID: PMC3056852  PMID: 21342488
4.  Cytosolic Phospholipase A2-α: A Potential Therapeutic Target for Prostate Cancer 
Purpose
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.
Results
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.
Conclusions
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.
doi:10.1158/1078-0432.CCR-08-0566
PMCID: PMC2605658  PMID: 19088022
prostate cancer; cPLA2-α; eicosanoids; angiogenesis

Results 1-4 (4)