Introduction

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  Cite this guideline

Prostate Cancer Foundation of Australia and Cancer Council Australia PSA Testing Guidelines Expert Advisory Panel. Clinical practice guidelines PSA Testing and Early Management of Test-Detected Prostate Cancer. Sydney: Cancer Council Australia. [Version URL: http://wiki.cancer.org.au/australiawiki/index.php?oldid=122821, cited 2023 Mar 30]. Available from: https://wiki.cancer.org.au/australia/Guidelines:PSA_Testing/Introduction.

This resource has been developed, reviewed or revised more than five years ago. It may no longer reflect current evidence or best practice.

Published: 2015

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These guidelines (recommendations) in the web-version of this guideline were approved by the Chief Executive Officer of the National Health and Medical Research Council (NHMRC) on 2 November 2015 under section 14A of the National Health and Medical Research Council Act 1992 In approving the guidelines (recommendations), NHMRC considers that they meet the NHMRC standard for clinical practice guidelines. This approval is valid for a period of five years. NHMRC is satisfied that the guidelines (recommendations) are systematically derived, based on the identification and synthesis of the best available scientific evidence, and developed for health professionals practising in an Australian health care setting.

This publication reflects the views of the authors and not necessarily the views of the Australian Government.





About this guideline

For information about this guideline, see here.

Prostate cancer in Australia

Prostate cancer is an important public health issue. It is the second most commonly diagnosed cancer in Australian men after non-melanoma skin cancer. Over the most recent decade of reports on cancer incidence in Australia, prostate cancer diagnoses increased, from 11,477 in 2000 to 19,993 in 2011.[1] In 2011, men were estimated to have a one in seven chance of being diagnosed with prostate cancer by age 75 and a one in five change of being diagnosed by age 85. With the growing Australian population, increasing life expectancy and the expectation of continuing increases in prostate cancer incidence (due mainly to increasing age), the Australian Institute of Health and Welfare has estimated that the number of prostate cancers diagnosed in Australia in 2020 will lie between 25,000 and 31,000.[2]

The latest figures from the Australian Institute of Health and Welfare show that 3,079 men died from prostate cancer in 2012.[3] That number represents 4.1% of all deaths in men and 12.6% of all cancer deaths in men, making prostate cancer second only to lung cancer as the most common cause of cancer death in men. Illness and disability associated with prostate cancer also has a large impact on Australian men’s lives. Based on 2010 data, it was estimated that 42,500 disability-adjusted life years (DALYs) were lost to prostate cancer – second only to lung cancer (56,800 DALYs).[4]

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Men at risk of dying from prostate cancer

The main objective of early diagnosis of prostate cancer is to reduce the rate of death from prostate cancer. Each year, on average, eight Australian men younger than 50 years of age die from prostate cancer (estimated from the annual average over the years 2002 to 2011[3] ). From a rate of about one death per year per 100,000 men aged 45–49 years, mortality in Australia increases two- to four-fold with each 5-year increase in age, to a maximum of about 800 deaths per year per 100,000 men aged 85 years and over.[3]

Rates of death due to prostate cancer are highest in countries with predominantly European origin populations; the lowest rates are observed in Middle Eastern and Asian populations.[5] While available data are limited, mortality rates also appear to be high in African countries, and African American men are at high risk of death from prostate cancer.[5][6]

Within Australia, mortality rates from prostate cancer are highest among men born in Australia, New Zealand, and Western, Northern and Southern Europe, and materially less in men born in Eastern Europe, the Middle East and Asia, consistent with the international patterns.[7] In addition, mortality rates are highest among men of lowest socioeconomic status, and become progressively higher with increasing remoteness of a man’s place of residence.[7]

Available evidence indicates that the rate of mortality from prostate cancer among Australian Aboriginal men is higher than in other Australian men but that incidence is lower.[8] This disparity suggests that diagnosis of prostate cancer is later or its treatment poorer in Aboriginal men. Recent research suggests the latter is the case.[9]

A family history of prostate cancer, especially having a male first-degree relative diagnosed with prostate cancer before age 65 years,[10] increases a man’s risk of developing it. The mutations best known to increase risk for prostate cancer are the BRCA1 and BRCA2 gene mutations, which are associated with a high risk of breast cancer, and the HOXB13 mutation. Other gene mutations that increase risk to a small or moderate degree are regularly reported. Various lifestyle factors have been reported as associated with prostate cancer risk, but only one – overweight and obesity (which may be associated with advanced prostate cancer only) – appears to be established with sufficient certainty to be a target for risk reduction.[11]

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Testing for the early diagnosis of prostate cancer

Efficacy of testing

This guideline informs testing for the early diagnosis of prostate cancer in men in whom prostate cancer is likely to occur and can be detected, and who do not currently have any symptoms that suggest they might have prostate cancer. Although testing in this context is commonly referred to as ‘screening’, we will avoid this term here. We do so to prevent confusion between testing offered in an organised way to a specified target group of men at risk of prostate cancer in the population (screening), and testing considered during men’s usual interactions with the health system, which is the context of this guideline.

A test for early diagnosis of cancer is a test that aims to detect a cancer before it causes symptoms and thus, through early treatment, to increase the likelihood that the cancer will be cured. There is currently no test that can accurately identify men who have prostate cancer among men who have no symptoms that suggest prostate cancer. To be considered accurate, a test for early diagnosis of prostate cancer would have to be highly sensitive and highly specific: that is, to be highly likely to be ‘positive’ when prostate cancer is present and highly likely to be ‘negative’ when it is not. The two tests that are commonly used to detect prostate cancers early are measurement of PSA in blood and digital rectal examination (DRE), in which a doctor examines the prostate by feeling it through the rectum. Both tests can identify men who may have prostate cancer, but they are not very accurate in doing so.

While the PSA test may not be accurate in detecting prostate cancer early, it may be accurate enough to be considered efficacious in reducing risk of death from prostate cancer, which is the main aim of early diagnosis. Australia’s National Health and Medical Research Council (NHMRC) recently commissioned a systematic review of evidence on the efficacy of PSA testing in reducing rates of mortality and morbidity due to prostate cancer in asymptomatic men. The NHMRC review’s conclusions included the following:[12]

In asymptomatic men:
  • The present evidence is inconsistent as to whether there is an effect of PSA testing, with or without DRE, on the risk of prostate cancer-specific mortality compared with no PSA testing, although the possibilities of no effect or a small protective effect cannot be excluded;
  • PSA testing with or without DRE reduces the risk of prostate cancer metastases at diagnosis compared with no PSA testing; and
  • It is unknown if PSA testing, with or without DRE affects quality of life due to advanced prostate cancer, compared with no PSA testing.

Inconsistency in the findings of the randomised controlled trials of PSA testing, with or without DRE, underlies NHMRC’s equivocal finding on the evidence that PSA testing reduces death from prostate cancer. The US Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) Trial[13] found a statistically non-significant 13% increase in prostate cancer-specific mortality after 13 years of follow-up in men 55–74 years of age offered annual PSA testing for 6 years and annual DRE for 4 years; the European Randomized Study of Screening for Prostate Cancer (ERSPC)[14] found a statistically significant 21% fall in prostate cancer-specific mortality after 11 years of follow-up in men aged 55–69 years offered PSA testing every two-to-four years, generally without DRE. Three other earlier and smaller randomised or pseudo-randomised trials obtained results similar to those of the PLCO.[15]

The pooled results of PLCO and the three earlier and smaller trials are statistically incompatible with those of the ERSPC, which is, in reality, a result of pooling the results of seven smaller, nationally defined trials working in cooperation but to somewhat different protocols. There is no way of resolving the inconsistency among these trials and reaching an evidence-based conclusion as to whether or not PSA testing is efficacious in reducing mortality from prostate cancer.

While the prevention of deaths due to cancer is the main goal of testing in asymptomatic men, there are other potential benefits. These include reduction in diagnosis of cancer when it is already advanced, a reduction in the suffering that can precede death from advanced cancer, and a reduction in adverse effects of therapy used to control advancing cancer. Available evidence indicates that PSA testing reduces the risk of diagnosis of prostate cancer with metastases already present, but is largely silent as to whether PSA testing can prevent reduction in quality of life due to advanced cancer.[12]

Rates of PSA-based testing in Australia

Analysis of Medicare Australia’s Medical Benefits Schedule (MBS) records shows that 778,469 PSA tests were recorded as Medicare item number 66655 in 2012.[16] This number underestimates the actual number of PSA tests done, perhaps by as much as 40%.[17] It suggests that each year at least 20% of men aged between 45 and 74 years have a PSA test, presumably for the purpose of early diagnosis of prostate cancer. By way of comparison, the latest figures from the Australian Institute of Health and Welfare show that the participation rate of eligible women (those aged 50–69 years) in the BreastScreen Australia program for 1997–1998 was 54.3%, which, being a program of biennial screening, averages at about 27% per year.[18]

A 2012 survey of 1,431 men suggests that GPs are the key influencers of testing either by suggesting that men have a PSA test as part of a routine check-up or by requesting a PSA test without consulting the men about it.[19]

There is evidence that many men are undergoing PSA testing with inappropriate frequency and that men in certain groups who should be excluded from testing on the basis of previous PSA test results, medical co-morbidity or limited life expectancy, are still being tested.[20][21][22]

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Harms associated with PSA testing

The outcome of prostate cancer is strongly related to the stage and grade of the disease at diagnosis. PSA testing can detect cancers at a clinically localised stage, and at a lower grade than prostate cancers detected in other ways. This fact underlies the likely ability of PSA testing of asymptomatic men to reduce mortality from prostate cancer, as suggested by the results of the ERSPC[23] and the Gøteborg prostate cancer screening trial.[24]

It also underlies the likelihood that a proportion of prostate cancers detected as a result of positive PSA tests would never have bothered the men in which they were detected, had these men not been tested. Such cancers are commonly referred to as ‘over-diagnosed’ cancers. They have been estimated to account for as many as 20–40% of cancers diagnosed following a positive PSA test.[25] There is currently no known way of distinguishing over-diagnosed cancers from cancers that would have gone on to cause symptoms and possibly death; thus, prostate cancers detected through PSA testing have to be treated with the same seriousness as any cancer of their stage and grade. Hence a positive PSA test can lead to a cascade of further investigation and treatment that may cause harm to men, some of whom would not otherwise have been diagnosed with prostate cancer and would not benefit from treatment.

The only harms PSA testing may cause directly are the anxiety and distress that a positive test engenders whether a cancer is subsequently diagnosed or not. Indirect harms include those associated with biopsy performed as a result of PSA testing – inconvenience, discomfort, and occasional, but potentially serious, adverse health effects (e.g. bleeding or infection) – especially when the test was a false positive test (i.e. no prostate cancer was found subsequently by biopsy) or the cancer found was an over-diagnosed cancer.

Treatment of a prostate cancer found following a positive test can be a cause of distress, discomfort and, quite frequently, adverse effects. The major adverse effects consequent on prostate cancer treatment are:[26]

  • urinary incontinence, which is common soon after treatment and persists in some 12–15% of men treated by radical prostatectomy, and other urinary problems in men treated by radiotherapy
  • erectile dysfunction in men treated by radical prostatectomy, radiotherapy or androgen deprivation therapy, which is common soon after treatment and persists in some 70% of men, although probably not attributable to the therapy in all cases
  • bowel problems, which are most common after external beam radiotherapy and affect some 20% of men.

These harms are usually offset by the cure or amelioration of the disease that treatment can bring. However, men with over-diagnosed cancer will experience harm without compensating benefit.

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Balance of benefits and harms

A test for early detection is often evaluated on the basis of whether the benefits exceed the harms. Indeed, Australia’s framework for population-based screening includes as an absolute requirement that screening programs offer more benefit than harm to the target population.[27] Uncertainty about the efficacy of PSA testing in reducing prostate cancer mortality, and about the extent of over-diagnosis, make any estimate of the balance of benefits and harms from PSA testing very uncertain. On this basis many reviews do not recommend PSA testing.

Two published estimates based on well-regarded statistical models of PSA testing, which assume the ERSPC’s estimate of the reduction in prostate cancer mortality due to testing, have reached different conclusions. Using the Dutch MISCAN model, Heijnsdijk et al (2012)[28] estimated that men who had annual PSA testing from age 55 to 69 years gained, on average, 0.056 quality-adjusted life years (QALYS) as a result of testing; that is, on average the benefits exceeded the harms. Using the Fred Hutchinson Cancer Research Centre model, Pataky et al (2014)[29] estimated an average loss of 0.0004 to 0.0105 QALYs per man tested depending on the testing protocol; that is, on average, the harms exceeded the benefits. The difference in these conclusions appears to have been due mainly to differences between the two studies in the quality adjustments made to years of life lived in particular health states.

From these estimates, therefore, it is uncertain, at best, whether the benefits of PSA testing, measured in terms of quality life gained, exceed its harms. This reality underlies the decision, taken a priori, not to make a recommendation regarding population screening for prostate cancer in these guidelines. This position is consistent with the Australian Government’s position. The 2014 update of the joint position statement Prostate cancer screening in Australia[30] by the Australian Health Ministers’ Advisory Council and Cancer Council Australia concludes: ‘An assessment of current evidence against the Population Based Screening Framework criteria indicates that the PSA test is not suitable for population screening, as the harms outweigh the benefits’. It is also consistent with recent international guidelines developed by the US Preventative Services Task Force[31] and Canadian Task Force on Preventative Health Care[32].

This position, however, does not exclude PSA testing as an informed choice taken by men in consultation with their doctors. The Australian Health Ministers’ Advisory Council and Cancer Council Australia joint position statement on prostate cancer screening[30] also concludes that ‘…men considering being tested for prostate cancer should do so with information on both the benefits and harms of testing and treatment. We encourage men to speak to their doctor so they can make an informed choice about prostate cancer testing.’ The Australian Government also facilitates PSA testing through the Medicare Australia Medical Benefits Schedule, Item 66655 of which allows payment of a benefit for PSA quantitation once in a 12-month period.[16]

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The need for a PSA testing guideline

Given the large number of men in Australia who are tested annually, it is important to determine how to maximise the benefits, if there are benefits, and minimise the harms from PSA testing. In Australia there is now no commonly accepted guidance that applies to men who have decided to undergo PSA testing, indicating the optimal age to start testing and the frequency of testing. Nor is there specific guidance for men in high-risk groups, particularly men with a family history of prostate cancer. Further, there is no commonly accepted guidance on what represents a positive test result and the actions that should follow from such a result. Importantly, there is indirect evidence from substantial variation in the frequency of prostate biopsy relative to PSA testing among Australian States and Territories that decisions about what represents a positive test result are highly variable.[33]

Given this evidence, the current situation is far from ideal:

  • Each year, according to figures derived from Medicare Benefits Schedule data, approximately 20% or more of men aged 45–74 years are tested for prostate cancer, presumably with the intent of early diagnosis.[33]
  • Many men are undergoing PSA testing with inappropriate frequency, and many men are being tested who are not suitable for testing, on the basis of medical co-morbidity and/or limited life expectancy.[20][21][22]
  • It is doubtful whether all, or even many, of the men who are tested have been given the opportunity for fully informed choice about whether or not to have a PSA test.
  • Guidance given to men about PSA testing is inconsistent and often confusing.
  • There is no consistent approach to determining the PSA concentration threshold that should prompt further investigation.
  • There is no clear guidance on testing for men in known high-risk groups, such as men with a family history of prostate cancer.
  • Some three to seven men must be diagnosed with and treated for prostate cancer to prevent one death from prostate cancer (assuming that the ERSPC results correctly characterise the efficacy of PSA testing in preventing prostate cancer death). These men diagnosed include an estimated 20–40% who, if they had not had a PSA test, would never have been bothered by their prostate cancer.
  • The quality of the guidance given to men about their treatment options when diagnosed with prostate cancer is uncertain. There may also be insufficient consideration of active surveillance as a management option. Active surveillance involves a program of ongoing PSA testing and other testing of men with early-stage, low-grade cancer, in which radical treatment is offered only if the cancer shows signs of progressing or the man requests it.
  • Men’s needs for support in managing adverse effects of treatment and their emotional response to the disease are often unmet.

As a result, there is a need for evidence-based clinical recommendations for prostate cancer testing that extend from informed decision-making about whether to be tested, through to decision-making and actions following a positive test result. In addressing this need, our overriding consideration was achieving the best balance between the benefits and harms of testing for early diagnosis of prostate cancer or, at the very least, minimising the harms consequent on testing. We hope that implementation of these recommendations will help achieve this balance for Australian men.

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Basis for making recommendations on testing protocols

Given the context of this guideline, which is to advise men who decide to have a PSA test after they have been informed of the benefits and harms of testing, the Expert Advisory Panel decided to base its recommendations for testing protocols on the results of ERSPC; its various sub-studies; and epidemiological modelling based on the ERSPC data. To do otherwise would have prevented the Expert Advisory Panel from producing any guidance because, absent ERSPC finding, there would be no evidence on what testing protocol might be efficacious in reducing prostate cancer mortality. Should further research find that the ERSPC results are more unreliable than we have judged them to be, we would have to reconsider this decision and this guideline.

We considered it appropriate to base our recommendations on the ERSPC data for the following main reasons:

1. The pattern of evolution of the difference in cumulative prostate cancer mortality between ERSPC intervention arm and control arm men is exactly that expected if PSA testing were efficacious in reducing prostate cancer mortality: there was little difference between them up to about 7 years from study entry, thereafter cumulative mortality has diverged progressively with the better outcome in men offered PSA testing.[14]

2. There is a high degree of internal consistency in the ERSPC findings that adds to strength to the evidence it provides. While there was appreciable heterogeneity in the way the ERSPC was conducted in its seven component national centres, the relative risk (RR) of prostate cancer death in the intervention arm relative to the control arm in six of the seven centres was consistent with protection against prostate cancer death, ranging between 0.56 and 0.89.[14] The lowest RR (0.56) was in the Swedish (Gøteborg) centre, which offered testing every 2 years, not every 4 years as in the other centres; and the one outlier, an RR of 2.15, came from the small Spanish centre that, at the time of the analysis, had observed two deaths in the intervention arm and one in the control arm.[14]

3. There are two aspects of study conduct that would cause PLCO to underestimate efficacy of PSA testing.[34] Of all men randomised by PLCO, 45% had a PSA test in the 3 years before study entry, and an estimated 52% of men in the control arm had one in the period of the last intervention arm PSA test.[35] By way of comparison, an estimated 30.7% of the ERSPC control group was tested once or more during the study.[36] Further, 40.1% of PLCO intervention group men with a positive PSA test had a prostate biopsy within 1 year and 64% within 3 years of the test,[37] while in ERSPC biopsy compliance was approximately 90%.[38]

The ERSPC has recently published results from 13 years of follow-up.[23] While the estimated relative cumulative benefit at 13 years remains the same is it was at 11 years (an estimated 21% reduction in risk of prostate cancer death due to PSA testing), the absolute effect has increased from 0.46 prostate cancer deaths prevented per 1000 men randomised to PSA testing after 9 years of follow up, to 1.02 prevented per 1000 men after 11 years and to 1.28 per 1000 men after 13 years of follow-up.[23] In parallel, the estimated number of cancers needed to diagnose to prevent one prostate cancer death fell from 48 at 9 years of follow-up to 35 at 11 years, and 27i at up to 13 years’ follow-up.[23] These are trends that would be expected from introduction of an effective cancer screening test; the extra cancers diagnosed begin on day one, but the benefits in terms of deaths prevented are not seen for a number years (some 6–7 years in the case of prostate cancer). Thereafter, the deaths prevented continue to accumulate while testing continues, and for a period after it is discontinued.[39][40]

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Purpose of this guideline

This guideline provides evidence-based recommendations for PSA testing and immediately consequent clinical care in Australia. Its main purpose is to provide guidance on:

  • which testing protocol to recommend to men who decide in favour of testing, depending on their age and underlying risk of prostate cancer
  • further investigation of an abnormal PSA test and the early management of prostate cancer diagnosed following such investigation.

The aim of the recommendations, through their application in practice, is to maximise the benefits and minimise the harms of PSA testing in men without symptoms suggestive of prostate cancer.

Intended users of this guideline

The target users of the guideline are:

  • health professionals in primary care, such as general practitioners, advising men who are considering testing or have decided to be tested
  • urologists and other health practitioners advising men who have had a positive PSA test, have had a prostate biopsy (either positive or negative for prostate cancer), or have been diagnosed with prostate cancer and are considering their management options.

The guideline will also be relevant to all other health service personnel involved in PSA testing and the diagnosis and management of prostate cancer, and to people involved in communicating risk, policy makers, and hospital and health service resource managers.

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Target population

The clinical populations covered by the recommendations in this guideline are:

  • asymptomatic men who on the basis of general knowledge ask their doctor about a PSA test
  • asymptomatic men who have been told about the test by their doctor and are considering having one
  • asymptomatic men without known prostate cancer who have decided to undergo PSA testing, after the benefits and risks have been explained to them
  • men with early prostate cancer diagnosed after PSA testing.

Healthcare setting to which this guideline applies

This guideline provides recommendations for the care of men using Australian health services, specifically:

  • primary care, including general practice and Aboriginal medical services
  • urology services
  • public and private hospitals.

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Scope of this guideline

The guideline addresses the following areas:

  • the increased risk of prostate cancer experienced by men who have a family history of prostate cancer
  • PSA testing (decision support for men considering a PSA test, PSA testing strategies, the role of digital rectal examination, PSA testing and life expectancy, and the contribution of PSA variants to PSA testing)
  • the increase in risk above average risk that would justify a change in PSA testing strategy, particularly the risk associated with a family history of prostate cancer
  • investigations (indications for further investigations, prostate biopsy quality criteria, and follow-up to negative prostate biopsy)
  • management (options for men with biopsy-diagnosed prostate cancer, the roles of active surveillance and watchful waiting, and protocols for implementing these management options)
  • sociocultural aspects of PSA testing (whether special considerations apply to Aboriginal and Torres Strait Islander men, and whether socioeconomic factors affect testing).

A full list of all clinical questions that form the basis of this guideline is available in Appendix 3.

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Methods used to develop this guideline

The guideline was developed in accordance with the 2011 NHMRC standard (Procedures and requirements for meeting the NHMRC standard for clinical practice guidelines).[41]

Literature searches were conducted for each clinical question to identify evidence relevant to pre-specified populations, interventions (or exposure, for question 1), comparators and outcomes. Outcomes were selected for clinical relevance and included biopsy-diagnosed prostate cancer, metastatic prostate cancer, and death due to prostate cancer, depending on the clinical question. The evidence for all clinical questions was filtered to identify any findings specific to Aboriginal and Torres Strait Islander men. A detailed description of the guideline development process and methodology is given in Appendix 1 Guideline development process.

An Expert Advisory Panel comprised of representatives from all specialities involved in the diagnosis and management of men affected by prostate cancer, other scientists and consumer representatives was convened to develop the PSA testing recommendations in this guideline. The list of all Expert Advisory Panel members is available in Appendix 2 Committee members and contributors and the statement of competing interests is available in Appendix 6 Conflict of interest register. Details in regards to the funding, dissemination and recommended future updates of the guidelines are described in Appendix 1 Guideline development process.

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Implementation

Cancer Council Australia and Prostate Cancer Foundation of Australia have initiated programs of work to develop tools to help men make informed choices about PSA testing, and to estimate life expectancy. When completed, these tools will be made available to health professionals.

In addition, both organisations plan to produce and publish a digest of the guideline that is easy for the average man to read and understand, and summaries of the guideline that are easy for health professionals to use in their day-to-day care for men’s health.

Further, they will work together with other interested parties in developing and seeking implementation of health service, both clinical and non-clinical, policies and procedures that will facilitate use of the guideline’s recommendations in practice.

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Life of this guideline

It is inevitable that parts of this guideline will quickly become out of date as knowledge advances. Newly published literature relevant to each systematic review question will be monitored. If strong evidence supporting a change in the guideline accumulates, the Expert Advisory Panel will reconvene to assess if a guideline update is warranted. The guideline as a whole will be reviewed every three years and a decision made as to whether partial or full updating is required.

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Footnotes

i The number needed to diagnose (NND) value of 17 in the latest ERSPC analysis may appear to be at variance with model-based NND estimates of 3 to 7.[13][28][29] It differs from the these estimates, however, in being based on only 13 years of follow-up from the beginning of screening, whereas the model estimates assume that members of the modelled cohort are followed until their death or attainment of a great age.

References

  1. ↑ Australian Institute of Health and Welfare. Cancer in Australia: an overview, 2014b. Cancer series no. 90. Cat no. CAN 88. Canberra: AIHW; 2014.
  2. ↑ Australian Institute of Health and Welfare. Cancer incidence projections: Australia, 2011 to 2020. Cancer series no. 66. Cat. no. CAN 62. Canberra: AIHW; 2012.
  3. ↑ 3.0 3.1 3.2 Australian Institute of Health and Welfare. Australian Cancer Incidence and Mortality (ACIM) books: Prostate cancer. Canberra: AIHW; 2014 Available from: http://www.aihw.gov.au/acim-books/.
  4. ↑ Australian Institute of Health and Welfare & Australasian Association of Cancer Registries. Cancer in Australia: an overview, 2010.; 2010. Report No.: Cancer series no. 60. Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=6442472684.
  5. ↑ 5.0 5.1 Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013 [cited 2014 Nov 20] Available from: http://globocan.iarc.fr.
  6. ↑ National Cancer Institute. Cancer of the Prostate (Invasive): Age-Adjusted SEER Incidence Rates by Registry, Race and Age.; 2014 [cited 2014 Nov 20] Available from: http://seer.cancer.gov/csr/1975_2011/results_merged/sect_23_prostate.pdf.
  7. ↑ 7.0 7.1 Tracey E, Kerr T, Dobrovic A, Currow D. Cancer in New South Wales: incidence and mortality, 2008. Sydney: Cancer Institure NSW; 2010.
  8. ↑ Morrell S, You H, Baker D. Estimates of cancer incidence, mortality and survival in aboriginal people from NSW, Australia. BMC Cancer 2012 May 6;12:168 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22559220.
  9. ↑ Rodger JC, Supramaniam R, Gibberd AJ, Smith DP, Armstrong BK, Dillon A, et al. Prostate cancer mortality outcomes and patterns of primary treatment for Aboriginal men in New South Wales, Australia. BJU Int 2015 Apr;115 Suppl 5:16-23 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25124107.
  10. ↑ Kicinski M, Vangronsveld J, Nawrot TS. An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis. PLoS One 2011;6: (10) e27130.
  11. ↑ World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity and the prevention of cancer: a global perspective. 2007 Available from: http://www.dietandcancerreport.org/.
  12. ↑ 12.0 12.1 National Health and Medical Research Council. PSA testing for prostate cancer in asymptomatic men. Information for health practitioners.; 2014 Available from: https://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/men4d_psa_testing_asymptomatic_men_140304.pdf.
  13. ↑ 13.0 13.1 Gulati R, Tsodikov A, Wever EM, Mariotto AB, Heijnsdijk EA, Katcher J, et al. The impact of PLCO control arm contamination on perceived PSA screening efficacy. Cancer Causes Control 2012 Jun;23(6):827-35 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22488488.
  14. ↑ 14.0 14.1 14.2 14.3 Schröder FH, Hugosson J, Carlsson S, Tammela T, Määttänen L, Auvinen A, et al. Screening for prostate cancer decreases the risk of developing metastatic disease: findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC). Eur Urol 2012 Nov;62(5):745-52 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22704366.
  15. ↑ Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database Syst Rev 2013 Jan 31;1:CD004720 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23440794.
  16. ↑ 16.0 16.1 Australian Government Department of Health. Medicare Benefits Schedule Book Category 6.; 2014.
  17. ↑ Trevena JA, Rogers KD, Jorm LR, Churches T, Armstrong B. Quantifying under-reporting of pathology tests in Medical Benefits Schedule claims data. Aust Health Rev 2013 Nov;37(5):649-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24160673.
  18. ↑ Australian Institute of Health and Welfare. BreastScreen Achievement Report 1997-1998.; 2000. Report No.: cancer series no. 13. Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=6442454304.
  19. ↑ Lowe A, Bennett M, Badenoch S. Research, awareness, support: ten years of progress in prostate cancer. Prostate Cancer Foundation of Australia; 2012.
  20. ↑ 20.0 20.1 Litchfield MJ, Cumming RG, Smith DP, Naganathan V, Le Couteur DG, Waite LM, et al. Prostate-specific antigen levels in men aged 70 years and over: findings from the CHAMP study. Med J Aust 2012 Apr 2;196(6):395-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22471541.
  21. ↑ 21.0 21.1 Carmichael LK, Goldsbury DE, O'Connell DL. Prostate cancer screening for men aged 75 to 84 years in New South Wales. Aust N Z J Public Health 2013 Oct;37(5):492-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24090337.
  22. ↑ 22.0 22.1 Ranasinghe WK, Kim SP, Lawrentschuk N, Sengupta S, Hounsome L, Barber J, et al. Population-based analysis of prostate-specific antigen (PSA) screening in younger men (<55 years) in Australia. BJU Int 2014 Jan;113(1):77-83 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24053128.
  23. ↑ 23.0 23.1 23.2 23.3 Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014 Aug 6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25108889.
  24. ↑ Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Lancet Oncol 2010 Aug;11(8):725-32 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20598634.
  25. ↑ Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R, et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst 2009 Mar 18;101(6):374-83 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19276453.
  26. ↑ Smith DP, King MT, Egger S, Berry MP, Stricker PD, Cozzi P, et al. Quality of life three years after diagnosis of localised prostate cancer: population based cohort study. BMJ 2009 Nov 27;339:b4817 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19945997.
  27. ↑ Australian Health Ministers' Advisory Council. Population based screening framework. Canberra: Commonwealth of Australia; 2008.
  28. ↑ 28.0 28.1 Heijnsdijk EA, Wever EM, Auvinen A, Hugosson J, Ciatto S, Nelen V, et al. Quality-of-life effects of prostate-specific antigen screening. N Engl J Med 2012 Aug 16;367(7):595-605 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22894572.
  29. ↑ 29.0 29.1 Pataky R, Gulati R, Etzioni R, Black P, Chi KN, Coldman AJ, et al. Is prostate cancer screening cost-effective? A microsimulation model of prostate-specific antigen-based screening for British Columbia, Canada. Int J Cancer 2014 Aug 15;135(4):939-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24443367.
  30. ↑ 30.0 30.1 Australian Health Ministers' Advisory Council. Prostate cancer screening in Australia: Position statement.; 2014.
  31. ↑ Moyer VA, U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012 Jul 17;157(2):120-34 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22801674.
  32. ↑ Bell N, Connor Gorber S, Shane A, Joffres M, Singh H, Dickinson J, et al. Recommendations on screening for prostate cancer with the prostate-specific antigen test. CMAJ 2014 Nov 4;186(16):1225-34 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25349003.
  33. ↑ 33.0 33.1 Australian Government Department of Human Services. Medicare Items Reports. [homepage on the internet]; 2014 [cited 2014 Nov 20; updated 2014 Oct 24]. Available from: http://medicarestatistics.humanservices.gov.au/statistics.
  34. ↑ Gulati R, Gore JL, Etzioni R. Comparative effectiveness of alternative prostate-specific antigen--based prostate cancer screening strategies: model estimates of potential benefits and harms. Ann Intern Med 2013 Feb 5;158(3):145-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23381039.
  35. ↑ Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009 Mar 26;360(13):1310-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19297565.
  36. ↑ Roobol MJ, Kranse R, Bangma CH, van Leenders AG, Blijenberg BG, van Schaik RH, et al. Screening for prostate cancer: results of the rotterdam section of the European randomized study of screening for prostate cancer. Eur Urol 2013 Oct;64(4):530-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23759326.
  37. ↑ Pinsky PF, Andriole GL, Kramer BS, Hayes RB, Prorok PC, Gohagan JK, et al. Prostate biopsy following a positive screen in the prostate, lung, colorectal and ovarian cancer screening trial. J Urol 2005 Mar;173(3):746-50; discussion 750-1 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15711261.
  38. ↑ Wever EM, Draisma G, Heijnsdijk EA, Roobol MJ, Boer R, Otto SJ, et al. Prostate-specific antigen screening in the United States vs in the European Randomized Study of Screening for Prostate Cancer-Rotterdam. J Natl Cancer Inst 2010 Mar 3;102(5):352-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20142584.
  39. ↑ Hanley JA. Measuring mortality reductions in cancer screening trials. Epidemiol Rev 2011 Jul;33(1):36-45 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21624962.
  40. ↑ Grenabo Bergdahl A, Holmberg E, Moss S, Hugosson J. Incidence of prostate cancer after termination of screening in a population-based randomised screening trial. Eur Urol 2013 Nov;64(5):703-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23721957.
  41. ↑ National Health and Medical Research Council. Procedures and requirements for meeting the NHMRC standard for clinical practice guidelines. Melbourne; 2011.

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