Testing times

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Activities to prevent chronic diseases developing | Overdiagnosis – a side effect of prevention? | Help or harm? | What makes a good population screening test? - PSA tests vs FOBTs | WHO guidelines on population screening | Putting evidence into practice: what do the guidelines mean for your patients?

Key points

  • Prevention in primary care is a vital component of health care in Australia.
  • Medical tests are an important part of preventive activities. However, be aware that:
    • Tests are not infallible, some come with a high false-positive or false-negative rate.
    • Some tests do not have sufficient evidence of benefit for identifying early disease in apparently healthy people.
    • Some tests have evidence of harm from overdiagnosis.
  • Prioritise tests that are supported by guidelines and for which there is a strong evidence base.
  • Give patients the opportunity and necessary information to make informed decisions about which tests are appropriate for them.

The decision about which tests are best for assessing risk in preventive health care depends on whether the evidence for benefit in terms of early detection outweighs the evidence for harm in terms of overdiagnosis. The evidence for two screening tests is explored here; the prostate-specific antigen test for prostate cancer and the faecal occult blood test for colorectal cancer.

Activities to prevent chronic diseases developing

In 2007 chronic disease contributed to 83% of premature deaths (those occurring before 75 years of age) in Australia.1

Of these premature deaths around 64% were potentially avoidable.1 Coronary heart disease, cancer and depression are among the leading contributors to premature death with those in the 45–64 age bracket most affected by premature death resulting from chronic disease.1

Reducing the burden – preventive health in primary care

Preventive health care aims to reduce the burden of chronic disease by identifying people with lifestyle and medical risk factors and applying appropriate interventions. Almost all Australians over the age of 15 have at least one risk factor for developing chronic disease and over 60% have three or more risk factors.2 The leading causes of disease burden are smoking, high blood pressure, obesity, physical inactivity and high blood cholesterol.3 Management of risk factors may lead to a reduction in chronic disease burden. For example, the reduction in the rate of smoking, from 50% in the 1950s to the current rate of around 15% in Australian males has been associated with a 40% to 70% reduction in deaths from, lung cancer and obstructive lung disease from a peak in the 1980s.2,4

Overdiagnosis – a side effect of prevention?

‘Prevention is better than cure’ is an intuitive concept.5 However, there is a growing body of evidence that some of the preventive activities currently being used on apparently healthy, asymptomatic people may actually cause harm.6-9

Some screening tests can detect conditions that would never cause symptoms, or lead to early death. This results in healthy individuals being treated unnecessarily.7,9-12 As a consequence, some people are burdened with therapy that has no clinical benefit for them but has the potential for significant harm.6

Australian guidelines outline best practice

The RACGP Red Book, the Australian guideline for preventive activities in primary care, outlines those tests for which there is sufficient evidence for benefit, while excluding those for which there is not.5 For example, assessment of lipid levels is recommended for people over the age of 45 as part of an absolute cardiovascular risk calculation (over 35 years for Aboriginal and Torres Strait Islander peoples).5 This is recommended because the screening of asymptomatic people for lipid disorders, and controlling cholesterol levels through healthy diet, adequate exercise and pharmacotherapy, can reduce the burden of ischaemic heart disease, especially in high-risk people where the benefit is substantial.13 Conversely, routine testing of thyroid function in asymptomatic patients is not recommended5 as there is little evidence that detecting and treating sub-clinical thyroid dysfunction has any benefit.14

Some screening tests can detect conditions that would never cause symptoms

Help or harm?

The ethical dilemma between prevention and harm is typified in cancer screening. Many people diagnosed with cancer will benefit from early detection and treatment and popular belief is that cancer is universally harmful and lack of treatment leads to premature death.6,8

... up to 70%, have subclinical cellular characteristics consistent with a cancer diagnosis but with no record of symptoms or treatment.

For many cancers survival rate has been dramatically improved by early detection, but for some progression is so slow that they may not cause harm within a person’s lifetime and some may even regress, although this is rare.6,8 It has been estimated from autopsy studies that a large proportion of the population, up to 70%, have subclinical cellular characteristics consistent with a cancer diagnosis but with no record of symptoms or treatment.7,8,10,11 When these numbers are compared to the lifetime risk of death or metastatic disease from the same cancers, there is a 40% to 99% probability that population screening will lead to the detection of cancers that would not cause disease in a person’s lifetime.8

What makes a good population screening test?

Not screening for a particular condition may put some people at risk, but comprehensive population screening may sacrifice the wellbeing of a significant proportion of the population. The challenge for GPs is to understand which screening tests are justified and where the benefits outweigh the harms.

Population screening for various cancers forms part of preventive activities. Currently Australia has national population screening programs for cervical cancer, colorectal cancer and breast cancer. These programs are the result of extensive planning and research to ensure that the target population and frequency of screening is sufficient to reduce mortality without significant cost to healthy people. However, there is no such program to screen for prostate cancer despite the availability of a simple diagnostic test, the prostate-specific antigen (PSA) test. Why is this not recommended as a screening test?

Prostate cancer screening using the PSA test

Prostate cancer is the most commonly diagnosed cancer in Australian men with an estimated 19 000 new cases in 2012, equivalent to 15% of the total cancer cases.15 Prostate cancer is the second leading cause of cancer-related death in males with an estimated 3200 deaths in 2012.15 Risk factors for prostate cancer include family history and increasing age. Prostate cancer is rare before the age of 50 with 80% of cases and 90% of deaths occurring after age 65.9,16

Screening with PSA – better survival?

Recent large trials in Europe17,18 and the US19 investigated the effect of screening for prostate cancer using the PSA test. In the US study no benefit of screening in terms of reduced prostate cancer–specific mortality was demonstrated, although results may have been confounded by frequent PSA testing in the control group.19 In contrast, the European study showed a 21% relative risk reduction for prostate cancer mortality in the screened group at 9 and 11 years follow-up, with no effect on all cause mortality.17,18 At 11 years follow-up, 1055 men would need to be invited for screening and 37 additional cancers would need to be detected to prevent one prostate cancer death.18

At commonly used cut off points for abnormal PSA around 80% of positive tests yield false-positive results9,17,20

There are harms associated with prostate cancer screening

Mortality is only part of the decision process as to whether a test is suitable for population-based screening of healthy individuals. A PSA test result above the normal range (4 ng/mL) triggers a series of diagnostic and treatment interventions and the associated adverse events of these tests need to be considered.9 At this upper limit of normal, around 80% of positive PSA tests are false positives.9,17,20

Over 10 years around 15–20% of men screened using the PSA test will have a biopsy.9 A high proportion of men having a biopsy for prostate cancer will experience adverse effects.23-25 One study reported up to 90% of men with blood in urine and semen post-biopsy, and 25% of men reported these effects as a moderate to serious problem.25 In two studies, somewhere between 2%24 and 7%23 of men were hospitalised because of complications after biopsy and in one study the associated mortality rate was 0.1%.24 In the same two studies, of all the men receiving prostate biopsies, only 44%24 and 17%23 respectively actually had prostate cancer diagnosed.

The lasting harm of a prostate cancer diagnosis

Identifying men with prostate cancers that should be treated aggressively (e.g. radical prostatectomy) is problematic.26 There is currently no method to adequately differentiate between indolent and aggressive cancers and some men receive therapy for disease that is unlikely to cause them harm in their lifetime.26 This is of particular concern because radical prostatectomy or radiation therapy often results in lasting harm affecting quality of life. One long-term follow-up study found that prostate cancer survivors had clinically significant treatment-related adverse effects up to 10 years after their cancer was diagnosed.27 These included sexual and urinary dysfunction which were not attributable to normal ageing.27

Does treatment improve quality of life?

Quality of life assessments performed on a European screening population showed that the benefit of PSA testing was offset by the loss of quality-adjusted life–years.12,18 For each 1000 men screened there were a total of 73 life–years gained, or an average of 8.4 years per prostate cancer death avoided. But the number of quality life–years gained was only 56, being a 23% reduction over life–years gained caused by post-diagnosis effects.12 

In the absence of a clear survival benefit from screening, and growing evidence of harm, it is up to the individual to decide whether the benefits of screening outweigh the potential risks of being exposed to unnecessary treatments with a high adverse event rate (Figure 1).

Comparing PSA tests with faecal occult blood tests

Figure 1: Comparing the PSA test20 and FOBT21,22 Click image to see full-size printed version.

Key points before requesting a PSA test

  • There is no national population screening program for prostate cancer using PSA and/or digital rectal exam.
  • Ensure people who specifically request or are considering prostate cancer screening are fully counselled on the potential benefits and risks involved.

Colorectal cancer screening using faecal occult blood tests

Colorectal cancer is the most common cancer affecting both men and women in Australia.15,28

In 2012 an estimated 16 000 people were diagnosed with colorectal cancer, representing 13% of all cancers diagnosed.15 Colorectal cancer is the second leading cause of cancer deaths in Australia and was the cause of almost 4000 deaths in 2010 alone.15 Between 1991 and 2010 the mortality rate fell by around 40%, the decline is attributed to earlier detection and improvements in treatments and surgical techniques.15

The natural history of colorectal cancer is well defined, most cancers develop from adenomatous polyps occurring in the wall of the colon.29,30 These adenomas are common in ageing populations and most (19 out of 20) will not become malignant.31 However, prognostic indicators, such as a diameter greater than 10 mm, indicate those which have a greater likelihood of progressing.31 These advanced adenomas are slow growing and if treated while still on the wall of the colon a 90% survival rate is achieved.29

Most people with early stage colorectal cancer have no obvious symptoms.31 The survival rate depends on the stage of disease at diagnosis (Table 1). Without population screening only around 15% of colorectal cancer cases are detected at the earliest stage.31

Table 1: Five year survival rates for colorectal cancer31
Cancer stage
Clinical characteristics
Five-year survival rate
Stage A
Locally contained cancer
88%
Stage B
Locally advanced cancer. No lymph node involvement
70%
Stage c
Locally advanced cancer with lymph node involvement
43%
Stage D
Metastatic disease
7%

Colorectal cancer screening is justified 

  • It is slow growing with potential for detection before metastasis, and treatment options have shown benefit.32
  • Screening with faecal occult blood test has a mortality benefit between 15% and 33% in randomised controlled trials.28,29,33-36 
  • Since the introduction of screening in Australia, the number of cancers identified at the earliest and most treatable stage has tripled from 15% to 40%.22,31
  • Over time, incidence of colorectal cancer has remained steady even after the introduction of a population screening program.15 However, mortality rates have fallen suggesting that the test is not leading to overdiagnosis, rather detecting the cancers at a more treatable stage leading to better survival (Figure 2).8,15
  • However, like most medical tests follow-up colonoscopy offered after colorectal cancer screening does not come without the risk of adverse events. Studies showed an adverse event rate for colonoscopy of around 3 per 1000 procedures performed.37
Incidence and mortality for colorectal cancer

Figure 2: Bowel cancer incidence and mortality. Click image to see the full-size printed version.

Plotting incidence and mortality from colorectal cancer in Australia shows a pattern consistent with a screening program that is not leading to overdiagnosis8

WHO guidelines on population screening

The World Health Organization has a set of guidelines that outline the testing and population characteristics that make an acceptable test for population screening of a condition (Table 2).38

Table 2: Does the FOBT or the PSA test meet WHO guidelines for screening tests?
WHO condition
PSA test for prostate cancer
FOBT for colorectal cancer
Is the condition an important health problem?
Yes – 19 000 new diagnoses and 2000 deaths per year in Australia. Yes – 4000 deaths in Australia in 2010.
Is the natural history of the disease well understood?
No – indolent and aggressive cancers cannot be readily distinguished.
Yes – removal of adenomatous polyps can prevent development into cancer.
Is there a recognisable early stage?
No – early stage is poorly understood.
Yes – cancer develops from colonic polyps and adenomas with opportunity for early treatment.
Is early treatment beneficial?
Yes – for patients with aggressive tumours, but it is not possible to distinguish aggressive from indolent tumours. PSA testing is not associated with a reduction in mortality.
Yes – early identification and removal of polyps and adenomas can prevent the development of cancer. FOBT is associated with a 15–30% reduction in mortality.
Is there a suitable test?
No – PSA is a non-specific test that can indicate numerous conditions, pathological and physiological
Yes – FOBT is a reasonable indicator of an individual who might need to be investigated further with colonoscopy.
Is the test acceptable to the population?
Yes – although positive tests require further investigation by biopsy.
Yes – although some patients may dislike the collection methods. Positive tests also require further investigation via colonoscopy. In the Australian pilot around 70% of people with positive FOBT tests went on to have a colonoscopy.
Are there adequate facilities to investigate abnormalities?
Yes – although some patients may experience delays in receiving biopsy.
Yes – although some patients may experience delays in receiving colonoscopy.
Is the chance of psychological or physical harm less than the chance of benefit?
No – current evidence suggests that the potential for harm outweighs the benefit of the PSA test as a population screening tool for healthy individuals.
Yes – the benefit of early identification and removal of potentially malignant growths in the colon of asymptomatic individuals outweighs the risks associated with the investigations.
Abbreviations: FOBT = faecal occult blood test; PSA = prostate-specific antigen.

The RACGP Red Book guidelines for preventive activities

The RACGP Red Book guidelines for preventive activities, define screening and case finding as quite different activities and accompanied by different ethical responsibilities.5

What is screening?

Screening is the examination of asymptomatic people in order to identify the likelihood of them having a disease and detect and treat any abnormalities before they impact the health of the patient.5 Examples include cervical cancer screening and breast cancer screening.5

What is case finding?

Case finding represents most of the tests performed in primary care and occurs when a patient presents with symptoms, risk factors or concerns about a particular condition. In this case the test is used for diagnostic purposes to facilitate diagnosis of the suspected disease.

Putting evidence into practice: what do the guidelines mean for your patients?

Guidelines provide direction on the best treatment for the greatest number of patients. The challenge for you is to match this global guidance against individual needs of your patients.

If your patient requests a PSA test, should you refuse the test because it is not recommended in guidelines? Will the test allay the man’s fears about developing the disease? Will it stop him worrying if he witnessed the effect of the condition personally?

Although PSA testing for the detection of prostate cancer is not recommended at a population level, your patient may still request this test for a variety of reasons which should not be ignored. The application of informed decision making means giving your patient a level of control by informing him of both the risks and benefits associated with the test. For some men the risks of overdiagnosis and adverse events may be acceptable.

There are a number of resources (see the Prostate Cancer Foundation of Australia website and The Bowel Cancer Australia website) available for you and your patients to help facilitate an informed decision. Ultimately it is up to your patient to decide whether they choose to have the test.

Expert reviewers
Professor Jennifer Doust, Professor of Clinical Epidemiology in the Centre for Research in Evidence Based Practice, Bond University, QLD.

Dr Clement Loy, Senior Lecturer, Clinical Epidemiology, School of Public Health, University of Sydney, NSW.

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