Prostate Cancer Testing

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Prostate Cancer Testing

Prostate cancer testing is performed to identify men at risk of harbouring prostate cancer, before it becomes symptomatic. Testing allows clinicians to diagnose prostate cancer in its early stages whilst it is still confined to the prostate. This gives patients the best chance of cure.

Prostate cancer testing involves two initial tests to determine if there is a risk of prostate cancer; a Prostate Specific Antigen (PSA) blood test and a Digital Rectal Examination (DRE) to feel part of the prostate and assess whether there are any abnormalities. Usually these two tests in combination provide the best chance of detecting prostate cancer, compared to just having one of these tests alone.

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PSA test

PSA (Prostate Specific Antigen) is a protein that is produced by the prostate and can be detected with a specific blood test. Any disease process, such as benign enlargement or infection, within the prostate can cause an increase in the levels of PSA found in the blood. Prostate cancer can also cause an elevation in PSA and this test, therefore, helps clinicians identify men at risk of prostate cancer, but the PSA test alone does not diagnose prostate cancer. An elevated PSA is not diagnostic of cancer and most men with a raised PSA do not have prostate cancer. In addition, it is important to note that some patients with prostate cancer will have a normal PSA.

The PSA is not the only indicator used to determine the risk of prostate cancer or the need for treatment. Other tests are discussed elsewhere.

The PSA is not a perfect test, as it does not identify the aggressive prostate cancers from the less aggressive. It is hoped that in the future a better test will be developed that will help to distinguish between those prostate cancers that are aggressive and those that are not.

In addition to its use in assessing individual patient risk for harbouring prostate cancer, PSA is an extremely useful test to monitor a patient’s response to treatment, but the change in PSA after treatment will depend on the type of treatment received. For example, after surgery, the PSA should become undetectable in blood tests. In contrast, the PSA will decline slowly after radiotherapy and may never reach undetectable levels. A detectable PSA, or a rise in PSA after surgery usually indicates recurrence of disease and usually precedes the development of symptomatic disease by years. A rise in PSA after radiotherapy can be more difficult to interpret, but there are specific criteria used to determine whether disease recurrence is likely or not.

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The debate about screening

Prostate cancer screening has received a lot of media attention in recent times and currently there is no consensus about whether all men in Australia should be advised to have PSA testing at specific times.

Population screening means all people are advised to have a certain test to screen for a disease, usually after a certain age. At the moment, population screening for prostate cancer is not recommended, as there are concerns that this would result in over-treatment of less aggressive prostate cancers, that may not require treatment, resulting in significant long-term side effects for patients.

  •  Over-diagnosis: a prostate cancer is found which would never have harmed the patient.
  • Over-treatment: patients are subject to the side effects of treatment but would not have benefited from the treatment because their cancer is not lethal, or they have other medical conditions that they will die from before they die from prostate cancer.

Currently the best advice is for each individual man to talk about the pros and cons of prostate cancer testing with their doctor and make their own individual decision about testing.

There were two large trials of PSA screening published in 2009 called the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) and the European Randomized Study of Screening for Prostate Cancer (ERSPC) trials. The PLCO trial included 76,693 men and concluded that there was no reduction in mortality in the population of men who underwent screening. There were many criticisms of this trial, including contamination of the control arm in which over half the men received PSA screening, as well as a follow-up period too short to detect a difference. The ERSPC trial included 162,243 men and found a 20% reduction in prostate cancer mortality, as well as a 41% reduction in the number of men diagnosed with metastatic disease. A further publication following about 20,000 men from the ERSPC trial but with longer follow-up found a 50% reduction in prostate cancer mortality in the screened population. However, there is considerable risk of over-diagnosis in men undergoing screening and many insignificant cancers are detected that can cause a significant psychological burden and unnecessary treatment in some patients.

In the ERSPC trial, it was estimated that 1,055 men would have to be invited for screening and 37 men diagnosed with prostate cancer to save one life after 11 years of follow-up. With longer follow-up, however, these numbers are expected to improve. For example, in one of the centres involved in the ERSPC trial, it was calculated that 293 men needed to be invited for screening and 12 cancers diagnosed to save one life after 14 years of follow-up.

A recent Cochrane Review has concluded that these studies did not show any significant benefit in reducing prostate cancer specific mortality. This review relied upon five studies, three of which the review concluded were of poor quality. The remaining two were the PLCO and ERSPC and the results of these two trials cancelled one another.

Overall, the benefit of detecting prostate cancer, and treating it, needs to be weighed against the risk of treatment of some cancers that may never spread and which will result in significant side effects. Each man needs to make this decision individually with consultation from their doctor.

Andriole GL, Crawford ED, Grubb RL 3rd, et al. “Mortality results from a randomized prostate-cancer screening trial”. N Engl J Med 2009 Mar 26;360(13):1310-9.

Hugosson J, Carlsson S, Aus G, et al. “Mortality results from the Göteborg randomised populationbased prostate-cancer screening trial”. Lancet Oncol 2010 Aug;11(8):725-32

Ilic, D., et al., Screening for prostate cancer. Cochrane Database Syst Rev, 2013. 1: p. CD004720.

Resnick, M.J., et al., Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med, 2013. 368(5): p. 436-45.

Schroder, F. H., Hugosson, J., Roobol, M. J., et al. (2009). "Screening and prostate-cancer mortality in a randomized European study." N Engl J Med 360(13): 1320-1328.

Schroder, F. H., Hugosson, J., Roobol, M. J., et al. (2012). "Prostate-cancer mortality at 11 years of follow-up." N Engl J Med 366(11): 981-990.

Schroder, F. H., Hugosson, J., Carlsson, S., et al. (2012). "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 62(5): 745-752.

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DRE

The DRE (Digital Rectal Examination) is a clinical examination of the prostate where a doctor inserts a gloved finger into the anus and palpates part of the prostate gland. The doctor is examining for any nodules or hard areas of the prostate that can indicate the possibility of cancer.

Not all cancers can be felt on palpation of the prostate and most cancers detected through PSA testing are impalpable. In addition to helping with the diagnosis of prostate cancer, DRE is an important part of identifying the level of risk associated with the prostate cancer. Even if your GP has performed a DRE, your urologist will want to examine the prostate as well.

 Depending on the results from the PSA and DRE you may require a prostate biopsy.

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What testing is recommended?

The two peak bodies, the Urological Society of Australia and New Zealand (USANZ) and the Royal Australian College of General Practitioners (RACGP), involved in supporting doctors who regularly play a role in prostate cancer testing have different recommendations for their members, which can be confusing.

USANZ currently recommends a single PSA test and DRE from 40 yrs. When compared with the mean PSA for a patient’s specific age, a single PSA can provide an estimate of the risk of being diagnosed with prostate cancer over the subsequent 10-20 yrs. Patients with a PSA above the median do not necessarily need to proceed to a prostate biopsy, but may require closer monitoring of their PSA and regular DRE to detect any worrying pattern or change. Men with a normal DRE and a PSA below the median can be reassured that they are at lower risk of prostate cancer and be offered monitoring at less frequent intervals.

The RACGP have recently changed their guidelines to GPs suggesting that prostate cancer testing should only be carried out at the patient’s request because their interpretation of the evidence is that the potential harms associated with PSA screening may outweigh any potential benefit.

Therefore, it is important for you to decide whether or not to be tested and request a test if you choose to. Despite these differing recommendations it is important for you to discuss your individual risk (e.g. family history) with your local doctor.

Greene, K. L., Albertsen, P. C., Babaian, R. J., et al. (2009). "Prostate specific antigen best practice statement: 2009 update." J Urol 182(5): 2232-2241.

Royal Australian College of General Practitioners (2012). “Guidelines for preventive activities in general practice” (8th Ed)

Zeegers, M. P., Jellema, A. and Ostrer, H. (2003). "Empiric risk of prostate carcinoma for relatives of patients with prostate carcinoma: a meta-analysis." Cancer 97(8): 1894-1903.

Schroder, F. H., Hugosson, J., Roobol, M. J., et al. (2009). "Screening and prostate-cancer mortality in a randomized European study." N Engl J Med 360(13): 1320-1328.

Urological Society of Australia and New Zealand (2009). “PSA testing policy 2009”

Lilja H, Ulmert D, Bjork T et al. Long term prediction of prostate cancer up to 25 years before the diagnosis of prostate cancer using prostate kallikreins measured at age 44‐50 years. J Clin Oncol 2007: 25, 431‐436.

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What is a normal PSA at different ages?

The level of circulating PSA increases with age by around 3% per year; therefore, the upper limit for a “normal” PSA will depend upon the patient’s age.

Age

Average PSA (ng/ml)

Upper limit PSA (ng/ml)

40-49

0.65

2.0

50-59

0.85

3.0

60-69

1.39

4.0

70-79

1.64

 5.5

It should be boted that even a man with a normal PSA could have prostate cancer

It is important to note, however, that PSA can only be used as a guide. Some patients with a normal PSA will be found to harbour prostate cancer, sometimes even high grade cancer, while most patients with a high PSA do not have cancer.

PSA values should therefore be considered to represent a spectrum of risk, whereby patients with a high PSA have a higher risk of prostate cancer and patients with low PSA have a lower risk of prostate cancer.

If your doctor finds your PSA reading is in the “grey area”, there are two more blood tests available to help interpret the risk level. The “PSA- Free to total ratio” and the “Prostate health index or phi” These can help your doctor in deciding whether you need to be referred for a biopsy or not.

PSA can be bound to proteins in the blood, or remain unbound (referred to as “free PSA”). In general, the proportion of PSA that is bound to protein will be increased in patients with prostate cancer and therefore the ratio of free to total PSA can be useful in determining prostate cancer risk and potentially reduce unnecessary biopsy.

Andrology Australia. (2012, 9 October 2012). "PSA test." Retrieved 3 August 2012, from https://www.andrologyaustralia.org/keeping-healthy/psa-test-2/.

Catalona, W. J., Partin, A. W., Slawin, K. M., et al. (1998). "Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial." JAMA 279(19): 1542-1547.

Catalona, W. J., Smith, D. S. and Ornstein, D. K. (1997). "Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements." JAMA 277(18): 1452-1455.

esterling, J. E., Kumamoto, Y., Tsukamoto, T., et al. (1995). "Serum prostate-specific antigen in a community-based population of healthy Japanese men: lower values than for similarly aged white men." Br J Urol 75(3): 347-353.

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PSA after treatment

PSA will be measured at periodic intervals after treatment. A patient’s PSA after treatment will be determined by the type of treatment they received. For example, the PSA after radiotherapy declines slowly over a number of years and may, in fact, increase at some stage during its decline (PSA bounce). After surgery, however, the PSA should decrease to undetectable levels rapidly and any increase is usually indicative of recurrent disease.

There may be a time after treatment when PSA testing is ceased.

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What about change in PSA?

The rate of change of PSA, or PSA velocity, is sometimes used by urologists to further stratify an individual patient’s risk of prostate cancer. The evidence for this, however, is mixed and some publications show that it is no more useful than PSA alone.

A calculation of free-to-total PSA can also be used to help understand PSA changes. PSA is found free in circulation or bound to other proteins; this complex is often caused by cancer. Using a ratio of “free” PSA to total PSA may give an indication of the risk of prostate cancer.

Catalona, W. J., Partin, A. W., Slawin, K. M., et al. (1998). "Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial." JAMA 279(19): 1542-1547.

National Comprehensive Cancer Network. Prostate cancer – v2.2010. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology.: NCCN, 2010 [accessed 3.3.2011].

Vickers AJ, Till C, Tangen CM, Lilja H, Thompson IM. “An empirical evaluation of guidelines on prostate-specific antigen velocity in prostate cancer detection”. JNCI, 2011;103(6):462–9.

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What is my risk if my PSA is over 4?

The higher the PSA, the higher the risk of prostate cancer. However a rise in PSA could be related to other factors such as inflammation.

Approximately 25-40% of men with a PSA between 4 and 10 will be diagnosed with prostate cancer on biopsy of the prostate.

Greene, K.L., et al., “Prostate specific antigen best practice statement: 2009 update”. J Urol, 2009. 182(5): p. 2232-41.

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Can other factors influence my PSA?

Serum PSA levels are dependent on weight and metabolic health status.

Overweight and obese men display reduced PSA compared to their lean counterparts, as do those who present with metabolic syndrome and diabetes. This does not mean less chance of having prostate cancer. In general though, the same reference ranges are used for all men of a particular age.

Other factors, such as sexual activity before a PSA test and even riding a bike can increase PSA values. It is recommended that a repeat PSA test be taken 6-8 weeks later if a PSA test has come back higher than expected as it could normalise during this time.

Baillargeon, J., Pollock, B. H., Kristal, A. R., et al. (2005). "The association of body mass index and prostate-specific antigen in a population-based study." Cancer 103(5): 1092-1095.

Han, J. H., Choi, N. Y., Bang, S. H., et al. (2008). "Relationship between serum prostate-specific antigen levels and components of metabolic syndrome in healthy men." Urology 72(4): 749-754; discussion 754-745.

Kim, Y. J., Cho, Y. J., Oh, J. E., et al. (2008). "The association between metabolic syndrome and prostate-specific antigen levels." Int J Urol 15(10): 905-909.

Lopez Fontana, C., Maselli, M. E., Perez Elizalde, R., et al. (2011). "Obesity modifies prostatic specific antigen in men over 45 years." Arch Esp Urol 64(1): 35-42.

Skolarus, T. A., Wolin, K. Y. and Grubb, R. L., 3rd (2007). "The effect of body mass index on PSA levels and the development, screening and treatment of prostate cancer." Nat Clin Pract Urol 4(11): 605-614.

Werny, D. M., Saraiya, M. and Gregg, E. W. (2006). "Prostate-specific antigen values in diabetic and nondiabetic US men, 2001-2002." Am J Epidemiol 164(10): 978-983.

Werny, D. M., Thompson, T., Saraiya, M., et al. (2007). "Obesity is negatively associated with prostate-specific antigen in U.S. men, 2001-2004." Cancer Epidemiol Biomarkers Prev 16(1): 70-76.

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Ethnicity and PSA

PSA levels can vary according to the ethnic background of the patient. For example, native Japanese men are known to have lower PSA levels than white men, and American-Japanese men. African-American males have higher PSA levels compared to their white American age-matched counterparts and are at increased risk of being diagnosed with prostate cancer.

Oesterling, J. E., Kumamoto, Y., Tsukamoto, T., et al. (1995). "Serum prostate-specific antigen in a community-based population of healthy Japanese men: lower values than for similarly aged white men." Br J Urol 75(3): 347-353.

Sawyer, R., Berman, J. J., Borkowski, A., et al. (1996). "Elevated prostate-specific antigen levels in black men and white men." Mod Pathol 9(11): 1029-1032.

Shibata, A., Whittemore, A. S., Imai, K., et al. (1997). "Serum levels of prostate-specific antigen among Japanese-American and native Japanese men." J Natl Cancer Inst 89(22): 1716-1720.

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National Guidelines

The National Health and Medical Research Council (NHMRC) established an Expert Advisory Group to consider and provide comment on the evidence and advise on the development of a PSA testing information document. NHMRC has released its evaluation of the evidence on PSA testing and an information document for healthproviders http://www.nhmrc.gov.au/guidelines/publications/men4.

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