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Prostate specific antigen testing for the diagnosis of prostate cancer

McKenzie, Paul*; Delahunt, Brett; deVoss, Kerry§; Ross, Bronwen; Tran, Huy; Sikaris, Kenneth||

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Pathology - Journal of the RCPA: August 2011 - Volume 43 - Issue 5 - p 403
doi: 10.1097/PAT.0b013e32834915fc
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Prostate cancer is the most common non-cutaneous malignancy diagnosed in Australia 1 and New Zealand, the second most common cause of cancer death in men, the third most common overall for both sexes 2 and the fourth ranked cancer overall for disability-adjusted life-years. 3 There is also considerable morbidity associated with non-lethal, locally advanced or metastatic disease and with androgen deprivation treatment, which has led to the desire for early detection, with the potential for curative treatment. The debate regarding the benefits of early detection is complex with potential side effects of surgery and radiotherapy needing to be considered. The definitive diagnosis of prostate cancer can only be made by histopathological examination of biopsies with the Gleason score offering the best indication of tumour aggressiveness. Conservative management of low risk disease can be considered in appropriate patients and this would minimise the number of men undergoing active treatment.

The purpose of this editorial is to outline the optimal use of serum prostate specific antigen (PSA) in testing for the likely presence of prostate cancer and to form the basis of a position statement by the Royal College of Pathologists of Australasia.

Blood levels of PSA are currently the best readily available biomarker for detecting prostate cancer. As PSA levels vary slightly between methods, repeat testing should ideally be performed using the same methodology or the same laboratory.

Risk of prostate cancer is related to family history, age, PSA levels and digital rectal examination (DRE) abnormalities. Men seeking to assess their risk of prostate cancer should be offered PSA testing and a DRE from the age of 40 years as a baseline measure. PSA measurements performed in men under the age of 50 years are predictive of future risk, rather than being a measure to detect the very small number of incident cases within this age group.

The ability of PSA to predict risk of prostate cancer is enhanced by the use of (i) age-related PSA reference limits, (ii) age-related PSA medians, (iii) free to total PSA ratio, and (iv) estimation of the rate of PSA rise.

Men with PSA levels above the age-related median should be tested annually. Those men with PSA levels below the median could be tested less frequently. PSA levels that suggest high risk should be followed up with biopsy.

I. Age-related reference intervals. The upper reference for PSA levels rises with age from close to 2.2 μg/L in a 40-year-old man to over 6.5 μg/L in men over the age of 70 years. PSA levels above the age-related upper reference limit carry an increased risk of prostate cancer and should be followed up immediately.

II. Age-related medians for any PSA measure represents the point of average risk. The median value for total PSA varies from close to 0.85 μg/L in a 40-year-old man to 1.5 μg/L in men over the age of 70 years. As stated above, men with PSA levels above the median have above average risk and should be tested annually. Those men with PSA levels below the median have lower risk and could be tested less frequently.

III. In patients with a result above the age-related reference interval a low free to total PSA ratio (below 10%) represents a high risk of prostate cancer and should be followed up immediately.

IV. PSA levels that rise quickly represent a high risk of prostate cancer. A PSA rise that equates to a doubling time that is faster than three years or a rise of more than 0.75 μg/L per year represents a high risk that should be followed up immediately.

Prostate cancer is a serious disease and all patients with concerns about their risks of having the disease and/or their prognosis if diagnosed, should discuss these with their doctor. The likely benefits of early detection and treatment diminish beyond the age of 70 years due to competing morbidity and mortality from other causes; however, these issues should be discussed with each patient individually.

References

1. Incidence of cancer. In: Australian Institute of Health and Welfare (AIHW) and Australasian Association of Cancer Registries. Cancer in Australia: An Overview, 2010. Canberra: AIHW, 2010; 10–9. Cancer series no. 60. Cat. no. CAN 56.
2. Mortality from cancer. In: Australian Institute of Health and Welfare (AIHW) and Australasian Association of Cancer Registries. Cancer in Australia: An Overview, 2010. Canberra: AIHW, 2010; 22–3. Cancer series no. 60. Cat. no. CAN 56.
3. Burden of disease due to cancer. In: Australian Institute of Health and Welfare (AIHW) and Australasian Association of Cancer Registries. Cancer in Australia: An Overview, 2010. Canberra: AIHW, 2010; 60–3. Cancer series no. 60. Cat. no. CAN 56.
© 2011 Royal College of Pathologists of Australasia