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Prostate
PSA Screening
Patient Information Document

PSA Screening

Updated 4 November 2010

Summary

  • The Genitourinary Tumour Group of the BC Cancer Agency and the Vancouver Prostate Centre are recommending PSA testing for asymptomatic men who are well informed about the risks of over-diagnosis and over-treatment, but still wish to pursue the benefits of early diagnosis of prostate cancer
  • There is evidence from randomized controlled trials that mortality decreases with PSA screening for the early detection of prostate cancer and its treatment, but that a significant number of men will need to be treated (with all the risks that that entails) who would otherwise not have had a problem with prostate cancer in their lifetime
  • The decision to use PSA for the early detection of prostate cancer should be individualized
  • Early detection and risk assessment of prostate cancer should be offered to asymptomatic men 50 years of age or older with an estimated life expectancy of more than 10 years, who wish to be tested
  • Abnormal results should trigger referral to a urologist
  • Early detection of prostate cancer should be linked to a treatment algorithm that includes discussion and prioritization of active surveillance for men with low risk prostate cancer

1. Prostate Cancer is a Common Disease and Cause of Morbidity and Mortality
 
Prostate cancer is the most common non-skin cancer in men in Canada and the third leading cause of male cancer mortality; 550 men die from it each year in BC and 3000 are diagnosed.  If diagnosed early when localized, it can be treated with high cure rates.  When advanced, it may cause significant morbidity and mortality, including fatigue, ureteral obstruction, and bone pain.  Early detection and treatment of prostate cancer aims to reduce the risks of suffering and death from advanced disease.
 
Prostate cancer is also a highly prevalent disease as approximately one in three men over the age of 50 years has histologic evidence of prostate cancer, with most of these tumors being clinically insignificant (i.e. not at risk of causing harm in a man’s lifetime).  Despite this high prevalence, the lifetime risk of death from prostate cancer is only about 3%, highlighting its generally indolent course, and competing causes of death.  Reduction in the risk of prostate cancer diagnosis is possible by the use of 5a-reductase inhibitors (level 1 evidence [1]), or by lifestyle modification including weight control, increased exercise, and decreased meat consumption, (level 3 evidence[2]). 
 
Level 1 evidence supports the treatment of localized disease. Prostate cancer mortality is reduced in men younger than 65yrs with surgery[3] or those with a 10 year life expectancy with radiation[4].
 
The disparity between the high prevalence of prostate cancer and its relatively low risk of death highlights the importance of distinguishing those cancers that are destined to cause significant illness and premature death from those that are not. Currently there is no test, including PSA that reliably makes this distinction.

2. Prostate Specific Antigen (PSA)

Serum PSA is widely used to aid detection of prostate cancer. Unfortunately it is not a particularly good screening test, with a positive predictive value of ~25%. While it is an independent predictor of disease progression and treatment failure, serum PSA does not distinguish between clinically indolent cancers and those that may go on to cause death.

A continuum of prostate cancer risk exists with varying PSA levels, and ‘normal’ levels vary by age.

PSA level (ng/ml)

Prostate cancer prevalence %

Age (years)

Age-specific median value

<1

6-10%

40-50 yrs

0.7ng/ml

1-4

17-25%

50-60

0.9ng/ml

4-10

20-30%

60-70

1.2ng/ml

>20

80%

>70

1.5ng/ml


Age-adjusted reference ranges, PSA velocity (rate of change over time), free/total PSA ratio, and PSA density (PSA level relative to gland volume) improves the sensitivity and specificity of PSA as a screening test. Currently, individualized risk assessments of not only of prostate cancer but also of “significant” prostate cancer, is based on these determinants of PSA, as well as digital rectal examination (DRE) of the prostate, patient age, co-morbidities, family history, ethnicity, and prior biopsy history.  These refinements have not been subject to randomized studies.

3. Evidence Supporting PSA Testing 

There has been a gradual 30% decline in prostate cancer mortality in the U.S. and Canada which started 4-5 years after the introduction of PSA testing. Statistical modeling studies indicate that PSA testing has played a role in this decline. PSA testing has also led to a marked increase in the diagnosis of early cancers that would not be expected to cause any symptoms had they not been detected (‘over diagnosis’).
 
Recent European randomized  trials [5],[6] demonstrated a 44% and 20% relative reduction in prostate cancer deaths among those offered screening when compared to those that were not. In the more mature Göteborg study (14 years median follow-up)[5]  the benefit was greater than in the less mature ERSPC study (9 years median).[6]   The Göteborg trial estimated that 293 men would need to be offered screening and 12 men diagnosed for prevention of one prostate cancer death over a 14 year period. The ERSPC trial estimates were 1410 and 48, respectively, but are expected to reduce as the trial matures further. The NCI-US PLCO study found no difference in prostate cancer deaths at 7-10 years of follow-up when comparing unscreened men[7].  However, in this immature, underpowered study, 44% of men were prescreened and screening in the control group was very substantial (52% in the 6th year) which would have masked any impact of screening on mortality. Given the protracted natural history of many prostate cancers, longer follow-up is necessary to address the balance of benefits and harms of screening for prostate cancer.
 
Nonetheless it is still unclear whether prostate cancer screening results in more benefit than harm, and thus a thoughtful and balanced approach to PSA testing is critical. The results of the European trials identify a clinically significant benefit from PSA screening, as well as an opportunity to guide prostate cancer screening (and treatment) algorithms in BC. However the use of PSA testing for the early detection of prostate cancer remains controversial owing to the risk for over-diagnosis and over-treatment.  The latter may be addressed by uncoupling treatment as an inevitable response to diagnosis.  Once this is done, the issue of prostate cancer screening becomes less controversial.
 
The Canadian Partnership Against Cancer, Screening Action Group recently assessed the current evidence regarding PSA screening and concluded that while expansion of PSA testing practices was not justified and might produce net harm, but there was insufficient evidence to discourage current ‘ad hoc’ PSA testing practices.[8] 
 
At the present time, PSA testing is common (~50% of men over 55yrs have been tested in BC) but is not ideally performed in BC or across Canada.  Considerable confusion and misinformation exists amongst public and primary care physicians, leading to inappropriate PSA testing (too young or too old, too frequent, duplication), inappropriate biopsies, leading to over-detection and over-treatment.  Hence, there is a need to refine PSA testing (in whom, and how) with guidelines to systematically manage indications for testing, biopsy, and subsequently treat only those who are likely to benefit from it. 
 
It is noted that a baseline PSA level from men in their 40s above the age-adjusted median value is a strong predictor of future risk of prostate cancer; those with a PSA value below the median (0.6 to 0.7ng/mL) are at very low risk while those above the median are at higher risk. [9]  At the present time, it is uncertain how and whether to incorporate this information into a PSA testing algorithm. 
 
DRE of the prostate has traditionally played a role in the early detection of prostate cancer.  The sensitivity of DRE to detect cancer is less than that of PSA, and the ERSPC trial dropped DRE as part of its screening protocol.  Nonetheless some men will develop significant cancers without a rise in PSA, and therefore it may also be considered in those who wish to pursue early detection of prostate cancer.

4. Recommendations
 
Because there is now evidence from two randomized controlled trials that mortality decreases with PSA screening and treatment, the Genitourinary Cancer Tumour Group of the BC Cancer Agency and the Vancouver Prostate Centre are recommending PSA screening for well-informed men who wish to pursue early diagnosis. 
  1. The decision to use PSA testing for the early detection of prostate cancer should be individualized. Patients should be informed of the known risks and the potential benefits PSA testing. 
    • Men need to be informed of the risks and benefits of testing before it is undertaken. The risks of over-detection and over-treatment should be included in this discussion.
    • The following is a brief summary of risks and benefits of early detection of prostate cancer. (Recommended reading: Andrew M. D. Wolf et al, American Cancer Society Guideline for the Early Detection of Prostate Cancer: Update 2010. CA CANCER J CLIN 2010; 60:70–98) 
    • Risks of PSA testing and Early Detection of Prostate Cancer
      • False negative and false positive PSA results. A low PSA test does not mean that a person does not have prostate cancer, and a high PSA does not necessarily mean a person does have prostate cancer.
      • Biopsy: Pain and very rarely infection.
      • Distress and anxiety. Being diagnosed with prostate cancer is associated with anxiety.
      • Overdiagnosis and treatment. Overdiagnosis refers to the detection of cancers that would not otherwise have become clinically apparent. This could result in treatment of a prostate cancer that may not have been a problem for a man in his lifetime. The risks of treatment such as radiation and surgery include urinary problems and incontinence, sexual dysfunction, and bowel problems. 
    • Benefits of PSA testing and Early Detection of Prostate Cancer
      • Early detection of prostate cancer can save lives. From what we know so far, at its best, 293 men need to be screened and 12 diagnosed with prostate cancer to prevent 1 death over a 14 year period.
      • Early detection and treatment of prostate cancer can avert future prostate cancer-related problems. 
  2. Early detection and risk assessment of prostate cancer should be offered to asymptomatic men 50 years of age or older with an estimated life expectancy of more than 10 years who wish to be screened.
    • Early detection begins at age 50 years for men at average risk of prostate cancer.
    • The optimal frequency of PSA testing is not known. The recent studies performed PSA testing every 2 to 4 years.
    • PSA testing should generally cease when life expectancy falls below 10 years.
    • Men with higher risk for prostate cancer should consider screening at age 40 to 45 (African American origin, family history of prostate cancer, BRCA1 or BRCA2 mutation carrier).
  3. Abnormal results trigger referral to urologists.
    • Any subsequent decision to recommend biopsy needs to include consideration of life expectancy, co-morbidities, prostate co-conditions (e.g. large BPH, prostatitis), PSA velocity, DRE findings, and patient risk factors and preference.
    • Men with a PSA of >3.0 μg/L should be referred to a urologist for consideration of biopsy. A PSA that is > 2.0 but increasing by more than 0.75-1.0 μg/L/year should also be referred.
    • Men with an abnormal digital rectal examination should also be referred to a urologist regardless of the PSA value.
  4. Treatment Guidelines for PSA-detected Cancer
    • Early detection of prostate cancer should be linked to a treatment algorithm that includes discussion and prioritization of active surveillance for appropriate candidates with low risk prostate cancer.[10]
    • Active surveillance in men with very low and low risk cancers, and some older men with intermediate risk cancer should be carried out in a programmatic manner.
    • Men with intermediate risk, high risk localized and other cancers should be treated as per current guidelines[11]

At present, PSA testing is not funded by the Medical Services Plan of British Columbia for men without urinary symptoms, an abnormal prostate examination or a history of prostate cancer. The BC Cancer Agency is currently undertaking a cost-effective analysis of PSA screening for the early detection of prostate cancer.

References

  1. Thompson, I.M., et al., The influence of finasteride on the development of prostate cancer. N Engl J Med, 2003. 349(3): p. 215-24.
  2. Ornish, D., et al., Intensive lifestyle changes may affect the progression of prostate cancer. J Urol, 2005. 174(3): p. 1065-9; discussion 1069-70.
  3. Bill-Axelson, A., et al., Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst, 2008. 100(16): p. 1144-54.
  4. Widmark, A., et al., Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet, 2009. 373(9660): p. 301-8.
  5. Hugosson, J., et al., Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. Lancet Oncol, 2010. Early view on line.
  6. Schroder, F.H., et al., Screening and prostate-cancer mortality in a randomized European study. N Engl J Med, 2009. 360(13): p. 1320-8.
  7. Andriole, G.L., et al., Mortality results from a randomized prostate-cancer screening trial. N Engl J Med, 2009. 360(13): p. 1310-9.
  8. Pickles, T. and S.A. Group, PSA Toolkit: PSA Screening and Testing for Prostate Cancer. 2009, Canadian Partnership Against Cancer.
  9. Lilja, H., et al., Long-term prediction of prostate cancer up to 25 years before diagnosis of prostate cancer using prostate kallikreins measured at age 44 to 50 years. J Clin Oncol, 2007. 25(4): p. 431-6.
  10. BCCA, Active Surveillance Guidelines. http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Genitourinary/Prostate/Management/LowRisk.htm , 2007.
  11. BCCA, Intermediate risk Guidelines. http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Genitourinary/Prostate/Management/IntermediateRisk.htm , 2007.

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