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Screening and Early Diagnosis of Prostate Cancer This guideline has been revised by the Toward Optimized Practice-Prostate Cancer Access Project ((TOP-PROCAP) Working Group and is based on current scientific evidence. Due to the evolving body of evidence related to population based screening for prostate cancer, this guideline will continue to be reviewed on a biannual basis. Issues • Although the mortality rates from prostate cancer are declining, it is unclear whether this decline is attributable to prostate specific antigen (PSA) testing • PSA testing is critical in the ongoing surveillance and management of men with proven prostate cancer • The natural history of prostate pathology is that most men with prostate cancer will die with it rather than from it Goals • To provide guidance about the appropriate use of PSA testing • To help physicians and their patients make informed decisions about the early diagnosis of prostate cancer in asymptomatic men of any age Recommendations There is increasing evidence to support the use of PSA in making an earlier diagnosis of prostate cancer. • We suggest men be advised of the reliability of PSA testing, as well as the potentialbenefits and risks of the test, as the latter may occur if further investigations are required • We suggest PSA testing be discussed with the following asymptomatic individuals: • Most men over 50 years of age1 • Men at higher risk for the development of prostate cancer (family history of prostate cancer*,2,5 or African- Canadian descent3,4) • Men who express a concern about the development of prostate cancer *What constitutes family history is somewhat uncertain but it has been suggested as a first degree relative with prostate cancer diagnosed before age 65.*,2,5 • The appropriate use of PSA testing can include: • Evaluation of a man with an abnormal digital rectal examination (DRE) • Evaluation of a man with lower urinary tract symptoms (LUTS) • Assisting in the early diagnosis of prostate cancer in a man who has been advised of the risks and benefits of the tests and through shared-informed decision making would like to proceed with testing • Follow-up of a man with prostate cancer • If proceeding with testing, then we suggest both DRE and PSA be performed. • DRE is not as sensitive as PSA, however, DRE may provide useful information: i. Might identify some cancers missed by PSA ii. Might help decision-making regarding referral iii. Is useful in assessing the size of the prostate and staging cancer if present • Please note that many of the associated risks of PSA also apply to DRE (eg, false positive) • Identified by urine cultures on two clean catch specimens that are positive in a resident who has no urinary tract infection symptoms Pratice Points Until the laboratory requisitions in current use are updated, family physicians wanting to order the serum PSA should add the test to the requisition form and indicate “medically required” (no cost to the patient) Utilization of the PSA as a screening procedure or for the early diagnosis of prostate cancer is inappropriate in men with a life expectancy of less than 10 years Background Prostate cancer is the most common cancer among Canadian men (excluding non melanoma skin cancer). In 2010, an estimated 24 600 men will be diagnosed with prostate cancer and 4300 will die of it. On average, 470 Canadian men will be diagnosed with prostate cancer every week. In Alberta, prostate cancer is the most frequently diagnosed type of cancer for men; an estimated 2500 Albertan males will be diagnosed with prostate cancer in 2010.4 The probability of developing prostate cancer is one in 7 men (the highest risk comes after age 60). The probability of dying from prostate cancer is one in 27.4 Role of PSA Testing Mild elevations of PSA are frequently associated with benign prostatic disease. For a given individual there may be variations in PSA levels independent of cancer. PRACTICE POINT PSA should not be measured in patients with a confirmed acute urinary tract infection (UTI), prostatitis, urinary retention or recent catheterization. Role of Dre A suspicious DRE is an indication for serum PSA testing and consideration of referral to an Urologist. Please see Appendix A: Recommendations for Referral of Patients with Suspected Prostate Cancer. PRACTICE POINT An abnormality in either DRE or PSA should trigger further assessment Risk Factors for Prostate Cancer Men at higher risk for the development of prostate cancer are those with a family history of prostate cancer or those of African Canadian descent.3,6 What constitutes family history is somewhat uncertain but it has been suggested as a first degree relative with prostate cancer diagnosed before age 65.2,7 Recommended Risk Adjusted Prostate Specific Antigen (PSA) Cut-Off Values6 Age (Years) PSA Cut-Off Values (ng/ml) AfricanCanadians 40-49 2.5 2.0 50-59 3.5 4.0 60-69 4.5 4.5 70-79 6.5 5.5 Assessment of Symptomatic Patients In aging men, both benign prostatic hyperplasia (BPH) and prostate cancer are common, and often coexist. LUTS can be associated with both, and warrant further investigation based on a number of factors that may include age and life expectancy of the patient. Some men with BPH will have mildly elevated PSA levels, but the possibility of a coexistent prostate cancer must be kept in mind. Concepts such as age related PSA values, which take into account some PSA change with increasing (benign) prostate enlargement, may be useful in determining which patient should be considered for further investigation. The most appropriate way to detect prostate cancer in these men is a combination of DRE and PSA. Transrectal ultrasound (TRUS) of the prostate is not useful in the diagnosis of prostate cancer. TRUS does however, provide an excellent means of guiding transrectal biopsies of the prostate. Please see Appendix A: Recommendations for Referral of Patients with Suspected Prostate Cancer Does an Increased PSA Mean Cancer? In assessing the potential benefits of any screening test the problems of false positive results and the potential harm of testing and the risks of treatment must also be evaluated. For example, in men over 50, the positive predictive value of a PSA>4.0 g/L is only 31%. (Although PSA>4.0 g/L alone has a positive predictive value of 31% if you add a positive DRE the PPV increases to 49-72%).8 Many men with an abnormal PSA will not have cancer. However, before cancer is ruled out, these men must undergo additional testing such as repeat PSA testing, urology assessment and biopsy. Interpretation of Prostate Specific Antigen (PSA) Values9 PSA value Interpretation 0.5-4.0 ng/mL Normal 4-10 ng/mL 20% chance of cancer >10 ng/mL 50%+ chance of cancer Rise of >20%/year Refer for biopsy Previous Studies The first two studies of prostate cancer screening had important concerns that limit interpretation and application to practice. In the first, 1 in every 6 males (1494 total) age 50-69 were randomly selected from the entire population of 9026 males in a municipality of Norrkoping, Sweden.10 The remaining group (7532) served as the control. Screening consisted of 4 rounds, 3 years apart. In all four rounds, DRE was performed; in the first round, a general practitioner and urologist completed the exam and in subsequent rounds the general practitioner completed the exam. PSA was not done in the first 2 rounds but was added in the last 2 rounds. Although long-term follow-up was quoted as 15 years (1987-2003), the PSA portion had follow-up of 10 years or less (1993-2003). The study was designed as a pilot to determine how to best design a screening program. Prostate cancer mortality was 1.29% in the screened group and 1.34% in the unscreened group, with no statistical difference. Concerns with this study are numerous. It was not a true randomized controlled trial (only a portion was randomized from a population), it was grossly underpowered to show any difference in prostate cancer mortality, and it used PSA only for second half of the screening time. This study adds little to our understanding of screening for prostate cancer. In the second study, all men aged 45-80 in the Quebec City area (46 486) were randomized at a ratio of 2 of every 3 males to an invitation for screening (31 133) or no invitation (15 353).11 Of those invited to screening, only 7348 (23.6%) agreed to participate and the remaining 23 785 (76.4%) did not have any screening. Screening in the first year (1988) was DRE and PSA but subsequent annual screening rounds included only PSA (plus DRE if positive). The trial lasted 11 years (completed 1999). Of those not invited for screening, 14 231 (92.7%) did not have any screening and 1122 (7.3%) did receive some screening. Therefore, the intention to treat analysis would compare 31 133 men of whom 23.6% got some screening to 12 353 men of whom 7.3% got some screening. The prostate cancer mortality in the invited group was 153 of 31 133 men (0.49%) and in the not invited group was 75 of 15,353 men (0.49%), with no statistical difference (p=0.56). Using a per-protocol type analysis, the prostate cancer mortality was 11 of 8470 men (0.13%) in the screened group and 217 of 38 016 men (0.57%) in the non-screened group, a statistically significant difference (p=0.0025) over 11 years. This would suggest a number needed to screen of 228 over 11 years but the results are biased as the people attending screening are likely different than those not-attending screening and may have better survival regardless of the screening. This study is severely challenged by the fact that only 16% more of the invited group received screening compared to the not-invited group and more than three quarters were not screened in the group invited for screening. Large National Studies of Prostate Cancer Screening In the last 2 years, our understanding of PSA based prostate cancer screening has grown considerably. The PLCO (Prostate, Lung, Colorectal and Ovarian) study12 is a randomized controlled trial of 76 693 men performed in 10 centers in the United States. Men, ages 5569 (mean 60.8), were randomized to annual screening PSA tests for 6 years and DRE exams for 4 years or no screening (control). PSA cut- Related Prostate Screening Studies In the last year, we have seen some of the studies within ERSPC published and these provided more understanding. The Göteborg Sweden study14 is a randomized controlled trial of 20 000 men performed in Göteborg Sweden. Men, ages 50-64 (mean 56), were randomized to PSA testing every 2 years (without DRE) or no screening (control). PSA cutoff for further work-up was 3 ng/mL (decreased to 2.5 ng/mL later). The trial was well designed with blinding of mortality assessors, the use of intention to treat analysis and randomization from the population. Although randomization of the population meant that only 76% of men randomized to screening actually accepted and attended any screening, this design would be similar to broad screening invitations in an unselected population. Although this was part of the ERSPC study, it actually started before ERSPC and joined later (so can be considered a distinct study and not a subgroup). After 14 years of follow-up, prostate cancer was diagnosed in 11.4% of those screened and 7.2% of those in control. Prostate cancer death occurred in 0.5% of those screened compared to 0.9% of those in control, rate ratio of 0.56 (CI 0.39-0.82). The absolute difference in prostate cancer death was 0.4% with a number needed to screen of 293 and number needed to treat of 12 to prevent one prostate cancer death over 14 years. Low to moderate risk prostate cancers represent 85% of cancers found by screening and 62% in the control. On first test, PSA results were <1 ng/ mL in 48%, 1-3 ng/mL in 39%, and >3 ng/mL in 12.5% and at follow-up, prostate cancer was diagnosed in those groups at 2.6%, 17.6%, and 45.5% respectively. Another study compared the screened population of the Netherlands portion of ERSPC with an unscreened population in Ireland (94% versus 6% having had a PSA, respectively).15 Although this is not a comparison of randomized subjects, it supports the results of the ERSPC13 in general and the longer trial of Göteborg.14 Over a median followup of 8.5 years, prostate cancer related death were 0.29% screened Netherlands group versus 0.47% Irish control, for a statistically significant (p=0.008) difference of 0.18%. This equates to a number needed to screen of 555 and a number needed to treat of 37 to prevent one prostate cancer death over 8.5 years. A recent systematic review and meta-analysis of prostate cancer screening has been published reporting that screening results in no reduction in prostate cancer mortality (0.88, 0.71 to 1.09; P=0.25).16 The systematic review includes 6 studies but one was too short and does not provide prostate cancer mortality data. The remaining studies have been reviewed in this document and include Norrkoping Sweden,10 Quebec City,11 PLCO,12 ERSPC13 and Göteborg.14 The authors report that the prostate cancer mortality results were “considerably heterogeneous,” on statistical testing, meaning the results were different between the studies. If we look back on these studies, Norrkoping had limitations including size, primarily DRE as screening and not being truly randomized, so it should likely not be included. In the case of PLCO and Quebec studies, the difference in percent actually screened between those randomized to screening and no screening was 33% or less (85% versus 52% PLCO and 23.6% versus 7.3% Quebec). Combining data like this can serve only to confuse the situation, not clarify it. It is preferable to look at these studies individually. Harms: What is the Dependability of our Screening Tests? Although we have significantly more data on the benefits of prostate screening in reducing prostate cancer death, we are missing data on the associated harms of screening. The PLCO study found false positive rates were 5.4% for a single PSA and 6.4% for a single DRE, which increased after 4 tests to 12.9% for PSA and 17.6% for DRE.17 That means that after 4 tests, a false positive belief that there is a prostate cancer when one does not exist will occur for one in every 8 men from PSA testing and one in every 6 men from DRE. The Finnish section of the ERSPC study examined PSA results over varying ages and rounds of testing.18 Using a cut-off of ≥4 ng/ mL, positive PSA results occurred in 4.8% at age 55, 7.5% at age 59, 12.4% at age 63 and 16.5% at age 67. The proportion of true positives (biopsy confirmed cancers) to false positives (elevated PSA with no cancer on biopsy) remained relatively consistent at approximately 30% versus 70%, respectively. From age 55 to 67, prostate cancer increased from 1.2% to 4.5% while the false positive rate also increased from 3.3% to 11.1%.17 Of those with a false positive PSA result, greater than 50% of patients will have another false positive PSA result. Men with an initial false positive are also more likely to have prostate cancer identified in subsequent testing rounds; 12.3%-19.7% compared to 1.4%-3.7% for those with negative PSA test.17 The impact of false positives on future investigations is mixed with one study showing men 1.5-2 times less likely to return for subsequent screening17 while other studies show men with false positives were more likely to have urologic follow-up tests and visits.18 Up to one year after testing, more men with false positive results worry about prostate cancer than men with negative results (26% versus 6%, p<0.001).19 In a previous study, 37% of positive age-specific PSA tests were in the normal range on the next test 1 year later.20 A more recent study found 40% of positive PSA (cut-off ≥4.0 ng/ mL) tests returned to normal after 1 year. The authors suggest that repeat testing might be helpful but say the timing would vary from a few weeks to 6 months later, based on a decision by patient and clinician concern arising from clinical characteristics of each case.5 To confirm a positive test and reduce the risk of false positive, repeat testing in 3-6 months is frequently advocated, but this should be influenced by clinical concerns and the decision to retest could be much sooner. PSA, depending on age and normal range used, carries about a 1% risk of being false negative (or negative test result when the patient does truly have prostate cancer).20 Harms: What are the Risks of a Work-up for a Positive Screen? The PLCO study12 reports 0.7% of patients had complications (infection, bleeding, clots and urinary difficulties) associated with the work-up of positive screening. In the Rotterdam section of the ERSPC, 5802 biopsies were performed between 1994 and 2001.21 Minor complications rates were 23% for hematuria of >3 days or 50% for hematospermia. Major complications included pain after biopsy (7.5%, with 6% of them requiring analgesia), fever (3.5% with 94% of them receiving antibiotics), hospitalization (0.5%), and urinary retention (0.4%). This information is difficult to weigh and put in context of other screening maneuvers (see below). How Does Prostate Cancer Screening Compare with other Screening? It may be helpful to compare some of these numbers to other common screening maneuvers. Mammography22 has a number needed to screen of 1235 or 614 for 7 or 13 years, respectively, to prevent one breast cancer death in women ≥50 years of age. Screening for colon cancer with fecal occult blood testing23 has a number needed to screen of 617 over 12-18 years to prevent one colorectal cancer death. The evidence for the DRE in prostate screening is less robust. As noted below, DRE has false positive rates at least as high as PSA testing. ERSPC13 and the Göteborg14 demonstrated benefit in prostate cancer mortality but screening was generally the offer of PSA without DRE in screening. However, in the Rotterdam section of the ERSPC, 17% of the cancers identified by screening were picked up with DRE while the PSA was below4 ng/mL.24 Fortunately, modeling of screening outcomes has been done for both mammography25 and PSA testing.24 The applications of these models are limited by the large number of assumptions and combination of different studies, but they do allow for basic comparisons. Of 1,000 women screened for 10 years with mammography at age 60, 185 will be recalled for more investigations, 56 will receive a biopsy, 38 will be diagnosed with breast cancer and 5 will die from it. In the unscreened group, 24 will be diagnosed with breast cancer and 8 will die from it.25 Of 1000 men screened for 10 years with PSA at age 60, 115 will have an abnormal PSA and receive a biopsy, 53 will be diagnosed with prostate cancer and 3.5 will die from it. In the unscreened group, 23 will be diagnosed with prostate cancer and 4.4 will die from it. Although mortality reductions appear worse, prostate disease is slower and longer modeling may be required. As noted above, the number needed to screen at years beyond 10 is very similar for mammogram and prostate. That said, the harms of a work-up are likely higher in prostate cancer screening. Breast biopsy, particularly core-needle biopsy 26 seems to be associated with fewer adverse events than prostate biopsy. For example, infections requiring antibiotics occur in 0.15% of core-needle breast biopsies compared to 3.3% of prostate biopsies. What are the Complications Related to the Treatment of Prostate Cancer? The quality of life impacts and risks of prostate cancer management (including radical prostatectomy and/or radiotherapy) are incontinence, urethral stricture, bowel damage, erectile dysfunction, as well as complications arising from anesthesia and major surgery, including death.27 Screening patients will identify cancer that may never have manifested clinically. These patients will not benefit from treatment but are subject to the potential risk associated with treatment. Although we are moving towards differentiating patients with clinically meaningful cancer from those with little or no clinical risk, this is still uncertain. Balancing these issues is part of the overall challenge of screening. We look forward to the continued publication of results of the European and PLCO studies on quality of life, which may help us to further understand the risks and benefits of prostate cancer screening. Advice to Patients The TOP-PROCAP Working Group supports the rights of patients to make informed decisions about their health care options. Patient education is paramount in decisions surrounding prostate cancer. It is important for the asymptomatic man to be aware of the consequences of his decision to be screened or not. Patient decisions will vary as a result of individual concerns of cancer, individual interpretation of the evidence related to benefits and risks along with consideration for the impact of procedures that may be recommended following an abnormal result. References: 1. Patel AR, Klein EA. Risk factors for prostate cancer. Nature Clinical Practice. Urology.2009:6(2):87-95. 2. Woolf C M. An investigation of the familial aspects of carcinoma of the prostate. Cancer.1960: 13:739-44. 3. Quinn M, Babb P. Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part II: individual countries. BJU Int. 2002:90:174-84. 4. Canadian Cancer Society. [Internet]. Toronto: Canadian Cancer Society; c2010 [updated 2010 May 19; cited 2010 Oct 12]. Prostate cancer statistics; [about 1 screen]. Available from: http://www.cancer.ca/Alberta-NWT/ About%20cancer/Cancer%20statistics/ Stats%20at%20a%2glance/Prostate%20 cancer.aspx?sc_lang=en&r=1 5. Ankerst DP, Miyamoto R, Nair PV, Pollock BH, Thompson IM, Parekh DJ. Yearly prostate specific antigen and digital rectal examination fluctuations in a screened population. J Urol. 2009;181(5):2071-5. 6. Prostate Cancer Canada [Internet]. Toronto: Prostate Cancer Society; c2010 [cited 2010 Oct 12]. Prostate Cancer Canada – Early Detection Guideline; [8 p.]. Available from: http://www.prostatecancer.ca/ProstateCancer/about-the-prostate/psa.aspx. 7. Brandt A, Bermejo JL, Sundquist J, Hemminki K. Age at diagnosis and age at death in familial prostate cancer. Oncologist. 2009;14(12):1209-17. 8. Wolf AM, Nasser JF, Wolf AM, Schorling JB. The impact of informed consent on patient interest in prostate-specific antigen screening. Arch Intern Med. 1996;156(12):1333-6. 9. East Coast Area Health Board. GP referral guidelines for suspected cancer. Chapter 5 Prostate Cancer. [Internet]. Bray: East Coast Area Health Board, Cancer and Palliative Care Services; 2004. [cited 2010 Nov 8]. Available from: http://hdl.handle. net/10147/44981. 10. Sandblom G, Varenhorst E, Löfman O, Rosell J, Carlsson P. Clinical consequences of screening for prostate cancer: 15 years followup of a randomised controlled trial in Sweden. Eur Urol. 2004;46(6):717-23. 11. Labrie F, Candas B, Cusan L, Gomez JL, Bélanger A, Brousseau G, Chevrette E, Lévesque J. Screening decreases prostate cancer mortality: 11-year follow-up of the 1988 Quebec prospective randomized controlled trial. Prostate. 2004;59(3):311-8. 12. Andriole GL, Crawford ED, Grubb RL, III, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostatecancer screening trial. N Engl J Med. 2009;360(13):1310-9. 13. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320-8. 14. Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, et al. Mortality results from the Goteborg randomised populationbased prostate-cancer screening trial. Lancet Oncol. 2010;11(8):725-32. 15. van Leeuwen PJ, Connolly D, Gavin A, Roobol MJ, Black A, Bangma CH, et al. Prostate: cancer mortality in screen and clinically detected prostate cancer: estimating the screening benefit. Eur J Cancer. 2010;46(2):377-83. 16. Djulbegovic M, Beyth RJ, Neuberger MM, Stoffs TL, Vieweg J, Djulbegovic B, Dahm P. Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ. 2010 Sep 14;341:c4543. 17. Croswell JM, Kramer BS, Kreimer AR, Prorok PC, Xu JL, Baker SG, et al. Cumulative incidence of false-positive results in repeated, multimodal cancer screening. Ann Fam Med. 2009;7(3):212-22. 18. Kilpelainen TP, Tammela TL, Maattanen L, Kujala P, Stenman UH, Ala-Opas M, et al. False-positive screening results in the Finnish prostate cancer screening trial. Br J Cancer. 2010;102(3):469-74. 19. Fowler FJ, Jr., Barry MJ, Walker-Corkery B, Caubet JF, Bates DW, Lee JM, et al. The impact of a suspicious prostate biopsy on patients’ psychological, socio-behavioral, and medical care outcomes. J Gen Intern Med. 2006;21(7):715-21. 20. Eastham JA, Riedel E, Scardino PT, Shike M, Fleisher M, Schatzkin A, et al. Variation of serum prostate-specific antigen levels: an evaluation of year-to-year fluctuations. JAMA. 2003;289(20):2695-700. 21. Raaijmakers R, Kirkels WJ, Roobol MJ, Wildhagen MF, Schrder FH. Complication rates and risk factors of 5802 transrectal ultrasound-guided sextant biopsies of the prostate within a population-based screening program. Urology. 2002;60(5):826-30. 22. Gotzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev. 2009 (4):CD001877. 23. Hewitson P, Glasziou P, Watson E, Towler B, Irwig L. Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (hemoccult): an update. Am J Gastroenterol. 2008;103(6):1541-9. 24. Ontario Prostate Specific Antigen (PSA) Clinical Guidelines: the PSA Clinical Guideline Expert Committee for the Laboratory Proficiency Testing Program (LPTP), 97.09.30: physician reference document [Internet]. [cited 2010 Oct 12]. Available from: http://www.health.gov.on.ca/english/providers/ pub/cancer/psa/psa_guide/psa_clinic al_ guidelines.pdf. 25. Barratt A, Howard K, Irwig L, Salkeld G, Houssami N. Model of outcomes of screening mammography: information to support informed choices. BMJ. 2005;330(7497):936. 26. Bruening W, Fontanarosa J, Tipton K, Treadwell JR, Launders J, Schoelles K. Systematic review: comparative effectiveness of core-needle and open surgical biopsy to diagnose breast lesions. Ann Intern Med. 2010;152(4):238-46. 27. Berry DL, Moinpour CM, Jiang CS, Ankerst DP, Petrylak DP, Vinson LV, et al. Quality of life and pain in advanced stage prostate cancer: results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone. J Clin Oncol. 2006;24(18):282835. 28. Smith RA, Cokkinides V, von Eschenbach AC, Levin B, Cohen C, Runowicz CD, Sener S, Saslow D, Eyre HJ; American Cancer Society. American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin. 2002;52(1):8-22. For those interested in more details regarding prostate cancer screening, benefits and risks, the American Cancer Society Guideline provides an excellent detailed review.28 More Information For full guideline and summary, please see the Clinical Practice Guideline for Screening and Early Diagnosis of Prostate Cancer at the TOP web site: http://www.topalbertadoctors.org/ informed_practice/cpgs/prostate_cancer.html 2010 prostate guideline revisions were completed by the Toward Optimized Practice- Prostate Cancer Access Project (TOP-PROCAP) Working Group. Suggested Citation: Toward Optimized Practice-Prostate Cancer Access Project (TOP-PROCAP) Working Group. Clinical practice guideline for screening and early diagnosis of prostate cancer. Edmonton, AB: Toward Optimized Practice. 2010. Available from: http://www.topalbertadoctors.org/ informed_practice/cpgs/prostate_cancer.html Toward Optimized Practice 12230-106 Avenue, NW Edmonton, Alberta T5N 3Z1