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 Primary Care Guide to Evaluation and Referral for Prostate Cancer Prostate Cancer Access Project (PROCAP) This Primary Care Guide to Evaluation and Referral for Prostate Cancer was developed by the Prostate Cancer Access Project (PROCAP)† as a clinical and educational resource for primary care practitioners in Alberta. Its aim is to support physicians in identifying and managing patients concerned about, at risk for, or suspicious of having prostate cancer in order to foster appropriate, timely referrals and communication between primary and specialist care. This guide is intended to complement and not supplant the Guideline for the Use of PSA and the Early Diagnosis of Prostate Cancer (1) developed by Toward Optimized Practice. Practice Highlights 1. In Alberta mass (population) screening for prostate cancer is not currently recommended, using any clinical methodologies (DRE or PSA). The Alberta Medical Association’s Toward Optimized Practice guideline supports an individualized (discriminate) approach and does not endorse or refute population (mass) screening. 2. PSA has important value in identifying individual patients who may be at risk for prostate cancer, particularly when used in combination with DRE which improves overall sensitivity, specificity and the positive predictive value of testing. 3. Informed patients who wish to undergo evaluation using DRE and PSA testing should be accommodated in most instances and counseled accordingly, using a shared decision‐making approach. A physician‐initiated discussion with average‐risk patients regarding DRE and PSA testing is appropriate within the context of primary care. 4. Regular evaluation using DRE and PSA testing may begin at age 50, and repeated every one to two years, for informed patients who are asymptomatic, average‐risk, and who wish to maintain regular testing intervals. 5. Periodic testing in low‐risk men under age 50 is becoming more common in practice, although the evidence supporting this change in practice is controversial and far from complete. There is no strong evidence base to routinely recommend periodic testing in this group. Practitioners should be guided by clinical judgment and the patient’s wishes. 6. Testing in asymptomatic men should generally not be undertaken when life expectancy is believed to be 10 years or less. †
The Prostate Cancer Access Project (PROCAP) is a 2007 initiative under the mandate of the Alberta Health and Wellness Wait Time Management Steering Committee (WTMSC). ©2010 Page
7. Higher‐risk patients should be offered annual DRE and PSA testing as part of routine primary care, possibly beginning as early as age 40. Higher risk patients are those with a family history (first‐degree relative diagnosed with prostate cancer diagnosed <65 years of age) and those of African‐Canadian descent. 8. Using age‐ and race‐adjusted values increases the positive predictive value of PSA testing and is therefore important in identifying men requiring specialist evaluation. 9. In most cases when there is a single, mildly elevated PSA reading, a second PSA test, conducted within 3 to 6 months, is warranted in order to confirm elevated PSA, assess velocity, and rule out spurious causes for the elevation. 10. PSA velocity (rate of PSA change over time) may be an important marker for prostate cancer, particularly in men under 60. PSA velocity ≥ 0.75 ng/mL/year, or a doubling of PSA value within two years, should raise the suspicion of prostate cancer, particularly in younger men. 11. An abnormal DRE, rapidly rising PSA, or doubling time within two years or less would normally trigger a specialist referral. 12. Patients with a history of prostate cancer should be monitored according to guidelines. In general, a rise in PSA following treatment for prostate cancer should raise the suspicion of recurrence. It is not appropriate to keep testing older men with a remote history of prostate cancer or men with significant co‐morbid conditions such as advanced Alzheimer’s disease or severe heart disease. Practice Points The diagnosis of Prostate Cancer is suspected on the basis of an abnormal DRE and elevated PSA. However, the following may lead to a false clinical diagnosis of Prostate Cancer on DRE: Similarly, PSA levels may be transiently elevated in a number of situations: •
•
•
•
•
•
•
Benign Prostatic Hyperplasia (BPH) Prostatic Calculi Prostatitis Ejaculatory Duct Abnormalities Seminal Vesicle Abnormalities Rectal Wall Phlebolith Rectal Muscosal Polyp or Tumour •
•
•
Acute Prostatitis Urinary Tract Infection Urinary Retention Page
©2010 Algorithm for Evaluation and Specialist Referral for Prostate Cancer Symptomatic patients or higher risk† patients ≥ 40 years of age and Average‐risk, asymptomatic patients ≥ 50 years of age and make an informed decision to have prostate cancer testing DRE & PSA testing
Normal DRE and normal* PSA
Age 40‐49
Average risk
Re‐
evaluate at age 50
Age 50+
Elevated PSA over time based on: ‐ 2‐3 test results, OR
‐ Rapidly rising PSA (velocity ≥ 0.75 ng/mL/yr), OR ‐PSA doubling Abnormal DRE
Single PSA >10 ng/mL in the absence of other cause
Single, mildly elevated*
Evaluate and treat
UTI Δ
Yes
No
Retest PSA at 3‐6 mos
Higher risk†
Consistently elevated* PSA or other clinical concerns
Re‐test every 1–2 years, until life expectancy ≤ 10 years Refer to Urology for evaluation
Normal* PSA & no clinical concerns
Resume routine evaluation as per patient wishes and/or age‐ and risk‐adjusted intervals
* Recommend using age‐ and race‐adjusted values for PSA † Higher risk patients include those with a family history of prostate cancer (first‐degree relative) and those of African‐Canadian descent Δ Or other benign conditions; see Practice Points above Should clinical concerns persist despite normal DRE and PSA, referral to Urology may be appropriate
Overview This Primary Care Guide to Evaluation and Referral for Prostate Cancer provides a summary of current practice and emerging research regarding evaluation for the detection of prostate cancer and management of patients with prostate cancer. Evaluation tools referenced in this document include clinical examination, digital rectal exam (DRE) and prostate specific antigen (PSA) testing. Page
DRE and PSA testing are widely accepted in the clinical evaluation of a number of lower urinary tract and lower digestive/pelvic symptoms. As well, PSA testing is widely accepted as an important tool in managing the care of men with a diagnosis of prostate cancer. However, the use of DRE or PSA testing as a population screening tool for the subclinical detection of prostate cancer remains controversial, as until 2009, neither had been consistently supported or refuted by evidence to show an overall reduction in mortality. ©2010 Interim results from two large, evidence‐based randomized controlled studies (prospective) emerged in 2009. The 182,000‐cohort European Randomized Study of Screening for Prostate Cancer (ERSPC) (2) reported a 20% drop in the death rate from prostate cancer due to annual screening. However, the Prostate, Lung, Colorectal, and Ovary (PLCO) trial in the US (3) concluded that annual population screening does not reduce the death rate from prostate cancer. Both studies are reported in more detail later in this document. Further research published in 2010 strongly affirms reduced mortality in patients over age 50 that are tested. (16) Data in favour of individualized testing continues to emerge, particularly evidence that DRE and PSA testing play an important role in detecting cancer at an earlier (organ‐confined) stage, thereby improving survival rates among those tested. As disease‐specific mortality data continue to emerge, clinicians must evaluate the emerging evidence regarding DRE and PSA testing in asymptomatic, average‐risk men. To support these testing decisions, this Primary Care Guide to Evaluation and Referral for Prostate Cancer offers practical guidance to clinicians in identifying patients who may benefit from appropriate evaluation for detection of clinically significant, treatable prostate cancer. Introduction Prostate cancer is the most common cancer among men in Canada (4) and the second leading cause of cancer death among men in the United States. (5) An estimated one in seven Alberta men (4) will develop prostate cancer during their lifetime. However, behaviour and progression of the disease varies considerably among individuals, and currently there is no single test that satisfies the need for sensitivity, specificity, and positive and negative predictive value for the detection of clinically significant and aggressive cancer(s). Countries around the world, and indeed credible urological organizations within those countries, have differing recommendations regarding the use and interpretation of PSA testing for both mass screening and individual testing. This lack of consensus, and the resulting variability in clinical practice, was discussed at length during the 2007 – 2008 steering committee meetings of the Prostate Cancer Access Project (PROCAP) (6) in Alberta. In light of the continuing debate in clinical and research circles, and the ensuing lack of consensus regarding screening and case finding at the point of care, PROCAP decided to compile this Primary Care Guide to Evaluation and Referral for Prostate Cancer as a clinical and educational resource for primary care practitioners in Alberta. Practice Tip #1: In Alberta there is currently no specific recommendation regarding mass (population) screening for prostate cancer using any clinical methodologies (DRE, PSA). This guideline supports an individualized (discriminate) approach and does not endorse or refute population (mass) screening. The term screening is often a source of ambiguity and confusion because it is not utilized or defined uniformly. Screening has been defined as the use of laboratory tests, physical examination or imaging modalities carried out on asymptomatic people with the aim of identifying subclinical disease, (7) with the primary goal of reducing the risk of death by detecting the disease at an early curable stage. (8) ©2010 Page
Use of PSA as a screening tool Screening may be subdivided into mass screening and individualized screening: (9) •
Mass screening (also called population screening) is indiscriminate and is performed with potentially less focus on the risk profile of the individual patient. (7) For prostate cancer, it involves the examination of asymptomatic men (at risk), and has taken place within the framework of a trial or study, and is initiated by a screener. (10) The result is the identification of more preclinical and asymptomatic cases of a disease in a population at risk using a suitable test, rather than making a diagnosis based on a patient’s presentation at a later stage with symptoms and signs. (11) •
Early detection (also called individualized screening) is discriminate and involves discovery of a disease or condition before the appearance of obvious signs or symptoms; in patients with cancer is more likely to lead to the detection of localized disease. (7) It represents individual case finding and is initiated by the (patient) and/or his physician (10) or as part of any other medical examination. (7) Most physicians are reportedly involved in individualized screening which consists of recommending screening tests to maintain a constant patient‐physician relationship. (7) Disease‐Specific Mortality In order to endorse or refute the efficacy of mass or population screening, the gold standard is a reduction in disease specific mortality. Indeed, the mortality rate from prostate cancer has reportedly dropped in a number of jurisdictions since the late 1980s/early 1990s, which roughly corresponds to the widespread adoption of PSA testing in the early 1990s. (12) Ontario, for example, has reported a drop since 1994, particularly among men aged 50 – 64 for whom there is a reduction of nearly 7% annually (12). In the US, death rates from prostate cancer have fallen about 30%, or 4% annually, since PSA testing was introduced. (13) However, evidence has not been clear or consistent in determining whether screening plays a role in mortality reduction overall. A Cochrane systematic review reported in 2007 that the drop in mortality cannot be attributed exclusively to population (mass) screening, concluding that “there is insufficient evidence to either support or refute the routine use of mass, selective or opportunistic screening compared to no screening for reducing prostate cancer mortality.” (14) New research findings released in 2009, however, suggest a significant drop in mortality associated with mass screening. Interim results from the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial – a large study of 162,245 subjects ‐‐ concluded that PSA screening without digital rectal examination was associated with a 20% relative reduction in the death rate from prostate cancer at a median follow‐up of 9 years. (2) This study included a control group that does not typically undergo screening for prostate cancer; therefore, results are considered a reasonable reflection of outcomes in screened versus unscreened populations. Page
ERSPC results suggest 1,400 men would need to be screened, and 48 additional cases of prostate cancer would need to be treated, to prevent one death from prostate cancer, over nine years (2). New data continues to emerge. The following table demonstrates the Number Needed to Screen (NNS) data in order to prevent one cancer death over ten years for other cancers that are commonly the focus of public screening programs (15): ©2010 Number needed to screen in order to prevent one cancer death over 10 years for different cancer sites (15) Site RRR‡ (%) Mortality§ Number Needed to Screen Cervix 20–40 20–40 600–2500 Breast 20 5–75 700–1000 Colorectal 15 30–60 1100–2200 In contrast, interim results of the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, also released in 2009, reported no mortality benefit from screening with PSA testing combined with DRE during a median follow‐up of 11 years. (3) However, study researchers acknowledge that the lack of mortality reduction observed in this trial may be due in part to widespread, routine screening practices in the US, which are believed to account for the high level of pre‐trial baseline PSA testing (44%) and the high rate of screening during the trial (52% of participants in year 6) among the study’s control group participants, leading to suggestions of “PSA contamination” in the trial. Finally, a Swedish study, the Göteborg randomized population‐based prostate‐cancer screening trial, studied 20,000 men who were randomized between PSA testing or not in 1994. The first publication of this study became available in July 2010. This study shows that prostate cancer mortality was reduced almost by half over 14 years. Overall, 293 (95% CI 177–799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. However, these data also indicate the risk of over‐diagnosis is substantial and the number needed to treat is at least as high as in breast‐cancer screening programs. As such, this study indicates that the benefit of prostate‐cancer screening compares favourably to other cancer screening programs. (16) It is important to note that all three of these studies ‐‐ the ERSPC, the PLCO and the Göteborg study ‐‐ are ongoing studies and should not be considered the definitive recommendation on mass prostate cancer screening. Morbidity and Other Measures Although a reduction in disease specific mortality, as reported from randomized clinical trials (RCTs), are the gold standard to measure the effect of population screening on disease‐specific mortality, there are also other valuable data emanating from more modest trials and interim RCT results, particularly regarding the incidence of advanced symptomatic disease as a surrogate measure for screening outcomes. (17) Preliminary results from the ongoing ERSPC produced such interim data (2007) in which authors reported a 49% reduction in the risk for metastatic prostate cancer in the biennial screening group after 10 years of follow up. (18) The Prostate, Lung, Colorectal, and Ovary (PLCO) trial in the US reported that the average lead time achieved by increased early diagnosis through screening was approximately two years. Relative risk reduction: estimates represent typical values in randomized trials for breast and colorectal cancer, while for cervix cancer RRR is based on effectiveness estimates for service screening. §
Mortality per 100,000, the range represents rates in unscreened populations (age‐specific rates for 25‐60 years for cervical cancer and 50‐70 years for breast and colorectal cancer). ©2010 Page
‡
PLCO also reported emerging evidence of a reduction in the incidence of tumors with a Gleason score of 8 to 10, which might portend a future reduction in mortality. (3) Risk of False Positives The case against mass screening is influenced not only by the inconsistency in evidence demonstrating a reduction in disease‐specific mortality, but also by the relatively high rate of false‐negatives in DRE and PSA testing, (19) which can lead to under‐diagnosis, delayed treatment, under‐treatment, or less efficacious treatment. False positives are also associated with PSA testing alone (20) ‐‐ estimated to be as high as 50% in the screening group of the European Randomized Study of Screening for Prostate Cancer (21)
– which may result in over‐diagnosis, morbidity associated with diagnostic workup (biopsies, ultrasound), unnecessary interventions, over‐treatment, and treatment‐related morbidity. This critical information should be included in the shared decision‐making process with patients. Mass Screening Recommendations Globally Regardless of the standard applied (i.e., mortality, advanced symptomatic disease, morbidity), as of 2009 population (mass) screening is not recommended by a majority of health organizations including the Canadian Cancer Society and the Canadian Task Force on Preventive Health Care, (22) nor by American organizations including the National Cancer Institute, the US Preventive Services Task Force, and the Centers for Disease Control and Prevention. However, the clinical guidelines of three prominent US organizations (The American Urological Association, (23) the American Cancer Society, (24) and the National Comprehensive Cancer Network (25)) support prostate cancer screening in average‐risk men beginning at age 50 (ACS and NCCN) or at age 40 (AUA), and in at‐risk men before age 50 (ACS, NCCN, AUA). As well, a survey of Canadian urologists and oncologists (published in 2008) shows a majority recommend routine PSA screening for men aged 50 to 70. (26) Use of DRE and PSA as Individual Case‐Finding Tools Practice Tip #2: PSA has an important role in identifying individual patients who may be at risk for prostate cancer, particularly when used in combination with DRE which improves overall sensitivity, specificity and positive predictive value of testing. The National Comprehensive Cancer Network report a 75% decrease in metastatic disease at diagnosis between 1992 and 2002, (13) and other studies credit PSA screening with a substantial shift towards detection of prostate cancer at earlier stages. (29) Given the poorer five‐year survival rate (37% to 53%) (24) ©2010 Page
There is strong evidence to suggest that a majority of prostate cancers being detected through individualized case finding are organ confined, clinically significant tumours which are more likely to result in curative treatment. (27) Between 70% (20) and 90% (24) of prostate cancers are now diagnosed during the early (organ‐confined) stage, and the American Cancer Society reports that the five‐year survival rate has increased from 67% to 100% since 1986. (24) Akin and Hricak attribute these gains to early detection practices. (28) (5)
for distant metastatic cancer, (24) it is probable that PSA testing resulting in earlier detection of organ‐
confined tumours reduces mortality and morbidity among tested patients. Because an estimated 15‐25% of all prostate cancers are not initially associated with elevated PSA, (30) (31) (32) (19) evaluation should include DRE: an abnormal DRE increases the positive predictive value of PSA (≥ 4.0) by 28% ‐ 44%. (33) (34) When used together, DRE and PSA play an important role in identifying individual men at risk of developing prostate cancer. A number of credible organizations, including the Canadian Urological Association and the Canadian Cancer Society, recommend discussing and offering DRE and PSA testing to individual patients using an informed decision‐making approach. Individualized Evaluation for Average‐Risk Men Practice Tip #3: Informed patients without life‐shortening co‐morbid conditions who wish to undergo evaluation using DRE and PSA testing should be accommodated in most instances and counseled accordingly using a shared decision‐making approach. A physician‐initiated discussion with average‐risk patients regarding DRE and PSA testing is appropriate within the context of primary care. Average‐risk asymptomatic patients should be provided with an opportunity to discuss DRE and PSA testing and the associated risks and benefits as part of a shared decision‐making approach. A physician‐
initiated discussion about testing and its associated risks and benefits is appropriate within the context of routine primary care. (35) An informed patient who wishes to proceed with evaluation should be accommodated in most instances and counseled accordingly. Age of Testing Initiation and Testing Intervals in Average‐Risk Men Practice Tip #4: Regular evaluation using DRE and PSA testing may begin at age 50, and repeated every one or two years, for informed patients who are asymptomatic, average‐risk, and who wish to maintain regular testing intervals. Practice Tip #5: Periodic testing in average‐risk men under age 50 is becoming more common in practice. However, the evidence supporting this change in practice is more controversial and is far from complete. There is no strong evidence base to routinely recommend periodic testing in this group, and practitioners should be guided by clinical judgment and the patient’s wishes. In practice, PSA testing in average‐risk men is commonly initiated at age 50. The Alberta Health Services (AHS) Cancer Care Clinical Practice Guideline on Prostate Cancer (36) recommends that “fit men between the ages of 50 and 75 with at least ten years life expectancy should be made aware of the availability of ©2010 Page
PSA as a detection test for prostate cancer . . . so they can make an informed decision as to whether to have the test performed.” Annual or biennial testing remains the common practice for those choosing to undergo evaluation. However, data is emerging to suggest that testing intervals could be safely widened – as infrequently as every four years – if mass screening were undertaken. (37) This observation was referenced in the 2008 statement of the US Preventive Services Task Force (5) but did not lead the USPSTF to make specific recommendations regarding testing intervals for individualized (discriminate) patient evaluation. There is growing evidence that elevated PSA in younger men has a higher positive predictive value (PPV) for cancer than elevated PSA in older men. (38) This has led to debate about the value of earlier testing initiation (age 40‐49) in average‐risk, asymptomatic men, with one study suggesting that a baseline PSA test at age 44 – 50 is predictive of a prostate cancer diagnosis up to 25 years later. (39) In light of emerging data, the American Urological Association, (22) which has long endorsed annual screening beginning at age 50, issued a best practice update in 2009 to lower the age of regular screening to 40 for relatively healthy, well‐informed men who want to be tested. However, there is a substantial risk of over diagnosis and there is a substantial burden to the patient and family when additional testing is recommended based on PSA testing. The overall yield of PSA screening appears much smaller in the less than 50 year old age group. In Alberta routine screening for average risk men is not recommended for men at low‐risk for prostate cancer aged 40‐49 years. In light of emerging evidence, clinicians should be prepared to discuss the risks and benefits of screening in average‐risk, asymptomatic men, allowing patients to make an informed decision about whether to be tested and at what age to begin. Individualized Evaluation for Higher‐Risk Men Practice Tip #6: Higher‐risk patients should be offered DRE and PSA testing as part of routine primary care. In an individualized case‐finding approach to evaluation for prostate cancer, annual testing starting at age 40 or 45 is recommended for patients with a family history (first‐degree relative diagnosed with prostate cancer before age 65) and those of African‐Canadian descent. It is established that the risk of developing prostate cancer is higher in men with a family history, defined as having one or more first‐degree relatives diagnosed with prostate cancer. (4) The relative risk of developing prostate cancer is reported to be 2.5 times higher in men with a family history (40) and potentially higher the earlier the age of onset among family members. (4) Men of African‐Canadian descent are also at increased risk with a prostate cancer incidence rate 1.6 times, and a mortality rate 2.4 times, that of white men. (5) The American Urological Association (AUA) and the National Comprehensive Cancer Network (NCCN) recommend offering PSA testing and DRE to higher risk men beginning at age 40, and the American Cancer Society (ACS) recommends starting testing at age 45. ©2010 Page
The Canadian Cancer Society (4) and the National Comprehensive Cancer Network (41) recommend an initial PSA test at age 40 or 45 in men who are at increased risk for early‐onset prostate cancer. Clinicians should discuss the risks and benefits of early (40 – 49) testing to ensure higher‐risk patients make an informed decision. When to Stop Testing Practice Tip #7: Testing in asymptomatic men should end when life expectancy is believed to be 10 years or less. A recent study concludes that men with a PSA of less than 3 ng/mL at age 75 to 80 are unlikely to die of or experience aggressive prostate cancer during their remaining years. (41) Due to increasing evidence suggesting that the incremental benefits of treating prostate cancer are small to none in men aged 75 or over, the US Preventive Services Task Force issued a statement in 2008 against screening men aged 75 or older. (5) This recommendation replaces the organization’s earlier (2002) recommendation. Current practice in Canada generally does not recommend routine PSA testing of asymptomatic men with a life expectancy of 10 years or less. However, due to the considerable variation in individual life expectancy, clinicians may elect to be guided by the present health of the patient rather than the average life expectancy of similar aged men and/or a fixed age cutoff of 75. In symptomatic men, PSA measurement may be considered a diagnostic test and should be undertaken in patients to establish a diagnosis regardless of life expectancy and should not be discontinued due to advancing age. PSA Test Results Interpretation Practice Tip #8: Although there remains some debate, age‐ and race‐adjusted values do increase the positive predictive value of PSA testing and are therefore important in identifying men requiring specialist evaluation. A PSA value greater than 4.0 ng/mL is well established in clinical practice as having a positive predictive value for prostate cancer. (43) However, normal PSA levels are known to change with age, and there is research suggesting that since men aged 40 – 49 have median PSA values between 0.7 to 1.23 ng/mL, (44) PSA values in the 2.5 to 4.0 ng/mL have positive predictive values for prostate cancer in younger men. (45) Likewise, PSA levels rise in older men and there is research to suggest that increasing the normal PSA thresholds in older men may reduce the number of unnecessary biopsies, (46) particularly in men aged 70 – 79. (47) These findings led to the establishment in 1997 of age‐adjusted thresholds for the PSA values considered suspicious for prostate cancer. Similar tables have been developed to reflect race‐adjusted values for men of African‐Canadian descent. ©2010 Page
Age 40 – 49 50 – 59 60 ‐ 69 70 ‐ 79 Age‐ and Race‐Adjusted Values for PSA (46) White African‐Canadian 0 – 2.5 ng/mL 0 – 2.0 ng/mL 0 – 3.5 ng/mL 0 – 4.0 ng/mL 0 – 4.5 ng/mL 0 – 4.5 ng/mL 0 – 6.5 ng/mL 0 – 5.5 ng/mL The National Comprehensive Cancer Network (NCCN) expert panel opted not to include age‐ and race‐
adjusted values in its 2007 Clinical Practice Guidelines (41) due to ongoing debate, instead endorsing the use of PSA velocity values for early detection of prostate cancer. Other Factors Influencing PSA Values and interpretation Practice Tip #9: In many cases involving a single, mildly elevated PSA reading, a second PSA test, conducted within 3 to 6 months, is warranted in order to confirm elevated PSA levels and rule out spurious causes. Clinicians should be aware that some factors may affect PSA levels and should be considered when assessing patients for further evaluation. •
There is some individual biological variability in normal PSA values; therefore a single PSA value may not reflect a definitive measure of suspicion, particularly in the absence of other clinical concerns. •
Urinary tract infection (UTI) in men is commonly associated with an element of prostatitis, which is known to increase serum PSA levels. (48) (49) Patients with signs of UTI should not routinely have their PSA tested, as it has no clinical value in this setting. When a PSA has, however, been drawn in the setting of a UTI, the patient’s PSA should be re‐measured following appropriate treatment prior to being referred for specialist evaluation. •
Ejaculation within 24 – 48 hours prior to PSA testing may raise PSA slightly. Repeat testing may be warranted following a 48‐hour abstention; however, patient sensitivity and the risks of delayed or repeat testing should also be considered. •
The 5‐alpha reductase inhibitors finsteride (Proscar™) and dutasteride (Avodart™) can lower PSA, regardless of the dose, and should therefore be considered in PSA results interpretation. For patients taking these medications regularly for more than a few months, multiplying the reported PSA laboratory value by 2 will closely approximate the patient’s true PSA level. Page
In most cases involving a single mildly elevated PSA reading, a second PSA test, conducted within 3 to 6 months, is warranted in order to confirm rising PSA levels, assess the velocity, and rule out spurious causes. Patients with a strong cancer concern based on a single significantly elevated PSA result, such as a result of >10 ng/ml without any other evident cause, may be referred immediately. Clinical judgment always takes precedence in making these decisions. ©2010 Velocity and Doubling Time Practice Tip #10: Although there remains some debate in scientific circles, PSA velocity (rate of PSA change over time) may be an important marker for prostate cancer, particularly in men under 60. PSA velocity ≥ 0.75 ng/mL/year, or a doubling of PSA value within two years (doubling time), should raise the suspicion of prostate cancer, particularly in younger men. Velocity refers to the change in PSA value over time based on a minimum of two readings over one year or three test results over 18 months. (41) Velocity is believed to be a marker of prostate cancer aggressiveness and mortality. (45) (50) PSA velocity of more than 0.75 ng/mL over one year, or rapid doubling time (i.e., a doubling of PSA value over a period of two years or less) is considered to increase the positive predictive value for clinically significant prostate cancer, (51) (52) (53) (41) particularly in younger men (≤60 years). Furthermore, there is emerging research to suggest that younger men who have PSA values within normal limits may be at increased risk of aggressive cancer when PSA rises by as little as 0.4 to 0.6 ng/mL annually. (45) (54) While a PSA velocity of 0.5 to 0.75 ng/mL per year increases the rate of cancer detection, larger increases (3.0 to 4.0 ng/mL) may be more indicative of prostatitis, warranting follow‐up PSA testing to assess for an expected drop in post‐inflammation PSA level. PROCAP Recommendations for Referral for Specialist Evaluation Practice Tip #11: An abnormal DRE, rapidly rising PSA, or short doubling time would normally trigger more frequent or aggressive monitoring intervals and/or a specialist referral. In most other cases of elevated PSA, a second test should be conducted within 3 – 6 months to rule out spurious causes and confirm the need for specialist evaluation. Primary care physicians are encouraged to use their best clinical judgment and patient history as a guide to specialist referral for prostate cancer assessment. In the absence of accompanying clinical concerns or history, patients generally do not require specialist evaluation on the basis of a single elevated PSA result except in the circumstances listed below. In most cases a second PSA test is warranted (conducted within 3 to 6 months) to rule out spurious causes and to confirm elevated PSA. Repeat PSA tests may be initiated by the primary care physician or urologist, depending on local practices and preferences. •
Abnormal DRE suspicious for prostate cancer with or without elevated PSA •
Consistently elevated PSA demonstrated over time (2 – 3 readings over a 1 – 2 year period) ©2010 Page
In general, specialist evaluation is recommended in the following circumstances for patients of all ages (refer to algorithm on page 2 for details): •
Rapidly rising PSA (≥ 0.75 ng/mL annually, particularly in younger men)
•
Doubling of PSA value in two years or less
•
A single PSA >10 ng/ml in the absence of other cause
•
Other concerns of the primary care physician or patient.
Monitoring and Re‐Referral of Patients Post‐Treatment for Prostate Cancer Practice Tip #12: In general, a rise in PSA following treatment for prostate cancer should raise the suspicion of recurrence. Patients with a history of prostate cancer should be monitored according to Alberta guidelines. Prostate cancer treatments such as radiotherapy or prostatectomy may result in levels of PSA well below the previously referred to age and race specific PSA levels – in fact they may become undetectable. For this group of patients the age and race specific PSA reference levels may not be relevant. Therefore, the published PSA reference thresholds should not be used when assessing patients previously treated for prostate cancer. In general, a rise in PSA following treatment for prostate cancer should raise the suspicion of recurrence. Whether treatment for prostate cancer is curative or palliative, all patients should be closely monitored post‐treatment for signs or symptoms of recurrence or progression: •
Patients who have undergone a radical prostatectomy (curative treatment) should be referred for
specialist evaluation on the basis of any measurable PSA level. •
Patients who have undergone any treatment other than a radical prostatectomy should be referred
for specialist evaluation on the basis of: o
Rising PSA
o
Signs or symptoms of metastases
Upon their return to primary care for ongoing management, patients should be followed and monitored dependent on factors such as tumour stage, grade, density, Gleason score, treatment modality, treatment efficacy, and patient age and health status. Practitioners should consult with the specialist care team or guidelines to establish the frequency of testing and any special considerations regarding monitoring and re‐referral Page
For full guideline and summary, please see the Clinical Practice Guideline for Screening and Early Diagnosis of Prostate Cancer at the TOP web site: www.topalbertadoctors.org/cpgs/2073602 ©2010 References 1. Alberta Medical Association. Guidline for the Use of PSA and the Early Diagnosis of Prostate Cancer (2006). [Online] 2006. [Cited: August 29, 2008.] http://www.topalbertadoctors.org/TOP/CPG/ProstateCancer/ProstateCancer.htm. 2. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate‐cancer mortality in a randomized European study. N Engl J Med. 2009, 360, pp. 1320‐
8. 3. Andriole GL, Grubb RL III, Buys SS et al. Mortality results from a randomized prostate‐cancer screening trial. N Engl J Med. 360, 2009, pp. 1310‐9.
4. Canadian Cancer Society. Prostate cancer stats. Canadian Cancer Society. [Online] 2008. [Cited: November 1, 2008.] http://www.cancer.ca/Canada‐
wide/About%20cancer/Cancer%20statistics/Stats%20at%20a%20glance/Prostate%20cancer.aspx?sc_lang=en. 5. Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement. US Prevention Services Task Force. 3, s.l. : Annals of Internal Medicine, 2008, Vol. 149, pp. 185‐191. 6. Prostate Cancer Access Project Steering Committee. Alberta Health and Wellness. s.l. : Alberta Health & Wellness Wait Time Management Steering
Committee (WTMSC), 2007‐2008. 7. Prostate cancer screening. Tenke P, Horti J, Balint P, Kovacs B. 2007, Recent Results in Cancer Research, Vol. 175, pp. 65‐81.
8. Diagnosis of prostate cancer. Pinthus JH, Pacik D, Ramon J. 2007, Recent Results in Cancer Research, Vol. 175, pp. 83‐99.
9. The story of the European randomized study of screening for prostate cancer. Schroder F, Denis L, Roobol M, et al. 2003, British Journal of Urology International, Vol. 92, pp. 1‐13. 10. Heidenreich A, Aus CC, Bolla M, et al. Guidelines on prostate cancer. European Association of Urology. [Online] 2007. [Cited: July 11, 2007.] http://www.uroweb.org/fileadmin/user_upload/Guidelines/07_Prostate_Cancer_2007.pdf. 11. Screening for prostate cancer: an update. Bryant RJ, Hamdy, FC. January 2008, European Urology, Vol. 53(1), pp. 37‐44.
12. Canadian Cancer Society; Cancer Care Ontario. Insight on Cancer: News and Information on Prostate Cancer. Canadian Cancer Society. [Online] May
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