2022 Canadian Urological Association recommendations on prostate cancer screening and early diagnosis

Question 1

What was the sample size of the PLCO trial in the 2017 update?

Answer 1

76,683

Question 2

What is the age range for participants in the ERSPC trial (2014 update)?

Answer 2

55-69

Question 3

How many European countries participated in the ERSPC trial?

Answer 3

8 European countries

Question 4

How frequently was PSA screening done in the Goteborg trial (2014 update)?

Answer 4

Every 2 years

Question 5

In the PLCO trial, how was a positive test defined?

Answer 5

PSA >4 ng/ml or an abnormal DRE

Question 6

In the ERSPC trial, how was a positive test defined?

Answer 6

PSA >3.4 ng/ml

Question 7

What was the rate ratio for CSS in the Goteborg trial (2014 update)?

Answer 7

0.58 (0.46-0.72)

Question 8

Which trial reported a 42% relative risk reduction in favor of screening?

Answer 8

Goteborg (2014 update)

Question 9

What does NNS stand for?

Answer 9

Number needed to screen

Question 10

How many prostate cancer deaths were reported in the screened group of the ERSPC trial?

Answer 10

355

Question 11

In the Goteborg trial, what was the NND?

Answer 11

1:13

Question 12

Which trial had a median follow-up of 18 years?

Answer 12

Goteborg (2014 update)

Question 13

What does CSS stand for?

Answer 13

Prostate cancer-specific survival

Question 14

Which trial conducted the PSA screening annually for 6 years and had an annual DRE for 4 years?

Answer 14

PLCO (2017 update)

Question 15

How many participants were in the ERSPC trial (2014 update)?

Answer 15

162,243

Question 16

Which trial was conducted across 10 US centers?

Answer 16

PLCO (2017 update)

Question 17

Where was the Goteborg trial (2014 update) conducted?

Answer 17

Goteborg, Sweden

Question 18

In the Goteborg trial, how was a positive test defined from 1999-2004?

Answer 18

PSA >2.9 ng/ml

Question 19

In the Goteborg trial, how was a positive test defined from 2005 onwards?

Answer 19

PSA >2.5 ng/ml

Question 20

How many prostate cancer deaths were reported in the control group of the Goteborg trial?

Answer 20

122

Question 21

What was the rate ratio for CSS in the ERSPC trial (2014 update)?

Answer 21

0.79 (0.69-0.91)

Question 22

How many prostate cancer deaths were reported in the control group of the PLCO trial?

Answer 22

244

Question 23

What was the NND for the ERSPC trial?

Answer 23

1:27

Question 24

What is the age range for participants in the Goteborg trial (2014 update)?

Answer 24

50-64

Question 25

Which trial showed a 21% relative risk reduction in favor of screening?

Answer 25

ERSPC (2014 update)

Question 26

What was the NNS for the Goteborg trial?

Answer 26

1:139

Question 27

Fig. 1. Prostate cancer screening pathway.

Question 28

According to the 2017 recommendations by the United States Preventative Services Task Force (USPSTF), is PSA-based screening for prostate cancer recommended for men aged 55-69?

Answer 28

Yes. Clinicians should inform men about the potential benefits and harms, and the decision should be individual. There are no separate recommendations for high-risk populations.

Question 29

What is the USPSTF’s stance on PSA-based screening for men aged 70 and above?

Answer 29

They recommend against it. The evidence indicates no mortality benefit for these men.

Question 30

For the European Association of Urology (2016), when is PSA testing recommended for men?

Answer 30

For men >50, with an individualized, risk-adapted strategy for those with a life-expectancy of at least 10-15 years. For those >45 at elevated risk.

Question 31

What is the European Association of Urology’s recommendation on follow-up based on initial PSA level?

Answer 31

Offer risk-adapted follow-up. If initially at risk, follow-up intervals of 2 years. If not at risk, postpone follow-up to 8 years.

Question 32

What does the National Comprehensive Cancer Network (2016) recommend for prostate screening in men aged 45-75?

Answer 32

Yes, with a baseline evaluation that includes history and physical exam, race, and family history of BRCA1/2 mutations. Risk assessment should consider baseline PSA and DRE.

Question 33

For the same organization (NCCN), what is the advised frequency based on PSA levels for men aged 45-75?

Answer 33

If PSA <1 ng/mL and DRE normal, 2-4-year intervals. If PSA 1-3 ng/mL and DRE normal, 1-2-year intervals. If PSA >3 ng/mL or suspicious DRE, consider biopsy.

Question 34

According to the Canadian Task Force on Preventative Health (2014), is PSA screening recommended for men aged <55?

Answer 34

No, due to low prostate cancer incidence, lack of evidence of benefit, and evidence of harms.

Question 35

What’s the stance of the American Urological Association (2013) on PSA screening for men aged 40-54?

Answer 35

It’s not routinely recommended for average-risk men. Decisions should be individualized for men <55 at higher risk. For those choosing screening, a 2-year interval or more may be preferred.

Question 36

How does the American College of Physicians (2013) view PSA screening for men aged <50 and ≥70?

Answer 36

They recommend against screening for both age groups.

Question 37

For men aged 50-69, what does the American College of Physicians (2013) suggest regarding PSA screening?

Answer 37

They recommend informing men about the limited benefits and substantial harms. The decision should be based on risk, discussion of benefits and harms, patient’s health and life expectancy, and preferences.

Question 38

What is the ranking of prostate cancer among malignancies in Canadian men excluding skin cancers?

Answer 38

Prostate cancer is the most commonly diagnosed noncutaneous malignancy among Canadian men.

Question 39

Where does prostate cancer rank in terms of causes of cancer-related death among Canadian men?

Answer 39

It is the third leading cause of cancer-related death.

Question 40

Approximately how many Canadian men were diagnosed with prostate cancer in 2016? And how many died from it?

Answer 40

An estimated 21,600 men were diagnosed, and 4,000 men died from the disease.

Question 41

How is the clinical course of prostate cancer described?

Answer 41

Prostate cancer is a heterogeneous disease with a clinical course that can range from indolent to life-threatening.

Question 42

What is the significant challenge in managing prostate cancer?

Answer 42

Identifying and treating men with clinically significant prostate cancer while avoiding the over-diagnosis and over-treatment of indolent disease.

Question 43

What has caused conflicting recommendations in prostate cancer screening and early diagnosis guidelines?

Answer 43

Various professional associations have developed different guidelines, leading to conflicting recommendations.

Question 44

What recent updates prompted the CUA to develop new recommendations?

Answer 44

Recent updates from several large, randomized, prospective trials and the emergence of several new diagnostic tests.

Question 45

What is the primary aim of the CUA’s recommendations on prostate cancer screening and early diagnosis?

Answer 45

To provide guidance on current best prostate cancer screening and early diagnosis practices and to inform on new and emerging diagnostic modalities.

Question 46

What were the five main questions guiding the literature searches and evidence synthesis on prostate cancer screening and diagnosis?

Answer 46

Should Canadian men undergo prostate cancer screening?
At what age should prostate cancer screening begin?
When can prostate cancer screening be stopped?
How frequently should prostate cancer screening be performed?
What diagnostic tests, besides PSA, are available for early prostate cancer diagnosis?

Question 47

What was the purpose of answering the first four questions about prostate cancer screening?

Answer 47

To provide guidance on prostate cancer screening in general.

Question 48

What was the aim of the fifth question about prostate cancer screening?

Answer 48

To provide information on additional available diagnostic tests beyond PSA.

Question 49

Describe the two-step approach used to synthesize evidence for the first four questions.
Back:

Answer 49

Complete bibliographic review of existing guidelines on prostate cancer screening and diagnosis.
Search of the literature using MEDLINE for articles related to prostate cancer screening and diagnosis published between January 1, 2016, and February 2, 2017. Additional search on PubMed without MEDLINE filters.

Question 50

How was the search conducted for the fifth question related to additional diagnostic tests?

Answer 50

A systematic search was performed similarly but without date restrictions for tests not covered by existing guidelines.

Question 51

Which types of articles were excluded from the literature search?

Answer 51

Case series, case reports, non-systematic reviews, editorials, and letters to the editor.

Question 52

What is the CUA’s stance on offering PSA screening?

Answer 52

PSA screening should be offered to men with a life expectancy greater than 10 years. The decision should be based on shared decision-making after discussing potential benefits and harms. (Level of evidence: 1; Grade of recommendation: B).

Question 53

Why is prostate cancer screening considered controversial?

Answer 53

There are varying recommendations on PSA screening and no consensus among several professional and government organizations.

Question 54

Name the three major randomized, controlled trials that provide credible Level 1 evidence concerning prostate cancer screening.

Answer 54

Prostate, Lung, Colon, and Ovarian screening trial (PLCO)
European Randomized Study of Screening for Prostate Cancer (ERSPC)
Goteborg randomized trial of PSA screening.

Question 55

What was the result of the PCLO trial concerning prostate cancer-specific mortality?

Answer 55

There was no difference in prostate cancer-specific mortality between the intervention (screening) and control arms. However, a high contamination rate may have biased this result.

Question 56

What significant outcomes were observed in the ERSPC and Goteborg trials?

Answer 56

The ERSPC showed a 21% relative risk reduction in prostate cancer mortality. The Goteborg study showed a relative risk reduction of 42% in prostate cancer mortality.

Question 57

How has prostate cancer mortality changed since the introduction of PSA screening in North America?

Answer 57

Prostate cancer mortality has declined. Modeling studies suggest the largest contribution to this reduction is from screening.

Question 58

What concerns are associated with PSA screening?

Answer 58

Over-diagnosis and over-treatment. Up to 67% of men diagnosed via screening might have clinically insignificant prostate cancer, leading to unnecessary exposure to potential harms of biopsy, treatment, and psychological effects.

Question 59

How has the practice of active surveillance impacted prostate cancer treatment in Canada?

Answer 59

Active surveillance for low-risk prostate cancer has reduced the over-treatment of prostate cancer. However, it doesn’t eliminate the issue of over-diagnosis and has potential detriments to quality of life.

Question 60

What does the CUA recommend regarding the decision-making process for PSA screening?

Answer 60

The CUA recommends engaging in a thorough discussion on the potential risks and benefits of PSA screening with patients. Shared decision-making should be performed, taking into account individualized decisions based on personal values.

Question 61

What is the primary goal of prostate cancer screening according to the 2022 Canadian Urological Association’s recommendations?

Answer 61

The primary goal should be the early detection of clinically significant prostate cancer in healthy men while minimizing the detection and treatment of low-risk disease.

Question 62

At what age does the CUA recommend starting PSA testing for most men?

Answer 62

The CUA suggests starting PSA testing at age 50 for most men.

Question 63

Which men are recommended to start PSA testing at age 45?

Answer 63

Men at an increased risk of prostate cancer, particularly those with a family history of prostate cancer in a first- or second-degree relative.

Question 64

What risk does a PSA >4 ng/ml in men aged 45-49 indicate?

Answer 64

A nearly 5% risk of developing lethal prostate cancer within 15 years.

Question 65

How do men aged <50 with a family history of prostate cancer in a first-degree relative differ in risk compared to those with a second-degree relative?

Answer 65

Men aged <50 with a family history of prostate cancer in a first-degree relative have an approximately five-fold increased risk, while those with a second-degree relative have a two-fold increased risk of receiving a prostate cancer diagnosis.

Question 66

Why is PSA testing not recommended for men less than age 45?

Answer 66

The potential benefits and harms have not been prospectively studied, and testing might lead to biopsies and diagnoses that are unlikely to provide benefit. Additionally, the potential delay in diagnosis in the small proportion of men at this age with significant prostate cancer is unlikely to lead to a missed opportunity for curative treatment.

Question 67

Which men are the CUA’s recommendations not directed towards, and what is the suggested approach for them?

Answer 67

The recommendations are not directed towards men with known germ-line mutations associated with prostate cancer development (e.g., BRCA1, BRCA2, HOXB13). An individualized testing strategy after consultation with a clinical geneticist is most appropriate for these cases.

Question 68

What is the recommended PSA testing interval for men with PSA <1 ng/ml according to the 2022 Canadian Urological Association?

Answer 68

Repeat PSA testing every four years. (Level of evidence: 3; Grade of recommendation: C)

Question 69

What is the recommended PSA testing interval for men with PSA levels between 1–3 ng/ml?

Answer 69

Repeat PSA testing every two years. (Level of evidence: 3; Grade of recommendation: C)

Question 70

How should men with PSA >3 ng/ml be approached regarding PSA testing intervals?

Answer 70

How should men with PSA >3 ng/ml be approached regarding PSA testing intervals?

Question 71

Which trials provide the basis for the PSA testing intervals recommendations by the Canadian Urological Association in 2022?

Answer 71

The ERSPC trial and the Goteborg trial.

Question 72

What’s the 10-year prostate cancer detection rate for men with a PSA <1 ng/ml?

Answer 72

3.4%, with 90% considered low-risk.

Question 73

Why are longer intervals between PSA testing appropriate for men with PSA <1 ng/ml?

Answer 73

Because the risk of developing metastatic disease within 15 years for these men is very low, reducing the risk of over-detection due to lead-time bias or natural fluctuations in PSA levels.

Question 74

As baseline PSA levels rise above 1 ng/ml, what happens to the risk related to prostate cancer?

Answer 74

The intermediate-term risk of developing both any prostate cancer and clinically significant prostate cancer increases substantially.

Question 75

In the ERSPC trial, what PSA level was considered a positive test?

Answer 75

A PSA level of 3 ng/ml.

Question 76

In the Goteborg trial, what PSA level range was considered a positive test?

Answer 76

Between 2.5 and 3.4 ng/ml (depending on the year of study).

Question 77

For men with PSA >3 ng/ml, what adjunctive strategy might be considered?

Answer 77

Testing strategies that estimate the risk of clinically significant disease, which can be helpful for biopsy decision-making.

Question 78

When should men consider discontinuing PSA screening based on age and PSA levels?

Answer 78

Men aged 60 with a PSA <1 ng/ml
All other men at age 70.

Question 79

What is the justification for discontinuing PSA screening for men aged 60 with a PSA <1 ng/ml?

Answer 79

The risk of developing or dying from metastatic prostate cancer is low. A large study found the 15-year cumulative incidence of metastatic prostate cancer was low in men with a PSA <1ng/ml at age 60 (0.4% and 0%, for screened and unscreened cohorts respectively).

Question 80

What risk does a PSA >1 ng/ml at age 60 carry?

Answer 80

For men at age 60 with a PSA >1 ng/ml, the risk of developing potentially lethal prostate cancer increases substantially. Thus, screening can be continued.

Question 81

Why is PSA screening likely not beneficial for men aged >70?

Answer 81

Highest incidence of prostate cancer over-diagnosis.
Several studies suggest no benefit.
High risk of over-diagnosis, especially > age 70.
ERSPC trial found no reduction in prostate cancer mortality when starting screening at >70.
Quality of life detriments may offset any potential benefit.

Question 82

What should be considered for men in excellent health at age 70 regarding PSA testing?

Answer 82

PSA testing can be considered, but there’s a lack of empirical data. Continued PSA testing for these men is based on clinical judgment and personal preferences.

Question 83

When should PSA screening be considered in relation to life expectancy?

Answer 83

For men with a life expectancy of less than 10 years, PSA screening should be discontinued.

Question 84

Why is PSA testing not beneficial for men with a high risk of mortality from other causes?

Answer 84

PSA testing is unlikely to provide any benefit. If life expectancy is limited by other illnesses or comorbidities, PSA screening shouldn’t be initiated or should be stopped.

Question 85

What has the past two decades seen in the realm of prostate cancer early diagnosis in addition to PSA?

Answer 85

The development or evaluation of several potential adjunctive measures to either increase benefits or reduce harms associated with screening. These include PSA kinetics, PSA density, percent free PSA, biomarker panels, prostate risk calculators, and the refinement of prostate mpMRI.

Question 86

Why is prostate mpMRI gaining attention in recent years?

Answer 86

Several landmark studies have been published leading to updated recommendations by Cancer Care Ontario (CCO). The 2021 CCO recommendations significantly differ from the previous ones, now recommending mpMRI in many biopsy-naive men at risk of prostate cancer.

Question 87

What is the stance of the Canadian Urological Association (CUA) on the 2021 CCO recommendations regarding mpMRI?

Answer 87

The CUA endorses the 2021 CCO recommendations on the use of mpMRI in biopsy-naive men at risk of prostate cancer, with some added practical considerations.

Question 88

Where can one find a summary of the updated recommendations by Cancer Care Ontario (CCO) on prostate mpMRI?

Answer 88

A summary was published in the February 2022 issue of CUAJ.

Question 89

In which patient group is mpMRI recommended prior to biopsy for prostate cancer early diagnosis?

Answer 89

Biopsy-naive patients at elevated risk of clinically significant prostate cancer (csPCa) who are candidates for curative management with suspected clinically localized prostate cancer.

Question 90

If a patient’s mpMRI is positive, what biopsy methods should be performed?

Answer 90

Both mpMRI-targeted biopsy (TB) and TRUS-guided systematic biopsy (TRUS-SB) should be performed together to maximize detection of csPCa.

Question 91

What is the recommended course of action if a patient’s mpMRI is negative?

Answer 91

Consider forgoing any biopsy after discussing the risks and benefits as part of shared decision-making with the patient and plan for ongoing follow-up.

Question 92

What percentage range of patients with csPCa might be missed by a negative mpMRI?

Answer 92

Between 8% and 24%.

Question 93

What should patients be informed about when their mpMRI result is negative?

Answer 93

They should be made aware of the risks and benefits of avoiding a biopsy.

Question 94

Under what conditions should mpMRI only be performed?

Answer 94

Only if there is the availability of high-quality mpMRI interpretation and operators experienced in performing targeted biopsies.

Question 95

When is mpMRI recommended given its limited availability?

Answer 95

Only for patients where there is an intent of curative management should the biopsy be positive for csPCa.

Question 96

What is the recommended diagnostic step for patients with a prior negative TRUS-SB showing a high risk of csPCa and for whom curative management is being considered?

Answer 96

An mpMRI should be performed.

Question 97

What percentage of patients with csPCa might be missed by a negative mpMRI?

Answer 97

Between 8% and 24%.

Question 98

Why should patients be informed about the risks and benefits of biopsy avoidance when an mpMRI is negative?

Answer 98

Because a negative mpMRI can miss between 8% and 24% of patients with csPCa.

Question 99

Under what conditions should an mpMRI be performed?

Answer 99

Only if there is availability of high-quality mpMRI interpretation and operators with experience in performing targeted biopsies.

Question 100

How is “Prior negative TRUS-SB” defined?

Answer 100

No cancer of any grade group on prior biopsy.

Question 101

When is mpMRI recommended according to the CCO guideline panel?

Answer 101

Only for patients where there is intent of curative treatment in the case of a positive biopsy, due to its limited availability.

Question 102

: What has evidence shown about the benefits of mpMRI in the context of prostate biopsies?

Answer 102

mpMRI, with the use of targeted and standard biopsies, can lead to a significant reduction in unnecessary prostate biopsies while improving the detection of csPCa.

Question 103

What practical limitations have been recognized by the CUA regarding the use of mpMRI?

Answer 103

Timely access to mpMRI and mpMRI-TB, and variations in quality and interpretation.

Question 104

For which patients should the use of mpMRI be limited?

Answer 104

Only for patients for whom the test result is likely to influence their management. It shouldn’t be used for men with clear clinical signs of csPCa or for men suspected of prostate cancer but won’t consider active management regardless of the result.

Question 105

What should be commenced for men with clear clinical signs of csPCa?

Answer 105

Systematic prostate biopsy or disease management, depending on the situation.

Question 106

What is the significance of PSA kinetics in prostate cancer early diagnosis?

Answer 106

PSA kinetics involve the evaluation of the rate of change of PSA levels over time. It can help in understanding the risk and prognosis of prostate cancer.

Question 107

Define PSA velocity (PSAV) and PSA doubling time (PSADT).

Answer 107

PSAV refers to the rate at which PSA levels increase annually. PSADT is the time taken for PSA levels to double.

Question 108

Historical reports identified that a PSAV greater than what value may indicate an increased risk of prostate cancer?

Answer 108

A PSAV greater than 0.75ng/ml/year.

Question 109

When the total PSA is less than 4.0 ng/ml, what PSAV is associated with a higher relative risk of prostate cancer death?

Answer 109

A PSAV greater than 0.35ng/ml/year.

Question 110

Is a stable or declining PSA reassuring?

Answer 110

Yes, a stable or declining PSA is reassuring, especially in men with PSA levels that slightly exceed PSA thresholds.

Question 111

What does the Canadian Urological Association (CUA) recommend regarding the use of PSAV alone for clinical decision-making in men undergoing routine screening?

Answer 111

The CUA does not recommend using PSAV alone for clinical decision-making in men undergoing routine screening. However, PSAV can provide additional information about a patient’s risk of prostate cancer.

Question 112

What is the stance on the incremental value of PSAV over absolute PSA level?

Answer 112

There is conflicting evidence on the incremental value of PSAV over absolute PSA level alone. Some studies suggest it provides value, while others do not.

Question 113

In the context of PSA kinetics, what is a concerning finding?

Answer 113

A sustained and substantial rise in PSA over time is a concerning finding that warrants investigation.

Question 114

What does PSAD stand for in the context of prostate cancer diagnosis?

Answer 114

PSA density.

Question 115

How is PSA density (PSAD) calculated?

Answer 115

PSAD is calculated as the serum PSA divided by prostate volume.

Question 116

What PSAD threshold has been suggested to identify men at risk from prostate cancer?

Answer 116

A PSAD threshold of >0.15 ng/ml/cm^3.

Question 117

True or False: Higher PSAD has always been linked with adverse pathological features at the time of prostatectomy.

Answer 117

False. While some studies have linked higher PSAD with adverse pathological features, others have failed to validate these findings.

Question 118

What concerns arise from the estimation of prostate volume on ultrasound in relation to PSAD?

Answer 118

There is substantial inter-observer variability, raising questions regarding the reliability of PSAD.

Question 119

Is the use of PSAD alone for clinical decision-making encouraged according to the 2022 Canadian Urological Association recommendations?

Answer 119

No. Due to the lack of empirical validation, the use of PSAD alone for clinical decision-making is discouraged.

Question 120

Under what circumstances can PSAD be considered for use, as per the 2022 Canadian Urological Association recommendations?

Answer 120

PSAD can be considered adjunctively in men with known prostate volumes.

Question 121

What is the purpose of measuring percent free PSA in prostate cancer screening

Answer 121

The measurement of percent free PSA is studied as a risk-stratifying tool aimed at distinguishing men at risk from prostate cancer vs. those with elevations in PSA from benign causes.

Question 122

In a multicenter, prospective study, what percentage of men with a free-to-total PSA ratio of less than 0.10 (for men with a PSA between 4 and 10 ng/ml) were detected with prostate cancer?

Answer 122

56%

Question 123

For men with a PSA between 4 and 10 ng/ml, what percentage of men with a free-to-total PSA ratio greater than 0.25 were detected with prostate cancer?

Answer 123

8%

Question 124

In a study with 6982 percent free and total PSA measurements over a 12-year time span, what percentage of unnecessary prostate biopsies could percent free PSA spare as a reflex marker?

Answer 124

66%

Question 125

True or False: Percent free PSA values remain consistent and do not fluctuate.

Answer 125

False. Similar to PSA, percent free PSA can also fluctuate, emphasizing the need for repeat confirmatory testing prior to clinical decision-making.

Question 126

Is it recommended to use percent free PSA alone for clinical decision-making?

Answer 126

No, the use of percent free PSA alone for clinical decision-making is not recommended. However, it can be useful in estimating the risk of underlying disease in men with elevations in PSA.

Question 127

What is the level of evidence and grade of recommendation for the use of percent free PSA in estimating the risk of underlying disease in men with elevations in PSA?

Answer 127

Level of evidence: 2; Grade of recommendation: C

Question 128

What is the 4Kscore®?

Answer 128

The 4Kscore® is a commercially available test that combines total PSA, free PSA, intact PSA, and human kallikrein 2 with age, DRE results, and prior biopsy status. It’s designed to generate a risk estimate of harbouring Gleason ≥7 prostate cancer.

Question 129

From which studies was the four-kallikrein panel (4Kscore®) initially developed?

Answer 129

The 4Kscore® was originally developed using data from the ERSPC (European Randomized Study of Screening for Prostate Cancer) and the ProtecT (Prostate Testing for Cancer and Treatment) studies.

Question 130

How does the 4Kscore® compare to PSA alone in predicting the presence of high-grade prostate cancer?

Answer 130

The 4Kscore® offers evidence of clinical utility over PSA alone for predicting the presence of high-grade prostate cancer.

Question 131

The 4Kscore® offers evidence of clinical utility over PSA alone for predicting the presence of high-grade prostate cancer.

Answer 131

The AUC values for the 4Kscore® ranged from 0.71 to 0.82 based on various validation studies.

Question 132

In a prospective study of 1012 men from 26 U.S. centers, how did the 4Kscore® perform in predicting Gleason ≥7 cancer compared to the modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model?

Answer 132

The 4Kscore® demonstrated better discrimination with an AUC of 0.82, compared to the modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model, which had an AUC of 0.74.

Question 133

What influence does the 4Kscore® have on biopsy decision-making?

Answer 133

The 4Kscore® influenced biopsy decision-making in 89% of men, and it reduced the number of biopsies by 65% in a study of 611 men evaluated by both academic and community urologists.

Question 134

For which PSA levels was the 4Kscore® originally developed? Has its use been extended?

Answer 134

The 4Kscore® was originally developed for men with a PSA <10 ng/ml. However, its use has since been extended and validated for men with a PSA up to 25 ng/ml.

Question 135

What does AUC stand for and what does it represent in the context of model performance?

Answer 135

AUC stands for “Area Under the Receiver Operating Characteristic Curve”. It measures the performance of a binary classification model. The value of the AUC ranges from 0 to 1, with 1 indicating perfect classification and 0.5 suggesting the model’s performance is no better than random chance.

Question 136

What is the Prostate Health Index (PHI)?

Answer 136

The Prostate Health Index (PHI) is a commercially available test derived from PSA and its isoforms (total PSA, free PSA, and [-2] pro PSA). It was originally developed to estimate the risk of harbouring Gleason 7 or greater disease in men with a PSA between 2 and 10 ng/ml.

Question 137

What was the purpose of the initial validation study for PHI?

Answer 137

: The initial validation study aimed to evaluate the ability of PHI to discriminate patients with or without clinically significant disease compared to PSA and free-to-total PSA.

Question 138

How did the PHI perform in the initial validation study in terms of AUC compared to PSA and free-to-total PSA?

Answer 138

The AUC for PHI was 0.72, while the AUC for PSA and free-to-total PSA was 0.67.

Question 139

What benefits does PHI offer over total and percent free PSA in predicting high-risk disease?

Answer 139

PHI can outperform total and percent free PSA in predicting high-risk disease, including in biopsy-naive men.

Question 140

How does the PHI impact the performance of the PCPT and ERSPC risk calculators?

Answer 140

In a large, multicenter, prospective study, PHI significantly improved the performance of the PCPT and ERSPC risk calculators in men with a PSA between 2 and 10 ng/ml for predicting the risk of Gleason ≥7 prostate cancer.

Question 141

What was the clinical utility of PHI in terms of reducing unnecessary biopsies and missing high-grade cancers?

Answer 141

A multicenter cohort study found that the clinical utility of PHI reduced unnecessary biopsies by 36% and only missed 2.5% of high-grade cancers.

Question 142

How do the discriminatory abilities of PHI and the 4K score compare for predicting high-risk prostate cancer in men with a PSA between 3 and 15 ng/ml?

Answer 142

Both tests demonstrate similar discriminatory ability, with the AUC for the 4K score being 0.718 and for PHI being 0.711.

Question 143

What is PCA3, and where is it expressed?

Answer 143

Prostate cancer antigen 3 (PCA3) is a non-coding RNA gene expressed solely in the prostate and is overexpressed in prostate cancer. It’s measured from a urine sample obtained after a DRE.

Question 144

How does the PCA3 test differ from the 4Kscore and PHI?

Answer 144

Unlike the 4Kscore and PHI, which are based on serum measurements, PCA3 is measured from a urine sample.

Question 145

How does the diagnostic accuracy of PCA3 for prostate cancer detection compare to PSA alone?

Answer 145

Multiple studies have shown that PCA3 has an improved diagnostic accuracy for prostate cancer detection relative to PSA alone.

Question 146

In men with a history of a negative biopsy, what does a PCA3 score of less than 25 indicate?

Answer 146

Those with a PCA3 score of less than 25 are almost five times more likely to have a negative repeat biopsy compared to those with a score ≥25.

Question 147

What is the role of PCA3 in men with no history of a prior biopsy?

Answer 147

The role is uncertain. However, in a biopsy-naive setting, a PCA3 score <20 led to a high rate of undiagnosed high-grade cancers (13%), compared to 3% in the repeat setting.

Question 148

How do the 4Kscore, PHI, and PCA3 tests augment the prediction of prostate cancer in men with moderately elevated PSA?

Answer 148

These tests can improve the prediction of clinically significant prostate cancer and offer additional information over PSA alone.

Question 149

What is the Canadian Urological Association’s (CUA) position on the widespread use of the 4Kscore, PHI, and PCA3 tests?

Answer 149

The CUA recognizes that these tests are expensive and not publicly funded in Canada. Currently, based on available data, the CUA does not encourage their widespread use.

Question 150

What is the purpose of prostate cancer risk nomograms?

Answer 150

They aid in the detection of clinically significant prostate cancer.

Question 151

What is the range of discrimination properties for prostate cancer detection in adequately validated nomograms?

Answer 151

AUC 0.66–0.79.

Question 152

How many of the available prostate cancer risk nomograms have been adequately validated across several study populations?

Answer 152

Six.

Question 153

Which factors does the PCPT prostate cancer risk calculator (PCPT-RC) use to estimate the risk of prostate cancer?

Answer 153

Age, PSA level, ethnic background, family history, DRE results, and prior biopsy results.

Question 154

Which factors does the ERSPC prostate cancer risk calculator (ERSPC-RC) use to determine the risk of prostate cancer?

Answer 154

PSA level, DRE results, prior biopsy results, prostate volume, and TRUS findings.

Question 155

What does the prostate risk calculator developed using data from Canadian men use to estimate the risk of prostate cancer?

Answer 155

PSA level, free-to-total PSA, age, voiding symptoms, ethnicity, family history, and DRE results.

Question 156

How would you describe the predictive accuracy of prostate risk calculators?

Answer 156

Moderate, and it varies across different study populations.

Question 157

When can prostate risk calculators be used?

Answer 157

To estimate the risk of clinically significant prostate cancer in men presenting with an elevated PSA.

Question 158

What is the primary consideration for deciding the threshold for performing a prostate biopsy?

Answer 158

The decision should be individualized. No uniform PSA cutoff can be recommended for all men.

Question 159

Why should a single PSA measurement not be solely relied upon for biopsy decision-making?

Answer 159

Due to the documented changes and fluctuations in PSA levels over time.

Question 160

What was the observation in the Canadian study with over 1000 men with elevated PSA (>4 ng/ml)?

Answer 160

By repeating PSA testing, 25% of the cohort had resolution to low levels, negating the need for further investigation.

Question 161

What factors should be considered when deciding to proceed with a prostate biopsy?

Answer 161

PSA level, results from adjunct tests or risk calculators, competing comorbidities, patient preferences, and potentially suspicious findings on DRE.

Question 162

What is the stance on the utility of DRE in addition to PSA?

Answer 162

It’s controversial. However, DRE may increase the detection of clinically significant disease and should be performed at the same interval as PSA testing.

Question 163

How does the CUA feel about the implementation of a successful screening program?

Answer 163

It must consider individual variations in patient preferences, and men should be involved in decision-making regarding prostate biopsy.

Question 164

What should the decision to pursue a biopsy be based upon?

Answer 164

A discussion of the best evidence for estimating the risk for aggressive prostate cancer, according to Expert opinion.