CUA: Prostate Cancer Screening (2017)

See Original Guideline

See 2018 AUA Guideline Notes on Prostate Cancer Screening

See Prostate Cancer Screening Chapter Notes

PSA Screening

• CUA suggests offering PSA screening to men with a life expectancy > 10 years. The decision of whether or not to pursue PSA screening should be based on shared-decision making after discussing the potential benefits and harms of screening
  • Up to 67% of men diagnosed with PC by screening will have clinically insignificant PC. Thus, if screened, men with insignificant disease may be unnecessarily exposed to the potential harms of both prostate biopsy and treatment in addition to the psychological effects. Increased use of active surveillance for low-risk PC has been important step in reducing the over-treatment of PC.
• There have been 6 randomized controlled trials investigated the role of PSA screening in adult men, however, 3 of these are at significant risk of bias and are not considered when weighting the evidence for or against prostate cancer screening. Thus, 3 randomized controlled trials constitute the credible Level 1 evidence concerning PC screening: PLCO, ERSPC, Gotteberg (since publication of trial, results of CAP published) (see Prostate Cancer Screening Chapter Notes)
  • Overall, PSA screening results in reduction in PC mortality.

Best screening practices

• For men electing to undergo PSA screening, we suggest starting PSA testing at age 50 in most men and at age 45 in men at an increased risk of prostate cancer
  • Remains unclear which men will benefit from early PSA screening, family history imparts a substantially increased risk of prostate cancer diagnosis at a younger age.
  • These recommendations are not directed towards men with known germ-line mutations associated with PC (e.g. BRCA1, BRCA2, HOXB13). In these cases, an individualized testing strategy after consultation with a clinical genetist is most appropriate.
• For men electing to undergo PSA screening, intervals between testing should be based on previous PSA levels:
  • For men with PSA < 1 ng/mL, repeat PSA testing every 4 years
  • For men with PSA 1 – 3 ng/mL, repeat PSA testing every 2 years
  • For men with PSA > 3 ng/mL, consider more frequent PSA testing intervals or adjunctive testing strategies
  • Although the added utility of DRE in addition to PSA is controversial, DRE may increase the detection of clinically significant disease; DRE should performed at the same interval as PSA testing
• For men electing to undergo PSA screening, consider discontinuing PSA screening for men:
  1. Aged 60 with a PSA < 1 ng/mL, consider discontinuing PSA screening
  2. At age 70
     • Men aged > 70 have the highest incidence of PC over-diagnosis and several studies have suggested that screening in this age group is likely not beneficial; a modelling study using data from ERSPC found that any potential benefit to screening in men over 70 was offset by the detriments to quality of life
     • For interested men in excellent health at age 70, PSA testing can be considered recognizing the lack of empirical data in this age group. As such, for these men, continued PSA testing is a matter of clinical judgement and personal preferences.
  3. With a life expectancy < 10 years

Adjunctive strategies for improving PC early diagnosis (4):

1. mpMRI
   • In patients with an elevated risk of clinically significant PC who are biopsy-naïve, mpMRI followed by targeted biopsy should not be considered the standard of care.
     • PROMIS – see Yo Notes Chapter 111
   • In men at risk of having clinically significant prostate cancer despite a prior negative TRUS-guided systematic biopsy, mpMRI followed by targeted biopsy may be considered to help in detecting more clinically significant PC patients compared with repeated TRUS-guided systematic biopsy
2. PSA derivatives
   1. PSA kinetics
      • The CUA does not recommend using PSA velocity alone for clinical decision-making in men undergoing routine screening; however, PSA velocity can provide additional information about a patient’s risk of prostate cancer.
   2. PSA density
      • PSA density is the serum PSA divided by prostate volume. A PSA density threshold of 0.15 ng/mL/cm3 has been suggested to distinguish men at risk from PC, and studies have also linked higher PSA density with adverse pathological features at the time of prostatectomy. However, others have failed to validate these findings.
      • Inter-observer variability from the estimation of prostate volume on ultrasound also raises further questions regarding the reliability of PSA density.
      • Due to the lack of empirical validation, the use of PSA density alone for clinical decision-making is discouraged; however, use of PSA density can be considered adjunctively in men with known prostate volumes.
   3. Percent free PSA
      • In a large, multicentre, prospective study, PC (all grades) was detected in 56% of men with a free-to-total PSA ratio of less than 0.10 (for men with a PSA between 4-10 ng/mL), whereas cancer was detected in 8% of men with a ratio >0.25.
      • The use of %free PSA alone for clinical-decision making is not recommended; however, %free PSA can be useful in estimating the risk of underlying disease in men with elevations in PSA.
3. Other biomarkers (See Yo Notes Chapter 108)
   1. Four-kalikrein panel (4Kscore)
      • Commercially available test combining total PSA, free PSA, intact PSA, and human kallikrein 2 with age, DRE results, and prior biopsy status in order to generate a risk estimate of harbouring Gleason ≥7 disease.
      • There is evidence of clinical utility over PSA alone for predicting the presence of high-grade PC.
      • Originally developed for use in men with a PSA <10 ng/mL, its use has also been extended and validated in men with a PSA up to 25 ng/mL.
   2. Prostate Health Index
      • Commercially available test derived from PSA and it’s isoforms (total PSA, free PSA, and -2proPSA) originally developed to estimate the risk of harbouring Gleason 7 or greater disease in men with a PSA between 2-10 ng/mL. Use of the test was initially validated in a multi-institutional, prospective trial evaluating 892 men for the presence of Gleason ≥4+3 PC, which found that PHI could improve the discrimination of patients with or without clinically significant disease compared with PSA and free-to-total PSA (AUC 0.72 vs. 0.67)
      • When comparing PHI and the 4k score, the two tests appear to demonstrate similar discriminatory ability in predicting high-risk PC in men with a PSA between 3 and 15 ng/mL (AUC 4k score 0.718 vs. PHI 0.711).
   3. Prostate cancer antigen 3 (PCA3) score
      • Prostate cancer antigen 3 (PCA3) is a non-coding RNA gene that is only expressed in the prostate and is overexpressed in prostate cancer. Unlike the 4Kscore and PHI, which are based on serum measurements, PCA3 is measured from a urine sample that is obtained after DRE.
      • Multiple studies evaluating the PCA3 in men undergoing repeat biopsy have demonstrated an improved diagnostic accuracy for prostate cancer detection relative to PSA alone. In a multicentre, prospective study of 466 men with a history of a negative biopsy, those with a score of less than 25 were almost five times more likely to have a negative repeat biopsy compared to those with a score ≥25; however, the role of PCA3 in men with no history of a prior biopsy is uncertain. In a prospective validation study conducted by the National Cancer Institute, the performance of PCA3 was assessed in 859 men that were enrolled from 11 centres. In the biopsy-naive setting, there was a high rate of undiagnosed high-grade cancers (13%) using a PCA3 score <20, compared to 3% in the repeat setting.
   4. In men with a moderately elevated PSA, the 4Kscore, PHI, and PCA3 may improve the prediction of clinically significant prostate cancer and provide additional information over PSA alone; however, the CUA recognizes that these are expensive tests that are not currently publicly funded in Canada. At the present time, based upon the available data, the CUA does not encourage the widespread use of these tests.
4. Prostate risk calculators
   • The most widely used calculators for the prediction of clinically significant disease include the PCPT and ERSPC prostate cancer risk calculators. These have moderate predictive accuracy, which varies across different populations

Prostate biopsy decision-making

• A single PSA measurement should not be used to guide biopsy decision-making

Questions

1. As per the CUA Guidelines on PCa screening, who should be offered screening?
2. When should screening be started?
3. What is the recommended frequency of screening?

1. What is the role of DRE in prostate cancer screening?
2. When should screening be stopped?
3. Describe the PROMIS trial
4. How do the CUA guidelines use data from PROMIS to recommend the role of mpMRI in the diagnosis of prostate cancer?
5. What PSA isoforms are included in the prostate health index score?

Answers

1. As per the CUA Guidelines on PCa screening, who should be offered screening?
   • Men with life expectancy >10 years
2. When should screening be started?
   • Age 50, age 45 if increased risk
3. What is the recommended frequency of screening?
   1. Based on PSA level
      • <1 – every 4 years
      • 1 – 3 every 2 years
      • >3 discretion of urologist
4. What is the role of DRE in prostate cancer screening?
   • Although the added utility of DRE in addition to PSA is controversial, DRE
5. When should screening be stopped?
   1. PSA <1 and age 60
   2. Age 70
   3. Life expectancy < 10 years
6. Describe the PROMIS trial
   • The objective of PROMIS was to compare the accuracy of mpMRI with TRUS biopsy to determine the utility of mpMRI as a triage test to decide which men with an elevated PSA may be able to avoid biopsy. The study included 576 men with clinical suspicious of prostate cancer that underwent mpMRI followed by standard TRUS biopsy with template prostate mapping biopsy as gold standard reference. The study found that mpMRI had moderate sensitivity but poor specificity for clinically significant prostate cancer.
7. How do the CUA guidelines use data from PROMIS to recommend the role of mpMRI in the diagnosis of prostate cancer?
   • mpMRI should not be used in biopsy niave patients, should be reserved for patients with negative biopsy
8. What PSA isoforms are included in the prostate health index score?
   • Total PSA, free PSA, -2proPSA