PSA Testing Clinical Practice Guidelines Perth CCWA GP Update August 2016

Jon Emery Herman Professor of Primary Care Cancer Research Victorian Comprehensive Cancer Centre

Prostate cancer

• 33% of male cancers • 1 in 7 risk of diagnosis by age 75 • 2nd cause of cancer deaths in men (6th

all male deaths) • 92% 5 year survival • By 2017 1.6% of male population

(185,000) men living with prostate cancer

Prostate cancer incidence

Clinical practice guidelines PSA Testing and Early Management of Test-Detected Prostate Cancer.

A plethora of guidelines about PSA testing

Prostate cancer screening

Consensus guidelines for Australia 2016

Ongoing source of confusion….

Overview

• Key recommendations about PSA testing

• Rationale and evidence • Implications for practice

PSA testing and effect on prostate cancer deaths: Cochrane review

D Ilic et al Cochrane review 2013

The two big trials and source of controversy

US PLCO trial results at 13 years

Andriole et al JNCI 2012 (n = 76,685 men randomised.)

European ERSPC trial results at 13 years

RR = 0.79 (95% CI = 0.69-0.91 p = 0.001

Schroder et al Lancet 2014 (n = 162,388 men randomised)

Greater weight given to results of ERSPC trial

• PLCO trial – 44% had PSA test in 3 years before trial – 52% men in control had PSA in period of last test

for intervention group (cf 30.7% in ERSPC) – Lower biopsy rates for PSA +ve (PLCO 41% vs

ERSPC 86%) • ERSPC trial

– Pattern of differences in mortality beginning at 7 years

– Internal consistency in results between centres

Summary of ERSPC results for 11 and 13 years follow-up

Clinical practice guidelines PSA Testing and Early Management of Test-Detected Prostate Cancer.

Evidence about metastatic prostate cancer

• PLCO and ERSPC showed lower risk of

metastatic prostate cancer at diagnosis in intervention group

• PLCO: RR 0.87 (95% CI 0.66-1.14) • ERSPC: RR 0.50 (95% CI 0.41-0.62)

Testing strategy in ERSPC

• Men aged 55-69 yrs • 4 yearly except one centre (2 yearly in

Goteborg) • PSA >3.0 ng/mL without DRE as

criterion to refer for biopsy • End testing 70-75 yrs

Models of different testing protocols: 4 yearly vs 2 yearly

Recommendation #1: testing average risk men aged 50-69

Evidence-based recommendation For men at average risk of prostate cancer who have been informed of the benefits and harms of testing and who decide to undergo regular testing for prostate cancer, offer PSA testing every 2 years from age 50 to age 69, and offer further investigation if total PSA is greater than 3.0 ng/mL.

Recommendation #2 and #3: PSA in older men or with reduced life expectancy

Consensus recommendation Advise men 70 years or older who have been informed of the benefits and harms of testing and who wish to start or continue regular testing that the harms of PSA testing may be greater than the benefits of testing in men of their age.

Evidence-based recommendation Since any mortality benefit from early diagnosis of prostate cancer due to PSA testing is not seen within less than 6–7 years from testing, PSA testing is not recommended for men who are unlikely to live another 7 years.

Role of the digital rectal examination?

PSA vs PSA + DRE?

Recommendation #4 No DRE

Remains important part of assessment by urologist as part of assessment and consideration for prostate biopsy

Evidence-based recommendation In asymptomatic men interested in undergoing testing for early diagnosis of prostate cancer, digital rectal examination is not recommended as a routine addition to PSA testing in the primary care setting.

Using PSA test to inform subsequent PSA testing

PSA as a screening test to

diagnose prostate cancer

PSA as a test to predict risk of future prostate

cancer

Risk of prostate cancer death according to PSA result in your 40s

• >75th centile PSA aged 45 RR for prostate cancer death = 3.9

• >90th centile PSA aged 45 RR for prostate cancer death = 9.2

Recommendation #5 PSA in men 45-50 as a risk predictor

Consensus recommendation For men younger than 50 years who are concerned about their risk for prostate cancer, have been informed of the benefits and harms of testing, and who wish to undergo regular testing for prostate cancer, offer testing every 2 years from age 45 to age 69 years. If initial PSA is at or below the 75th percentile for age, advise no further testing until age 50. If initial PSA is above the 75th percentile for age, but at or below the 95th percentile for age, reconfirm the offer of testing every 2 years. If a PSA test result before age 50 years is greater than the 95th percentile for age, offer further investigation. Offer testing from age 50 years according to the protocol for all other men who are at average risk of prostate cancer.

PSA testing in men with a family history of prostate cancer

Recommendation #6: men with a family history of prostate cancer:

Consensus recommendation For men whose risk of prostate cancer is estimated to be at least 2.5–3 times higher than average (e.g. a brother with prostate cancer, particularly if <60 years at diagnosis), and who decide to undergo testing after being informed of the benefits and harms, offer testing every 2 years from age 45–69 years. For men whose risk of prostate cancer is estimated to be at least 9–10 times higher than average (e.g. father and two brothers diagnosed with prostate cancer), and who decide to undergo testing after being informed of the benefits and harms, offer testing every 2 years from age 40–69 years. If initial PSA is at or below the 75th percentile for age, advise no further testing until age 50. If initial PSA is above the 75th percentile for age, but at or below the 95th percentile for age, reconfirm the offer of testing every 2 years. If a PSA test result before age 50 years is greater than 95th percentile for age, offer further investigation. Offer testing from age 50 years according to the protocol for men who are at average risk of prostate cancer.

What to do with a PSA >3.0?

• Single PSA >3.0: PPV = 20-25% • Day-to-day variability in PSA level by

15%

• How to increase PPV and reduce prostate biopsy rate?

Recommendations #7 and 8: repeat testing and free-to-total PSA

Consensus recommendation Offer prostate biopsy: — if repeat total PSA is greater than 5.5 ng/mL, regardless of free- to-total PSA percentage — if repeat total PSA is greater than 3.0 ng/mL and less than or equal to 5.5ng/mL and free-to-total PSA <25%

Evidence-based recommendation For men aged 50–69 years with initial total PSA greater than 3.0 ng/mL, offer repeat PSA within 1–3 months. For those with initial total PSA greater than 3.0 ng/mL and up to 5.5 ng/mL, measure free-to-total PSA percentage at the same time as repeating the total PSA.

Recommendations #9 & 10: use of PSA Velocity and Prostate Health Index

Additional recommendation confirming no clear benefit to increase sensitivity to detect prostate cancer

Measurement of PSA velocity is not recommended to increase specificity of a total PSA test result of 3.0 ng/mL or greater.

Do not use the PHI test to increase specificity of a total PSA test result of 3.0 ng/mL or greater, except in the context of research conducted to assess its utility for this purpose.

Supporting men to decide about PSA testing

• Decision aids: – Improve men’s knowledge about harms

and benefits of PSA testing – Reduce decisional conflict/distress – Increase men’s satisfaction with their

decision

Recommendation #11

• Do not just add a PSA onto a list of other tests without a discussion

• Need to find time to discuss the test and use a decision aid as part of that discussion

• Recommend use of NHMRC fact sheet

Evidence-based recommendation Offer evidence-based decisional support to men considering whether or not to have a PSA test, including the opportunity to discuss the benefits and harms of PSA testing before making the decision.

NHMRC factsheet

https://www.nhmrc.gov.au/guidelines-publications/men4

http://www.racgp.org.au/your-practice/guidelines/prostate-cancer/

RACGP decision aid

http://www.racgp.org.au/your-practice/guidelines/prostate-cancer/

Extra 67 men with prostate cancer

http://www.racgp.org.au/your-practice/guidelines/prostate-cancer/

• 87 men have biopsy and no prostate cancer (false positive) • 28 men have side effects from biopsy requiring

healthcare/hospitalisation • 37 men have slow-growing cancers (over-diagnosis) and 25 men

with choose to be treated (over-treatment) • 7-10 men experience impotence and/or urinary incontinence or

bowel problems • 0.5 men have heart attack due to treatment

Weighing up life gained against treatment side-effects

M King et al NSW Prostate Cancer Care and Outcomes Study: discrete choice experiment BJC 2012

Take home messages

Offer men opportunity to discuss benefits and harms of PSA testing before making a decision

Harms of PSA testing may outweigh benefits particularly in men >70

Men at average who decide to have regular testing should be offered PSA every 2 years from 50-69

Men with family history of prostate cancer who decide to be tested should be offered PSA every 2 years from 40/45 to 69 depending on risk of prostate cancer

DRE not recommended for asymptomatic men as part of PSA testing

Take home mesaage

Discuss and inform first