PSA screening

Population / mass screening = systematic examination of asymptomatic individuals to identify those at risk of a disease who may benefit from further investigation (not diagnostic).

Aims of screening programs:

• Reduce mortality by early diagnosis and treatment of a condition
• Reduce incidence of a condition by identifying and treating pre-cursors
• Reduce severity of a condition by identifying people with condition and offering elective treatment
• Increase choice by identifying conditions or risk factors early when more options are available

Principles of screening:

• Should be an important health problem
• Accepted treatment for the disease
• Facilities for diagnosis and treatment available
• Recognisable early or latent phase
• Suitable test or exanimation
• The test should be acceptable to the population
• Natural history of condition understood
• Agreed policy on whom to treat
• Economically balanced
• Continuous process

 

What are the proposed benefits and potential harms of prostate cancer screening?

 

 

PSA Screening Trials

 

PLCO

76 000 men aged 55 – 74 in America.

Routine screening – annual PSA + DRE vs “usual care” control group (patients could elect screening).

Findings:

• Statistically non-significant 13 % increase in prostate cancer specific mortality after 13 years

Issues:

• 45 % of all included men had had a PSA test in 3 years prior to commencement of study
• PSA testing was very common in the control group – est. 52 % had PSA checked during the study period (and likely more during follow up period)
• Only 64 % of men in the screened group with a positive PSA had a biopsy

Essentially, this trial compared organised screening to opportunistic screening

 

ERSPC

180 000 men aged 50 – 74 in 7 European countries.

Screening interval varied between 2 – 4 years vs control group

Findings (after 16 years):

• Reduction in prostate cancer specific mortality by 20 % (only in men under 70)
• No reduction in all-cause mortality
• Number needed to screen 570; number needed to diagnose 18; to prevent one prostate cancer death (trending down with each follow up)

Issues:

• 20 – 30 % contamination of screening arm (lower than PLCO) and better biopsy compliance (86 %)
• Quite heterogenous protocols between different centres (different screening times, biopsy triggers)

 

 

Goteborg

20 000 men between 50 – 64 in Sweden – part of the ERSPC trial

Routine PSA screening every 2 years vs control.

Findings (after 18 years):

• 35 % reduction in prostate cancer mortality (more pronounced for those who start screening < 60)
• Number needed to screen 231; number needed to diagnose 10; to prevent one prostate cancer death
• **Updated after 22 years – Number needed to screen 221, number needed to diagnose 9

Issues:

• Little contamination and good biopsy compliance

 

CAP

408 000 men in the UK between 50 – 69 randomised to single PSA test or control (PSA test if patient asked) – 10 year follow up

Findings:

• Similar risk of prostate cancer death between groups
• No difference in all-cause mortality

Issues:

• About 15 % screening in control group; ? not all men in intervention group had proper PSA test
• Only single PSA not representative of screening. Not a true control group.

 

General limitations cf. contemporary practice

Current PSA testing incorporates adjuncts to risk stratify biopsy

MRI and biopsy methods changed – likely more clinically significant prostate found, and less insignificant disease missed

Data is only now maturing to capture mortality from prostate cancer

?Applicability to Australian men and other at-risk groups such as African-Americans

 

 

 

PCFA Guidelines on PSA Testing (2015)

Avoids the term ‘screening’ which refers to structured programs – guidelines refer to ‘testing’ as a tool for early diagnosis in primary care.

Mainly uses data from ESRPC and modelling related – due to issues with PLCO and other studies.

1. Offer evidence based decisional support to men considering whether to have a PSA test, including the opportunity to discuss benefits and harms
   1. Testing can only be expected to prevent prostate cancer death at least 7 years in the future
   2. Quality of life might be worse in the short term with prostate cancer treatment, but medium to long term quality of life likely to be better

 

2. For men at average risk who have been informed of risks and benefits and wish to undergo screening, offer PSA testing every 2 years from 50 – 69 years, and further investigation if PSA is > 3.0 ng / mL
   1. Do not offer PSA testing at age 40 to predict future risk
   2. For men younger than 50 who want to be tested, offer testing every 2 years from 45, and if < 75^th centile at 45, do not test again until 50
   3. Advise men older than 70 that harms may outweigh benefits

 

3. For men at higher risk due to family history, offer testing every 2 years from 45 – 69
   1. For men at very high risk (i.e. 3 first degree relatives), offer testing from 40
   2. If < 75^th centile at 40 or 45, can defer to 50
   3. If between 75^th and 95^th centile, continue second yearly testing
   4. If > 95^th centile, investigate further

 

4. DRE is not recommended as a routine addition to testing in primary care, but remains important part of specialist assessment

 

5. PSA testing is not recommended for men who are unlikely to live another 7 years

 

September 2022 USANZ updated statement

• Offer individualised risk-adapted strategy for early detection to a well-informed man 50 years and older, with minimum 10 year life expectancy
• Offer early PSA testing to well-informed men at an elevated risk of prostate cancer
  • 45 years and family history
  • 45 years and high risk ethnicity (including ATSI)
  • 40 and BRCA2 mutations
• Stop early diagnosis of prostate cancer based on limited life expectancy and poor performance status (e.g. men with life expectancy < 10 years unlikely to benefit)
• Initial PSA > 3 ng/mL – risk stratification (age, family history, PSA density, DRE) guides further testing (MRI, biopsy).