An overview of issues associated with prostate cancer testing and screening. Part of a larger online course.

1. Part of the “Enhancing Prostate Cancer Care” MOOC
Catherine Holborn
Senior Lecturer in Radiotherapy & Oncology
Sheffield Hallam University

2. Introduction
Debate and discussion regarding testing and screening
for prostate cancer, focuses on men who are without any
symptoms (asymptomatic)
Men with early prostate cancer very often do not have
any symptoms
So a test is arguably needed to detect prostate cancer at
an early stage, whilst it is still very treatable
In turn, this should reduce mortality rates, whilst also
maintaining quality of life
This presentation provides an insight into the complexity
of this topic, and the research undertaken

3. The PSA test
The current available test
Not a test for prostate cancer, just prostate cancer risk
Further, more invasive tests may be needed
False positives and false negatives are possible with the
PSA test
Nevertheless….It can lead to the diagnosis of a prostate
cancer that requires treatment, and is still treatable
For many men who did not receive a diagnosis of
prostate cancer until they had developed symptoms, and
often more advanced disease, the benefit of PSA testing
in asymptomatic men, is in no doubt!

4. Population vs. Opportunistic
Population based screening
All asymptomatic men, within a given age range would
be invited to have the PSA blood test
Opportunistic testing
Initiated by the man and/or their doctor, based on an
individual case findings and an assessment of risk vs. the
benefits of testing

5. Benefits, risks, implications…
The PSA test is responsible for significant increases in the incidence and
detection of early stage prostate cancers
Reductions in mortality rates have been observed in some population based
screening trials
However, they have also demonstrated the significant problem of over-diagnosis
and over-treatment
Men are diagnosed with an early stage cancer, very early in it’s
development and if it is slow growing it may take up to 10-12yrs to become
clinically significant
In a mans lifetime they may never cause any significant problems
As a result, men may arguably receive unnecessary treatment and be
subjected to the side effects associated with this
Unfortunately, there is currently no test that can definitively tell us whether
a very early prostate cancer is indolent/slow growing or more aggressive

6. PLCO cancer screening trial¹
Prostate, Lung, Colorectal and Ovarian screening
Recruited 76,693 men.
After 7 years follow up, no significant difference in
reduced mortality between the control and screening
groups.
Histology and Gleason grade did not differ significantly
between the two groups. The majority of cases were
stage 2.
There was ‘contamination’ in the control group though.
This might help to explain the lack of difference.

7. ERSPC trial¹ ² ³
European Randomised Study of Screening for Prostate
Cancer.
Recruited 182,000 men.
A reduction in mortality was observed in the screening
group (214 deaths compared to 326 in the control).
Screening most beneficial in the 55-69yrs age group.
Accounting for non-attendance and contamination it was
calculated that screening would reduce risk of dying from
prostate cancer by up to 31%
Similar analysis of just the Rotterdam section, calculated
this as up to 51%

8. However…
Over-diagnosis and over-treatment was evident
ERSPC also calculated that to prevent 1 death from
prostate cancer 1410 men would need to be screened
(1068 adjusting for non-compliance) and 48 men would
need to be treated ¹ ²

9. Potential impact of over-diagnosis
A man is healthy and without symptoms
He has a PSA test that leads to the diagnosis of an early
prostate cancer, that may not cause any problems in his
lifetime
He knows he has a prostate cancer but will now be most
likely advised to embark on an active surveillance
programme (close monitoring for signs of progression, NOT definitive
treatment)
He may choose to have definitive treatment with surgery
or radiotherapy but this will affect his urinary and sexual
function (and possibly bowel function), when arguably
treatment was not needed

10. Other relevant findings
High rate of false positives in ERSPC trial
3 out of 4 men (75%)with an elevated PSA were not
found to have cancer
Significant increases in distress at the time of biopsy
compared with levels of distress associated with the PSA
test have been found (analysis of data from the UK ProtecT trial; 195 men
who had received a negative biopsy) ⁴
Distress levels remained immediately after the negative
biopsy result and also 12 weeks later ⁴

11. Informing asymptomatic men
The PSA test can lead to the diagnosis of a cancer that requires immediate
treatment, but may still be treatable, or at least can be controlled
PSA only enables assessment of risk, alongside the DRE and other risk
factors
Other tests are needed
The TRUS guided biopsy has associated risks/complications
Research has shown 75% of men will not be found to have cancer upon
biopsy
False negatives are also possible with the biopsy. Further testing and long
term monitoring may be required if PSA levels remain elevated
For a very early stage cancer, the advice may be NOT to treat; BUT you will
be closely monitored for signs of progression/need for treatment
If you are treated then this may affect your urinary and sexual function
(possibly bowel)

12. Opportunistic testing
Approach adopted by UK and many other countries
Tendency to promote the opportunity to be tested after
a certain age BUT….
Stress that this should include information about the
benefits and risks, enabling men to make an informed
decision
Questions still remain though and variations exist
What age to start providing the opportunity to be PSA tested?
How frequently to test?
What age to not test/stop testing?
Should targeted screening programmes be adopted for men with high
risk features e.g. Black men or those with familial links?

13. The Melbourne Consensus Statement⁵
1. For men aged 50-69 years, evidence shows that PSA testing reduces the
incidence of metastatic prostate cancer and prostate cancer specific
mortality rates
2. Prostate cancer diagnosis must be uncoupled from prostate cancer
intervention (treatment)
3. PSA testing should not be considered on its own but as part of a multi-variable
approach to early prostate cancer detection
4. Baseline PSA testing for men in their 40’s is useful for predicting the
future risk of prostate cancer and its aggressive forms
5. Older men in good health with a life expectancy of >10 years should not
be denied PSA testing based on their age

14. Focus of current research
Finding a better test for prostate cancer or at least the
risk of prostate cancer
Tumour markers e.g. PCA3 urine test
Imaging methods e.g. multi-parametric MRI
Learning about the genetics of prostate cancer
Which genes predispose a man to developing prostate
cancer?
Are there specific characteristics that help to distinguish
between indolent and aggressive cancers?

15. Suggested activity
A number of organisations have provided stances on the use
of PSA testing for prostate cancer. For example:
United Kingdom (PCRMP)
US Preventative Services Task Force
American Urological Association
American Cancer Society
Cancer Council Australia / Australian Health Ministers Advisory Council
Urological Society of Australia and New Zealand
You may want to find out more about what position they take
and the detail in their advice e.g. age when PSA testing could
start.
What is the position in your country? How well is this
publicised?

16. References
1. Eckersberger E, Finkelstein J, Sadri H, Margreiter M, Taneja SS, Lepor H, Djavan B.
Screening for Prostate Cancer: A Review of the ERSPC and PLCO trials. Review in
Urology. 2009. 11(3) pp. 127-133
2. Roobol MJ, Kerkhof M, Schroder FH, Sasieni P, Hakama M, Stenman UH et al. Prostate
Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for
Nonattendance and Contamination in the European Randomised Study of Screening
for Prostate Cancer (ERSPC). European Urology. 2009. 56 pp. 584-591
3. Bokhurst LP, Bangma CH, van Leenders GJLH, Lous JL, Moss SM, Schroder FH, Roobol
MJ. Prostate-Specific Antigen-Based Prostate Cancer Screening: Reduction of Prostate
Cancer Mortality after Correction for Nonattendance and Contamination in the
Rotterdam Section of the European Randomised Study of Screening for Prostate
Cancer. European Urology. 2014. 65 pp. 329-336
4. Macefield RC, Metcalfe C, Lane JA, Donovan JL, Avery KN, Blazeby JM et al. Impact of
prostate cancer testing: an evaluation of the emotional consequences of a negative
biospy results. British Journal of Cancer. 2010. 102. pp. 1335-1340
5. Murphy DG, Ahlering T, Catalona WJ, Crowe H, Crowe J, Clarke N et al. The Melbourne
Consensus Statement on the Early Detection of Prostate Cancer. BJU International.
2014. 113(2) pp. 186-188