Part of the “Enhancing Prostate Cancer Care” MOOC

Catherine HolbornSenior Lecturer in Radiotherapy & Oncology

Sheffield Hallam University

IntroductionDebate 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

The PSA testThe current available testNot a test for prostate cancer, just prostate cancer riskFurther, more invasive tests may be neededFalse positives and false negatives are possible with the PSA

testNevertheless….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!

Population vs. Opportunistic Population based screeningAll asymptomatic men, within a given age range would

be invited to have the PSA blood test

Opportunistic testingInitiated by the man and/or their doctor, based on an

individual case findings and an assessment of risk vs. the benefits of testing

Benefits, risks, implications…The PSA test is responsible for significant increases in the incidence and detection

of early stage prostate cancersReductions in mortality rates have been observed in some population based

screening trialsHowever, they have also demonstrated the significant problem of over-diagnosis

and over-treatmentMen 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 problemsAs a result, men may arguably receive unnecessary treatment and be subjected

to the side effects associated with thisUnfortunately, there is currently no test that can definitively tell us whether a

very early prostate cancer is indolent/slow growing or more aggressive

PLCO cancer screening trial¹Prostate, Lung, Colorectal and Ovarian screeningRecruited 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.

ERSPC trial¹ ² ³European 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%

However…Over-diagnosis and over-treatment was evidentERSPC 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

Potential impact of over-diagnosisA 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

Other relevant findingsHigh rate of false positives in ERSPC trial3 out of 4 men (75%)with an elevated PSA were not

found to have cancerSignificant 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) ⁴Distress levels remained immediately after the negative

biopsy result and also 12 weeks later ⁴

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 neededThe TRUS guided biopsy has associated risks/complicationsResearch has shown 75% of men will not be found to have cancer upon

biopsyFalse negatives are also possible with the biopsy. Further testing and long

term monitoring may be required if PSA levels remain elevatedFor 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)

Informing asymptomatic men

Opportunistic testingApproach adopted by UK and many other countriesTendency 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 decisionQuestions 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?

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

Focus of current researchFinding a better test for prostate cancer or at least the

risk of prostate cancerTumour markers e.g. PCA3 urine testImaging methods e.g. multi-parametric MRI

Learning about the genetics of prostate cancerWhich genes predispose a man to developing prostate

cancer?Are there specific characteristics that help to distinguish

between indolent and aggressive cancers?

Suggested activityA number of organisations have provided stances on the use of

PSA testing for prostate cancer. For example:United Kingdom (PCRMP)US Preventative Services Task ForceAmerican Urological AssociationAmerican Cancer SocietyCancer Council Australia / Australian Health Ministers Advisory CouncilUrological 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?

References1. 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. 127-1332. 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