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National Public Health Service for Wales
Population screening for prostate cancer
Population screening for
prostate cancer
Authors: Deacon T; Jones A
Caerphilly Local Public Health Team; NPHS
Date: 2/2/07
Page: 1 of 14
Status: FINAL
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Population screening for prostate cancer
Contents
1
BACKGROUND ........................................................................................................... 3
2
THE CONDITION ....................................................................................................... 3
3
THE SCREENING TEST ............................................................................................ 4
3.1
Digital rectal examination (DRE) ................................................................ 4
3.2
Prostate specific antigen (PSA) ................................................................... 5
3.2
Biopsy .......................................................................................................... 6
4
TREATMENT .............................................................................................................. 6
5
EVIDENCE FOR PROSTATE CANCER SCREENING ........................................ 7
5.1
Results ......................................................................................................... 7
5.1.1 Outcome measures ................................................................................. 8
5.1.2 Conclusions ............................................................................................ 9
6
PROSTATE CANCER RISK MANAGEMENT PROGRAMME .......................... 9
7
CONCLUSION ........................................................................................................... 10
GLOSSARY ............................................................................................................................ 11
REFERENCES ....................................................................................................................... 12
APPENDIX
Acknowledgements
Thanks go to the following people for their comments during the drafting of this paper:
Dr Gill Richardson, Dr Karen Gully, Dr Iain Robbé, Dr Sarah Aitken, Sandra Caple, Dr
Hilary Fielder.
© 2007 National Public Health Service for Wales
Material contained in this document may be reproduced freely without prior permission,
provided it is done so accurately and is not used in a misleading context. Acknowledgement to
the National Public Health Service for Wales to be stated.
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1
Population screening for prostate cancer
Background
The 10 principles which a screening programme should meet were originally set out in 1968
by Wilson and Junger:1
1. Important health problem
2. Natural history well understood
3. Recognisable at an early stage
4. Treatment better at an early stage
5. A suitable test exists
6. An acceptable test exists
7. Adequate facilities exist to cope with abnormalities detected
8. Screening at repeated intervals when insidious onset
9. Chance of harm is less than the chance of benefit
10. Cost balanced against benefit
Based on the above, the UK National Screening Committee (NSC) * has produced criteria
against which it appraises the viability, effectiveness and appropriateness of programmes.2
On consideration of the evidence, the NSC concluded that that there was no evidence of
benefit from population screening for prostate cancer,3 and that only the first principle could
be met.1 A recent Cochrane review4 (summarised in section 5) has supported this perspective.
The NSC policy position allows for prostate cancer screening to be provided on an individual
request basis, provided that the man fully understands the lack of good quality evidence about
the benefits and risks of testing. The source of relevant information is stated as the Prostate
Cancer Risk Management Programme (see section 6 for details).5
The NSC criteria fall under the headings of: the condition itself, the screening test, the
treatment and the screening programme.2 This report briefly discusses the first three of these
headings and outlines the reasons why there is no population screening programme for
prostate cancer in the UK.
2
The condition
According to the screening criteria, the condition must be an important health problem.2
Prostate cancer is the most commonly diagnosed non-skin cancer in most developed countries,
and is the second most common cause of cancer deaths in men.6
In addition, the natural history of the condition should be understood,2 but this is uncertain for
prostate cancer.6 In many cases it is slow-growing, so slow-growing that it may never become
clinically important,7 or would not even have presented clinically within a man’s lifetime,8
resulting in men dying from another cause.6,7 It is difficult to differentiate between relatively
*
The NSC is the body responsible for advising government on all aspects of screening policy in the UK.
Authors: Deacon T; Jones A
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harmless tumours and those that are likely to be fatal7 and requiring treatment.9 There are
ethical issues surrounding the decision not to treat after identifying a condition, but treating
prostate cancer has risks9 (this is discussed in section 4 below).
3
The screening test
The test should be simple, safe and precise.2 Currently, the two tests that could be used in
population screening are prostate specific antigen (PSA) and digital rectal examination
(DRE).
3.1
Digital rectal examination (DRE)
During a DRE a doctor may be able to feel that the prostate is abnormal.8 DRE is useful in
detecting palpable† prostatic tumours; approximately 50% to 90% of localised prostatic
tumours have been reported as palpable.10 Nearly 30% of cancers found where PSA values
were within the normal range were detectable by DRE.10
Although quick and easy to perform, there are concerns about the accuracy of DRE.10 DRE
misses approximately 20% of cancers which can be identified by PSA but which are not
palpable.10 Also, a palpable mass may not be malignant; the incidence of which increases
with age. The positive predictive value of DRE therefore decreases with age, from 25% in
men aged under 65 years compared with 12.5% in men over 65 years.10
A health technology assessment systematic review reported the following findings from
studies examining DRE: 10
Range
False positives
40% to 50%
Sensitivity‡
44% to 97%
Specificity§
22% to 96%
Positive predictive value**
13% to 69%
The Prostate Cancer Risk Management Programme advises that DRE is a useful diagnostic
test for men with symptoms, but is not recommended as a screening test in asymptomatic
men.8
In addition, the screening criteria specifies that the test should be acceptable to the
population,2 however, DRE is not as acceptable as PSA.7
†
Palpable = capable of being felt when touched.
Sensitivity = probability of identifying true positives with the disease.
§
Specificity = probability of identifying true negatives.
**
Positive predictive value = probability that a test positive individual actually has the disease.
‡
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3.2
Population screening for prostate cancer
Prostate specific antigen (PSA)
Prostate specific antigen (PSA) is a protein produced by the prostate gland.11 All men have
some PSA in their blood,11 and the PSA test is a simple blood test that measures the amount of
this protein. A high level can be indicative of prostate cancer. However, the level can also be
raised due to benign prostate conditions12 such as benign enlargement of the prostate,
prostatitis and lower urinary tract infections.10 The level also rises with age.11 About two
thirds of men with an elevated PSA do not have prostate cancer detectable at biopsy.10 In
addition, some men with clinically significant prostate cancer have normal PSA levels, up to
20% of men have been reported as such.13
The accuracy (sensitivity and specificity) of the PSA test is difficult to determine.7 In order to
measure how good the test is, it needs to be assessed against a ‘gold standard.’ For the PSA
test, biopsies are regarded as the gold standard for diagnosis of localised prostate cancer.
However, biopsies are not normally performed on men with a negative PSA, so it is difficult
to assess the number of false negative tests and measure the sensitivity of the PSA test.7 Also,
biopsies are themselves not completely accurate10 and are reported to miss 10 to 30% of
cases.7
The health technology assessment systematic review reported the following range of results
from studies examining PSA: 10
 Sensitivity - 57%-99% (70% regarded as most likely during screening)
 Specificity - 59%-97%
The accuracy varies according to the cut-off level. There is some debate about what is the
‘normal’ PSA range. Up to 4ng/ml is regarded as normal, however studies have found
between 25% and 73% of men with no evidence of prostate cancer to have PSA levels higher
than 4ng/ml.10 In addition, as PSA values tend to rise with age8, 10 age-specific reference
levels should be used.
In summary, the benefits and disadvantages of PSA are:
Result
Benefits of PSA
Disadvantages of PSA
Above ‘normal’ range
 May find cancer before  Can cause unnecessary
symptoms develop.
anxiety
and
follow-up
medical tests if wrong.
 May detect slow growing
cancer that may never cause
any symptoms.
 May expose a man to
treatment which may not be
successful and may have
side-effects.
Within ‘normal’ range
 Provides reassurance.
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 Provides false reassurance if
it is wrong.
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3.3
Population screening for prostate cancer
Biopsy
After a raised PSA level, a prostatic biopsy would be required to investigate.8 As mentioned
above, biopsies do not pick up all tumours; up to 20% of tumours are missed.8 In addition,
most men find it an uncomfortable experience and some describe it as painful.8 Post-biopsy
complications include:
 bleeding and infection.8
 haematuria/haematospermia.†† Approximately one-third of men get some in the three
months following the biopsy.8
 risk of infection. All patients should receive prophylactic antibiotics to reduce the risk of
infection. Reported rates of septic symptoms even after prophylactic antibiotics can be over 1%.8
These complications have to be considered along with the fact that approximately 2 out of
every 3 men who have a biopsy will not have prostate cancer. 14
4
Treatment
The NSC screening criteria states that there should be an effective treatment or intervention
for patients identified through early detection.2 There is a lack of good quality evidence about
the relative effectiveness of the three main treatment options for localised prostate cancer:10
 Active monitoring – involves regular checkups to monitor if the cancer has advanced. It
avoids the side effects of treatment, but the cancer may grow to a more advanced stage, and
some men find the uncertainty difficult to cope with. 14
 Radiotherapy – a course of radiotherapy treatment on the prostate gland to try to cure.
 Radical prostatectomy – the aim is to cure through surgery to remove the prostate gland.
However, the tumour may not be completely cleared.8
Comparisons between treatments are difficult because of differences in case mix, staging and
treatment techniques.8 Research is underway which will inform discussions in the future.
The ProtecT clinical trial is a large study across 9 centres in the UK (including Cardiff) that
will provide invaluable information on the effectiveness of current treatments in the future.
Treatment can cause harm as well as benefit; the risk of complications found in various
studies are summarised below:7
††
Blood in the urine/sperm
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Risk
Population screening for prostate cancer
Surgery
Radiotherapy
Death
 0.1% - 0.3%7
 <1%7
Bladder problems
 Up to 20%14
 Up to 5%14
 Urinary
leakage
in
up
to
50%.15
Incontinence
 9.6%7
 3.5%
 Severe
incontinence
in
7
2-
5%.16
 Up to 10% may experience
Bowel problems
diarrhoea or bowel problems14
Erectile problems
 79.6%* 2 years post-op7
 6.5% 2 years post-op7
 80%15
Impotence
 20-80%14
 10-90%
17,18
 25-60%.14
(70% on average)
*Rate may be as low as 32%, dependent upon the surgeon.
5
Evidence for prostate cancer screening
5.1 Results
A systematic review of the evidence for screening for prostate cancer was published in 2006.4
The primary objective of the review was to determine whether screening for prostate cancer
reduces mortality and has an impact on quality of life. Secondary objectives were to
determine the impact of prostate cancer screening on quality of life and adverse effect; and to
identify the cost effectiveness, cost utility and cost benefit of mass screening for prostate
cancer. The search criteria were robust looking in electronic databases (40 years) and hand
searching and personal communications for published (3-8 years) or unpublished trials with
no language restrictions. There were no conflicts of interest declared by the authors and the
review received no external sources of support.
The primary outcome measures were:
 Mortality rate (Prostate cancer specific and all cause)
 Number of men diagnosed with prostate cancer (including classification by stage and
grade of the cancer)
The secondary outcome measures were:
 Incident prostate cancers by stage and grade at diagnosis
 Metastatic disease at follow up
 Quality of life
 Costs associated with screening programmes
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 Harms of screening (including both adverse outcomes from false positives and/or false
negative results and their impact upon resulting treatment procedures)
The search identified 99 potentially relevant articles; two authors independently selected trials
for inclusion against a predetermined checklist, also for susceptibility for bias and extracted
data using a standard data extraction form. Where data was available and if the trial did not
report intention-to treat analysis results, the authors performed this using the groups to which
the participants were originally randomised. Two randomised controlled trials met the
inclusion criteria (Quebec, Canada and Norrkoping, Sweden) although both were assessed as
having a high risk for bias. A third study (Rotterdam) is ongoing with data due to be
published on 4 of 5 pilots, and the 5th pilot is part of the final protocol for the European
Randomised study of Screening for Prostate cancer (ERSPC), which will be published in the
next few years.
The Quebec study had methodological issues related to contamination and crossover in the
analysis, unclear allocation and unblended assessment of outcome. Raw data was re-analysed
on an intention to screen basis. It is important to analyse on “intention-to-screen” rather that
actual screening as in a population screening programme there will be individuals who do not
take up the invitation to screen, as with this study and this needs to be considered. The
Norrkoping study used a quasi random method of allocation, had a lack of allocation
concealment, potentially unblended outcome assessment and unknown crossover in the group.
5.1.1
Outcome measures
Primary outcome measures
1. Prostate cancer mortality:
Study
Relative Risk of death from
prostate cancer in men
screened
95% Confidence
Intervals
1. Quebec – original analysis
0.39
0.19 – 0.65
2. Quebec - re-analysed
(intention to screen)
1.01
0.76 – 1.33
3. Norrkoping
1.04
0.64 – 1.68
4. Pooled 2&3
1.01
0.80 – 1.29
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2. Prostate cancer detected
Quebec Study reported a 3.0% prostate cancer diagnosis form the first screening
(244/8,137).
The Norrkoping Study reported a 47% higher rate of prostate cancer diagnosis in the
screened than the control group (RR 1.47; 95% CI 1.16 – 1.86).
Clinical Stage Distribution: The study results were not comparable as different staging
systems were used.
Secondary outcome measures
Neither study reported on these measures.
5.1.2
Conclusions
There is insufficient evidence to either support or refute the routine use of mass, selective,
opportunistic or no screening to reduce prostate cancer specific mortality. The trials found that
men randomised to screening had prostate cancer more frequently detected but did not have a
reduction in prostate cancer specific mortality. No robust evidence exists to determine the
impact of screening on quality of life, harms of screening or economic value.
It is recommended that the results of the Rotterdam, ERSPC (European) and PLCO (USA)
trials should be reviewed upon publication and population screening for prostate cancer
reassessed in light of the findings.
6
Prostate Cancer Risk Management Programme
The Prostate Cancer Risk Management Programme (PCRMP) was launched by the Secretary
of State for Health in 2000.19 It had been recognised that there was increasing demand from
men for a PSA test from their general practitioner (GP).19 The PCRMP was set up to ensure
that men who are concerned about the risk of prostate cancer receive clear and balanced
information about the advantages and disadvantages of the PSA test and treatment for prostate
cancer.20
In 2002 resource packs were published and sent to GPs to assist them in counselling men who
enquire about testing.21 The packs include a detailed booklet for the primary care team and a
patient information leaflet.21 The evidence-based materials aim to help men reach an
informed choice about whether or not to proceed with the test.19
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7
Population screening for prostate cancer
Conclusion
Many of the criteria against which a population screening programme should be assessed have
not been met for prostate cancer. In particular, there is a lack of knowledge about the natural
history of the disease, the screening tests are not accurate, and there is a lack of good quality
evidence concerning the effectiveness of treatments for localised prostate cancer.10 Based on
current evidence, there is a risk of more harm than good resulting from a population screening
programme. However, research is underway that will help to inform the debate in the future.
The Prostate Cancer Risk Management Programme aims to provide clear and balanced
information on screening and treatment of prostate cancer and its website
(www.cancerscreening.nhs.uk) is a useful source of reference. It is recommended that any
individual considering a PSA test should discuss the options with their GP.
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Glossary
Prostate gland
A male accessory sex gland that opens into the urethra just below the
bladder and vas deferens. During ejaculation it secretes an alkaline
fluid that forms part of the semen. The prostate may become enlarged
in elderly men (benign prostatic hyperplasia; BPH). This may result in
obstruction of the neck of the bladder, impairing urination. The
bladder dilates and the increasing pressure is transmitted through the
ureters to the kidney nephrons, leading to damage and impaired
function of the kidneys.
Prostate cancer
A malignant tumour (carcinoma) of the prostate gland, a common form
of cancer in elderly men. In most men it progresses slowly over many
years and gives symptoms similar to those of benign enlargement of
the prostate.
Prostate specific
antigen (PSA)
An enzyme produced by the glandular epithelium of the prostate.
Increased quantities are secreted when the gland enlarges. PSA levels
tend to be much higher in advanced prostate cancer and the rate of fall
on treatment is a good prognostic indicator.22
Screening
The presumptive identification of unrecognised disease or defect by
the application of tests, examinations or other procedures which can be
applied rapidly. Screening tests sort out apparently well persons who
probably have a disease from those who probably do not. A screening
test is not intended to be diagnostic. Persons with positive or
suspicious findings must be referred to their physicians for diagnosis
and necessary treatment.23
Population
screening
The application of a systematic screening process to a defined
population
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References
1
NHS Cancer Screening Programmes. Prostate cancer risk management. Questions and
answers. Available http://www.cancerscreening.nhs.uk/prostate/faqs.html [Accessed 7th
Nov 2006].
2
UK National Screening Committee. Critera for appraising the viability, effectiveness and
appropriateness of a screening programme. Available
http://www.nsc.nhs.uk/pdfs/criteria.pdf [Accessed 2nd Nov 2006].
3
NHS Executive. Population screening for prostate cancer. EL(97)12. Available
http://www.nsc.nhs.uk/pdfs/el9712.pdf [Accessed 2nd Nov 2006].
4
Ilic D, O'Connor D, Green S, Wilt T. Screening for prostate cancer. Cochrane Database of
Systematic Reviews 2006, Issue 3. Available
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[Accessed 21st Nov 2006].
5
National Screening Committee. Policy position. July 2006. Available from:
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1347 [Accessed 1st Feb 2007].
6
Frankel S, Davey Smith G, Donovan J, Neal D. Screening for prostate cancer. Lancet 2003;
361:1122-28.
7
Davidson P, Gabbay J. Should mass screening for prostate cancer be introduced at the
national level? Copenhagen: WHO Regional Office for Europe (Health Evidence Network
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2006].
8
Watson E, Jenkins L, Bukash C, Austoker J. The PSA test and prostate cancer: information
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10
Selley S, Donovan J, Faulkner A, Coast J, Gillatt D. Diagnosis, management and screening
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Nov 2006].
11
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http://www.netdoctor.co.uk/diseases/facts/prostatecancer.htm [Accessed 2nd Nov 2006].
12
Netdoctor web page. Available from:
http://www.netdoctor.co.uk/features/prostate_screening.htm [Accessed 2nd Nov 2006].
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13
Catalona W, Smith D, Ratliff T, Basler J. Detection of organ-confined prostate cancer is
increased through prostate-specific antigen-based screening. JAMA 1993; 270: 948-54.
In: Watson E, Jenkins L, Bukash C, Austoker J. The PSA test and prostate cancer:
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2006].
14
Brett J, Watson E, Bukach C, Austoker J. PSA testing for prostate cancer. An information
sheet for men considering a PSA test. Sheffield: NHS Cancer Screening Programmes;
2002.
Available http://www.cancerscreening.nhs.uk/prostate/prostate-patient-info-sheet.pdf
[Accessed 2nd Nov 2006].
15
Steineck G, Helgesen F, Adolfsson J, et al. Quality of life after radical prostatectomy or
watchful waiting. N Engl J Med 2002; 347:790-96. In: Frankel S, Davey Smith G,
Donovan J, Neal D. Screening for prostate cancer. Lancet 2003; 361:1122-28.
16
Weldon V, Tavel F, Neuwirth H. Continence, potency and morbidity after radical perineal
prostatectomy. J Urol 1997; 158: 1470-75. In: Frankel S, Davey Smith G, Donovan J, Neal
D. Screening for prostate cancer. Lancet 2003; 361:1122-28.
17
Stanford J, Feng Z, Hamilton A, et al. Urinary and sexual function after radical
prostatectomy for clinically localized prostate cancer. JAMA 2000; 283:354-60. In: Frankel
S, Davey Smith G, Donovan J, Neal D. Screening for prostate cancer. Lancet 2003;
361:1122-28.
18
Siegel T, Moul J, Spevak M, Alford G, Costabile R. The development of erectile
dysfunction in men treated for prostate cancer. J Urol 2001; 165: 430-435. In: Frankel S,
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361:1122-1128.
19
Richards R. Letter about the implications for pathology of the GP resource pack on PSA
testing. Available
http://www.dh.gov.uk/PublicationsAndStatistics/LettersAndCirculars/DearColleagueLetters/
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Feb 2007].
20
NHS Cancer Screening Programmes [webpage]. Available from:
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21
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22
Martin E (Ed). Oxford concise colour medical dictionary. 3rd edition. Oxford: Oxford
University Press; 2004.
23
Last J, editor. A dictionary of epidemiology. 4th edition. Oxford: Oxford University Press;
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Appendix
Patient information leaflet http://www.cancerscreening.nhs.uk/prostate/prostate-patient-infosheet.pdf
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