Volume 17, Issue 4 , June 2005, Pages 231-233
Prostate Cancer Screening in Australasia
D.S. Lamb*, J.W. Denham?, and B. Delahunt?
*Wellington Cancer Centre, Wellington Hospital, Wellington, New Zealand
Department of Radiation Oncology, Newcastle Mater Misericordiae Hospital,
New South Wales, Australia
Department of Pathology and Molecular Medicine, Wellington School of
Medicine and Health Sciences, Wellington South, New Zealand
Received 9 September 2004; revised 14 February 2005; accepted 23 March
2005. Available online 25 May 2005.
Article Outline
Introduction
The Prostate Cancer Screening Process
Can the Prostatic Cancer Screening Process Meet Expectations?
Randomised Clinical Trials on Systematic Population-based Screening
Current Screening Practices in Australasia
The Way Forward
Summary of Recommendations
- References
Introduction
Debate, sometimes highly emotive, continues in Australia and New Zealand
about the value of prostate cancer screening. Many epidemiologists and
public-health physicians have taken the position that, because there is
insufficient evidence of benefit to introduce systematic population-based
screening (PBS), self-requested screening (SRS) should be actively
discouraged. These doctors claim that SRS merely leads to unnecessary
treatment of many patients with indolent cancers unlikely to cause health
problems in the patient's lifetime. They advocate that patients should
only be investigated for prostate cancer when they present with urinary
symptoms.
Not surprisingly, governments of Australia and New Zealand are happy to
receive such a cost-neutral recommendation, which endorses further periods
of inactivity. Unfortunately, however, the recommendation is made on the
mistaken belief that prostate cancer causes characteristic urinary
symptoms if treatment is required, either when the tumour reaches a
certain size or if the tumour is a biologically active one. In fact,
prostate cancer is nearly always a silent disease, even when the tumour is
locally advanced [1]. Curtailing the practice of SRS would, therefore,
inevitably result in the diagnosis of fewer cancers while they were still
potentially curable.
We look at the main contentious issues that have caused the debate to
polarise in Australia and New Zealand, and make recommendations for
resolving these to allow forward progress. The establishment of the
Prostate Cancer Risk Management Programme in the UK suggests that some of
our problems are generic to other countries, and that we have been slow to
address them.
The Prostate Cancer Screening Process
Measurement of serum prostate-specific antigen (PSA), digital rectal
examination (DRE) and prostate biopsy are the basic tools of prostate
cancer screening. A PSA value on its own, or even when combined with DRE,
has unacceptably low specificity as a screening test for prostate cancer.
Raising the threshold for a 'positive' PSA makes the specificity closer to
ideal, but at the expense of major loss of sensitivity. Both the
sensitivity and specificity of the screening process only become
acceptable when prostate biopsies are added to PSA and DRE. This 'two
step' screening process is similar to that for breast cancer, in which
biopsy of suspicious lesions detected by mammography, clinical
examination, or both, is routinely performed.
Can the Prostatic Cancer Screening Process Meet Expectations?
The requirements for a useful cancer-screening test have been defined by
the World Health Organization 2 and 3. The cancer should have a high
prevalence in a detectable pre-clinical state, and should be responsible
for substantial morbidity and mortality. The testing process should be
simple, safe and affordable, as well as having high sensitivity and high
specificity. Finally, there should be treatment(s) available that have
been demonstrated to lead to improved outcomes when used earlier in the
natural history of the cancer.
There is no doubt that prostate cancer does have a high prevalence in a
detectable pre-clinical state. Only a quarter to a third of men with
prostate cancer present with cancer in an advanced and incurable state
[4]. The remainder of the group will have potentially curable disease, and
most will not have symptoms, even if the cancer is extensive within the
prostate. Only 7% of 800 men with locally advanced prostate cancer treated
in a recently conducted Australasian clinical trial presented with urinary
symptoms causing 'moderate bother' or worse [1].
Some evidence shows that currently available treatments can reduce deaths
from prostate cancer when used earlier in the natural history of the
disease. The strongest direct support comes from a recent publication on
the results of the Scandinavian Prostate Cancer Group study 4 [5]. This
was a large, randomised trial comparing radical prostatectomy with
watchful waiting in early prostate cancer. At 6.2 years median follow-up,
the relative hazard of death from prostate cancer was 0.50 (0.27-0.91),
and the relative hazard of distant metastases 0.63 (0.41-0.96) in those
patients assigned to radical prostatectomy. Furthermore, indirect evidence
supports a link between earlier treatment and a reduced risk of death from
prostate cancer. Between 1993 and 1997, the fall in death rates was
greater in the USA [6], where screening has been prevalent for many years,
compared with the UK [7], where few men are screened on an annual basis.
At least part of this difference is likely to be due to screening, which
results in more early stage cancers being diagnosed and treated in the
USA.
Randomised Clinical Trials on Systematic Population-based Screening
So far, only the Quebec trial [8] has published its definitive results. A
reduction in the risk of dying from prostate cancer was reported for the
screened group, but this conclusion has been heavily challenged because of
concerns about the trial design and analysis.
An ongoing randomised trial of biennial PBS on 20 000 Swedish men, which
started in 1995, recently reported that cancers detected in the screened
group were typically early stage, when curative treatment is usually
effective [9]. In addition, there was a clear trend towards down-staging
and down-grading on repeat screening, and few symptomatic interval cancers
developed in the screened group.
The results of two large ongoing PBS trials, one in the USA [10], and the
other in Europe [11], will hopefully shed more light on the value of
systematic programmes. Definitive reporting on the European ERSPC trial,
which includes the 20 000 Swedish men mentioned above, is expected in
2008.
Current Screening Practices in Australasia
A recent survey in New Zealand showed that general practitioners had
diverse screening practices [12]. Forty-two per cent of doctors were
prepared to screen patients up to 79 years of age. This variation is
likely to be due to an absence of any applicable recommendations for SRS
(i.e. screening requested by individuals when there is no PBS programme in
place). In August 1996, a joint policy statement was issued by Health
Departments in Australia and New Zealand advising against 'routine
prostate cancer screening in asymptomatic men' [13]. In 2004, the National
Health Committee in New Zealand re-issued its recommendations on prostate
cancer screening [14], and the conclusions drawn in that report were
similar to those issued in 1996.
We believe that one explanation for policy failing to progress over this
8-year period is the unbalanced composition of governmental advisory
bodies. Most of the medical input has been from public health physicians
and epidemiologists, with little opportunity for specialists involved in
treatment delivery to contribute. As a result, the advisory bodies have
only been able to address the issue of systematic PBS, and have not had
the collective expertise to make useful recommendations on SRS. The
repeated suggestion that widely practised SRS should cease altogether has
created confusion and resentment in many middle-aged and older men, as
well as the medical practitioners who look after them.
The Way Forward
Lessons need to be learned from the breast-cancer screening experience. No
single clinical trial can be expected to provide all the answers
concerning the benefit or otherwise of a screening process. For breast
cancer, the benefits of systematic population-based screening were
quantified from the results of eight randomised clinical trials involving
500 000 women over a 35-year period [15]. However, even now, debate
continues on the age at which screening should commence, and the optimal
screening interval for individuals enrolled in the screening programme.
This debate is reflected in currently different breast-cancer screening
practices in Australia and New Zealand. A similar slow accumulation of
evidence on the value of systematic PBS for prostate cancer can also be
anticipated, and it is likely to be many years before all the present
uncertainties have been addressed. Until then, a gradual evolution in
screening practices can be expected to occur, rather than a sudden change
once a threshold of knowledge has been passed. This means that the
polarised 'all or nothing' debate on prostate cancer screening, currently
taking place in New Zealand and Australia, is setting unrealistic
expectations.
Guidelines for SRS need to be urgently developed and widely distributed in
Australia and New Zealand. These guidelines should be readily accessible
to the general public, so anomalies in current SRS practice are corrected.
First, some men at high risk of prostate cancer are missing the
opportunity of early diagnosis and treatment. This is especially relevant
to the 10% of cases diagnosed with the disease who have a family history
of prostate cancer 16, 17 and 18, as men who have one or more first-degree
relatives with prostate cancer have up to 11 times the risk of developing
the cancer themselves [18]. Second, and conversely, the existing practice
of screening very elderly men makes unrealistic demands on prostate biopsy
services, and gives these men expectations, often false, that they will
require treatment if a cancer is discovered. For older men, external beam
radiotherapy is often the only treatment option, and this is a service in
Australasia already under great pressure.
Governments can only make decisions as good as the advice they receive.
They need input from independent advisory groups on all aspects of
prostate-cancer screening. These groups should consist of health
professionals experienced in prostate cancer epidemiology, diagnosis and
treatment. Patient advocacy bodies should also be represented. As a first
step, the advisory groups would develop the SRS guidelines discussed
previously, so that scant health resources were targeted on those more
likely to benefit. The production of comprehensive educational literature
for men with newly diagnosed prostate cancer would also have high
priority, to assist them in making informed decisions on the diverse, and
sometimes bewildering, management options open to them. At a later date,
and as more information becomes available, the advisory groups would
recommend when and how systematic PBS could be initiated on selected
groups of men. Logically, these are all activities that should be part of
national cancer-control programmes that are being implemented, or are
already running, in many Western countries.
Summary of Recommendations
(1) Expert advisory committees, consisting of a balance of medical
disciplines, and with patient input, should be established. Ideally, they
should have reporting channels to national cancer-control programmes; (2)
these advisory committees would define the important differences between
PBS and SRS, acknowledging the right of the individual to make a 'personal
choice' on SRS. To help make this choice, the committees would ensure that
men were provided with balanced easy-to-comprehend written information on
the screening process, on those most likely to benefit from screening, and
on the risks associated with screening. A better informed public should
lead to SRS being used more appropriately; (3) the committees would also
ensure that men with newly diagnosed prostate cancer were provided with
balanced easy-to-comprehend written information on the management
alternatives. The decision on which treatment, if any, should not be a
lottery dependent on referral patterns; (4) later, as more evidence
becomes available, the committees would recommend when and how systematic
PBS should be introduced for selected men. Those with genetic risks are
likely to be the first to be targeted.
References
1 D.S. Lamb, J.W. Denham and H. Mameghan et al., Acceptability of short
term neo-adjuvant androgen deprivation in patients with locally advanced
prostate cancer, Radiother Oncol 68 (2003), pp. 255-267. SummaryPlus |
Full Text + Links | PDF (374 K)
2 B.S. Kramer, J.K. Gohagan and P.C. Prorok, Cancer screening: screening
and practice, Marcel Dekker Inc., New York (1999).
3 US Preventative Services Task Force, Guide to clinical preventative
services, International Medical Publishing, Alexandria, VA (1996).
4 D.P. Smith, R. Supramaniam, M.S. Coates and B.K. Armstrong, Prostate
cancer in New South Wales in 1972 to 1994, NSW Cancer Council, Sydney
(1998).
5 L. Holmberg, A. Bill-Axelson, F. Helgeses and M. Thun, A randomised
trial comparing radical prostatectomy with watchful waiting in early
prostate cancer, N Engl J Med 347 (2002), pp. 781-789. Abstract-EMBASE |
$Order Document Abstract-Elsevier BIOBASE | $Order Document
Abstract-MEDLINE | $Order Document | $Order Document | Full Text via
CrossRef
6 R.T. Greenlee, M.B. Hill-Harmon, T. Murray and M. Thun, Cancer
statistics, CA Cancer J Clin 51 (2001), pp. 15-36. Abstract-EMBASE |
$Order Document Abstract-MEDLINE | $Order Document | $Order Document
7 S.E. Oliver, D. Gunnell and J.L. Donovan, Comparison of trends in
prostate-cancer mortality in England and Wales and the USA, Lancet 355
(2000), pp. 1788-1789. SummaryPlus | Full Text + Links | PDF (61 K)
8 F. Labrie, B. Candas and A. Dupont et al., Screening decreases prostate
cancer death: first analysis of the 1988 Quebec prospective randomized
controlled trial, Prostate 38 (1999), pp. 83-91. Abstract-EMBASE | $Order
Document Abstract-MEDLINE | $Order Document | $Order Document | Full
Text via CrossRef
9 J. Hugosson, G. Aus, H. Lilja, P. Codding and C.G. Pihl, Results of a
randomised, population-based study of biennial screening using serum
prostate-specific antigen measurement to detect prostate carcinoma, Cancer
100 (2004), pp. 1397-1405. Abstract-EMBASE | $Order Document
Abstract-Elsevier BIOBASE | $Order Document Abstract-MEDLINE | $Order
Document | $Order Document | Full Text via CrossRef
10 P.C. Prorok, G.L. Andriole and R.S. Bresalier et al., Design of the
prostate, lung, colorectal and ovarian (PLCO) cancer screening trial,
Control Clin Trials 21 (2000), pp. 273S-309S. Abstract | Abstract +
References | PDF (2095 K)
11 P.M. Beemsterboear, H.J. de Koning, R. Kranse, P.H. Trienekens, P.J.
van der Maas and F.H. Schroder, Prostate specific antigen testing and
digital rectal examination before and during a randomized trial of
screening for prostate cancer: European randomized study of screening for
prostate cancer, Rotterdam, J Urol 164 (2000), pp. 1216-1220.
12 J. Durham, M. Low and D. McLeod, Screening for prostate cancer: a
survey of New Zealand general practitioners, N Z Med J 116 (2003), p.
U476.
|
