Screening for prostate cancer in the UK
BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7316.763 (Published 06 October 2001) Cite this as: BMJ 2001;323:763All rapid responses
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Dear Sir,
Thanks a lot for publishing the editorial article on "Screening for
Prostatic Cancer in U.K" by Donovan J.L et al,which is
interesting.Recently there is a wide range of controversy in interprating
PSA and its different positive and negative implications.
Prostatic cancer is the commonest cancer seen in American men and the
second leading cause of cancer related death in USA.In 2001 alone 198,000
new prostatic cancers were detected and over 31,500 deaths noted.(1).Our
medical faternity cannot remain a silent spectator,we must improve our
state of knowledge through a critical SWOT
(Strength,Weakness,Opportunities,Threat) analysis of the screening
procedure and community knowledge should be strengthened through feedback
and POIME(Planning,Organisation,Implementation ,Monitering and Evaluation)
analysis. A multidisciplinary prostatic cancer monitering group with RAA
(Responsibility,Authenticity and Accountability) to the medical faternity
and patients at large should be formed to take initiative on this issue.
Any cancer related discussion is incomplete,or the text will suffer
from scientific oversimplification, if we do not recognize the antigenic
heterogenicity of the neoplasm,the intrinsic immunogenicity of the
metastatic cells,and the variation of the host's ability to recognize and
destroy cancer cells. Moreover, there is a possibility of variation of the
antigenicity of the primary tumor and the metastsis, and even among two
different metastatic lesions.(2).
Cancer is a clonal disorder.When the cells grow more,become immortal,
and loose normal cell to cell interaction, it has a definite cancer
component.Several types of gene are involved in the process with the
progressive loss of balance in the growth promoting and the growth
suppression genes.When activated through activation or mutation to a hyper
-functioning form, these become oncogenes. The loss of function of growth
suppressor genes or tumor suppressor genes (both homologous copies) lead
to a powerful growth promoting effect. Other genes which are involved in
DNA repair and programmed cell death also have their impact on overall
cancer growth, proliferation and metastasis.
In the background of this information, if we assess why Hong Kong and
Japan have the lowest prostatic cancer mortality,(3) while African-
Americans have the highest rate, we would have to analyze not only the bio
-available age specific testerone in its different forms along with its
interaction with Type 5 alpha reductase gene (SRD 5A2) of chromosome 2P
and androgen receptor gene interaction, before we hurriedly come to
clinical conclusions incorporating various life style parameters.
With this preamble, let us analyze the prostatic specific antigen
(PSA), which is a glycoprotein produced only in the cytoplasm of benign
and malignant cells of the prostate and has a direct positive
corelationship with the bulk of the prostatic tissue. PSA is a tissue
specific enzyme and not a cancer specific enzyme.In patients with higher
than 40 ng/ml PSA result, there should be features of metastasis. In 98
percent of the prostatic cancer patients with metastasis, the PSA would be
elevated, but occasionally, prostatic cancers can remain localized, but
present with substantial elevation of PSA. Searial measurement of PSA can
improve specificity of cancer detection, provided that it is more than .75
ng/ml per year. Incorpration of PSA density (serum PSA/ vol. of prostate
as measured by ultrasound) data and age specific PSA level along with the
different fragments of PSA components (alpha 1 antichymotrypsin or alpha 2
macroglobulin bound portion and the free or unbound portion) should be
taken into consideration before interpreting the PSA data of any patient,
with or without features of prostatism.(4)
Thanking you,
Sincerely yours,
Dr. Niranjan Bhattacharya,MD,MS,FACS(USA),Principal
Investigator,Project on Epidemiology of Cancer, Calcutta;
Dr. Tarashankar
Bandopadhyay, Ph.D.; Dr. Sajal Ghosh, MD; Dr. Mahua Bhattacharya,MBBS,
DGO, DA; Ms.Ananya Bhadra,M.Sc.;Ms.Malabika Majumdar,M.Sc.;Dr. Anuradha
Das, MD; Dr. Sanjukta Bhattacharya, Ph.D
References:
(1)Stoller ML, Presti CJ, Carrol PR, "Urology", in Tierney
Jr,LM, McPhee SJ, Papadakis MA, eds.,CURRENT MEDICAL DIAGNOSIS AND
TREATMENT,2002, 41st ed.,Lange Medical Books, McGraw Hill,2002.
(2)Bystryn JC, Bernstein P, Lui P, Valentine F,"Immunophenotype of
Human Melanoma Cells in Different Metastasis",CANCER RES, 1985;45:5603.
(3)Muir C, Waterhouse J, Mack T, Powell J, Whelan S, "Cancer
Incidence in Five Continents", vol 5, Lyon, IARC, 1987.
(4)Oesterling J, Fuks J, Lee CT,Scher HI, "Cancer of the Prostate",
in Devita Jr.VT, Hellman S, Rosenberg SA, eds., CANCER: PRINCIPLES AND
PRACTICE IN ONCOLOGY, 5th ed., Lippincott Raven, 1997.
Competing interests: No competing interests
Can the demand for prostate specific antigen (PSA) testing in primary
care be managed?
SIR – The editorial by Donovan et al highlights that screening for
prostate cancer using the prostate specific antigen (PSA) test will become
increasingly prevalent in the NHS in the UK.(1) This is despite the fact
that population based screening for prostate cancer with current screening
technology does not satisfy the criteria set by the National Screening
Committee.(2) The 2000 NHS Prostate Cancer Care Programme document states
that screening will only be introduced if, and when, screening and
treatment techniques are sufficiently developed. However, any man thinking
of a PSA test should have the appropriate and relevant information to
enable him to make an informed choice about whether to be screened or
not.(3) Previously to this publication, a 1997 National Guidance
(Executive Letter)EL(97)12 was sent to commissioners of health care which
clearly stated that PSA testing should not be provided by the NHS, or be
offered to the public until there is effective screening technology for
prostate cancer.(4) As yet I am not aware of any significant developments
in this technology.
In 1998, my colleagues and I carried out a postal questionnaire
survey to determine the views of all North Staffordshire general
practitioners on prostate cancer screening in primary care, the details of
which are available elsewhere.(5) In brief, a copy of EL(97)12 was
enclosed with our questionnaire. This was because the majority of general
practitioners were not involved in commissioning and it was thus assumed
that most would not have come across the contents of EL(97)12. Our survey
received a good response rate of 71% (168/238) and offered some
quantification of the demand for prostate cancer screening as perceived by
the responding general practitioners.
Our results then showed that approximately 9% of respondents screened
asymptomatic men for prostate cancer using the PSA test, and that about
13% asked their patients first about prostate cancer screening. On the
other hand, 64% reported that patients asked them about prostate cancer
screening. Over half (57%) felt that patients should be allowed to choose
for themselves whether they wished to be screened or not, but only after
having been counselled about the benefits and harms of screening using the
PSA test.
This group of general practitioners were also asked if EL(97)12 had
changed their views about prostate cancer screening. Nearly 10% of
respondents replied that it had, that is, not to screen for prostate
cancer on receiving this type of guidance. One key inference from this for
the future for the Department of Health/NHS Executive was to disseminate
any new, clear and unambiguous guidance on prostate cancer screening in a
timely manner to general practitioners in order to influence their
clinical behaviour. Otherwise there may remain a number of general
practitioners requesting PSA tests which could be detrimental to the
overall health of the men screened. It may have been possible to prevent
some of these tests if general practitioners had received some form of
national guidance to inform their clinical decision-making. This quota of
PSA tested men will also probably contribute to the total number of men
screened who Donovan et al(1) refer to as ‘creeping in by the back door’.
In summary, it may be possible to manage some of the demand for PSA
testing in primary care. The bottom line however remains that health care
professionals must continue to take great care in making the decision to
undertake any screening especially when the evidence-base is poor.(6)
REFERENCES
1.Donovan J, Frankel SF, Neal DE, Handy FC. Screening for prostate
cancer in the UK. BMJ 2001; 323:763-754.
2.National Screening Committee. First Report of the National Screening
Committee. Health Departments of the United Kingdom, 1998. Department of
Health. London.
3.Department of Health. The NHS Prostate Cancer Programme.
http://www.doh.gov.uk/cancer/prostate.htm (accessed 9 October 2001).
4.NHS Executive. Executive letter on population screening for prostate
cancer. June 1997. EL(97)12: Leeds.
5.Kalsi GS, Rajaratnam G, Bridgman SA. Primary care perspective of
prostate cancer screening after national guidance: a questionnaire survey.
Journal of Medical Screening 2000; 7:116-117.
6.Muir Gray JA. Evidence-based healthcare. 1997. Churchill Livingstone,
New York.
CONTACT DETAILS:
Dr Gurmukh Singh Kalsi MBA MPH MRCGP
Specialist Registrar in Public Health Medicine
Directorate of Public Health and Health Policy,
North Derbyshire Health Authority,
Scarsdale,
Newbold Road,
Chesterfield S41 7PF
E-mail: kalsigs@yahoo.co.uk
Competing interests: No competing interests
EDITOR
Well done to Donovan et al for highlighting the fact that current
policy for testing PSA amounts to screening by the back door. The authors
overlook another insidious form of screening by PSA, though.
Men who present with the well known `prostatic' type symptoms in primary
care typically receive PSA testing as part of their work up, either from
their GP or after referral. But these symptoms are not good markers for
prostatic cancer - in fact, men with obstructive urinary symptoms are no
more likely than men without to have prostate cancer.
In other words, in terms of prostate cancer, these men are asymptomatic.
To perform a PSA test in these individuals therefore amounts to screening,
a fact which seems to be overlooked by GPs and urologists alike, even
those who are clear that PSA screening is a bad idea. Indeed, it could be
argued that this group is particularly inappropriate for PSA testing as
most will have benign prostatic hypertrophy, a common cause of PSA false
positives.
Educating patients is being put forward as the answer to salvaging a
situation which has arisen because PSA testing is, like a mountain,
`there'. I would suggest that this is only half the answer - we need to
get our own house in order too, otherwise an anxiety-free retirement will
be a thing of the past for the majority of men.
Competing interests: No competing interests
Sirs,
the authors correctly write that asymptomatic men may have the test (i.e.
screening for prostate by means of PSA) if they want, so there is now
ambiguity about whether screening is supported and confusion about what
this policy means in practice.
In addition, the assumption may be that most men will not want to be
tested once they are informed of the uncertainties.
However, more interestingly for the best result of whatever cancer
screening, in my opinion, is to apply it to “all” people at real risk,
and, therefore, to ascertain at first, in a “quantitative” manner, if the
subjects are positive for “Oncological Terrain”, based on mitochondrial
cytopathology, I termed Congenital Acidosic Enzyme-Metabolic Cytopathology,
(1). (See: "There is a fundamental bias in our clinical research".
bmj.com,14 may 2001 and site
http://digilander.iol.it/semeioticabiofisica).
I think that because this congenital functional mitochondrial
cytopathology is overlooked--a "conditio sine qua non" of the most
frequent and dangerous human disorders, including malignancies--all
current clinical research is fundamentally biased. That is, it does not
consider the existence or assess the seriousness as well as the location
of Congenital Acidosic Enzyme-Metabolic Histangiopathy (1, 2).
As far as screening of prostate cancer is concerned during a 44-years long
well established “clinical” experience, a bed-side evaluation, described
earlier (3), proved to be really reliable, even matched with histological
examination. Moreover, this "clinical" method, easy to be performed, is
carried out in only a few minutes.
Stagnaro Sergio MD,
Member NYAS and AAAS.
Riva Trigoso (Genoa), Italy.
1) Stagnaro S., Stagnaro-Neri M.Istangiopatia Congenita Acidosica
Enzimo Metabolica. Gazz. Med. It.- Arch. Sci. Med. 144, 423, 1985.
2) Stagnaro S., Stagnaro-Neri M. Una patologia mitocondriale ignorata: la
Istangiopatia Congenita Acidosica Enzimo-Metabolica. Gazz. Med. It. -
Arch. Sci. Med. 149, 67 1990.
3) Stagnaro-Neri M., Stagnaro S., Microangiologia clinica della
ipertrofia prostatica benigna. Ruolo patogenetico delle modificazioni del
sistema microlovascolotessutale valutate con la Semeiotica Biofisica. Acta
Cardiol. Medit. 14, 21 1986
Competing interests: No competing interests
Screening for prostate cancer in the UK
Dear Sir
We were surprised that Donovan et al’s prominent article on prostate
cancer screening [1] which criticised the current NHS Prostate Cancer Risk
Management Programme neglected to mention the European Randomised Study of
Screening for Prostate Cancer. This study is due to report in 2008 with
preliminary results in 2006 and should provide evidence on whether
screening for prostate cancer affects mortality. Hence any ambiguity on
the part of the NHS should be temporary.
We were more concerned to read Dr Hopcroft’s letter [2] which
suggested that doing the PSA test in men with LUTS (lower urinary tract
symptoms) is inappropriate because men with LUTS were 'no more likely than
men without symptoms to have prostate cancer'. This is not correct. It
maybe the case that very early prostate cancer is not associated with LUTS
but this is certainly not true of larger volume disease.
It is recognised that a man with LUTS presenting to his GP is looking
for a diagnosis and a diagnosis of prostate cancer is likely to affect his
management. There may also be medicolegal reasons why a PSA test should be
done.
Large screening studies in men 50-70 years old using PSA>4 ng/ml
and rectal exam consistently detect prostate cancer in only 2-3% [3].
However groups of men with LUTS referred to urologists exhibit a greater
proportion of prostate cancer [4,5]. Two studies have demonstrated a 3-
fold cancer detection rate in men with LUTS compared to those who did not,
suggesting the presence of LUTS to be a risk factor for cancer detection.
Cooner et al studied 1807 men; excluding those with abnormal rectal
examinations the detection rate in symptomatic men 50-70years old was
still 9%. Further evidence comes from The National Prostatectomy Audit
[6]. Of 5361 men undergoing TURP, 66% of whom did not have a catheter,
prostate cancer was found in 21%.
If Dr Hopcroft would not do a PSA test in a man with LUTS, would he
not offer a rectal exam either?
Yours sincerely
Mr J J Ord MRCS
Research Registrar
e-mail : jord@doctors.org.uk
Mr S.F.Brewster MD FRCS(Urol)
Consultant Urologist
Department of Urology,
The Churchill Hospital,
Oxford
1. Donovan J, L, Frankel SJ, Neal DE, Hamdy FC. Screening for
prostate cancer in the UK - Seems to be creeping in by the back door. BMJ
2001;323:763-764.
2. Hopcroft K. Demand for prostate specific antigen testing in primary
care. BMJ 2002;324:547.
3. Catalona WJ, Smith DS, Ratliff TL, Basler JW. Detection of organ-
confined prostate cancer is increased through prostate-specific antigen-
based screening. JAMA 1993;270:948-954.
4. Babaian RJ, Miyashita H, Evans RB, von Eschenbach AC, Ramirez EI. Early
detection program for prostate cancer: result and identifiction of high-
risk patient population. Urology 1991;33:193-197.
5. Cooner WH, Mosley BR, Rutherford CL, Beard JH, Pond HS, Terry WJ, et
al. Prostate Cancer detection in a clinical urological practice by
ultrasonography, digital rectal examination and prostate specific antigen.
The Journal of Urology 1990;143:1146-1154.
6. Emberton DE, Neal DE, Black N, Harrison M, Fordhams M, McBrien MP,
Williams RE, McPherson K, Devlin HB. The National Prostatectomy Audit: the
clinical management of patients during hospital admission. British Journal
of Urology, 1995;75 : 301-316.
Competing interests: No competing interests