Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Firstly, bed side assessing Oncological Terrain in all cancer screening.
- Sergio Stagnaro (6 February 2004)
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Useless or Fraud?
- Ron Law (6 February 2004)
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Thyroid ultrasound, for example
- Yair Liel (6 February 2004)
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The author omits systematic reviews
- Joseph C Watine (6 February 2004)
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It's time we stopped talking about breast self examination
- Louisa Beejay (6 February 2004)
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Screening uncertainties: of evidence, of efficacy, of decisions
- Hazel Thornton (7 February 2004)
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evaluation of risk and benefit of a screening programme vs a new drug therapy
- Arash Bakhtyari (8 February 2004)
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Talking testicles, but, for once, not b******ks
- Keith A Hopcroft (9 February 2004)
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PC survivor
- charles brownhill (10 February 2004)
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A problem with knowledge translation
- Giuseppe Giocoli (10 February 2004)
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Re: Useless or Fraud?
- Ron Law (10 February 2004)
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Prostate Cancer Hysteria
- lorenzo q squarf (10 February 2004)
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Re: PC survivor
- Tom P Marshall (10 February 2004)
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Randomized controlled trials versus clinical realities: prostate cancer screening
- Vinod K Gupta (11 February 2004)
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Correction
- Tom P Marshall (11 February 2004)
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Re: A problem with knowledge translation
- Sergio Stagnaro (11 February 2004)
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Cardiovascular disease prevention: Screening without evidence of efficacy
- Peter M Brindle, Mark Upton, Tom Fahey, Deborah Sharp, and Shah Ebrahim (18 February 2004)
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Freedom of choice for women and men
- Éva Rásky (20 February 2004)
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Screening: how to produce the evidence of efficacy
- Gerben ter Riet, Alfons G.H. Kessels and Lucas M. Bachmann (24 February 2004)
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PSA Screening: Honest information is always better than patronising advice
- Santhanam Sundar (24 February 2004)
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screening without evidence of efficacy
- Stefano Ciatto (27 February 2004)
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The Balance Between Screening and Testing
- Atef R Markos (27 February 2004)
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PSA Screening: Medicolegal issues
- Santhanam Sundar (3 March 2004)
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Sergio Stagnaro, Specialist in Blood, Gastrointestinal, and Metabolic Diseases. Researcher in Biophysical Semeiotics. Via erasmo Piaggio 23/8. 16037 Riva Trigoso (Genova) Italy
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Sirs, Once again, an overlooked fundamental bias in all researches accounts for the reason of such as intriguing conclusion: “Before any screening for cancer is introduced, however, large randomised trials with mortality end points should be conducted to establish and quantify any benefit” (1). This statement is apparently right, but really wrong: necessarily, successful screening for cancer must be unavoidably performed only in all individuals involved by Oncological Terrain (2, 3) (See HONCode site 233736, www.semeioticabiofisica.it). For instance, as regards the cancer of the prostate, why men without Oncological Terrain and those with Oncological Terrain, but without “real risk” of prostate cancer (!) have to be measured prostate specific antigen, even every two or more years or once in their life? In my opinion that is senseless action, usual around the world. In addition, prostate specific antigen between 4 ng. and 10 ng. is notoriously not significant at all in 50% of cases, not to speak, of course..., of oncological terrain negative subjects. On the contrary, in a lot of cases (about 20%), wherein PSA blood level is less than 4 ng, there is already a cancer, in presence of Oncological Terrain, obviously (4). The efficacious war against malignancy must begin, firstly,with clinical detecting, in a quantitative way, both the Oncological Terrain, and, secondly, the “real risk” of cancer in a well defined biological system. 1) Law M. Screening without evidence of efficacy. BMJ 2004;328:301- 302 (7 February), doi:10.1136/bmj.328.7435.301 2) Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e diagnosi precoce con la percussione ascoltata. Gazz. Med. It. – Arch. Sc. Med. 152, 447, 1993 3) Stagnaro-Neri Marina, Stagnaro Sergio. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Travel Factory SRL., Rome, in press. 4) 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: None declared |
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Ron Law, Risk & Policy Analyst Beyond Alternative Solutions
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Malcolm Law [no relation] states that Public health authorities should not advocate screening of unproved value. This is excellent advice, and should extend also to prophylaxis such as flu vaccination. How many tens, if not hundreds of millions of citizens exposed themselves to the risks associated with vaccines for no demonstrable benefit? Except to the pharmaceutical companies and prescribing doctors bottom line. [1] Law says that giving information to people considering screening (on prostate specific antigen testing, for example) when the only honest information is complete uncertainty is useless. One could perhaps also include the word fraud. Let's say that there have been 50 million doses of flu vaccine prescribed this past flu season. At, say $50 plus, say, $50 prescribing/administering fee, that's a lot of billions of dollars. And still there were 35,000 deaths in the USA alone! The recommendations of the Advisory Committee on Immunization Practices (ACIP)Influenza in the USA [echoed throughout the world] that "vaccination is the primary method for preventing influenza and its severe complications." [2] It made this recomendation, knowing that the most likely strain of flu virus for the upcoming flu season was not in the vaccine and that it was therefore be unlikely to work. Law also states that "For a new drug a rigorous set of experimental data must be presented before it is licensed for use, and until it is licensed patients cannot obtain it. The same rigour should apply to medical screening." Whilst this sentiment is lauded, it is in fact not true. Recent revelations about SSRI peer reviewed 'science' approvals and use makes very depressing reading. [3,4] Modern Medicine is arguably the most dangerous industry on the planet.[5,6] It should be mandatory for every medical office and hospital to have a warning sign - "ENTER AT OWN RISK!" Law's editorial should not only be mandatory reading for all public health communicators and medical practitioners; but it should become the basis of health policy... Note that some will say that references 3-6 are not peer reviewed and therefore are unreliable. A quick read of refs 3-4 should quickly dismantle the logic of that argument. In an information vaccuum consumers become increasingly informed behind the "bike shed." [1] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5301a3.htm [2] http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5208a1.htm [3] http://energycommerce.house.gov/108/News/02032004_1211.htm [4] http://www.guardian.co.uk/uk_news/story/0,3604,1137542,00.html [5] http://www.newmediaexplorer.org/sepp/2003/10/29/medical_system_is_leading_cause_of_death_and_injury_in_us.htm [6] http://www.newmediaexplorer.org/sepp/Relative%20risks%20- %20bubbles%202.PDF Competing interests: Ron Law was an invited member of the New Zealand Ministry of Health expert working group that advised the Ministry on the reporting and management of medical injury |
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Yair Liel, Head, Endocrine Service Soroka University Medical Center, Beer-Sheva, Israel
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I agree with the view presented by Dr. Law. From my position as a clinical endocrinologist, I often have to deal with patients' anxieties over non-palpable incidental findings on thyroid ultrasound examinations, often performed for wrong and/or unjustified reasons. Sometimes patients arrive with already established surgical complications following unnecessary thyroid operations. Even though a substantial number of incidental thyroid nodules may be histologically malignant (1), their clinical importance has never been proven. Moreover, a recent preliminary study indicates that the progression rate of non-palpable proven thyroid malignant nodules to clinically significant lesions may be very low (2). Thyroid ultrasound is an additional example of a frequently used, often non-efficacious screening modality that may lead to “cascade iatrogenesis” (3). References: 1. Hagag P, Strauss S, Weiss M. Role of ultrasound guided fine needle aspiration biopsy in evaluation of nonpalpable thyroid nodules. Thyroid 1998;8:989-95. 2. Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003;13:381-7. 3. Hofer TP, Hayward RA. Are bad outcomes from questionable clinical decisions preventable medical errors? A case of cascade iatrogenesis. Ann Intern Med 2002;137:327-33. Competing interests: None declared |
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Joseph C Watine, Consultant, Laboratory Medicine Hôpital de Rodez, France
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Systematic reviews are the cornerstone in practicing evidence-based medicine. Regarding the utility of PSA for the screening for prostate cancer, Law’s conclusion might have been slightly more objective if he had taken into account the two systematic reviews which were published on the subject in 1997 [1] and in 2002 [2]. The conclusion of the latest of these two systematic reviews was: “although potential harms of screening for prostate cancer can be established, the presence or magnitude of potential benefits cannot. Therefore, the net benefit of screening cannot be determined” [2]. Isn’t this conclusion slightly less pessimistic than what is suggested by Law? [1] Selley S, Donovan J, Faulkner A, Coast J, Gillatt D. Diagnosis, management and screening of early localised prostate cancer. Health Technol Assess 1997; 1:1-96 (full text available free of charge at: http://www.hta.nhsweb.nhs.uk/fullmono/mon102.pdf). [2] Harris R, Lohr KN. Screening for prostate cancer: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002; 137:917-29 (full text available free of charge at: http://www.annals.org). Competing interests: I am a member of the Committee on Evidence-Based Laboratory Medicine of the International Federation of Clinical Chemistry and Laboratory Medicine |
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Louisa Beejay, Press Officer Breast Cancer Care, London, SW6 4NZ
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We were both alarmed and deeply disappointed to read Malcolm Law’s editorial opinion in the BMJ, that ‘self-examination of the breasts [is a form of] cancer screening that [has] not been shown to work’. It has been over ten years (1989) since the Department of Health (DoH) highlighted the ineffectiveness of breast self examination (BSE) in reducing mortality from breast cancer. Since then, Breast Cancer Care, together with the Royal College of Nursing (RCN) and DoH, developed the ‘breast awareness 5-point code’ to replace BSE. Breast awareness is about people getting to know their breasts look and feel normally, during everyday activities, such as showering, so that they can notice and report and changes promptly. We know that breast awareness is effective because 80 per cent of patients who attend breast clinics have noticed symptoms or signs themselves (NICE, 2002). Fifteen years on, we are aware that there is still a lot of confusion surrounding the breast awareness message. In a survey we conducted last year with Boots, 20% of women over 50 said they still practised BSE rather than being breast aware. Law’s editorial comments on BSE only add to the confusion around breast awareness and undermine our work to help women, of all ages, to practise breast awareness. Competing interests: None declared |
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Hazel Thornton, Honorary Visiting Fellow, Department of Health Sciences, University of Leicester. "Saionara", 31 Regent Street, Rowhedge, Colchester, CO5 7EA. UK
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"Encouraging people to decide for themselves" whether to attend for screening or not, might only be said to be "ducking the issue" [1] if a well-founded public health programme for that specific disease has not been set up. In that case, setting up a programme, as Law advocates, should be based on evidence, through rigorous scientific evaluation of efficacy through systematic review of high quality trials. Outcomes assessed should be both mortality and all associated adverse effects that affect an individual`s quality of life. When a programme is set up, good quality evidence-based information should be made available to suit all citizens, so that they have a better chance of arriving at an informed decision with their (equally well-informed) health professional, if desired. Provision of such evidence takes time. But the screening industry and the public are not prepared to wait: mammographic screening for the 40-50 year old age group is widely practised, yet we still await publication of the findings from the `AGE` trial (NCRI Clinical Studies Group trial of breast screening by mammography in young women) that began in 1991 and closed in November 2000. Is there not an ethical obligation to make these findings public without further delay? Is it not right that this age group should be given an updated review of available high quality evidence so that they can make a better decision? "Encouraging people to decide for themselves" through provision of better information [2] is, on the contrary, absolutely necessary in well established screening programmes such as the NHS Breast Screening Programme for 50-65 year olds. More than a decade of persuasive information [3] has reinforced in the public`s mind the intuitive appeal that screening to "find it early" "could save your life", in a social and cultural climate that has blossomed on frequently re-iterated beliefs. [4] Evidence comes a poor second in decision-making in a population not educated to see the need for fair tests of treatments, interventions, systems and processes, to underpin what and what is not offered in our healthcare systems. [5] [1] Malcolm Law. Screening without evidence of efficacy. Screening of unproved value should not be advocated. BMJ, 2004; 328:301-2 [2] Hazel Thornton, Adrian Edwards, Michael Baum. Women need better information about routine mammography. BMJ, 2003; 327:101-3 [3] NHS Breast Screening Programme. THE FACTS. London. Department of Health 2001. [4] Barron H. Lerner. The Breast Cancer Wars. Fear, Hope and the Pursuit of a Cure in Twentieth Century America. Oxford University Press. 2003. [5] Stewart DC. Draft ideas for learning from Lind`s controlled trial. In: Chalmers I, Milne I, Troehler U (eds). The James Lind Library (www.jameslindlibrary.org). Accessed Saturday 7 February 2004. Competing interests: None declared |
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Arash Bakhtyari, Medical Director Simbec Research,Merthyr Tydfil CF48 4DR
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I read with interest Professor Laws article on the necessity of a thorough evaluation of a screeing programme before it is launched on the unsuspecting public. The comparison with clinical trials of a new medicine, overlooks a systematic difference. Drug discovery and development process is driven by a system of intellectual property laws and govermental regulation, whereby if a pharmaceutical company demonstrates a new medicinal entity to be safe and efficacious in a particular condition, then they stand a chance of making good on the research and development costs (in the region of several hundred million pounds per compound reaching the market), by being given patent protection and exclusivity rights for a few years. As there is no patents for screening programmes, the funding for a thorough evaulation of the risk and benefits of screening programme will have to come from the public purse. Competing interests: None declared |
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Keith A Hopcroft, GP Laindon Health Centre, Laindon, Basildon, Essex SS15 5TR
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Hats off to Malcolm Law. At last someone with real clout has had the courage to state that testicular self examination should not be advocated 1. I have been saying the same for years through various channels (lectures, correspondence, newspaper articles, men's health magazines and so on) citing evidence based, theoretical, historical and common sensical arguments - but without the necessary authority to create any real impact. The only consistent response I have elicited from the general public has been one of indignant self righteousness or even downright vitriol: I have been accused of setting back the men's health movement many years and of wishing cancer upon men. I understand these reactions, but have always regretted that the blind evangelism and knee-jerk outrage at being challenged has prevented constructive debate. Hopefully, now, the media and public health movers and shakers will take note and end their obsession with testicular self examination. If they do insist on some take-home message for men it is should be that delays in diagnosis aren't caused by failing to notice problems - so stop the obsessional checking - but by failing to act on them 2. Keith Hopcroft 1 Law M. Screening without evidence of efficacy. BMJ 2004;328:301- 302. 2 Austoker J. Screening for ovarian, prostatic and testicular cancers. BMJ 1194;309:315-320. Competing interests: None declared |
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charles brownhill, patient ca9 3dy
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I am very glad that Dr Hopcroft is not my GP and that Prof Law is not my Consultant. In my case a routine PSA test indicated the need for a biopsy. The biopsy indicated the need for surgery. The tumor was removed many years ago. I am clear of PC. Prof Law strayed from research when he talked about "certainty of testing causing harm" incontinence is controllable, impotence can be treated. Gentlemen, your arrogance is breathtaking! Competing interests: None declared |
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Giuseppe Giocoli, Gdl EBM AMCLI (Associazione Microbiologi Clinici Italiani) Via C.Farini, 81. 20159 Milano (Italia)
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Sir, This discussion reminds me of a case not mentioned so far by respondents. In 2003, a physician and his residency in Virginia (USA) were sued for malpractice; the residency was found liable for $ 1 million (1). The case arose in 1999, when Dr M. saw a 53-year-old patient for a physical examination. He discussed with him and presented the risks and benefits of screening for prostate cancer. The patient was later seen by another physician, who insisted on a PSA test, and offered no discussion of the risks and benefits of that test. It happened that the patient had a high PSA level and was diagnosed with incurable prostate cancer (Gleason 8). “A major part of the plaintiff's case was that the defendant did not practice the standard of care in the Commonwealth of Virginia. Four physicians testified that when they see male patients older than 50 years, they have no discussion with the patient about prostate cancer screening: they simply do the test. This was a very cogent argument, since in all likelihood more than 50% of physicians do practice this way”. “During closing arguments the plaintiff's lawyer put evidence-based medicine on trial. ... He urged the jury to return a verdict to teach residencies not to send any more residents on the street believing in evidence-based medicine” (1). In my opinion, when the only honest information about a screening is complete uncertainty (as with the for a long time now widespread PSA testing), Public health authorities should present the reality (the evidence) not only to health professionals, but also – with demanding effort – to the lay public. For a new test “a rigorous set of experimental data should be presented before it is licensed for use, and until it is licensed patients cannot obtain it”, as Malcolm Law states. Even in that case, people should be informed about the reasons why the test is not available. It would act as a counterbalance to manufacturers’ advertising, so often based on preliminary studies. Thanks, Giuseppe Giocoli (1) Daniel Merenstein. Winners and losers. JAMA 2004 (January 7);291:15-16 (2) Malcolm Law. Screening without evidence of efficacy. Screening of unproved value should not be advocated. BMJ, 2004; 328:301-2 Competing interests: None declared |
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Ron Law, Risk & Policy Analyst Beyond Alternative Solutions
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Reference [6] in my earlier posting had an extra space in the URL. The chart can now be downloaded at http://www.newmediaexplorer.org/sepp/Relativeriskbubbles.pdf Competing interests: None declared |
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lorenzo q squarf, Chairman The Highland Group 30075
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Prostate cancer screening and associated destructive diagnostic and therapeutic procedures can cause more harm than merely ingoring hypothetical and theoretically negative test results when there are no physical symptoms. For an iconoclastic yet refreshingly clear exposition on the subject, my web pages, commencing with http://www.squarf.com/cancer.htm provide an analytical matrix for patient (and enlightened doctor) decision making. Competing interests: I have a firm (and therefore biased) view on the subject. |
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Tom P Marshall, Lecturer Birmingham University B15 2TT
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To make an informed decision to undergo PSA screening a 65 year old man should be told that about 20 in 100 people like him may test positive and be referred for a biopsy. Without screening 1 in 100 people like him will die from prostate cancer by the age of 75 (25 will die from other causes). Without screening 4 in 100 will die from prostate cancer by the age of 85 (63 in 100 will die from other causes). [1] However screening may identify a much larger number of cancers: 30% of men over 50 have localised prostate cancer. Since only 4% of men die of prostate cancer by the age of 85, it is clear that only a tiny number of these localised cancers ever progress. [2] Nevertheless this is what PSA screening and biopsy tends to diagnose. If cancer is diagnosed it may be Grade 1 or Grade 2 or Grade 3. Of those found to have Grade 1 or Grade 2 cancer, with conservative treatment 80% will not die from the cancer in the next 15 years (i.e. they will either die from other causes or live until at least 80). [3] Of those found to have Grade 3 cancer with conservative treatment 25% will die from the cancer in the next 15 years. It is possible that PSA screening could have detected a Grade 3 cancer and that surgical treatment effected a cure. It is more likely that PSA screening and biopsy will identify an early tumour that would best be managed without surgery. In such a case surgery and its consequences would have been unnecessary. It is perfectly reasonable to weigh up the pros and cons of screening and conclude that it is a good thing. No doubt the correspondent did just this. It is quite another to advocate a screening programme to others - this implies an unequivocal benefit - clearly the picture is more complex. References: 1. Office of National Statistics mortality rates for 2000 2. Holund B. Latent prostatic cancer in a consecutive autopsy series. Scand J Urol Nephrol 1980;14:29-35. 3. Chodak GW, Thisted RA, Gerber GS, Johansson JE, Adolfsson J, Jones GW, et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med 1994;330:242-8. Competing interests: None declared |
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Vinod K Gupta, Physician Dubai Police Medical Services, P.O. Box 12005, Dubai, United Arab Emirates
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Law addresses two medical myths (1). It does take courage to state the obvious to a biological species that is in perpetual denial right from birth. The human race denies finite existence, disease, infirmity, aging and death. Clinicians, being only human, accept clinical futility with reluctance while public perception of health is a vague and variable mixture of in-vogue perceptions. The first myth regarding the utility of prostate cancer screening is well discussed (1). What is left out is the fear that doctors face today in deciding to deny any screening test to any patient. The icy cardiac- constricting trepidation of legal consequences in case the cancer is missed or the outcome is unsavoury has upset rational balance and compassionate debate. With incompetence being squarely determined in courts of law, fancy malpractice insurance premiums and fancier settlements, few clinicians will follow Law’s recommendation despite the logic. For the legal profession it will be very difficult to understand and accept that there are several grey areas in most consultations that are more often than not patched over by the generous safety margins afforded by nature. Nevertheless, the reality check imposed by the law is here to stay because errors of commission or omission do devastate patients and their families. Law’s comment on the general noticeability of malignant breast lesions gives reason, however, to pause as does Beejay’s impression (2) that “looking and feeling” breasts is fundamentally different from breast self-examination. The second myth that Law handles well is that of encouraging people to participate in clinical decisions, an issue linked inextricably to yet another myth—that of written informed consent. The long shadow of the law again colours this aspect of clinical management with contributions from the patient-victim somewhat attenuating the clinician’s liability. Despite the best efforts to inform patients, it is recognized that they will rarely, if ever, be as well informed about their treatment options as their therapists (3). Being “informed” and executing in writing the transfer of information selected by the therapist does not guarantee that the information was complete or properly comprehended (4). Generally, subjects do not understand methodology (5). Written informed consent cannot be sufficiently comprehended by most lay patients in order to effectively balance all available options. If the scientific logic of prostate cancer screening seems nebulous to the therapist, what can the patient possibly contribute? It sometimes takes an incongruous analogy to see how wrong we are. If after take-off, the pilot asks the passengers for the optimal flight speed and height -- well, to the critical eye, that is how, in general, the patient’s contribution in the prostate cancer screening programme or other medical decisions of consequence might appear. Law, in simple conformity to the times, places great emphasis on the randomized controlled trial (RCT) (1). “Randomization is a purely mathematical strategy that uses the uncertainty principle. RCTs attempt to eliminate through mathematical logic natural patient-to-patient idiosyncracy, including the placebo-effect, these being biologically irreducible realities…RCTs tend to misguide clinicians particularly in conditions that are subject to spontaneous variations” (6). RCT was principally designed to compare therapeutic agents or strategies and not to, as has become generally and unquestioningly accepted today, answer questions about pathogenesis, (7) supplant basic conceptual groundwork, (8) or even settle issues about cancer screening. While it took several years after the first mammographic screen to show reduction of mortality (1), prostate cancer is quite different from breast cancer. A much older population, low grade tumours unlikely to present clinically, and indolent tumours not destined to be fatal are critical variables that will confound any RCT designed to test prostate cancer screening by measurements of serum prostate specific antigen. As an investigative tool, even the gold standard that the RCT represents has its limitations. Longer the time interval that might be required to see a difference, greater is the number and significance of confounding idiosyncratic variables. Tumours with shorter natural histories, such as prostate cancer, simply do not afford clinicians the time to obtain critical data from a large RCT. Law correctly emphasizes the need for mortality end points in RCTs for cancer screening (1), these being large unambiguous differences in outcome. Once a set of data even slightly suggestive of some clinical improvement has been obtained in a RCT and hallowed by the arcane non- biological logic of statistics, the original idea is (or can be) only rarely challenged. In a rare reversal of theoretical principles, the putative utility of magnesium supplementation in acute myocardial infarction was disproved in a RCT because the end point was mortality (9). Magnesium supplementation also finds use, often through RCT, in other fields, such as migraine, neuroprotection in very preterm babies (10), and eclampsia of pregnancy. Transport of magnesium from blood to cerebrospinal fluid (CSF) across the blood-brain barrier is limited in normal humans; even intravenous administration of magnesium sulphate does not increase CSF magnesium concentration (11). Orally or intravenously administered magnesium cannot significantly affect brain neuronal function, an issue hitherto unconsidered in migraine pathophysiology (12) as well as in the management of very preterm neonates or eclampsia. In the absence of sufficient conceptual groundwork, the otherwise valuable RCT risks becoming a tool to test speculative hypotheses. Currently, the RCT is being mis-used to perpetuate myths and to answer questions that it cannot, thereby distancing investigators from clinical realities. References 1. Law M. Screening without evidence of efficacy. BMJ 2004;328: 301-2. 2. Beejay L. It’s time we stopped talking about breast self examination. BMJ Rapid response to Law M. (6 February 2004). 3. Cassileth BR, Zupkis RV, Sutton-Smith K, March V. Informed consent-why are its goals imperfectly realized. N Eng J Med 1980;302: 896-900. 4. Thornton H. Understanding “informed consent”. Lancet 1995;346: 1047-8. 5. Bulger RE, Heitman E, Reiser SJ. eds. The ethical dimensions of biological sciences. Cambridge: Cambridge University Press, 1993. 6. Gupta VK. Does hypomagnesemia have an adaptive role in hypertension? Hypertension 2004 (In press). 7. Gupta VK. Chlamydia pneumoniae and atherosclerosis: a speculative hypothesis. Published electronic response to Cagli S et al., Failure to detect Chlamydia pneumoniae DNA in cerebral aneurysmal sac tissue with two different polymerase chain reaction methods. J Neurol Neurosurg Psychiatry 2003 http://www.jnnp.com/cgi/content/abstract/74/6/756?etoc (9 June 2003). 8. Gupta VK. Does magnesium supplementation have any role in acute myocardial infarction? No. Cardiovasc Drugs Ther 1996;10: 303-5. 9. Magnesium in Coronaries (MAGIC) Trial Investigators. Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial. Lancet 2002;360: 1189-96. 10. Crowther CA, Hiller JE, Doyle LW, Haslam RR for the Australasian Collaborative Trial of Magnesium Sulphate (ACTOMgSO4) Collaborative Group. Effect of magnesium sulfate Given for Neuroprotection Before Preterm Birth. A Randomized Controlled Trial. JAMA 2003;290: 2669-76. 11. Ko SH, Lim HR, Kim DC, Han YJ, Choe H, Song HS. Magnesium sulfate does not reduce postoperative analgesic requirements. Anesthesiology 2001;95:640-6. 12. Gupta VK. Magnesium therapy for migraine: do we need more trials or more reflection? Headache 2004 (In press). Competing interests: None declared |
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Tom P Marshall, Lecturer University of Birmingham
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The above information on survival with localised prostate cancer contains an error. It should read: "If cancer is diagnosed it may be Grade 1 or Grade 2 or Grade 3. Of those found to have Grade 1 or Grade 2 cancer, with conservative treatment 80% will not die from the cancer in the next 15 years (i.e. they will either die from other causes or live until at least 80). [3] Of those found to have Grade 3 cancer with conservative treatment 25% will NOT die from the cancer in the next 15 years." i.e. - with conservative treatment of most Grade 1 or Grade 2 localised prostate cancer does not progress, but most Grade 3 will progress (and therefore needs more radical treatment). Competing interests: None declared |
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Sergio Stagnaro, Specialist in Blood, Gastrointestinal, and Metabolic Diseases. Via Erasmo Piaggio 23/8 16037 Riva Trigoso (Genova) Italy
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In my opinion, there is a lot of sense in Giuseppe Giocoli's Rapid Response that is worthy of physician's consideration (e.g., to avoid legal misadventures) and particularly of authority's attention (e.g., Health Ministers). Unfortunately, to stimulate new tests to be licensed for use are surely not a rigorous set of experimental data, but other reasons, that can be understood fully and easily. Competing interests: None declared |
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Peter M Brindle, Wellcome fellow in health services research Department of Social Medicine, University of Bristol, BS8 2PR, Mark Upton, Tom Fahey, Deborah Sharp, and Shah Ebrahim
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Law uses several examples from malignant disease to argue a strong case against screening without evidence of efficacy and rightly suggests that health authorities should not advocate screening of unproven value.1 Unfortunately, this situation has already occurred in the case of primary prevention of cardiovascular disease in the UK. This policy has substantial implications for most British adults. The National Service Framework for coronary heart disease, advocates the identification of individuals at ‘high risk’ from cardiovascular disease followed by the prescription of anti-hypertensive drugs, statins and aspirin.2 This policy constitutes screening by default and has been passed to primary care teams to deliver without meeting the rigorous evidence of efficacy that Law recommends. In comparison with screening tests for malignant disease, the discriminatory ability of the screening tool for identifying ‘high-risk’ individuals is even worse. The critical importance of the choice of threshold in assigning patients to a high-risk group has been shown in a sample of British men. With the threshold set at a 10-year coronary risk of >30%, 84% of the coronary heart disease events occurred in 93% of men who were in the ‘low risk’ group - men who might potentially be reassured that treatment was not indicated. When the threshold was lowered to >15%, this false negative rate fell to 25% but the proportion of the population identified as being at high risk but not suffering a coronary event, rose from 6% to 45%.3 Furthermore, trials of targeted multiple interventions in UK primary care have been disappointing in their ability to show a cost effective reduction in cardiovascular outcomes, in contrast to showcase trials sponsored by the pharmaceutical industry usually conducted in highly selected populations that are not representative of everyday practice.4 An indiscriminate screening tool makes it hard for asymptomatic individuals to make an informed decision to commit themselves to lifelong treatment and to the side effects and medicalisation that entails. With vigorous endorsement from the pharmaceutical industry and from policy makers, it is probable that mass ‘screening and treating’ for the primary prevention of cardiovascular disease in UK primary care has become too established to reverse or, indeed, to halt a massive proposed expansion of treatment to everyone over the age of 55 years.5 We can learn a lesson from cardiovascular disease prevention on how political and financial imperatives to screen and treat are powerful inducements to change routine practice. 1. Law M. Screening without evidence of efficacy. BMJ 2004;328:301- 302 2. Department of Health. National Service Framework for Coronary Heart Disease. London: Department of Health, 2000. 3. Brindle, P., Emberson, J., Lampe, F., Walker, M., Whincup, P., Fahey, T., and Ebrahim, S. The Framingham score overestimates coronary risk in British men. A prospective study. BMJ 2003. 327;1267-70 4. Ebrahim S, Davey Smith G. Multiple risk factor interventions for primary prevention of coronary heart disease (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd. 5. Wald NJ, Law MR. A strategy to reduce cardiovascular risk by more than 80%. BMJ 2003;326:1419. Competing interests: None declared |
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Éva Rásky, Institut of Social Medicine and Epidemiology Universitaetsstrasse 6/I, Austria, A-8010 Graz
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Sir, As Law1 points out evidence based screening for prostate specific antigen should not be funded nor supported since evidence is lacking. While making the same claims for mammography screening health authorities in many countries opt for this screening method despite evidence2. In Austria, opportunistic screening mammography has been in place for many years without being evaluated even though guidelines concerning physical and technical aspects of the X-ray equipment were set by the Chamber of Physicians. No rules of procedure have been enforced. More than 550.000 mammograms are performed yearly in Austria without a specified target population. Data on the reasons for mammography, whether for suspicious node or for screening purposes, age of the woman, interval between mammographic examinations or on the numbers performed per woman is lacking. A pilot project in Vienna, Austria, from 2001 to 2002, did not meet the quality criteria set by the EU, e.g. 5.000 mammogram readings per evaluator or double readings of mammograms, reaching 70% of the target population. Disappointing implementation experiences and the lack of monitoring of the Viennese programme do not prevent health decision makers from favoring implementation of an Austrian nationwide screening program. One baseline expert study lacks scientific grounding and does not list all issues relevant3. A central aspect of screening should be the well informed consumer. Women participate in screening mammography assuming benefits. It is not yet understood in which way women apply information available and decide whether to accept screening mammography. Research information made available to the general public in Austria does not present all aspects of mammography, particularly benefits presented far outweigh possible harm4. Given adequate information, what if more than 30% of the target population decide - evidence based - against mammography and thus jeopardise a program? It took twenty years into practising screening mammography to start discussing women's decision making process. In the case of prostate cancer, in contrast, campaigns for screening have, from the very beginning, encompassed options for men. This leads to the impression that screening for men is discussed on a broader evidence base allowing freedom of choice to male consumers. Women deserve equal rights. 1 Law M. Screening without evidence of efficacy. BMJ 2004; 328: 301- 2. 2 Olsen O, Goetzsche PC. Screening for breast cancer with mammography. In: Cochrane Library, issue 4. Oxford: Update Software, 2001. 3 OEBIG. Mammographie-Screening. Vienna: OEBIG, 2001. 4 Slaytor EK, Ward JE. How risk of breast cancer and benefits of screening are communicated to women: analysis of 58 pamphlets. BMJ 1998; 317: 263-4. ao. Univ. Prof. Dr. Éva Rásky, MME, Institute of Social Medicine and Epidemiology, Medical University Graz, Universitaetsstrasse 6/I, A-8010 Graz, Austria. e-mail: eva.rasky@meduni-graz.at. Competing interests: None declared |
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Gerben ter Riet, Assistant professor Dept of General Practice, Academic Medical Center, Univ Amsterdam, 1105 AZ Amsterdam, Netherlands, Alfons G.H. Kessels and Lucas M. Bachmann
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Sir, Law,
in his editorial on screening without
evidence of efficacy argues that “in the randomised trials of mammography
no reduction in mortality was seen until several years after the first screen”.
He adds that “a cancer that is within three years of killing a person may be
too extensive for treatment to be curative” (1). It is unclear what conclusions
Dr. Law draws from these statements. However, we should like to point out that
it is only natural that the effect of screening starts to emerge after
a delay (of several years). That is, the effect starts to emerge from the moment at which the first person stays
alive who would have died just then, had he or she not been screened. More
importantly, the maximal effect of screening can only be measured if
screening continues long enough (see graph) (2). 
Legend to
figure 1A. The maximal effect of screening on the breast cancer mortality can only
be measured after screening has been continued for long enough. To be exact,
the screening period should not be shorter than the difference between the time
interval that lies between the moment of detection of cancer by screening and
the moment at which the first woman
stays alive who would have died just then, had she not been screened (point A
in figure 1A). Think, for example, of a screen-detected tumour, which could
just be cured, but would have ended fatally very quickly without screening. Lmax is the time interval between the moment of
detection of cancer by screening and the moment at which the last woman stays alive who would have
died just then, had she not been screened. Think for example, of a
screen-detected tumour at a very early stage, which would have ended fatally
only after many years, had this woman not been screened. FRR denotes the
fatality rate ratio, the measure of interest. It is the ratio between the
breast cancer specific mortality in the women who were invited for screening
and that mortality in those who were not so invited. Note that there are no
beneficial effects of screening previous to point A: FRR = 1. Note also that
the FRR will not be reached if the screening period, S, is shorter than lmax minus lmin (Figure 1B). 
Legend to
figure 1B. If the screening period, S,
is continued for a time interval exactly equal to the difference between lmax and lmin,
the maximal effect of screening on FRR is - in theory - just detectable. If S
is shorter, the effect of screening will be underestimated.
Competing interests: None declared |
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Santhanam Sundar, Consultant Oncologist Dept of Oncology, Nottinghma City Hospital, NG5 1PB
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The implied conclusion of Malcolm Law’s editorial is that PSA testing should be banned(1). Leaving aside the scientific arguments, the ‘genie is out of the bottle’ and the PSA (prostate specific antigen) screening of prostate cancer is here to stay. The current MMR vaccine fiasco demonstrates that even when a policy is underpinned by good scientific evidence, public can remain skeptical of the public health authorities. Hence it is better to provide honest information and let the men decide rather be patronising and deny PSA testing to all. I agree with most of the comments in the editorial but PSA screening of prostate cancer differs in one subtle but important aspect from screening of other cancers. Breast screening, for example, is done in completely asymptomatic women. But PSA screening takes place in men who have atleast mild urinary tract symptoms. The symptoms of prostate cancer are very similar to the symptoms of benign enlargement of prostate. Lower urinary symptoms due to benign prostatic hyperplasia (BPH) are quite common in elderly in whom the incidence of prostate cancer is the highest. With increasing awareness of prostate cancer, it is going to be quite difficult for a general practitioner to deny a PSA test to patients who request it. Furthermore, effective treatment is available for prostate cancer(2). Its entirely a different matter that the cure of prostate cancer doesn’t lead to an increase in life expectancy. But it’s not for the clinicians to decide the trade off between side effects of potentially curative treatment and the risks of cancer progression related symptoms (3). Patients views matter most and it is definitely not useless to provide honest information. 1. Law M. Screening without evidence of efficacy. BMJ 2004;328:301- 302. 2. Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Haggman M, et al. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med. 2002;347(11):781- 789. 3. Steineck G, Helgesen F, Adolfsson J, Dickman PW, Johansson JE, Norlen BJ, et al. Quality of life after radical prostatectomy or watchful waiting. N Engl J Med. 2002;347(11):790-796. Competing interests: I treat prostate cancer patients and have research interests in prostate cancer. |
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Stefano Ciatto, Head od Department Diagnostic Imaging Centro per lo Studio e la Prevenzione Oncologica, Viale A. Volta 171, 50131 Florence, Italy
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Although I totally agree that here is no evidence of efficacy of screening for prostate cancer, I disagree with Dr. Law's statement that "PSA is a good screening test only for prostate cancer that causes death within three years". In men aged 50 to 69 years enrolled in the population based European Study of Screening for Prostate Cancer (ERSPC)in Florence, Italy, average PSA value was 1.52 ng/ml (1). According to these figures and to Dr. Law's statement that PSA is 4 times higher that the median age specific concentration in subjects dying of prostate cancer after six to 10 years, a PSA cut off of 4 ng/ml would identify prostate cancer far in advance before death. This is consistent with the findings of Draisma et al. (2) who, in the ERSPC study cohort, have estimated average diagnostic anticipation by PSA screening to be largely over 10 years. Thus, it is not because PSA is not a good screening test (in terms of sensitivity) that we should refuse screening as a current practice, as there is plenty of evidence from pilot and non-controlled screening studies that PSA anticipates diagnosis to a great extent. The trouble with screening is that a) PSA is poorly specific, and combined with routine sextant biopsy for a PSA >4 ng/ml causes screening to be quite aggressive, b)due to overdiagnosis screening detects a large proportion of latent carcinomas which would never have surfaced clinically and are unnecessarily treated (2,3) and b) we ignore the impact on mortality(if any) of early detection and treatment achieved by screening. Answer to the latter question will probably come from the ongoing randomized studies, which will also allow cost-effectiveness analysis. Until that date, it is obvious that recommending screening as a current practice is unethical (4). References 1. Ciatto S, Bonardi R, Lombardi C, et al. Analysis of PSA velocity in 1666 healthy subjects undergoing total PSA determination at two consecutive screening rounds. Int J Biol Markers 2002;17:79-83 2. Draisma G, Boer R, Otto SJ, et al. Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst. 2003;95:868-878. 3. Ciatto S, Zappa M, Bonardi R, Gervasi G. Prostate cancer screening: the problem of overdiagnosis and lessons to be learned from breast cancer screening. Eur J Cancer 2000;36:1347-1350. 4. Boccardo F, Ciatto S, Martorana G. Italian National Consensus Conference on Prostate Cancer Screening (Florence, May 17, 2003) – Final Consensus Document. Int J Biol Markers 2003;18:238-240. Competing interests: None declared |
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Atef R Markos, Consultant In Genito Urinary Medicine & Sexual Health Staffordshire General Hospital, ST16 3SA
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Editor - The manuscript advocating the abolition of screening without
evidence of efficacy (1) is interesting, but argumentatively a one-sided
view. The principle of regulating national mass screening should be
upheld; but the proposals ignore the individual patient's knowledge,
expectations, demands and anxieties. It is not uncommon to see senior
citizens presenting with the concern "I am worried that I may have
cancer". Patients may also present with symptoms, directed to a part of
their body that concerns them, in relation to cancer. This is becoming
one of the increasing presentations, particularly with an ageing
population. The medical practitioner is then faced with the task of
assessing the patient's condition (in terms of symptoms, physical signs
and investigations). The availability of supportive tests in this case
would provide the clinician and the patient with the assurance, that they
both need. Withholding tests, that may help the process of assurance, is
not going to be acceptable to either party and would prove medico-legally
contentious.
The manuscript ignores the value of assurance that is gained from a "negative test" result (eg a woman who is worried about breast cancer and would gain assurance from a negative mammogram). The appearance of a cancerous condition in a patient who was denied the test is arguably not defensible. The clinical scenario may even prove more demanding, with patients who may have the foreknowledge of a test and specifically request it (eg "I want to have a mammogram"). The argument concentrates on mortality, as the end point of benefit for any screening test, which is practically flawed. The benefit of planning life, death and/or wills is widely appreciated by patients and their families, but sadly has been ignored (2) in the argument. We understand that this may not be the first interest of statisticians, but it is one that continues to be appreciated by patients and their carers. The manuscript is self-contradictory. It lays the principles of requiring "evidence prior to a confirmed conclusion" but, in the meantime, makes assertions without proven evidence: eg "more surgical biopsies … and undoubtedly more anxiety". It is quite possible that some of these patients may have had more assurance from the "negative test" result, rather than living with the doubts of uncertainty or the anxiety of the unknown. Licensing for tests will lead to over regulation and ramifications of excessive bureaucracy. There are existing bodies to advise on evidence and value of screening for medical care (eg Cochrane database and NICE), and clinicians will continue to consider their advice. REFERENCES 1. Law M: Screening without evidence of efficacy: screening of unproved value should not be advocated. BMJ 2004, 328:301-302. 2. Gill PG, Farshid G, Luke CG, Roder DM: Detection by screening: mammography is a powerful independent predictor of survival in women diagnosed with breast cancer. Breast 2004, 13(1):15-22. Competing interests: None declared |
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Santhanam Sundar, Consultant Oncologist Dept of Oncology, Nottingham City Hospital, NG5 1PB.
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Theoretically, a patient with a PSA screen detected prostate cancer can sue his General practitioner for psychological distress if he has not been properly counseled about the pros and cons of PSA screening. But the case would hinge on whether the PSA test was done as a screening or diagnostic test. Benign enlargement of prostrate due to BPH and lower urinary tract symptoms (LUTS) are present in almost all elderly men and the PSA test could have been done as part of the diagnostic workup. The high incidence of LUTS in elderly also means that nearly all prostate cancer patients have a history of LUTS ranging from months to years. As the awareness of prostate cancer increases in men, it is also possible that these prostate cancer patients might feel that there has been delay in diagnosis and this has consequentially affected their prognosis. While we wait for randomised evidence, I would be very interested to hear the views of general practitioners about PSA screening. If one accepts that the primary purpose of an editorial or commentary is to inform, educate, stimulate discussion and change clinical practice, then it would be useful to know what the readers think about an article. ‘Rapid responses’ in BMJ serves this purpose very well only if someone disagrees with a viewpoint or has something important to add (and then has the time to sit-down and draft a reply). The practice of medicine in real world is not always based on gold- standard double-blind randomised trial evidence. Sometimes it is based on what our colleagues around the country do and what is considered to be acceptable. So it would be very helpful if there is scope for a ‘reality’ television style yes /no or agree/disagree response facility to certain articles in BMJ. I suppose some critics might say that BMJ is being ‘sexed up’ to appeal to the lowest common denominator but I feel this facility would make the BMJ more relevant to people at the ‘coal face’. Competing interests: I treat prostate cancer patients |
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