Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Misleading conclusions and very little utility
- Dr. Harsha Kumar H N (12 May 2007)
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Oral self examination in the early detection of oropharyngeal cancer
- Eduardo M. Curbeira-Hernandez. MDD, Enrique Castillo Betancourt MDD, Moisés A. Santos Peña MD, Juana Hernández Fernández MsC, Milagros Fernández González (15 May 2007)
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Likelihood of cancer is insufficient to define referral policy for alarm symptoms.
- David Carr (18 May 2007)
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Alarm symptoms must be assessed in the context of age-specific cancer incidence
- Mark N Upton (19 May 2007)
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Re: Alarm symptoms must be assessed in the context of age-specific cancer incidence
- LS Lewis (20 May 2007)
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Re: Re: Alarm symptoms must be assessed in the context of age-specific cancer incidence
- Mark N Upton (21 May 2007)
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Re: Re: Re: Alarm symptoms must be assessed in the context of age-specific cancer incidence
- LS Lewis (22 May 2007)
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Re: Re: Re: Re: Alarm symptoms must be assessed in the context of age-specific cancer incidence
- Mark N. Upton (22 May 2007)
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Re: Re: Re: Re: Re: Alarm symptoms must be assessed in the context of age-specific cancer incidence
- LS Lewis (22 May 2007)
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Re: Re: Re: Re: Re: Re: Alarm symptoms must be assessed in the context of age-specific cancer incidence
- Mark N. Upton (23 May 2007)
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It’s all in the recording: quality versus quantity
- Carl Heneghan (25 May 2007)
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Re: Re: Re: Re: Re: Re: Re: Alarm symptoms must be assessed in the context of age-specific cancer incidence
- LS Lewis (25 May 2007)
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When is an alarm symptom not an alarm symptom?
- David Kernick (29 May 2007)
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Dysphonia as an alarming symptom in patients aged 40 or more years old.
- Alejandro Díaz-González MD, Moisés Santos-Peña MD, Jesús Fleites-Wong MD, René Moreno-Rajadel MD, Juana Hernández-Fernández MsC. (2 June 2007)
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Early Diagnosis of Colorectal Cancer
- Brian Gareth Ellis, Iona Heath, Michael R Thompson (7 June 2007)
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Alarm symptoms in primary care: Further evidence
- Knut A Holtedahl (1 October 2007)
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Dr. Harsha Kumar H N, Epidemiologist and Asst Professor, Department of Community Medicine, KMC, Mangalore, India. Mangalore, Karnataka State, India. 91-- 575001
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1. It is well known that symptoms like the ones chosen by the authors ( Hematuria, Dysphagia etc..) are symptoms suggestive of complications ( Mostly indicating spread of the neoplastic cells to the neighbouring vessels, neighbouring tissues )which occur during later stages of disease. For instance dysphagia in cancer of oesophagus stage 4, similarly hemaoptysis in Respiratory tract malignancies occurs in advanced stages. Hence the conclusions of the authors that the cancers may be more amenable to treatment is unjustified. 2. Poor positive predictive values mean that majority of the people would not have any cancer. which means wasting of resources in investigating "every case with alarm symptom" 3. Poor positive predictive values means that we cause false alram and cause lot of distress to the patients. so, the challange to the present day population based research on cancers is to find ways to detect cancers in the early stages reliably ( with higher positive predicitive values ). so the use of alarm symptoms has very little utility as the outcome of the advanced cancers is poor ( Oesophagus, Bladder) inspite of treatment Competing interests: None declared |
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Eduardo M. Curbeira-Hernandez. MDD, Dentistry and Epidemiology Departments Gustavo Aldereguía Lima University Hospital. Cienfuegos, Cuba, Enrique Castillo Betancourt MDD, Moisés A. Santos Peña MD, Juana Hernández Fernández MsC, Milagros Fernández González
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After having read the article published in the BMJ entitled “Alarm
Symptoms in Early Diagnosis of Cancer in Primary Care: Cohort Study using
General Practice Research Database” 1, and feeling motivated with its
content we wish to share some considerations about the article taking a
view from our medical field.
Malignant tumors of the oral cavity, as those of other parts of the human body, are able to affect the patient’s life. They have a world rate of 7.9 in men and 2.2 in women per 100 000 inhabitants. Tumors of the upper part of the aerodigestive apparatus predominantly appear in the fifth and sixth decades of life and mainly affect males . 2 If we take into account the updated knowlege in regards to this topic and the therapeutical faccilities to cure oral cancers, the unique measure that can increase an index of curability is the diagnosis of the disease in an early stage in any of the histological types that tumors develop in this important area of the human structure. 3 Dentists play an important role in the prevention and diagnosis of cancer of the oral cavity. It is not a secret that the mouth is the thermometer of many diseases since they start their manifestations precisely within the mouth, that is why it is of great importance to prepare dentists for the early detection of malignant lesions in the oral cavity, as dentists play the main role in the basic tasks of education, prevention and diagnosis of pre malignant conditions and neoplasic lesions of the oral cavity in the population or individuals under their action field. Self-examination of the oral cavity is a variant for exploring the buccal complex. Patients are taught how to develop mouth and neck self- examination looking for possible premalignant or malignant conditions. Self- examination is a very useful maneuver that is used as a complement to the different programs for the detection of oral cancer. The educative part of these programs include training members of the community about self-examination methodology . Instructions are clear and brief so that self-examination can be performed by any individual of any cultural level. It is the onset of a possible diagnosis and of the medical assistance that favors the early detection of a malignancy and a way to save a life. References: 1. Jones R, Latinovic R, Charlton J, Gulliford MC. Alarm symptoms in early diagnosis of cancer in primary care: cohort study using General Practice Research Database. BMJ , doi:10.1136/bmj.39171.637106. AE 2. Cuba. MINSAP. Anuario estadístico de salud. ECIMED. 2005 3. Santana JC. Prevención y diagnóstico del cáncer bucal. La Habana: ECIMED. 2002 Competing interests: None declared |
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David Carr, consultant physician University Hospital of North Tees, Stockton on Tees , TS19 8PE
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When a patient presents with an alarm symptom for possible cancer, the decision whether to investigate urgently (2-week rule, say) depends on more than simply knowing the likelihood ratio for the diagnosis actually being one of cancer. A better guide would surely be the likelihood that urgent referral will make a difference to outcome. For example, from the data in the paper by R Jones et al. (BMJ 2007; 334: 1040 – 4), in the case of the 2628 men with dysphagia, some of those 138 with cancer may already have been incurable at the time of presentation: and of those curable at presentation, some may still have been curable if referral were delayed for a month in order to try a course of treatment appropriate for the more common diagnosis of reflux oesophagitis. The residue (those curable only if referred immediately) could be a much smaller number. Moreover, too rapid referral of the 2490 individuals without cancer could lead to some undergoing unnecessary investigations carrying their own risks. The decision to refer may also depend on the severity of the symptom; “complete” dysphagia would need urgent referral regardless of the underlying cause. The data presented in this paper are interesting and important, but should not be used in isolation to define referral policy. Competing interests: None declared |
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Mark N Upton, General Practitioner Woodlands Family Medical Centre, 106 Yarm Lane, Stockton-on-Tees, TS18 1YE
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Sir Jones and colleagues have used the world’s largest primary care database to estimate three epidemiological parameters relevant to the diagnosis of cancer in the presence of alarm symptoms, namely positive predictive value, sensitivity, and likelihood ratio. Unfortunately, there are weaknesses in the way these potentially important data have been presented that, at best, limit the usefulness of their data, and at worst, may lead to erroneous conclusions being drawn. For example, it is almost meaningless to report a summary estimate of a positive predictive value for cancer incidence associated with a particular symptom aggregated over a population of individuals aged 15 to 100 years (table 3, and the accompanying editorial), when cancer registry data and clinical experience teach us that cancer incidence is so closely linked to age. Table 2 reports age and sex specific incidences of alarm symptoms, but the essential age-specific companion data for cancer incidence are missing. Please could the authors report these data, because it is impossible to interpret age specific positive predictive values without them. Cohort-specific data about cancer incidence will also increase the utility of the reported likelihood ratios, because the latter can then be combined with a cohort specific estimate of the pre-test (i.e., “pre-alarm symptom”) odds of cancer to estimate the post-test odds of cancer. Information about age-specific cancer incidence is also essential for the assessment of external validity, and the completeness of cancer case ascertainment (taking due account of study methodology). The latter is particularly relevant to interpretation of the reported sensitivities of the alarm symptoms for the cancers in question. The authors cite two studies (references 27 and 28) in support of their claims about the quality of data in the General Practice Research Database (GPRD). It is possible that the first of these involves a citation error, because the study in question did not report any involvement of the GPRD. The second cited study compared database coding to the content of consultant letters received by the practices concerned, rather than involve a comparison with data from cancer registries. If there are published data comparing cancer incidence between the GPRD and cancer registries, please could the authors enlighten us. If not, then the authors seem to have missed an opportunity to address this in their current manuscript. A single table comparing age and sex specific cancer incidence in the GPRD alongside nationally aggregated cancer incidence data should suffice. Competing interests: None declared |
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LS Lewis, GP Surgery, Newport, Pembrokeshire, SA42 0TJ
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Mark,
You missed the version of this paper in the electronic BMJ.
see:-
Table 2 Age and sex specific incidence of alarm symptoms
Competing interests: None declared |
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Mark N Upton, General Practitioner Woodlands Family Medical Centre, 106 Yarm Lane, Stockton-on-Tees, TS18 1YE
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Dear Dr Lewis Thanks for your message Table 2 of the copy of the paper published online that I have seen shows age and sex specific incidence of alarm symptoms, but not age and sex-specific incidence of the relevant cancers themselves. Are the latter reported somewhere else? Have I missed them? Competing interests: None declared |
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LS Lewis, GP SA42 0TJ
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does table 4's 'broad age group' meet your need ? Table 4 Observed related cancer diagnoses in first three years after first alarm symptom and positive predictive value for cancer by broad age group and sex Competing interests: None declared |
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Mark N. Upton, General Practitioner Woodlands Family Medical Centre, 106 Yarm Lane, Stockton-on-Tees, TS18 1YE
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Dear Dr Lewis Once again, thanks for your reply Positive predictive value (PPV) depends upon (1) incidence (or prevalence) and (2) the discriminatory ability of the symptom, sign or test - in this case, the alarm symptom in question. Table 4 shows how PPV changes with age. Unfortunately there are no data in Table 4 to show how cancer incidence changes with age. Competing interests: None declared |
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LS Lewis, GP Surgery, Newport, Pembs, SA42 0TJ
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The age specific incidence 0f the relevant cancers is calculable combining tables 2 and 4. Table 4 details only the cancer numbers , and the associated PPV. It is NOT necessary to include the cancer incidence to compute the PPV = "Proportion of patients with positive test results who are correctly diagnosed. " .. Table 4 includes the relevant data for the PPV calculation ( [ number of Cancers / number with symptom ], ie: the denominator population cancels itself). If you want to compute the actual Cancer incidence, then combine Table 2's Symptom incidence with Table 4's 'number with Cancer' and 'number with symptom', to derive the denominator population, and divide it into 'number of cancers'. I think for reasons of space the BMJ may have culled the data presented, but the essence remains. Competing interests: None declared |
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Mark N. Upton, General Practitioner Woodlands Family Medical Centre, 106 Yarm Lane, Stockton-on-Tees, TS18 1YE
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Dear Dr Lewis You point out that it is not necessary to know the incidence of cancer in order to estimate positive predictive value (PPV). This is not in dispute, and is a correct statement because PPV is estimated horizontally across the standard 2x2 table. However, because PPV depends upon both cancer incidence and "test" discrimination, any age-related change in PPV could, in principle, be a function of age-related changes in cancer incidence, discrimination, or both of these. In order to interpret the reported age-related changes in PPV, I would like to see data on age specific cancer incidence. If, for example, there were age-related biases in cancer-case ascertainment, then this will affect the estimates for PPV. It may, or may not, be possible to derive accurate person-years denominator data in the way that you describe. It is not clear from the published report that censoring of person-years was the same for alarm symptoms and for cancer incidence. Further, the definition of the person- years denominator might have to vary, depending on how these data were to be used. For example, combining cancer incidence estimated over (say) 6 months with a likelihood ratio estimated over 6 months follow-up, as against a comparison with an external reference standard (see below). As readers and potential users of these data we should be presented with sufficient information for us to decide whether or not we can trust the study methods. It seems odd to me that a report about the clinical epidemiology of cancer should omit key information about age-related cancer incidence, possibly leaving readers to derive this for themselves. To help me decide whether or not the results of this study are applicable to my patients, I would like to see a comparison of age-related changes in cancer incidence between the GPRD cohort and some external standard, such as nationally aggregated cancer incidence data from registries (allowing for study methods). You make the point that the authors may have submitted information about cancer incidence, only for it to be culled from the manuscript during the editorial process. If you are correct, then this is unfortunate. Competing interests: None declared |
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Carl Heneghan, Deputy Director Centre for Evidence-Based Medicine Dept of Primary Health Care, University of Oxford
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Roger Jones paper on alarm symptoms [1] provides an insight in to the use of the general practice research database (GPRD). The size of the GPRD practice database gives precise answers – small confidence intervals in this case. However, it doesn’t necessarily follow that the estimates will prove accurate for that population. Readers should think of this like shooting arrows at a target. Although the arrows are clustered close together (precision) they may be some distance from the bulls-eye (accuracy). The GPRD is a useful tool when the data is proven to be accurately recorded. For instance drug usage, cancer diagnoses. However, to date no validation exists for the accuracy of reported symptoms in the GPRD. Recording and coding in practice varies greatly. General practitioners tend to record the main problem only [2] which leads to a selective under reporting and coding of secondary problems. So what can be inferred from this paper? When GPs perceive the problem to be an alarm symptom, such as haematuria, but in the presence of a urinary tract infection, they are more likely to code the latter than the former due to its prominence as the main diagnoses. Thus the estimates in the Jones paper are likely to reflect those patients with no alternative diagnoses; warranting further investigation. The result of the paper should not be interpreted as a blanket policy for cancer evaluation of all patients with alarm symptoms such as haematuria when a diagnosis of UTI or renal calculi is more probable. [1] Jones R, Latinovic R, Charlton J, Gulliford MC. Alarm symptoms in early diagnosis of cancer in primary care: cohort study using General Practice Research Database. BMJ , doi:10.1136/bmj.39171.637106. AE [2] Britt H, Mezza RA, DelMar C. Methodology of morbidity and treatment data collection in general practice in Australia: a comparison of two methods. Fam Pract. 1996 Oct;13(5):462-7. Competing interests: None declared |
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LS Lewis, GP Surgery, Newport, Pembrokeshire, SA42 0TJ
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Dear Mark, Spurred on by your letter, I computed the missing Cancer Incidences, as best I could, and placed a printout on my Surgery consulting desk I agree that interpretation of the value of alarm symptoms does need an appreciation of both the cancer Incidence, and the Positive Predictive Value. For example, Haemoptysis in older men has an increasing predictive value, even though incidence of cancer appears to be falling. I felt this paper was well worthwhile, and furnished me with much valuable information, with which I could explain to a patient presenting with, say, Rectal Bleeding, just what the chance of cancer was, and just how likely they were to be diagnosed – thus enabling an ‘evidence-based’ referral decision. Competing interests: None declared |
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David Kernick, General Practitioner St Thomas Health Centre, Exeter EX4 1HJ
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The paper by Jones et al identifying predictive values for common presentations of tumour in primary care suggests that the data can identify patients needing urgent attention. It overlooks an important question - what level of risk constitutes an alarm symptom? From a rational perspective, the positive predictive value at which to investigate should be dictated by economic factors and in particular the quality adjusted life year (QALY) ultimately gained. For example, screening for brain tumour in children at a risk of 4% using MRI yields a cost per QALY of approximately £66,000 (1). Clearly, many other emotive and complex issues are at play in the decision to refer particularly where serious pathology may be present.(2) However, a framework that clarifies the relevance of positive predictive values remains elusive. Why should 4% be a red flag and not 0.4%? Until one is forthcoming, an appropriate response to the data that Jones presents is – interesting but so what? 1 - Medina LS, Kuntz K, Pomeroy S. Children with headache suspected of having a brain tumor: a cost-effectiveness analysis of diagnostic strategies. Pediatrics 2001;108(2):255-63. 2 - Morgan M, Jenkins L, Ridsdale L. Patient pressure for referral for headache: a qualitative study of GP’s referral behaviour. British Journal of General Practice 2007;57:29-35. Competing interests: None declared |
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Alejandro Díaz-González MD, ENT Service . University Hospital Dr. Gustavo Aldereguía Lima. Cienfuegos. Cuba, Moisés Santos-Peña MD, Jesús Fleites-Wong MD, René Moreno-Rajadel MD, Juana Hernández-Fernández MsC.
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Cancer of the Larynx is the most frequent neoplasic disease at the ENT service. It has an increasing incidence and mortality at present. In Cuba it has the fourth place out of all types of cancer in males following only lung, skin and prostatic gland cancers. The highest incidence occurs in elders ( with a rate of
17.5 x 100 000 habitants) 1, dysphonia being the main symptom at onset of the disease when the patients comes to the physician depending on treatment and prognosis in early and rapid cases if the diagnosis is performed fast. That is why it constitutes an essential aim in the teaching learning process of medical students. In this sense we always rephrase an aphorism that states that all adult smokers with a dysphonia of more than 15 days should be explored and studied exhaustively due to the risk of a laryngeal cancer. The principal objective is to train community doctors for their work in the early detection of even precancerous lesions. Dysphonia is an alarming symptom that should never be unassessed when it is present.2
References: 1. Cuba. MINSAP. Anuario estadístico de salud. ECIMED. 2006 2. http//:www.gal.sld.cu/gbpc/orl/cáncer de laringe Competing interests: None declared |
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Brian Gareth Ellis, GP The Swan Surgery, Swan Street, Petersfield, Hants, GU32 3AB, Iona Heath, Michael R Thompson
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For those in Primary Care the diagnostic emphasis is on distinguishing those patients with serious illness, and requiring further investigation and management, from the large number with self limiting conditions requiring little further action. This is especially true in the case of cancers and the article by Jones et al1 highlights some symptoms suggestive of cancer. In this article reference is made to the low sensitivity of rectal bleeding for the diagnosis of rectal cancer but promulgates the recommendation for full investigation for all patients with rectal bleeding. As over 96% of patients with rectal bleeding do not have cancer2 such an approach risks exposing a large number of patients to unnecessary and invasive investigation. Greater awareness of the different symptom combinations of rectal bleeding3 is a more sensitive approach. The combination of rectal bleeding with a change in bowel habit to increased frequency of defecation with or without loose motions, and without perianal symptoms and increasing age will identify those patients at higher risk of cancer for more prompt investigation. Patients at lower risk, with a low level of anxiety regarding their symptoms, can be treated for longer in Primary Care and investigated if their symptoms fail to improve or develop into higher risk symptoms. The identification of high risk symptoms or symptoms combinations could prove invaluable to those in Primary Care trying to identify the few with serious underlying disease from the large number of patients seeking medical advice and safeguard these patients from hospital investigations. Brian G Ellis, general practitioner, The Swan Surgery, Petersfield, Hants, GU32 3AB Iona Heath, general practitioner, Caversham Group Practice, 4 Peckwater Street, London, NW5 2UP. Michael R Thompson, Consultant Colorectal Surgeon, Queen Alexandra Hospital, Cosham, Portsmouth, PO6 3LY. Competing interests: none 1, Roger Jones, Radoslav Latinovic, Judith Charlton, Martin C Gulliford, Alarm symptoms in early diagnosis od cancer in primary care:cohort study using General Practice Research Database, BMJ 2007;334:1040-4 2, Brian G Ellis and Michael R Thompson, Factors identifying higher risk rectal bleeding in general practice, BJGP 2005; 55: 949-955 3, Thompson M.R. ACPGBI Referral guidelines for colorectal cancer Colorectal Dis 2002;4: 287-97 Competing interests: None declared |
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Knut A Holtedahl, Professor of General Practice Institute of Community Medicine, University of Tromsø, 9037 Tromsø, Norway
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Dear Editor The article by Jones et al (1) in your 19 May issue of BMJ gives solid evidence for the low predictive value of single symptoms in relation to relevant forms of cancer. In line with this, I would like to draw attention to my around twenty-five year old studies about alarm symptoms in Norwegian general practice (2;3), mainly published in a non-Medline acknowledged journal and thus difficult to find to-day. Single symptoms, examplified by “the seven warning signals of cancer”, are poor diagnostic indicators of cancer, although not without validity, as suggested by an odds ratio of 1.9 in a prospective part of the study. However, considering single symptoms alone is artificial when considering possibilities in the consultation in general practice. The GP always has access to further information, modifying initial probabilities, as examplified in our study (4). In a previous study, published in Norwegian with an English summary, it was shown that such information is accessible through ordinary medical work including a good medical history and a focussed clinical examination and, slightly less important, an appropriate selection of laboratory tests and imaging (5). The individual symptoms were further analysed in two other articles, accessible in Medline (6;7). At the time, a manual of early cancer diagnosis for GPs was published as well (8). Like Jones et al., I was concerned in my studies not only about how the GP can contribute to earlier diagnosis, but also to how to avoid patient delay. Andersen & Cacioppo (9) have written an interesting article about this. p.t. Cherbourg, France 011007 Knut Holtedahl,
Reference List (1) Jones R, Latinovic R, Charlton J, Gulliford MC. Alarm symptoms in early diagnosis of cancer in primary care: cohort study using General Practice Research Database. BMJ 2007; 334(7602):1040. doi:10.1136/bmj.39171.637106.AE (2) Holtedahl KA. A method of calculating diagnostic indexes for possible cancer symptoms in general practice. , 1990; 19: 74-79. Allgemeinmedizin 1990; 19:74-79. (3) Holtedahl KA. More diagnostic indexes from general practice for some important forms of cancer. Allgemeinmedizin 1990; 19:80-85. (4) Holtedahl KA. Probability revision in general practice: the cases of occult blood in stool in patients with indigestion, and daily smoking in patients who cough. Allgemeinmedizin 1990; 19:35-38. (5) Holtedahl KA. [Diagnosis of cancer in general practice. I. Can diagnosis be made earlier?]. Tidsskr Nor Laegeforen 1980; 100(19-21):1219- 1223. English summary. (6) Holtedahl KA. Inter-observer variation on registration of signals of cancer. Scand J Prim Health Care 1987; 5:133-139. (7) Holtedahl KA. The value of warning signals of cancer in general practice. Scand J Prim Health Care 1987; 5:140-143. (8) Holtedahl KA. Early diagnosis of cancer in general practice. A manual. Berlin: Springer Verlag 1990. (9) Andersen BL, Cacioppo JT. Delay in seeking a cancer diagnosis: delay stages and psychophysiological processes. Br J Soc Psychol 1995; 34:33-52. Competing interests: None declared |
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