Family Practice

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Family Practice Vol. 21, No. 1, 99-106
© Oxford University Press 2004, all rights reserved.

Article

Diagnosis of colorectal cancer in primary care: the evidence base for guidelines

William Hamilton and Deborah Sharp

Division of Primary Health Care, Cotham House, Cotham Hill, Bristol BS6 6JL, UK

E-mail: w.hamilton{at}bristol.ac.uk

Received 10 March 2003; Revised 15 July 2003; Accepted 8 September 2003.

Hamilton W and Sharp D. Diagnosis of colorectal cancer in primary care: the evidence base for guidelines. Family Practice 2004; 21: 99–106.

	Abstract

Top Abstract Introduction Methods The rationale for and... Mode of presentation Symptomatic diagnosis Discussion References

 
Background. Colorectal cancer is common, causing 11% of cancer deaths in the UK. However, a GP would only expect to see one new presentation each year. Referral guidelines outlining clinical scenarios of high risk have been published. These aim to help GPs select patients for rapid investigation.

Objectives. The purpose of this study was to review the presenting features of colorectal cancer in primary care, using the basic structure of the UK Referral Guidelines for Suspected Cancer.

Methods. A structured literature review was carried out.

Results. Two symptoms have a high predictive value for cancer: rectal bleeding and change in bowel habit towards increased looseness or increased stool frequency. Other symptoms, such as abdominal pain, are so prevalent in the community that they have little predictive value. There is little published evidence on abdominal or rectal masses and iron deficiency anaemia as presenting features for colorectal cancer. However, these are so likely to have an important cause, investigation is mandated. Two areas in the Referral Guidelines are questioned: the need to defer investigation of change in bowel habit towards increased looseness or increased stool frequency for 6 weeks, and the low risk nature of constipation.

Conclusion. The Referral Guidelines have a reasonable evidence base.

Keywords. Colorectal cancer, diagnosis, primary care.

	Introduction

Top Abstract Introduction Methods The rationale for and... Mode of presentation Symptomatic diagnosis Discussion References

 
Colorectal cancer (CRC) is common, with >30 000 new cases each year in the UK.¹ It accounts for 14% of male and 12% of female cancers, and 11% of cancer deaths in both sexes.¹ Incidence rates have risen slowly in the last 30 years, but mortality has steadily declined.

Although common nationally, a full-time GP would expect to encounter only one new patient each year with CRC.^2,3 As each GP will diagnose relatively few cancers during their career, various guidelines have been written to assist in selection of patients for investigation.^4,5 Other guidelines make recommendations about surveillance of particular populations at higher risk, such as patients with polyposis coli or inflammatory bowel disease.^6,7 The UK Referral Guidelines for Suspected Cancer, devised by the Department of Health, were sent to all GPs in 2000.⁴ They are currently being revised. The Scottish Intercollegiate Guideline Network published a guideline on CRC in 1997, which was updated 2 years later.⁵ The National Institute for Clinical Effectiveness are currently updating guidance first issued in 1997 aimed at the whole NHS entitled, ‘Improving Outcomes in Colorectal Cancer’.^8,9 These latter two documents give recommendations across the whole spectrum from prevention and surveillance to hospital organization. In both, the sections relating to primary care diagnosis are brief, and so this review uses as its base the UK Referral Guidelines for Suspected Cancer. These are called simply the UK guidelines from now on.

The UK Referral Guidelines for Suspected Cancer
These outline criteria for urgent referral. They were published to coincide with the establishment of ‘2-week clinics’, which offer a specialist appointment within 2 weeks of a GP referral for suspected cancer.

Six criteria are documented: two symptoms, rectal bleeding and change in bowel habit; two secondary effects, iron deficiency anaemia and intestinal obstruction; and two physical findings, abdominal or rectal masses. In addition, three symptoms associated with a low risk of cancer are described: rectal bleeding with anal symptoms; change in bowel habit to decreased frequency of defecation and harder stools; and abdominal pain without clear evidence of intestinal obstruction. The purpose of this review is to examine the research evidence for these nine criteria: the six positive criteria and three negative ones.

	Methods

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We searched Medline and Embase from 1966 (Embase 1980) to 2002 for common symptoms of CRC: rectal bleeding, abdominal pain, change in bowel habit and weight loss. Inclusion criteria were: studies from the general population, primary care or hospital series of CRC patients. Exclusion criteria were: reports on children or non-Western societies. This list was then expanded by secondary searches of reference lists. Referral guidelines were found by Medline, Embase and Internet searches using the words colorectal cancer and guidelines.

	The rationale for and derivation of guidelines

Top Abstract Introduction Methods The rationale for and... Mode of presentation Symptomatic diagnosis Discussion References

 
The diagnosis of cancer in general practice is not straightforward.^10,11 Symptoms and physical signs that may signify an underlying cancer can be, and frequently are, of benign origin. Guidelines attempt to define clinical scenarios with a reasonably high chance of finding an underlying cancer. If they can help GPs to discriminate between malignant and benign conditions, two complementary outcomes occur: patients with cancer will be investigated rapidly; and those without cancer will not be subjected to inappropriate investigation. Over-investigation may have psychological or physical ill effects,^12,13 as well as having opportunity costs.¹⁴ Furthermore, if investigations are used indiscriminately in a system with finite capacity, waiting times will rise.

Guidelines do not tell if a patient has cancer. They are designed to assist the GP in identifying patients in whom the risk of cancer is high enough to warrant urgent investigation. This implies that there is a threshold level of risk mandating urgent investigation (and below which urgent investigation is not required). However, this threshold level is not made explicit in any of the guidelines.¹⁵

The most useful figure to use in setting a threshold level is the positive predictive value (PPV). It is the probability of having the condition when you have the symptom.¹⁶ PPVs are usually calculated for single symptoms, for pairs, or even for groups, of symptoms. Where possible, we have quoted PPVs in this review. One problem, however, is that the CRC research literature is dominated by hospital series, with few reports from primary care. This matters because the presenting features in primary care differ from those in secondary care.^17,18 Furthermore, most hospital research reports are retrospective cohort studies, or case–control series, elucidating symptoms from patients after the diagnosis has been made. These methods may introduce several biases: selection bias, whereby hospital series are unrepresentative of primary care presentation; recall bias, whereby patients—perhaps prompted by interviewers—remember symptoms they would otherwise have forgotten; and bias induced by progression of the disease between primary care and secondary care presentation. The relative rarity of CRC in primary care makes it difficult to design a study large enough to yield meaningful results.¹⁹ This is particularly so for prospective studies.

	Mode of presentation

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Some CRCs present with surgical emergencies, principally obstruction or perforation; these account for 3–21% of hospital series, with UK figures among the highest.^20–25 Although the majority of patients presenting with bowel obstruction have a very short duration of symptoms, some have persistent symptoms before the emergency presentation.^25,26 Indeed, early diagnosis may benefit this group most of all by avoiding the mortality and morbidity that accompany a surgical emergency.²⁵

At the other end of the spectrum, asymptomatic cancers account for 5–20% of hospital series, with the highest figures from the USA.^{20,22,23,27–33} These cancers have usually been detected in a screening procedure in those who are recognized to be at additional risk: this is usually because of a family history of CRC, or because the patient has inflammatory bowel disease. Cancers diagnosed by screening have a better Duke's staging^28–30,32 and, as screening increases, fewer CRCs present as an emergency.³⁴ Thus the pattern of presentation is changing, with a slow move towards more asymptomatic cancers being identified. Despite these changes, the large majority of patients with CRC in the UK present with symptoms to their GP, and this is likely to continue to be the case for the foreseeable future.^19,35

	Symptomatic diagnosis

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Rectal bleeding
This is a classical symptom of CRC and a frequent first symptom.^36,37 However, it is also a symptom of haemorrhoids, inflammatory bowel disease and many other non-malignant conditions.³⁸ The UK guidelines for rectal bleeding are given in Box 1.

BOX 1 Referral guidelines relating to rectal bleeding Urgent referral: rectal bleeding WITH a change in bowel habit to looser stools and/or increased frequency of defecation persistent for 6 weeks at all ages Urgent referral: rectal bleeding persistently without anal symptoms (such as soreness, discomfort, itching, lumps or prolapse) in patients over 60 years Low risk: rectal bleeding with anal symptoms

 

The prevalence of rectal bleeding in different populations is illustrated in Figure 1. In questionnaire studies of the general population, 14–33% report that they have experienced rectal bleeding at some time in their life.^39–44 Rectal bleeding in the last year is reported by 14–19% in UK surveys, but new onset bleeding in the last year by only 2.2%.^39,40 The symptom is reported less in older age groups.³⁹ However, the majority of those with rectal bleeding do not report it to their GP.³⁹ An estimated seven per 1000 people consult their GP each year with the symptom, with 2 per 1000 per year deemed by the GP to have clinically important bleeding.⁴⁵ The difference between the community incidence of rectal bleeding and the reporting of it to primary care is accounted for by patients considering themselves to have benign disease, principally haemorrhoids.^39,42,46,47 Other patients may delay presentation of their bleeding from a wish not to create work for their doctor.⁴⁸ One possible marker for a malignant diagnosis is the gap between primary care consultations: as the interval since the patient last attended increases, so does the chance of cancer.⁴⁹ The duration of bleeding is, however, not related to the likelihood of reporting the symptom to primary care.^33,40,50

View larger version (20K): [in this window] [in a new window]   FIGURE 1 Incidence of rectal bleeding in the community and in primary care. The figures have been adjusted to an approximate GP list size of 2000 patients

 
The prevalence of rectal bleeding in the population who have been referred to hospital is much higher than in primary care. Although this presumably reflects the selection process by the GP, some may be new onset bleeding in the interval between referral and assessment. One study of 2268 GP referrals for investigation of distal colonic symptoms has been published after the referral guidelines were disseminated. Seventy percent of referred patients described rectal bleeding in response to a questionnaire.⁵¹ This is the highest percentage in hospital series of cancers, with others finding rates of 20–58%.^{20–24,33,41,51–54}

The PPV of rectal bleeding for CRC depends on the rate of bleeding in the cancer population, the rate in the non-cancer population and the prevalence of the cancer in the studied population. For the general population, the PPV of rectal bleeding is very small, estimated to be 0.1%.^45,55 Once the symptom has been reported to primary care, the PPV rises to 2–3%.^55,56 GPs are selective in making referrals in patients reporting rectal bleeding;^57,58 this is reflected in a rise in the PPV for referred patients to 5–7%.^51,55,59,60 When a history of rectal bleeding is confirmed by a positive test for fecal occult blood, implying continuous bleeding, the PPV increases to 36%.^60,61

The nature of the bleeding itself may be helpful in deciding on the importance of the symptom. Blood mixed with the stool has a higher PPV than blood coating the stool.^18,51,62 Dark blood is particularly unfavourable, with a PPV in referred patients of 10–13%.⁵¹

Other factors used in combination with rectal bleeding Age. The UK guidelines in Box 1 use additional factors in suggesting which patients to select for urgent referral. In studies of primary care patients with rectal bleeding, the only additional factors with predictive power are change in bowel habit, age and abdominal pain.^18,58 The reported incidence of rectal bleeding in the general population decreases with age, while the risk of CRC increases. Rectal bleeding occurs in the same proportion of older CRC patients as it does in younger patients.^21,63 Thus, the PPV of the symptom increases as the patient ages, with figures of 2% in the age group 50–59 rising to 21% at ages 70–79.^56,64 Despite the lower PPV at younger ages, one analysis suggests that investigation of younger patients with rectal bleeding as a sole symptom is still cost-effective.¹⁴ This is acknowledged by the UK guidelines, which regard 60 years as a maximum, but allow local cancer networks to use a lower age threshold. For instance, the Scottish guidelines use 45 years as their cut-off.⁵

Inflammatory bowel disease. Both ulcerative colitis and Crohn's disease can cause rectal bleeding, and both conditions predispose to cancer,⁷ with 1–2% of all CRCs arising in patients with inflammatory bowel disease.^65,66 The risk of developing a complicating cancer is similar in the two diseases, and increases with the duration and extent of the inflammatory bowel disease.⁶⁷ Inflammatory bowel disease and CRC share the same symptoms: rectal bleeding, diarrhoea and sometimes fatigue, abdominal pain and anaemia. Therefore, the predictive value of these symptoms for CRC in inflammatory bowel disease patients is very low. The severity and pattern of symptoms may change when a CRC develops, and this is an area that is likely to remain one of clinical judgement rather than illumination by research. Partly for this reason, one guideline recommends surveillance by colonoscopy starting 10 years after onset of symptoms.⁷ These recommendations are not based on randomized controlled trials, however, and decision analysis suggests that they may be ineffective.⁶⁸ Neither condition is mentioned in the UK guidelines.⁴

Local symptoms. The UK guidelines differentiate between rectal bleeding with and without local symptoms. The assumption is that local symptoms suggest a local cause such as haemorrhoids, or an anal fissure. Although intuitive, this is not supported by research evidence. Symptoms such as pain on defecation, tenesmus and pruritis have all been reported in cancer series.^20,41,51 In the referred population, each of these symptoms predicts cancer after investigation.⁵¹ However, their frequencies in the general population are largely unknown, making calculation of the predictive value in primary care impossible.

Change in bowel habit
This symptom is probably as important as rectal bleeding.⁶⁹ In most studies, it is described more specifically as constipation or diarrhoea. Diarrhoea, either increased loosening or increased frequency of the stools, is more predictive of cancer than constipation.⁵¹ These symptoms have been studied less than rectal bleeding, perhaps because of the categorical nature of bleeding (one either bleeds or one does not), but perhaps also because of the variability of bowel habit in the general population. Change in bowel habit is the symptom most associated with patient delay in presentation,³³ and diarrhoea the symptom most associated with doctor delay.⁵³

Recommendations for urgent referral in the UK guidelines are summarized in Box 2.

BOX 2 Referral guidelines relating to change in bowel habit Urgent referral: rectal bleeding with a change in bowel habit to looser stools and/or increased frequency of defecation persistent for 6 weeks at all ages (as above) Urgent referral: change of bowel habit to looser stools and/or increased frequency of defecation, without rectal bleeding and persistent for 6 weeks Low risk: change in bowel habit to decreased frequency of defecation and harder stools

 

Constipation and diarrhoea are very common in the general population. Between 10 and 25% of the UK population describe that they have to strain to pass a stool,^40,70,71 with 14% describing themselves as constipated.⁴⁰ Some 23% describe urgency of defecation, and 10% have loose stools frequently.⁴⁰ However, only 9% of the population describe a recent change in bowel habit,⁴⁰ and 1.5% describe a change which they regard as significant enough to report to primary care.⁷² In patients referred for investigation, 13% describe constipation and 40% increased stool frequency.⁵¹ In hospital series of CRC patients, the percentage reporting any of diarrhoea, constipation or a change in bowel habit is 39–86%.^{22,24,41,51,73} Change in bowel habit is a more common symptom of cancer in the elderly.⁶³ The presence of mucus in the stool may predict cancer, being described by 6–29% of cancer patients,^20,41,51 but only 3–5% of the general population.⁷¹

Using the figure of 1.5% who describe a change in bowel habit that they deem significant enough to report to their doctor and using an approximate incidence of CRC as one person in 2000, a PPV of 3% can be estimated.⁷² In the referred population, the PPV of increased stool frequency is 7% and looseness of the stools 8%. In contrast, constipation has a PPV of 1.4%.⁵¹ The UK guidelines reflect this in stating that constipation alone is not a good predictor of cancer.

Duration of symptoms
No studies have reported on the relationship between duration of symptoms and the likelihood of CRC. There is a complex relationship between the duration of symptoms and Duke's staging (and thus survival). Cancers with a longer duration of symptoms are more likely to be Duke's A or B.⁷⁴ This counter-intuitive finding may be explained by differences in tumour aggressiveness,⁷⁵ whereby aggressive tumours have a shorter period of symptoms but have more advanced disease at diagnosis. Overall, there is no relationship between duration of symptoms and survival.^75,76 Thus, there is no research evidence to support the recommendation in the UK guidelines that change in bowel habit should be persistent for 6 weeks before the patient qualifies for urgent referral.

Abdominal or rectal masses and iron deficiency anaemia
The guidelines recommend urgent referral of any of these three findings (Box 3).

BOX 3 Referral guidelines relating to masses and anaemia Urgent referral: a definite palpable right-sided abdominal mass Urgent referral: a definite palpable rectal mass Urgent referral: iron deficiency anaemia without an obvious cause

 

These recommendations are uncontroversial. The proportion of CRC patients with a palpable abdominal mass is reported as 4–6% in hospital series.^53,77 Rectal masses are more common; reported as being present in 24–50% of CRCs in two hospital series.⁷⁸ However, no figures are available from primary care.⁷⁸ Whatever the true proportion of palpable masses in primary care presentations of CRC, it is clear that, once detected, they merit urgent referral.

Iron deficiency anaemia is a classical pointer to CRC.⁷⁹ It generally signifies an underlying illness, so would be investigated as a matter of course. CRC is the initial differential diagnosis, but may not initially be the most likely cause. Iron deficiency is present in 11–57% of cancers,^20,52,63,73 and is particularly suggestive of caecal tumours.⁷⁷ The PPV of anaemia for CRC in adults is 14%,⁶² so investigation is mandatory, and positive findings should lead to a rapid referral.

Abdominal pain
The guidelines only mention abdominal pain as a symptom of low risk (Box 4).

BOX 4 Referral guidelines relating to abdominal pain Low risk: abdominal pain without clear evidence of intestinal obstruction

 

Abdominal pain is extremely prevalent in the general population. In population surveys, >20% of the US population reported abdominal pain in the previous month.^80,81 A quarter of the UK population reported it in the previous year.^40,82 Pain is reported less frequently by the elderly.^{63,80,83–85} As with rectal bleeding, the patient's decision to consult their doctor depends on whether they perceive the symptom as a health problem or part of normal experience.⁸⁶ Roughly a quarter do consult, and most of these have a self-limited illness for which no definitive diagnosis can be found.⁸⁷ In a large prospective study, only 0.4% of primary care patients who attended with abdominal pain had a diagnosis of CRC established within the next year.⁸⁸ The number of CRCs in this study was too small for further analysis, so all neoplasms (including benign polyps) were put into a single group. The only features to significantly predict a neoplastic cause were: the pain having no specific character, the patient being male, increasing age, and a raised erythrocyte sedimentation rate.⁸⁹ The proportion of patients describing abdominal pain in the population referred for investigation of suspected cancer is 54%, with a PPV of 2.7%.⁵¹ However, the PPV for patients with rectal bleeding and abdominal pain is no higher than for rectal bleeding alone.⁵⁶ Colonoscopies for investigation of non-specific abdominal symptoms (without rectal bleeding, weight loss or change in bowel habit) have the same yield of significant pathology as in asymptomatic patients.^90,91 This all suggests that abdominal pain on its own is a very poor predictor of cancer, in marked contrast to rectal bleeding and change in bowel habit.

The role of family history
The UK guidelines make no mention of family history of CRC. There are several inherited syndromes with CRC as a feature, such as polyposis coli, hereditary non-polyposis coli and Peutz–Jegers syndrome. Guidelines for the management of individuals with these syndromes have been published.⁹² Management of these conditions is usually in secondary care. For those outside such families, the contribution of inheritable factors has been estimated from twin studies to be 35%.⁹³ Recent guidelines recommend referral of patients with two first-degree relatives with CRC or one first-degree relative under 45 years, although the author acknowledged that the evidence for this recommendation was indirect, and benefit marginal.⁹⁴ The value of using the family history in primary care is illustrated by a study from one UK general practice. A postal questionnaire was sent to all patients aged 30–69 enquiring about any family history of CRC and led to the diagnosis of two cancers in symptomatic patients who had not consulted their doctor.⁹⁵

	Discussion

Top Abstract Introduction Methods The rationale for and... Mode of presentation Symptomatic diagnosis Discussion References

 
The major single predictors of cancer are rectal bleeding and change in bowel habit towards increased looseness or increased stool frequency. These are strongly supported by research evidence. One of these symptoms, plus being aged over 60, is as powerful a predictor as any of the other symptom complexes described in the guidelines.³ In contrast, other symptoms in isolation have very low predictive power, although when they accompany rectal bleeding or change in bowel habit the likelihood of cancer is increased. The evidence base is weak for the three rarer presentations of CRC, abdominal or rectal masses, or iron deficiency anaemia. This may not matter: all three presentations require investigation, and CRC is a likely diagnosis for them all. Although the UK guidelines were established to help GPs with referral decisions, local services will determine the exact patient pathway. In some instances, the GP may perform the initial investigations in primary care instead of selecting immediate referral to a rapid access clinic.

However, two points in the UK guidelines are questionable. First, there is no evidence for deferring investigation of increased stool frequency for 6 weeks. In the absence of a clear cause for diarrhoea, we suggest immediate referral. This applies particularly to the elderly. Even with an apparently clear cause, such as infective diarrhoea, it may be wise to set a time limit before referral lest the initial diagnosis be wrong. Change in bowel habit is the symptom most associated with both patient and doctor delay:^33,53 deferring investigation risks perpetuating this. It is also illogical to require a 6 week delay before requesting a referral with a maximum 2 week wait. No doubt this was a practical decision. However, it ignores the issue that patients select which symptoms to report and, once they have chosen to report a change in bowel habit, the PPV is already high enough to warrant referral.

Secondly, it is debatable whether constipation can safely be regarded as low risk. A PPV of 1.4% (albeit in the referred population) is one chance in 70. We would caution against labelling all constipation as low risk.

The research literature largely bypasses one other important issue: the experience of the doctor and patient. The higher predictive value of symptoms in the population referred for investigation when compared with the predictive value on first presentation to primary care shows that doctors are able to identify (at least partly) those who are likely to harbour cancer.^{11,19,51,59,96} This is not to forget that there has been a higher relative rise from the predictive value in the general population to those presenting to primary care, so patients can also identify which symptoms matter.^45,55,97 It is a sobering thought that patients do this at least as well as doctors.

	Acknowledgments

 
We wish to thank an anonymous referee for helpful comments on an earlier version. WH is funded through his research practice (Barnfield Hill, Exeter) and RCGP/BUPA and NHS Fellowships.

	References

Top Abstract Introduction Methods The rationale for and... Mode of presentation Symptomatic diagnosis Discussion References

 
¹ Quinn M, Babb P, Brock A, Jones J. Cancer Trends in England and Wales 1950–1999. London: The Stationery Office; 2001.

² Summerton N. Diagnosing Cancer in primary Care. Abingdon: Radcliffe Medical Press; 1999.

³ Cade D, Selvachandran S, Hodder R, Ballal M. Prediction of colorectal cancer by consultation questionnaire. Lancet 2002; 360: 2080.[Web of Science][Medline]

⁴ Department of Health. Referral Guidelines for Suspected Cancer. London: Department of Health; 2000.

⁵ Colorectal Cancer—A National Clinical Guideline. Scottish Intercollegiate Network; 1997.

⁶ Cairns S, Scholefoeld J. Guidelines for colorectal cancer screening in high risk groups. Gut 2002; 51 (Suppl V): v1–v2.[Abstract/Free Full Text]

⁷ Eaden J, Mayberry J. Guidelines for screening and surveillance of asymptomatic colorectal cancer in patients with inflammatory bowel disease. Gut 2002; 51 (Suppl V): v10–v12.[Free Full Text]

⁸ NHSE. Improving Outcomes in Colorectal Cancer: The Manual. London: Department of Health; 1997.

⁹ Service guidance for the NHS in England and Wales. Improving Outcomes for Colorectal Cancer. www.nice.org.uk/cat.asp?c=20069

¹⁰ Summerton N. The changing role of UK primary cancer care. Lancet Oncol 2001; 2: 717–718.[Web of Science][Medline]

¹¹ Hamilton WT, Round AP, Sharp D, Peters T. GPs can separate oncological wheat from chaff. Br Med J 2003; 326: 397.[Free Full Text]

¹² Robinson MH, Hardcastle JD, Moss SM et al. The risks of screening: data from the Nottingham randomised controlled trial of faecal occult blood screening for colorectal cancer. Gut 1999; 45: 588–592.[Abstract/Free Full Text]

¹³ WONCA. The European Definition of General Practice/Family Medicine, 2002. www.sgam.ch/pdf/Europ_Definition_GP_FM1.pdf

¹⁴ Lewis JD, Brown A, Localio AR, Schwartz JS. Initial evaluation of rectal bleeding in young persons: a cost-effectiveness analysis. Ann Intern Med 2002; 136: 99–110.[Abstract/Free Full Text]

¹⁵ NICE. Guideline development methods: NICE, 2003. www.nice.org.uk/pdf/guidelinedevelopmentmethodschapters.pdf

¹⁶ Zhou X-H, Obuchowski N, McClish D. Statistical Methods in Diagnostic Medicine. New York: Wiley; 2002.

¹⁷ Summerton N. Cancer recognition and primary care. Br J Gen Pract 2002; 52: 5–6.[Web of Science][Medline]

¹⁸ Metcalf JV, Smith J, Jones R, Record CO. Incidence and causes of rectal bleeding in general practice as detected by colonoscopy. Br J Gen Pract 1996; 46: 161–164.[Web of Science][Medline]

¹⁹ Summerton N. Symptoms of possible oncological significance: separating the wheat from the chaff. Br Med J 2002; 325: 1254–1255.[Free Full Text]

²⁰ Majumdar SR, Fletcher RH, Evans AT. How does colorectal cancer present? Symptoms, duration, and clues to location. Am J Gastroenterol 1999; 94: 3039–3045.[CrossRef][Web of Science][Medline]

²¹ Kemppainen M, Raiha I, Rajala T, Sourander L. Delay in diagnosis of colorectal cancer in elderly patients. Age Ageing 1993; 22: 260–264.[Abstract/Free Full Text]

²² Kyle SM, Isbister WH, Yeong ML. Presentation, duration of symptoms and staging of colorectal carcinoma. Aust NZ J Surg 1991; 61: 137–140.[Web of Science][Medline]

²³ Speights VO, Johnson MW, Stoltenberg PH, Rappaport ES, Helbert B, Riggs M. Colorectal cancer: current trends in initial clinical manifestations. South Med J 1991; 84: 575–578.[Web of Science][Medline]

²⁴ Umpleby HC, Bristol JB, Rainey JB, Williamson RC. Survival of 727 patients with single carcinomas of the large bowel. Dis Colon Rectum 1984; 27: 803–810.[Web of Science][Medline]

²⁵ Mulcahy HE, O'Donoghue DP. Duration of colorectal cancer symptoms and survival: the effect of confounding clinical and pathological variables. Eur J Cancer 1997; 33: 1461–1467.[CrossRef][Web of Science][Medline]

²⁶ Hargarten SW, Richards MJ, Anderson AJ, Roberts MJ. Cancer presentation in the emergency department: a failure of primary care. Am J Emergency Med 1992; 10: 290–293.[CrossRef][Web of Science][Medline]

²⁷ Campbell NC, MacLeod U, Weller D. Primary care oncology: essential if high quality cancer care is to be achieved for all. Fam Pract 2002; 19: 577–578.[Free Full Text]

²⁸ Mandel JS, Bond JH, Church TR et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328: 1365–1371.[Abstract/Free Full Text]

²⁹ Jorgensen OD, Kronborg O, Fenger C. A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds. Gut 2002; 50: 29–32.[Abstract/Free Full Text]

³⁰ UK Flexible Sigmoidoscopy Screening Trial Investigators. Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet 2002; 359: 1291–1300.[CrossRef][Web of Science][Medline]

³¹ Hardcastle JD, Chamberlain JO, Robinson MH et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348: 1472–1477.[CrossRef][Web of Science][Medline]

³² Ponz de Leon M, Benatti P, Di Gregorio C et al. Staging and survival of colorectal cancer: are we making progress? The 14-year experience of a specialized cancer registry. Dig Liver Dis 2000; 32: 312–317.[CrossRef][Web of Science][Medline]

³³ Mor V, Masterson-Allen S, Goldberg R, Guadagnoli E, Wool MS. Pre-diagnostic symptom recognition and help seeking among cancer patients. J Community Health 1990; 15: 253–266.[CrossRef][Medline]

³⁴ Scholefield JH, Robinson MH, Mangham CM, Hardcastle JD. Screening for colorectal cancer reduces emergency admissions. Eur J Surg Oncol 1998; 24: 47–50.[CrossRef][Web of Science][Medline]

³⁵ The changing face of UK primary cancer care. Lancet Oncol 2001; 2: 624.

³⁶ Mansson J. The diagnosis of colorectal cancer—experiences from the community of Kungsbacka, Sweden. Scand J Primary Health Care Suppl 1990; 8: 31–35.

³⁷ Mansson J, Bjorkelund C, Hultborn R. Symptom pattern and diagnostic work-up of malignancy at first symptom presentation as related to level of care. A retrospective study from the primary health care centre area of Kungsbacka, Sweden. Neoplasma 1999; 46: 93–99.[Web of Science][Medline]

³⁸ Goulston K, Cook I, Dent O. How important is rectal bleeding in the diagnosis of bowel cancer and polyps? Lancet 1986; ii: 261–265.

³⁹ Crosland A, Jones R. Rectal bleeding: prevalence and consultation behaviour. Br Med J 1995; 311: 486–488.[Abstract/Free Full Text]

⁴⁰ Chaplin A, Curless R, Thomson R, Barton R. Prevalence of lower gastrointestinal symptoms and associated consultation behaviour in a British elderly population determined by face-to-face interview. Br J Gen Pract 2000; 50: 798–802.[Web of Science][Medline]

⁴¹ Curless R, French J, Williams GV, James OF. Comparison of gastrointestinal symptoms in colorectal carcinoma patients and community controls with respect to age. Gut 1994; 35: 1267–1270.[Abstract/Free Full Text]

⁴² Byles JE, Redman S, Hennrikus D, Sanson-Fisher RW, Dickinson J. Delay in consulting a medical practitioner about rectal bleeding. J Epidemiol Community Health 1992; 46: 241–244.[Abstract/Free Full Text]

⁴³ Talley NJ, Jones M. Self-reported rectal bleeding in a United States community: prevalence, risk factors, and health care seeking. Am J Gastroenterol 1998; 93: 2179–2183.[CrossRef][Web of Science][Medline]

⁴⁴ Sladden MJ, Thomson AN, Lombard CJ. Rectal bleeding in general practice patients. Aust Fam Physician 1999; 28: 750–754.[Medline]

⁴⁵ Fijten G, Muris J, Starmans R, Knottnerus JA, Blijham G, Krebber TF. The incidence and outcome of rectal bleeding in general practice. Fam Pract 1993; 10: 283–287.[Abstract/Free Full Text]

⁴⁶ Jones IS. An analysis of bowel habit and its significance in the diagnosis of carcinoma of the colon. Am J Proctol 1976; 27: 45–56.[Medline]

⁴⁷ Macadam DB. A study in general practice of the symptoms and delay patterns in the diagnosis of gastrointestinal cancer. J R Coll Gen Pract 1979; 29: 723–729.[Medline]

⁴⁸ Bain NS, Campbell NC, Ritchie LD, Cassidy J. Striking the right balance in colorectal cancer care—a qualitative study of rural and urban patients. Fam Pract 2002; 19: 369–374.[Abstract/Free Full Text]

⁴⁹ Summerton N, Rigby A, Mann S, Summerton A. The general practitioner–patient consultation pattern as a tool for cancer diagnosis in general practice. Br J Gen Pract 2003; 53: 50–52.[Web of Science][Medline]

⁵⁰ Dent OF, Goulston KJ, Tennant CC et al. Rectal bleeding. Patient delay in presentation. Dis Colon Rectum 1990; 33: 851–857.[CrossRef][Web of Science][Medline]

⁵¹ Selvachandran S, Hodder R, Ballal M, Jones P, Cade D. Prediction of colorectal cancer by a patient consultation questionnaire and scoring system: a prospective study. Lancet 2002; 360: 278–283.[CrossRef][Web of Science][Medline]

⁵² Young CJ, Sweeney JL, Hunter A. Implications of delayed diagnosis in colorectal cancer. Aust NZ J Surg 2000; 70: 635–638.[CrossRef][Web of Science][Medline]

⁵³ MacArthur C, Smith A. Factors associated with speed of diagnosis, referral, and treatment in colorectal cancer. J Epidemiol Community Health 1984; 38: 122–126.[Abstract/Free Full Text]

⁵⁴ Rizk SN, Ryan JJ. Clinicopathologic review of 92 cases of colon cancer. S Dakota J Med 1994; 47: 89–93.[Medline]

⁵⁵ Fijten G, Blijham G, Knottnerus JA. Occurrence and clinical significance of overt blood loss per rectum in the general population and in medical practice. Br J Gen Pract 1994; 44: 320–325.[Web of Science][Medline]

⁵⁶ Wauters H, Van Casteren V, Buntinx F. Rectal bleeding and colorectal cancer in general practice: diagnostic study. Br Med J 2000; 321: 998–999.[Free Full Text]

⁵⁷ Sladden MJ, Thomson AN. How do general practitioners manage rectal bleeding? Aust Fam Physician 1998; 27: 78–82.[Medline]

⁵⁸ Norrelund N, Norrelund H. Colorectal cancer and polyps in patients aged 40 years and over who consult a GP with rectal bleeding. Fam Pract 1996; 13: 160–165.[Abstract/Free Full Text]

⁵⁹ Siles S, Garrigues V, Ponce J, Galvez C, Berenguer J. Analysis of the predictive value of clinical data in patients with suspected colonic disease. Rev Esp Enferm Dig 1997; 89: 445–456.[Medline]

⁶⁰ Nakama H, Kayano T, Katsuura T et al. Comparison of predictive value for colorectal cancer in subjects with and without rectal bleeding. Hepato-Gastroenterology 1999; 46: 1730–1732.[Medline]

⁶¹ Kewenter J, Haglind E, Smith L. Value of a risk questionnaire in screening for colorectal neoplasm. Br J Surg 1989; 76: 280–283.[Web of Science][Medline]

⁶² Fijten G, Starmans R, Muris J, Schouten H, Blijham G, Knottnerus JA. Predictive value of signs and symptoms for colorectal cancer in patients with rectal bleeding in general practice. Fam Pract 1995; 12: 279–286.[Abstract/Free Full Text]

⁶³ Curless R, French JM, Williams GV, James OF. Colorectal carcinoma: do elderly patients present differently? Age Ageing 1994; 23: 102–107.[Abstract/Free Full Text]

⁶⁴ Bat L, Pines A, Shemesh E et al. Colonoscopy in patients aged 80 years or older and its contribution to the evaluation of rectal bleeding. Postgrad Med J 1992; 68: 355–358.[Abstract/Free Full Text]

⁶⁵ Gillen C, Walmsley R, Prior P, Andrews H, Allan R. Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut 1994; 35: 1590–1592.[Abstract/Free Full Text]

⁶⁶ Choi P, Zelig M. Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention. Gut 1994; 35: 950–954.[Abstract/Free Full Text]

⁶⁷ Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001; 48: 526–535.[Abstract/Free Full Text]

⁶⁸ Delco F, Sonnenberg A. A decision analysis of surveillance for colorectal cancer in ulcerative colitis. Gut 2000; 46: 500–506.[Abstract/Free Full Text]

⁶⁹ Neugut AI, GC G. Diagnostic yield of colorectal neoplasia with colonoscopy for abdominal pain, change in bowel habits and rectal bleeding. Am J Gastroenterol 1993; 88: 1179–1183.[Web of Science][Medline]

⁷⁰ Dent OF, Goulston KJ, Zubrzycki J, Chapuis PH. Bowel symptoms in an apparently well population. Dis Colon Rectum 1986; 29: 243–247.[Web of Science][Medline]

⁷¹ Goulston K, Chapuis P, Dent O, Bokey L. Significance of bowel symptoms. Med J Aust 1987; 146: 631–633.[Web of Science][Medline]

⁷² Carlsson L, Hakansson A, Nordenskjold B. Common cancer-related symptoms among GP patients. Opportunistic screening in primary health care. Scand J Primary Health Care Suppl 2001; 19: 199–203.[CrossRef]

⁷³ Roncoroni L, Pietra N, Violi V, Sarli L, Choua O, Peracchia A. Delay in the diagnosis and outcome of colorectal cancer: a prospective study. Eur J Surg Oncol 1999; 25: 173–178.[CrossRef][Web of Science][Medline]

⁷⁴ Stubbs RS, Long MG. Symptom duration and pathologic staging of colorectal cancer. Eur J Surg Oncol 1986; 12: 127–130.[Web of Science][Medline]

⁷⁵ Khubchandani M. Relationship of symptom duration and survival in patients with carcinoma of the colon and rectum. Dis Colon Rectum 1985; 28: 585–587.[Web of Science][Medline]

⁷⁶ Barillari P, de Angelis R, Valabrega S et al. Relationship of symptom duration and survival in patients with colorectal carcinoma. Eur J Surg Oncol 1989; 15: 441–445.[Web of Science][Medline]

⁷⁷ Dunne JR, Gannon CJ, Osborn TM, Taylor MD, Malone DL, Napolitano LM. Preoperative anemia in colon cancer: assessment of risk factors. Am Surg 2002; 68: 582–587.[Web of Science][Medline]

⁷⁸ Muris JW, Starmans R, Wolfs GG, Pop P, Knottnerus JA. The diagnostic value of rectal examination. Fam Pract 1993; 10: 34–37.[Abstract/Free Full Text]

⁷⁹ Goodman D, Irvin TT. Delay in the diagnosis and prognosis of carcinoma of the right colon. Br J Surg 1993; 80: 1327–1329.[Web of Science][Medline]

⁸⁰ Sandler RS, Stewart WF, Liberman JN, Ricci JA, Zorich NL. Abdominal pain, bloating, and diarrhea in the United States: prevalence and impact. Dig Dis Sci 2000; 45: 1166–1171.[CrossRef][Web of Science][Medline]

⁸¹ Talley NJ, O'Keefe EA, Zinsmeister AR, Melton LJ, 3rd. Prevalence of gastrointestinal symptoms in the elderly: a population-based study. Gastroenterology 1992; 102: 895–901.[Web of Science][Medline]

⁸² Jones R, Lydeard S. Irritable bowel syndrome in the general population. Br Med J 1992; 304: 87–90.[Abstract/Free Full Text]

⁸³ Kay L, Jorgensen T, Jensen KH. Epidemiology of abdominal symptoms in a random population: prevalence, incidence, and natural history. Eur J Epidemiol 1994; 10: 559–566.[CrossRef][Web of Science][Medline]

⁸⁴ Agreus L, Svardsudd K, Nyren O, Tibblin G. The epidemiology of abdominal symptoms: prevalence and demographic characteristics in a Swedish adult population. A report from the Abdominal Symptom Study. Scand J Gastroenterol 1994; 29: 102–109.[Web of Science][Medline]

⁸⁵ Kay L, Jorgensen T, Schultz-Larsen K. Abdominal pain in a 70-year-old Danish population. An epidemiological study of the prevalence and importance of abdominal pain. J Clin Epidemiol 1992; 45: 1377–1382.[CrossRef][Web of Science][Medline]

⁸⁶ Kay L. Abdominal symptoms, visits to the doctor, and medicine consumption among the elderly. A population based study. Dan Med Bull 1994; 41: 466–469.[Web of Science][Medline]

⁸⁷ Adelman A. Abdominal pain in the primary care setting. J Fam Pract 1987; 25: 27–32.[Web of Science][Medline]

⁸⁸ Muris JW, Starmans R, Fijten GH, Knottnerus JA. One-year prognosis of abdominal complaints in general practice: a prospective study of patients in whom no organic cause is found. Br J Gen Pract 1996; 46: 715–719.[Web of Science][Medline]

⁸⁹ Muris JW, Starmans R, Fijten GH, Crebolder HF, Schouten HJ, Knottnerus JA. Non-acute abdominal complaints in general practice: diagnostic value of signs and symptoms. Br J Gen Pract 1995; 45: 313–316.[Web of Science][Medline]

⁹⁰ Lieberman DA, de Garmo PL, Fleischer DE, Eisen GM, Chan BK, Helfand M. Colonic neoplasia in patients with nonspecific GI symptoms. Gastrointest Endosc 2000; 51: 647–651.[CrossRef][Web of Science][Medline]

⁹¹ Bellentani S, Baldoni P, Petrella S et al. A simple score for the identification of patients at high risk of organic diseases of the colon in the family doctor consulting room. The Local IBS Study Group. Fam Pract 1990; 7: 307–312.[Abstract/Free Full Text]

⁹² Dunlop M. Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, juvenile polyposis and Peutz–Jeghers syndrome. Gut 2002; 51 (Suppl V): v21–v27.[Free Full Text]

⁹³ Lichtenstein P, Holm NV, Verkasalo PK et al. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000; 343: 78–85.[Abstract/Free Full Text]

⁹⁴ Dunlop M. Guidance on large bowel surveillance for people with two first degree relatives with colorectal cancer or one first degree relative diagnosed with colorectal cancer under 45 years. Gut 2002; 51 (Suppl V): v17–v20.[Free Full Text]

⁹⁵ House W, Sharp D, Sheridan E. Identifying and screening patients at high risk of colorectal cancer in general practice. J Med Screening 1999; 6: 205–208.[Abstract/Free Full Text]

⁹⁶ Mansson J, Marklun B, Hultborn R. The diagnosis of cancer in the ‘roar’ of potential cancer symptoms of patients in primary health care. Research by means of the computerised journal. Scand J Primary Health Care Suppl 2001; 19: 83–89.[CrossRef]

⁹⁷ Green LA, Fryer GE Jr, Yawn BP, Lanier D, Dovey SM. The ecology of medical care revisited. N Engl J Med 2001; 344: 2021–2025.[Free Full Text]

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