Background
Methods
Search strategy
Study selection
Data extraction and synthesis
Quality assessment
Results
Included studies
Author, date, country, setting | Qualityf
| Outcome | Data collection | Selection of variables | Identification of study population | Identification of outcome cases | Exclusions | Study population | ||
---|---|---|---|---|---|---|---|---|---|---|
Model development; Case-control studies | ||||||||||
Cases | Controls | Cases | Controls | |||||||
ᅟHamilton, 2005, UK, primary care [22] | M | CRC | Primary care records from 21 practices | Occurring in at least 2.5 % of cases or controls | >40 years with primary CRC | 5 controls per case matched for sex, general practice and age and alive at point of case diagnosis | Cancer registry at one hospital | Unobtainable records, no consultations in 2 years before diagnosis, previous CRC, residence outside Exeter at time of diagnosis. | 349 | 1,744 |
ᅟHamilton, 2009, UK, primary care [23] | M | CRC | THIN database | Literature review | > 30 years with CRC | Up to 7 controls without CRC matched for practice, sex and age | Diagnosis of CRC within study period | < 2 years of full electronic records before date of case diagnosis. | 5,477 | 38,314 |
Model development and external validation; Case-control study | ||||||||||
Cases | Controls | Cases | Controls | |||||||
ᅟMarshall, 2011, UK, primary care [24] | H | CRC | BB equation development and CAPER Score external validation | |||||||
See Hamilton, 2009 [23] | As in Hamilton, 2009 plus patients with severe anaemia (Hb < 10 g/dl), rectal bleeding, abnormal rectal examination or positive FOBT, or without any of abdominal pain, weight loss, diarrhoea or constipation | 117 | 433 | |||||||
CRC | CAPER Score development and BB equation external validation | |||||||||
See Hamilton, 2005 [22] | ||||||||||
Model development and random split-sample internal validation; Cohort studies | ||||||||||
Included | Cases (% of included) | |||||||||
ᅟHippisley-Cox, 2012, UK, primary care ᅟ(QCancer® (colon)) [25] | H | CRC | QResearch database | 'Established predictor variables' and red flag symptoms | 30–84 year-old patients registered with practices between 1/1/2000 and 30/09/2010 and without CRC | Incident cancer diagnosis in the 2 years after cohort entry recorded in GP records or ONS cause-of-death record | History of CRC, recorded red flag symptomf in the 12 months preceding the study date, or missing Townsend deprivation score. | Development | ||
F: 1,172,670 | F:4,798 (0.2 %) | |||||||||
M:1,178,382 | M:4,798 (0.2 %) | |||||||||
Internal validation | ||||||||||
F: 616,361 | F: 2603 (0.2 %) | |||||||||
M: 620,240 | M:2603 (0.2 %) | |||||||||
ᅟHippisley-Cox, 2013 (female), UK, primary care ᅟ(QCancer® (combined)) [26] | H | CRC and 11 other cancersa
| QResearch database | Previous study, and literature review | 25–89 year-old patients registered with practices between 1/1/2000 and 1/04/2012 and without CRC | Incident cancer diagnosis in the 2 years after cohort entry recorded in GP records or ONS cause-of-death record | Recorded red flag symptomf in the 12 months before the study entry date, or missing Townsend deprivation score. | Development | ||
1,240,864 | 2607 (0.18 %) | |||||||||
Internal validation | ||||||||||
679,174 | 1725 (0.25 %) | |||||||||
ᅟHippisley-Cox, 2013 (male), UK, primary care ᅟ(QCancer® (combined)) [27] | H | CRC and 9 other cancersb
| QResearch database | Previous study, and literature review | 25–89 year-old patients registered with practices between 1/1/2000 and 1/04/2012 and without CRC | Incident cancer diagnosis in the 2 years after cohort entry recorded in GP records or ONS cause-of-death record | Recorded red flag symptomf in the 12 months before the study entry date, or missing Townsend deprivation score. | Development | ||
1,263,071 | 3250 (0.26 %) | |||||||||
Internal validation | ||||||||||
667,603 | 1356 (0.2 %) | |||||||||
Model development; Cross-sectional studies | ||||||||||
Included | Cases (% of included) | |||||||||
ᅟAdelstein, 2010, Australia, secondary care [32] | H | CRC | Self-administered questionnaire | Not reported | Patients > 18 years old scheduled for colonoscopy at hospitals | Complete colonoscopy and histology | Completion of questionnaire > 6 months before colonoscopy, advanced adenomac, incomplete colon evaluation | 7,736 | 159 (2.1 %) | |
ᅟAdelstein, 2011, Australia, secondary care [31] | H | CRC | See Adelstein 2010 [32] | Completion of questionnaire > 6 months before colonoscopy, adenomad, incomplete colon evaluation | 6943 | 159 (2.3 %) | ||||
ᅟFijten, 1995, Netherlands, primary care [21] | L | CRC | Patient and doctor questionnaires, and blood sample | Literature review | Patients presenting to 83 GP practices with overt rectal bleeding or a history of visible rectal blood loss in previous 3 months. | Medical record review coded using the International Classification of Primary Care for diagnostic classification | Patients aged <18 or >75, pregnancy, urgent admission to hospital or follow-up not available. | 290 | 9 (3.4 %) | |
ᅟHurst, 2007, UK, secondary care [28] | M | CRC or pre-malignant adenomas | Proforma-based history, examination and blood sample | Not reported | All adult patients referred to a specialist colorectal clinic | Patients tracked until a definitive diagnosis was reached | Patients not further investigated after initial consultation or who did not attend follow up | 300 | 95 (31.7 %) | |
ᅟLam, 2002, Hong Kong, secondary care [20] | L | CRC or significant neoplasiae
| Questionnaire conducted by non-medically trained interviewers | Not reported | New patients attending surgical department for rectal bleeding | Rigid sigmoidoscopy and proctoscopy, followed by barium enema or colonoscopy at the physician's discretion | Refusal for colonoscopy or barium enema | 174 | 29 (16.7 %) | |
ᅟMahadavan, 2011, UK, secondary care [29] | M | CRC | Self-administered questionnaire, history, faecal, blood and rectal samples | Not reported | All patients >40 years referred to a surgical clinic via the 2wwg system for colorectal cancer | Incident diagnosis of CRC within 6 months of study entry from primary care or hospital records confirmed histologically | Previous confirmed IBD, GI cancer, investigation of the bowel within the last 6 months or absent rectal sampling result | 714 | 72 (10.1 %) | |
Model development and external validation; Cross-sectional study | ||||||||||
Included | Cases (% of included) | |||||||||
ᅟSelvachandran, 2002, UK, secondary care (WNS) [30] h
| H | CRC | Self-administered questionnaire | Not reported | Patients referred by GPs with symptoms suggestive of distal colonic or anorectal disease | Not reported (all patient's received endoscopy) | Not reported | 2,268 | 95 (4.2 %) | |
Model external validation; Cohort study | ||||||||||
Model(s) validated | Included | Cases (% of included) | ||||||||
ᅟCollins, 2012, UK, primary care [33] | H | QCancer® (colon) (female and male) [25] | THIN database | N/A | 30–84 year-old patients registered with practices between 1/1/2000 and 30/09/2010 and without CRC | Incident cancer diagnosis of CRC in the 2 years after cohort entry | Patients with a history of CRC, a recorded red flag symptomf in the 12 months preceding the study date, registered <12 months with practice or with invalid dates | Female: 1,075,775 | Female:1,676 (0.15 %) | |
Male: 1,059,765 | Male: 2,036 (0.19 %) | |||||||||
Model external validation; Cross-sectional studies | ||||||||||
Model(s) Validated | Included (% of eligible) | Cases (% of included) | ||||||||
ᅟBallal, 2009, UK, secondary care [35] | H | WNS [30] | Self-administered questionnaire | N/A | Patients with colorectal symptoms referred by GPs | A combination of rigid sigmoidoscopy, flexible sigmoidoscopy, colonoscopy or barium enema | Patients thought (on the basis of the referral) most likely to have right-sided CRC, or but did not attend for investigation | 3,457 | 186 (5.4 %) | |
ᅟHodder, 2005, UK, secondary care [34] | H | Self-administered questionnaire | N/A | Patients referred from primary care with colorectal symptoms | Secondary care investigations - minimum flexible sigmoidoscopy | Not reported | 3,302 | 156 (4.7 %) | ||
ᅟRai, 2008, UK, secondary care [11] | H | WNS [30] | Self-administered questionnaire | N/A | GP referral with any of: lower bowel-related symptoms, unexplained iron deficiency anaemia, positive FOBT, or palpable rectal/abdominal mass | Follow up during course of hospital investigations until a final diagnosis made | Patients admitted hospital as an emergency and subsequently diagnosed with CRC | 1,422 | 83 (5.84 %) | |
Model utility; cohort study | ||||||||||
Model used | Outcome measures | Included | Interviews | |||||||
ᅟHamilton, 2013, UK, primary care [19] | L | Hamilton 2005 [22] | GP usage and outcomes from practices and local trusts; qualitative interviews | Not reported | Risk assessment tools (RATs) supplied to 614 GPs at 164 practices for 6 months; interviews with GP cancer network leads and sample of GP users from practices with differing patient demographics. | Number of 2WW referrals and colonoscopies for patients >40; symptoms used in RATs; qualitative interview data. | RATs performed on patients <40; RATs that did not identify the reported symptoms. | 1433 | 23 GP responders |
Risk model development and validation
Variables included in the risk models
Author, year | TRIPOD levela
| Demographic variables | Personal and Family Medical History | Symptoms | Signs | Investigations | |||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Age | Sex | Smoking | Alcohol | Other | Family history of GI cancer | Other | Rectal bleeding | Change in bowel habit | Diarrhoea | Constipation | Abdominal pain | Weight loss | Loss of appetite | Mucous | Other | Abnor mal rectal examination | Other | Haemoglobinb
| MCV | FOBT | Other | ||
Models predicting gastrointestinal cancers and neoplasms | |||||||||||||||||||||||
Adelstein, 2010 [32] | 1b | ● | ● | Colonoscopy in last 10 years; history of diverticular disease, NSAID use, or aspirin use. | ● | ● | ● | Anaemiab. | |||||||||||||||
Adelstein, 2011 [31] | 1a | ● | ● | ● | Education level. | Colonoscopy in last 10 years; history of colorectal polyps, IBS, NSAID use or aspirin use. | ● | ● | Anaemiab; fatigue. | ||||||||||||||
Fijten, 1995 [21] | 1a, 4 | ● | ●d
| ● | |||||||||||||||||||
Hamilton, 2005 [22] | 1a | ● | ● | ● | ● | ● | Abdominal tenderness | ● | ● | Blood glucose | |||||||||||||
Hamilton, 2009 [23] | 1a | ● | ● | ● | ● | ● | ● | ● | ● | ||||||||||||||
Hippisley-Cox, 2012 (Male) [25] | 2a, 4 | ● | N/A | ● | ● | ● | ● | ● | ● | ● | ● | ||||||||||||
Hippisley-Cox, 2012 (Female) [25] | 2a, 4 | ● | N/A | ● | ● | ● | ● | ● | ● | ||||||||||||||
Hurst, 2007 [28] | 1a | ● | ● | ● | ● | ● | sMMP-9 | ||||||||||||||||
Lam, 2002 [20] | 1a | ● | ●e
| ● | |||||||||||||||||||
Mahadavan, 2011 [29] | 1a | ● | ● | ● | ● | ● | eDNA; CEA | ||||||||||||||||
Marshall, 2011 (BB equation) [24] | 3 | ● | ● | ●f
| ●f
| ●f
| ● | ● | Abdominal mass | ● | ● | ● | |||||||||||
Marshall, 2011 (CAPER score) [24] | 4 | ● | ● | ● | ● | ● | Abdominal mass | ● | |||||||||||||||
Selvachandran, 2002 (WNS) [30] c
| 4, 4, 4, 4 | ● | ● | ‘Family history’, ‘relevant medical history’. | ● | ● | ● | ● | Tenesmus; urgency; incomplete emptying; perianal symptoms; ‘abdominal symptoms’; tiredness. | ||||||||||||||
Models predicting cancers of multiple organ systems alongside colorectal cancer | |||||||||||||||||||||||
Hippisley-Cox, 2013 (Male) [27] | 2a | ● | N/A | ● | ● | BMI; Townsend deprivation score. | ● | History of chronic pancreatitis, type 2 diabetes, or COPD; family history of prostate cancer. | ● | ● | ● | ● | ● | ● | Abdominal distension; heartburn; indigestion; dysphagia, haematemesis; haematuria; haemoptysis; neck lump; Night sweats; testicular lump; testicular pain; first occurrence of a venous thromboembolism; bruising; cough; impotence; nocturia; urinary frequency; urinary retention. | ● | |||||||
Hippisley-Cox, 2013 (Female) [26] | 2a | ● | N/A | ● | ● | BMI; Townsend deprivation score. | ● | History of chronic pancreatitis, type 2 diabetes, COPD, or endometrial hyperplasia/polyps; family history of breast cancer or ovarian cancer. | ● | ● | ● | ● | ● | ● | Abdominal distension; heartburn; indigestion; dysphagia; haematemesis; rectal bleeding; haematuria; haemoptysis; neck lump; weight loss; night sweats; breast lump; breast pain; nipple discharge or breast skin changes; inter-menstrual bleeding; post-menopausal bleeding; post-coital bleeding; first occurrence of a venous thromboembolism; bruising; cough. | ● |