Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes. DESIGN: RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants. RESULTS: Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders. CONCLUSION: Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years.

Clinical features of bowel disease in patients aged <50 years in primary care: a large case-control study.

BACKGROUND: Incidences of colorectal cancer (CRC) and inflammatory bowel disease (IBD) are increasing in those aged <50 years. AIM: To identify and quantify clinical features in primary care of CRC/IBD in those aged <50 years. This study considered the two conditions together and aimed to determine which younger patients, presenting in primary care with symptoms, would benefit from investigation for potentially serious colorectal disease. DESIGN AND SETTING: Matched case-control study using primary care records from the Clinical Practice Research Datalink, UK. METHOD: Incident cases (aged <50 years) of CRC (n = 1661) and IBD (n = 9578) diagnosed between 2000 and 2013 were each matched with up to three controls (n = 3979 CRC; n = 22 947 IBD). Odds ratios (OR) and positive predictive values (PPV) were estimated for features of CRC/IBD in the year before diagnosis. RESULTS: Ten features were independently associated with CRC/IBD (all P<0.001): rectal bleeding, change in bowel habit, diarrhoea, raised inflammatory markers, thrombocytosis, abdominal pain, low mean cell volume (MCV), low haemoglobin, raised white cell count, and raised hepatic enzymes. PPVs were >3% for rectal bleeding with diarrhoea, thrombocytosis, low MCV, low haemoglobin or raised inflammatory markers; for change in bowel habit with low MCV, thrombocytosis or low haemoglobin; and for diarrhoea with thrombocytosis. CONCLUSION: This study quantified the risk of serious bowel disease in symptomatic patients aged <50 years in primary care. Rectal bleeding and change in bowel habit are strongly predictive of CRC/IBD when combined with abnormal haematology. The present findings help prioritise patients for colonoscopy where the diagnosis is not immediately apparent.