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: : Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; : Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; : Pressing need for prevention trials; : Lack of integration of different prevention approaches; : Lack of optimal strategies for CRC screening; : Lack of effective triage systems for invasive investigations; : Imprecise pathological assessment of CRC; : Lack of qualified personnel in genomics, data sciences and digital pathology; : Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; : Need for novel technologies/interventions to improve curative outcomes; : Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; : Lack of reliable biomarkers to guide stage IV treatment; : Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; : Lack of coordination of CRC research/funding; : 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.