Lynch syndrome screening in colorectal cancer: results of a prospective 2-year regional programme validating the NICE diagnostics guidance pathway throughout a 5.2-million population.

AIMS: Screening all patients newly diagnosed with colorectal cancer (CRC) for possible Lynch syndrome (LS) has been recommended in the United Kingdom since the National Institute for Health and Care Excellence (NICE) released new diagnostics guidance in February 2017. We sought to validate the NICE screening pathway through a prospective regional programme throughout a 5.2-million population during a 2-year period. METHODS AND RESULTS: Pathology departments at 14 hospital trusts in the Yorkshire and Humber region of the United Kingdom were invited to refer material from patients with newly diagnosed CRC aged 50 years or over between 1 April 2017 and 31 March 2019 for LS screening. Testing consisted of immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 followed by BRAF mutation analysis ± MLH1 promoter methylation testing in cases showing MLH1 loss. A total of 3141 individual specimens were submitted for testing from 12 departments consisting of 3061 unique tumours and 2791 prospectively acquired patients with CRC. Defective mismatch repair (dMMR) was observed in 15% of cases. In cases showing MLH1 loss, 76% contained a detectable BRAF mutation and, of the remainder, 77% showed MLH1 promoter hypermethylation. Of the patients included in the final analysis, 81 (2.9%) had an indication for germline testing. CONCLUSION: LS screening using the NICE diagnostics guidance pathway is deliverable at scale identifying significant numbers of patients with dMMR. This information is used to refer patients to regional clinical genetics services in addition to informing treatment pathways including the use of adjuvant/neoadjuvant chemotherapy and immunotherapy.

Addressing the variation in adjuvant chemotherapy treatment for colorectal cancer: Can a regional intervention promote national change?

Analysis of routine population-based data has previously shown that patterns of surgical treatment for colorectal cancer can vary widely, but there is limited evidence available to determine if such variation is also seen in the use of chemotherapy. This study quantified variation in adjuvant chemotherapy across both England using cancer registry data and in more detail across the representative Yorkshire and Humber regions. Individuals with Stages II and III colorectal cancer who underwent major resection from 2014 to 2015 were identified. Rates of chemotherapy were calculated from the Systemic Anticancer Treatment database using multilevel logistic regression. Additionally, questionnaires addressing different clinical scenarios were sent to regional oncologists to investigate the treatment preferences of clinicians. The national adjusted chemotherapy treatment rate ranged from 2% to 46% (Stage II cancers), 19% to 81% (Stage III cancers), 24% to 75% (patients aged <70 years) and 5% to 46% (patients aged ≥70 years). Regionally, the rates of treatment and the proportions of treated patients receiving combination chemotherapy varied by stage (Stage II 4%-26% and 0%-55%, Stage III 48%-71% and 40%-84%) and by age (<70 years 35%-68% and 49%-91%; ≥70 years 15%-39% and 6%-75%). Questionnaire responses showed significant variations in opinions for high-risk Stage II patients with both deficient and proficient mismatch repair tumours and Stage IIIB patients aged ≥70 years. Following a review of the evidence, open discussion in our region has enabled a consensus agreement on an algorithm for colorectal cancer that is intended to reduce variation in practice.

Regional multidisciplinary team intervention programme to improve colorectal cancer outcomes: study protocol for the Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR BCIP).

INTRODUCTION: Although colorectal cancer outcomes in England are improving, they remain poorer than many comparable countries. Yorkshire Cancer Research has, therefore, established a Bowel Cancer Improvement Programme (YCR BCIP) to improve colorectal cancer outcomes within Yorkshire and Humber, a region representative of the nation. It aims to do this by quantifying variation in practice, engaging with the colorectal multidisciplinary teams (MDTs) to understand this and developing educational interventions to minimise it and improve outcomes. METHODS AND ANALYSIS: Initially, routine health datasets will be used to quantify variation in the demographics, management and outcomes of patients across the Yorkshire and Humber region and results presented to MDTs. The YCR BCIP is seeking to supplement these existing data with patient-reported health-related quality of life information (patient-reported outcome measures, PROMs) and tissue sample analysis. Specialty groups (surgery, radiology, pathology, clinical oncology, medical oncology, clinical nurse specialists and anaesthetics) have been established to provide oversight and direction for their clinical area within the programme, to review data and analysis and to develop appropriate educational initiatives. ETHICS AND DISSEMINATION: The YCR BCIP is aiming to address the variation in practice to significantly improve colorectal cancer outcomes across the Yorkshire and Humber region. PROMs and tissue sample collection and analysis will help to capture the information required to fully assess care in the region. Engagement of the region's MDTs with their data will lead to a range of educational initiatives, studies and clinical audits that aim to optimise practice across the region.