Impact case study database

Gastrointestinal clinical cancer research designed, led and delivered by University of Southampton researchers has, since 2014, directly included over 14,000 people and changed practice in multiple domains, resulting in better patient outcomes and estimated world-wide cost savings of approximately GBP2,000,000,000 per year.

Colorectal cancer

In colorectal cancer, a disease that affects 1.4 million people a year globally, Southampton researchers have performed the definitive studies in treatment and follow-up after surgery. The FACS trial has set the standard on the follow up of patients with resected colorectal cancer and has informed all guidance on colorectal cancer follow up globally since the results were published in 2014, including NICE Guidance NG151 [ 5.1]. This recommends the follow-up protocol tested in the FACS trial: “For people who have had potentially curative surgical treatment for non-metastatic colorectal cancer, offer follow-up for detection of local recurrence and distant metastases for the first 3 years. Follow-up should include serum CEA and CT scan of the chest, abdomen and pelvis”. In a 2018 analysis of 21 national guidelines from countries represented in the European Society of Coloproctology [ 5.2], the guidelines committee recognised the singular importance of the FACS trial findings as underpinning follow up protocols including CEA testing and CT scans. Adherence to these protocols has been subject to published nation-level audits in countries including the Netherlands, where guidance is based specifically on FACS, and Norway which is proposing reducing intensity of guideline. The lower intensities of follow up have equal efficacy in detecting recurrence and have identical overall survival. A 2017 economic analysis [ 5.3] suggests a saving of around GBP2,000 per patient suitable for reduced surveillance (20,000 annually) resulting in around GBP40,000,000 per year saving in the UK alone, mainly by reducing the number of CTs. Globally around a million patients will suffer colorectal cancer requiring follow-up, and hence very substantial global savings could be expected depending on local practices.

Chemotherapy following potentially curative surgery has been shown to improve survival in many cases of colorectal cancer, but at the cost of significant toxicity. The toxicity relates to duration of chemotherapy but until now the duration to achieve efficacy was unknown. In combination the MRC SCOT and the IDEA Collaboration studies included over 13,000 people with stage III colorectal cancer from around the world. Results were immediately incorporated into national and international guidelines 2018-2019 [ 5.4, 5.5]. NICE Guidance NG151 (2020) [ 5.1], makes recommendations based directly on the SCOT study findings: “Halving the standard care from six months to three months (for people who can have CAPOX) will reduce treatment time and costs, meaning people have chemotherapy side effects for a shorter time, and will lower the incidence of long-term toxicity (neuropathy) and its consequences”. Analysis undertaken in 2020 of these findings [ 5.6] concluded that the survival difference between three and six months was minimal, especially if CAPOX is used, but the toxicity markedly reduced with three months treatment. An economic analysis of SCOT [ 5.7] suggests a saving of GBP4,881 which, applied globally to 700,000 stage 3 patients annually (based on a conservative estimate of 50% of patients receiving post-operative chemotherapy) results in a saving of approximately GBP1,700,000,000 per year.

There are around 3,200 patients annually in the UK with operable colorectal liver metastases. These patients were commonly treated with neoadjuvant chemotherapy to treat micro-metastatic disease, and increasingly with an anti-epidermal growth factor receptor antibody, cetuximab. The New EPOC study demonstrated the harm in the use of cetuximab in patients with operable colorectal liver metastases, resulting in a two-year reduction in median overall survival and a 15% reduction in survival at five years. As this schedule was commonly used, changing practice has had major impact on the survival of patients in this cohort globally. The 2016 guidelines of the European Society of Medical Oncology (ESMO) [ 5.8] makes the change in practice clear, stating: “EGFR-targeting monoclonal antibodies (cetuximab and panitumumab) are not to be used in this setting, based on the data from the New EPOC trial”. This is further supported by a 2020 Lancet editorial [ 5.9]. Based on UK rates of operable colorectal liver metastases, 240 lives are saved every year by not using cetuximab. This increases into the thousands when applied globally.

Biliary Tract cancer

The BILCAP trial showed that adjuvant capecitabine following surgery for biliary tract cancer improved median overall survival by 16% with no measurable reduction in quality of life. Treatment was well tolerated. The result of the study was published in 2019 [ 5.10] and immediately incorporated into standard of care in EUROPE and the USA; American Society of Clinical Oncology (ASCO) guidelines were also produced as a result of the trial outcome [ 5.11]. Based on a conservative estimate of 500,000 annual biliary tract cancer cases globally, implementation of this process around the world could result in a saving more than 4,000 lives every year in a disease with large unmet need and no major Pharma interest. A heath economic assessment suggested treatment was also highly cost effective at GBP2,725 per Quality Adjusted Life Year (QALY) [ 5.10].

Minimally invasive surgery

Minimally invasive surgery (MIS) is developing rapidly in surgery of the liver and pancreas but this is technology-driven with little evidence of patient benefit. Primrose and colleagues have led efforts in the UK to develop an evidence base and standards of training and care in this area. The group have led three randomised trials, one completed (ORANGE 2), and two ongoing (ORANGE SEGMENTS and DIPLOMA). The University of Southampton (Primrose, Cook and colleagues) organised two global consensus conferences in MIS in liver (Southampton) and pancreas (Miami), which were attended by approximately 100 leading cancer experts. Guidelines have been developed from the events and set global standards for safe practice and training in these areas [ 5.12, 5.13]. The recommendation for more research in MIS is included in the 2018 NICE guidance NG85 on pancreas cancer, which was chaired by Primrose [ 5.14].