MR1257: CReST Trial (Role of Endoluminal Stenting in the acute management of obstructing colorectal cancer) Extension Request for Patient Tracking Service

The Birmingham Clinical trial Unit (BCTU) at University of Birmingham (UoB) are requesting an extension of their current agreement, for the purposes of archiving only, no further processing will be performed on the archived data. This extension will allow (UoB) to hold the current data until 16/12/2025.

The Birmingham Clinical Trials Unit (BCTU) at University of Birmingham (UoB) requires to continue to hold identifiable data relating to the date and cause of death, including the incidence and the outcome of any cancers, of any participants who consented to participate in the full ‘ColoRectal Stenting Trial’ (CReST - Role of endoluminal stenting in the acute management of obstructing colorectal cancer trial). This data was disseminated to BCTU under the previous version of this agreement.

UoB are the sole Data Controller who also process data for the CReST trial.

The legal basis for processing the data BCTU have collected for the CReST study is that it is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller which under the principles of GDPR is Article 6(1)(e), also as it involves health data, Article 9(2)(j) is also applicable, as this details that processing is necessary for scientific and research purposes, subject to appropriate safeguards.

CReST was a large, pragmatic, phase III multi-centre randomized controlled trial (RCT) aiming to establish if endoluminal stenting, rather than emergency surgery, for patients admitted acutely with large bowel obstruction (LBO) can reduce perioperative morbidity (as assessed by length of hospital stay) and reduce 30-day mortality.

Colorectal cancer is the second most common malignant disease in developed countries, with about a million new cases and 500,000 deaths worldwide each year. Up to 30% of colorectal cancers present as an emergency with large bowel obstruction. Emergency surgery for obstructing colorectal cancer is associated with high morbidity and mortality, prolonged hospital stay and a high frequency of stoma formation, compromising the patient's quality of life. Patients treated in the emergency setting are also compromised in their subsequent care, notably because they are frequently unable to tolerate adjuvant chemotherapy.

The current standard treatment of emergency surgery is associated with high surgical morbidity and mortality. The morbidity and mortality rates have been quoted as up to 40% after emergency surgery for obstructing colorectal lesions. Stenting of large bowel obstructions provides the potential to avoid emergency surgery, allow full assessment and preparation of the patient for surgery, with the potential to reduce operative morbidity and improve quality of life and survival. However, stenting can sometimes perforate the bowel wall and may increase the risk of tumour dissemination. The balance of benefits and risks has not yet been reliably assessed. CReST (ColoRectal Stenting Trial) was a randomised controlled trial to investigate whether endoluminal colonic stenting for obstructing colorectal cancer will result in reduced operative morbidity, reduced length of hospital stay, a reduced rate of stoma formation and improved quality of life and survival compared to conventional treatment.

Primary trial objectives:

To determine if endoluminal stenting for obstructing colonic cancers can result in:

- Reduced perioperative morbidity as assessed by length of hospital stay

- Reduced 30-day mortality

Secondary trial objectives:

To determine if endoluminal stenting for obstructing colonic cancers:

- Reduces stoma formation

- Improves quality of life

- Increases ability to tolerate adjuvant chemotherapy

- Has demonstrable benefits in the palliative and attempted curative settings

- Improves overall survival

Participants presenting in the emergency setting with left-sided colonic obstruction and radiological features consistent with a carcinoma who are considered to require urgent decompression were randomised to either endoluminal stenting or to surgical decompression with or without resection of the primary tumour.

Data for the CReST Study was collected from NHS Digital, Hospital and GPs records of those who consented to participate in the CReST Study (The role of endoluminal stenting in the acute management of obstructing colorectal cancer).

Data collected from the Hospital and General practices throughout England and Wales, who enrolled patients to the CReST study and who gained consent from the patient either for entry to the full trial or for access to medical records only. These data include the date and cause of death, details on any cancer recurrence of any participants in the CReST Study who consented to participate in the trial.

The collection of mortality data and cancer registration from NHS Digital aided in improving the quality of the trial dataset and thus ensuring the correct outcomes were reached for CReST. As one of the primary outcomes for CReST was reduced 30-day mortality, the mortality data collected was directly related and highly relevant to the final results of the trial. The data was also used to ensure that the team have collected all relevant death data (including the correct causes and dates of death) for patients involved in CReST.

The team also wanted to confirm the correct cancer classifications for those randomised into the study. Using the Mortality data the team were able to confirm whether there were patients entered into the study who were non-cancer patients. This could then be discussed with the relevant hospital site and was an important aspect of calculating the compliance rate for the trial.

CReST was funded by Cancer Research UK and organised by the Department of Health funded University of Birmingham Clinical Trials Unit.

This is a request for an extension of the existing agreement to continue to hold data previously supplied by NHS Digital for archiving purposes only, data will be held for 5 years till 16/12/2025.

As this is a request for an extension of an existing agreement to continue to hold data previously supplied by NHS Digital no further processing activities are envisaged. These data will be held to allow calculations to be repeated should any further queries arise whilst the paper is being prepared.

BCTU provided the patient identifiable data (NHS number and Date of Birth) for consented individuals in the CReST cohort (245) to NHS Digital. NHS Digital linked the cohort to the requested identifiable data relating to the date and cause of death, including the incidence and the outcome of any cancers and disseminated to BCTU.

The data was then downloaded by BCTU via secure file transfer and saved on a secure server dedicated to hold data from NHS Digital at the University of Birmingham. These data supplied by NHS Digital and the Hospital / GP practices were shared with a small number of named researchers at the University of Birmingham who were working on the CReST study and only had access to these data from secure computers on University of Birmingham premises. The staff members who processed the data are substantive employees of the UoB.

All death data received from NHS Digital was compared with the death data that Birmingham Clinical Trials Unit (BCTU) had already collected from Case report Forms (CRFs) and correspondence with individual hospital sites. Any additional data was added to the secure password protected database and relevant spreadsheets for the trial. A death certificate was compiled from a BCTU generic template that contains the patient’s date of death, the cause of death text provided by NHS Digital, the underlying cause of death code and any other multiple cause of death codes provided. This was then filed electronically in the Mortality CReST folder and in the patient’s paper file kept in a lockable filing cabinet, in a secure swipe office.

Similarly, the cancer registrations were checked against the current information that BCTU hold about the relevant patients. If there are any discrepancies between the data that has been collected and the cancer registration data the team would contact the relevant hospital site and amend the records accordingly.

The data supplied by NHS Digital contained sufficient information to ensure that the information is assigned to the correct patient record on the database. Once imported into the database the information used to link the study fields was modified to ensure that it was not sufficient for any researcher on the CReST study, or member of staff of the University of Birmingham, to personally identify anyone who consented to participate in the full trial.

Researchers from the University of Birmingham prepared algorithms for the analysis of the database. Once these analysis algorithms were correct they would be run against the database which contains the Crest data. This allowed the follow up of the original participants in the CReST study to be extended.

The CReST analyses do not identify any individuals, but instead look at the overall patterns of a large set of anonymised records to identify patterns and trends.

NHS Digital reminds all organisations party to this agreement of the need to comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data).

The data collected will form part of the basis of the publication of the CReST trial results. The |Trial Management Group are reviewing the trial data and expect to publish the main results of the trial in 2020 in a high impact journal preferably ‘The Lancet’ or ‘Lancet Oncology’.

The results of the trial have also been presented at targeted, specialism-specific conferences, including The Association of Coloproctology of Great Britain and Ireland Annual Meeting in July 2016, The European Society of Coloproctology Annual

Meeting in September 2016 and The British Society of Gastrointestinal and Abdominal Radiology Conference.

There was a CReST Collaborators meeting in June 2016 where all participating Principal Investigators (mostly made up of Surgeons and several Radiologists) were invited to hear the results of the trial from members of the Trials Management Group. CReST had 44 participating centres, across the UK and Ireland, by the end of the study. The results may therefore be presented to a large demographic of clinicians and potentially impact on their clinical practice.

The National Institute for Health and Care Excellence (NICE) – The CReST Chief Investigator and the CReST Lead Radiologist, were on the writing committee for the latest update of NICE guidelines on colorectal cancer in January 2020. The Chief Investigator presented the results at a form NICE committee who were updating the Stenting guidelines for colorectal cancer.

Publication of data and dissemination of results to patients will be important and achieved via the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and their patient groups and also by the colorectal cancer charities (which enjoy a good relationship with ACPGBI). The data will also be shared more widely by presentations at international society meetings.

Due to the CReST trial, patients admitted acutely with large bowel obstructions arising from colorectal cancer will have appropriate treatment which will now be guided by evidence based medicine. The results from CReST will provide definitive evidence to show how these patients should be treated.

The team were hopeful that NICE will take into account the findings of CReST and amend their guidance accordingly should there be the need.

The team hope that through publication in a high profile journal and presentation at various prestigious conferences the results of CReST will have an effect on the current practice of dealing with patients who present in the emergency setting with a left-sided colonic obstruction.

The study will publish 3 year follow up data. Longer term follow up data will be relevant for the patients recruited into the study. 5-year follow up data represents definitive cure rates which are important in any cancer study. There are residual concerns about increased recurrence rates in patient’s treated with stenting as a bridge to surgery. Longer term follow up data will be important in this regard. CReST remains the largest study of stenting as a bridge to surgery and therefore represents the largest body of evidence in patients presenting with large bowel obstruction secondary to colorectal cancer. Maintaining data in these patients also allows us to participate in collaborative studies with other researchers who have performed similar, albeit smaller studies.

Data generated by the CReST study will have important worldwide application as obstructing colorectal cancer remains an important health care problem in most countries.

The data produced to date from the CReST study has significantly changed the recently updated European guidelines for stenting in obstructing colorectal cancer. This guidance has changed form not recommending stenting as a bridge to surgery to; ‘Recommendation 2019 ESGE recommends stent as bridge to surgery to be discussed as a treatment option in patients with potentially curable left-sided obstructing colon cancer as an alternative to emergency resection within a shared decision making process. This discussion should include the following factors: availability of expertise, similar overall survival and postoperative mortality, lower overall complication rates and permanent stoma rates, more laparoscopic one-stage surgery, and higher recurrence rates, technical and clinical failure rates, and risk of perforation (strong recommendation, high quality evidence).’ This guidance is awaiting publication in the journal Endoscopy (Impact factor 6.831)

There is increasing recognition for the requirement for long term oncological outcomes after definitive treatments. Ten-year follow up data collected from the sites will provide definitive outcomes on patients presenting acutely with obstructing colorectal cancer.

There have been requests for collaborative work with international colleagues from Holland and Italy to share the trial outcomes data for the purpose of meta-analysis of outcomes following stenting for colorectal cancer. Meta-analysis of randomised trials is recognised to provide the highest level of evidence to direct treatment. Retainment of CReST1 data will allow participation in this international collaboration.