Creation of a research database and management of patients who achieve a clinical complete response (cCR) after neoadjuvant chemo/radiotherapy for rectal cancer through surveillance in order to avoid the risks of surgery

Narrative

Colorectal (bowel) cancer is the third most common cancer type in the world. Around a third of cases arise in the rectum. There are around 15,000 new cases of rectal cancer diagnosed annually in the UK alone. The standard treatment for people with locally advanced rectal cancer is pre-operative chemo- radiotherapy treatment followed by surgery around 12 weeks later. However, surgery can lead to major complications in up to 15% of cases and up to half of patients require a colostomy after surgery which can affect their quality of life.

In 2004 researchers from Brazil (Habr-Gama A et al , 2004) were the first to suggest an alternative, watch and wait approach recognising that in around 15-20% of people treated with chemo-radiotherapy, the tumour may disappear completely -known as a clinical complete response (cCR) and they may therefore not require surgery, rather a 'watch and wait' policy of monitoring could be an alternative.

At the time this represented a new paradigm for treating rectal cancer.  The Rectal Cancer Complete Response Registry was  established in 2009 across 24 cancer centres covering Greater Manchester, Cheshire, Merseyside, North Wales, Lancashire and South Cumbria. Patients who had cCR could therefore choose either to proceed with surgery or enter a surveillance programme of regular monitoring.

In order to address the shortage of evidence regarding the safety of the watch and wait approach, we undertook The Oncological Outcomes after Clinical Complete Response in Patients with Rectal Cancer (OnCoRe) study. 259 patients were included.  Analysis was carried out between patients who were managed by watch and wait and those who had surgical resection. Our results, published in 2016, found no differences in 3-year non-regrowth disease-free survival or overall survival, approximately a ¼ of patients avoided permanent colostomy, confirmed that watch and wait is oncologically safe. A third of cCR patients had local regrowth requiring salvage surgery. 

In 2017, the response registry was converted to the national 'OnCoRe Research Database' and registered with the Health Research Authority. This allows additional patients to be added and follow up of data to further investigate the outcomes of these patients.

In 2017 the Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) – Multidisciplinary Management recommended that "In selected patients with complete clinical response (cCR) after preoperative long course CRT, a watch and wait approach can be considered. A defined surveillance protocol, such as used in OnCoRe, is necessary to identify local disease regrowth at the earliest stage possible".

In January 2020 National Institute for Health and Care Excellence (NICE) issued guidelines for Colorectal cancer in which the committee acknowledged "that some people whose rectal cancer shows a complete clinical response to neoadjuvant therapy choose to defer surgery and opt for an organ preserving 'watch-and-wait' strategy instead". Nice stated "For those who choose to defer, encourage their participation in a clinical trial and ensure that data is collected via a national registry". OnCore is currently the only UK national registry. 

In December 2020, national clinical guidance on 'Diagnosis, Staging and treatment of patients with rectal cancer' from Ireland's Department of Health stated that "a watch and wait approach should be discussed with the patient and may be considered following shared decision making."

The National Bowel Cancel Annual Audit 2022 (published Jan 2023) stated since 2016/2017 the proportion of patients with rectal cancer having major resection reduced from 54% to 47%. This reduction has been has been "associated with an increase in the use of local excision for early rectal cancer, complete clinical response after neoadjuvant therapy precipitating enhanced surveillance following publication of OnCoRe, and an increase in total neo-adjuvant therapy (TNT) for locally advanced rectal cancers."

Impact date	2014
Category of impact	Health and wellbeing
Impact level	Benefit