Clinical trial NCT04103372: Pre-therapeutic MRI Assessment of Early-Stage Rectal Cancer and Significant Rectal Polyps to Avoid Major Resectional Surgery
Official title: Pre-therapeutic MRI Assessment of Early-Stage Rectal Cancer and Significant Rectal Polyps to Avoid Major Resectional Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Cancer
Colo-rectal Cancer
Keywords: early stage
early phase
Endoscopic Mucosal Resection
Endoscopic Submucosal Dissection
Histopathological Staging
MDT Decision Making
MRI Staging
Quality of Life
Radiotherapy
Rectal preservation
Shared decision making
Significant Rectal Polyps
Transanal Endoscopic Microsurgery
Transanal Minimally Invasive Surgery
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Pelican Cancer Foundation
name: RM Partners West London Cancer Alliance
First posted: 2019-09-25
Enrollment: 200
Sex: ALL
Minimum age (years): 16
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Multicentre, stepped-wedge cluster randomised trial. This pilot study will run for 9 months and utilise a stepped wedge cluster randomised controlled trial design (including transition period). Sites will enter data from the diagnostic and treatment pathways of all rectal cancer patients who are eligible for primary surgical treatment, eg those radiologically staged as less than or equal to T3b or with confirmed as less than or equal to pT2N0 pathological staging.

Prior to the trial opening the participating sites will be randomly allocated a number, which will determine the number of months the site will remain in the control and then subsequently the intervention phase of the trial.
Primary purpose: DIAGNOSTIC

Brief summary: When a patient is diagnosed with a rectal (bowel) polyp or cancer, radiology doctors read MRI scans to describe how deeply the cancer invades into the bowel wall (this is the 'stage' of the cancer). In this project, we will teach radiologists to find more early-stage rectal cancers. These are cancers that have only grown partially into the bowel wall. If we succeed, more patients could have these lesions removed by a local procedure that preserves the bowel and avoids the risks and complications of major surgery.

We have developed a new method for radiology doctors to read MRI scans, which is more accurate than current practice. Currently only 3/10 of early rectal cancers are found by radiologists but by using our MRI reading system, 9/10 patients can be accurately identified as having early rectal cancer. We have proven that we can teach this method to other radiology doctors whose reports help to accurately inform patients of all possible treatment options, so they can be offered the option of a local procedure.

In this initial work we will train radiology doctors in our MRI reading method in 20 hospitals. We will compare MRI reports before and after training to see if an accurate reading method improves treatments choices for patients. We will also determine whether more patients have local procedures after our training. The results of this initial work will help us to apply for national funding for a trial that we can quickly roll out to all NHS hospitals.

Detailed description: Many patients diagnosed with Early Rectal Cancer (ERC) are currently over-treated. Most patients with confirmed ERC will undergo an MRI, but some are not correctly identified in endoscopy and immediately removed. Of those who undergo MRI, 69% are over-staged and undergo major surgery or unnecessary radiotherapy when local excision surgery to preserve the patients rectum, and quality of life, would have been possible. \<10% of patients with ERC are staged accurately and offered local excision, with the majority who are staged as ERC on MRI still undergoing major surgery, likely due to uncertainty in the staging report.

Prof Gina Brown developed a more accurate radiological staging system (PRESERVE) or ERC, whereby T2 tumours are identified and classified according to the degree of preservation of the individual layers of the rectal wall. It has been shown that PRESERVE enabled better identification of ERC suitable for local excision from the expected 30% to 89% accuracy. This improved accuracy was replicated in a further study by training a cohort of 12 radiologists. It is predicted that wider adoption of PRESERVE will result in increased organ-preserving surgery from the current rates of 10% to \>50%.

Eligibility criteria: Inclusion Criteria:

1. Have a rectal tumour or suspected tumour less than or equal to T3b on MRI stage or pT2 or less after excision, or 20mm or more on endoscopy with suspicion of malignancy
2. Be aged 16 years or over

Exclusion Criteria:

1. Have metastatic disease at time of initial staging
2. Have a biopsy-proven rectal malignancy which is not adenocarcinoma
3. Are contraindicated for MRI

Primary outcomes:
measure: Impact of a training intervention on the accuracy of the tumour staging diagnosis through systematic reporting approach to MRI scans against current (pre intervention) practice.
timeFrame: 1 year
Secondary outcomes:
measure: Proportion of patients with technically adequacate scans before and after intervention
timeFrame: 1 year
measure: Proportion of primary tumour characterised by morphology and other features associated with malignancy before and after intervention
timeFrame: 1 year
measure: Proportion of MRI reports with T substage given before and after intervention
timeFrame: 1 year
measure: Number of patients identified on imaging as suitable for rectal preservation by local excision
timeFrame: 1 year
measure: Number of patients identified by MDT as suitable for rectal preservation by local excision
timeFrame: 1 year
measure: Correlation of accuracy in the identification of safe plane of excision for rectal preservation by the radiologist
timeFrame: 1 year
measure: Numebr of patients with R0 by local excision or TME as appropriate
timeFrame: 1 year
measure: Qualitative EORTC QLQ-CR29 Questionnaire on Quality of Life of patients undergoing local excision vs major surgery
timeFrame: 1 year, 3 years, 5 years
measure: Qualitative EORTC QLQ-CR30 Questionnaire on Quality of Life of patients undergoing local excision vs major surgery
timeFrame: 1 year, 3 years, 5 years
measure: Qualitative LARS Questionnaire on Quality of Life of patients undergoing local excision vs major surgery
timeFrame: 1 year, 3 years, 5 years
measure: Qualitative Questionnaire on Quality of Life of patients undergoing local excision vs major surgery
timeFrame: 1 year, 3 years, 5 years
measure: Comparison of total costs of procedures performed between patients undergoing local excision surgery to those undergoing major surgery
timeFrame: 1 year
measure: Comparison of inpatient costs between patients undergoing local excision surgery to those undergoing major surgery
timeFrame: 1 year
measure: Comparison of total cost of outpatient visits between patients undergoing local excision surgery to those undergoing major surgery
timeFrame: 1 year
measure: Comparison of total community costs between patients undergoing local excision surgery to those undergoing major surgery
timeFrame: 1 year
measure: Number of patients without disease and/or without stoma between patients undergoing local excision surgery, compared to those undergoing major surgery
timeFrame: 1 year, 3 years, 5 years
measure: Assessment results for the effectiveness of mrSRT after a year from training
timeFrame: 1 year
measure: Identification of histopathological biomarkers to improve selection of patients who can undergo rectal preserving strategies for Early Recal Cancer
timeFrame: 2 months, 1 year, 3 years, 5 years
Other outcomes:
Locations:
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
state: Berkshire
city: Amersham
country: United Kingdom
facility: Buckinghamshire Healthcare Nhs Trust
state: Buckinghamshire
city: London
country: United Kingdom
facility: University College London Hospitals Nhs Foundation Trust
state: Greater London
city: London
country: United Kingdom
facility: King'S College Hospital Nhs Foundation Trust
state: Greater London
city: London
country: United Kingdom
facility: West Middlesex Hospital
state: Greater London
city: London
country: United Kingdom
facility: Imperial College Healthcare Nhs Trus
state: Greater London
city: Uxbridge
country: United Kingdom
facility: The Hillingdon Hospitals Nhs Foundation Trust
state: Greater London
city: Basingstoke
country: United Kingdom
facility: Hampshire Hospitals Nhs Foundation Trust
state: Hampshire
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Canterbury
country: United Kingdom
facility: Kent & Canterbury Hospital
state: Kent
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: Kent
city: Kendal
country: United Kingdom
facility: Westmorland General Hospital
state: Lancashire
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: Leicestershire
city: Tooting
country: United Kingdom
facility: St George'S Hospital
state: London
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
state: Oxfordshire
city: Stafford
country: United Kingdom
facility: Nhs Staffordshire and Stoke-on-Trent Integrated Care Board
state: Staffordshire
city: Camberley
country: United Kingdom
facility: Frimley Health Nhs Foundation Trust
state: Surrey
city: Carshalton
country: United Kingdom
facility: St Helier Hospital
state: Surrey
city: Kingston Upon Thames
country: United Kingdom
facility: Kingston Hospital Nhs Foundation Trust
state: Surrey
city: Thornton Heath
country: United Kingdom
facility: Croydon Health Services Nhs Trust
state: Surrey
city: Swansea
country: United Kingdom
facility: Tonna Hospital
state: Wales
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
state: Wiltshire
city: Harrow
country: United Kingdom
facility: St Marks Bowel Cancer Screening Centre
Study officials:
affiliation: Imperial College London
name: Gina Brown, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Detering R, van Oostendorp SE, Meyer VM, van Dieren S, Bos ACRK, Dekker JWT, Reerink O, van Waesberghe JHTM, Marijnen CAM, Moons LMG, Beets-Tan RGH, Hompes R, van Westreenen HL, Tanis PJ, Tuynman JB; Dutch ColoRectal Audit Group*. MRI cT1-2 rectal cancer staging accuracy: a population-based study. Br J Surg. 2020 Sep;107(10):1372-1382. doi: 10.1002/bjs.11590. Epub 2020 Apr 16.
citation: Balyasnikova S, Read J, Wotherspoon A, Rasheed S, Tekkis P, Tait D, Cunningham D, Brown G. Diagnostic accuracy of high-resolution MRI as a method to predict potentially safe endoscopic and surgical planes in patients with early rectal cancer. BMJ Open Gastroenterol. 2017 Aug 14;4(1):e000151. doi: 10.1136/bmjgast-2017-000151. eCollection 2017.