Clinical trial NCT06440174: Understanding the Variation of Modern Endoscopic Ultrasound Use in Patients with Oesophageal Cancer (VALUE)
Official title: Understanding the Variation of Modern Endoscopic Ultrasound Use in Patients with Oesophageal Cancer (VALUE): a Multi-methods Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Oesophageal Cancer
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2024-06-03
Enrollment: 180
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited through MDTs at participating secondary care centres in the UK. Those deemed suitable will be approached by their care team to take part.

Brief summary: This is an observational trial that will look at patients undergoing endoscopic ultrasound (EUS) in patients with oesophageal cancer and to determine the proportion of cases in which EUS changes disease management in these patients.

Detailed description: Over 9,000 patients are diagnosed with oesophageal cancer in the United Kingdom (UK) annually. The prognosis of these patients is poor, with an overall 5-year survival rate of 15%.

Most patients (60%) present with advanced disease and palliation is the only treatment option. Accordingly, oesophageal cancer has considerable unmet research need.

The VALUE trial is a prospective observational study investigating EUS in the modern era of oesophageal cancer staging. A quantitative study component will examine how often and why EUS changes treatment decisions after initial staging with CT and PET-CT. A qualitative study component will explore both clinician and patient attitudes and opinions towards the utility of EUS in the staging pathway.

EUS is an invasive procedure combining upper gastrointestinal endoscopy with ultrasonography. An ultrasound probe located at the end of the endoscope allows direct visualisation of the oesophageal wall layers and adjacent tissues providing local assessment of the depth of tumour invasion and lymph nodes. This assessment informs local tumour (T-) and node (N-) staging which are important prognostic indicators of survival. Patients undergoing EUS require sedation and there are risks of complication. EUS is a specialist investigation requiring many years of dedicated training to perform competently.

VALUE aims to recruit patients with oesophageal cancer who are deemed to have potentially curable disease and who are fit for, and wish to have, radical treatment, and who receive EUS as part of their standard of care staging pathway. Patients with a range of disease status (T1-T4; N0-N3) will be considered for recruitment to allow diverse consideration of the reasons whether EUS impacts treatment decisions in current clinical practice. VALUE will also recruit clinicians who regularly care for oesophageal cancer patients in a multi-disciplinary setting to gather their opinions regarding the use of EUS in this patient population.

A systematic review, updating a prior review, found that current evidence concerning the impact of EUS on the management and outcome of oesophageal cancer patients in modern staging with PET-CT was of limited quality. In total, 18 studies with 11,836 patients were included. Overall, 2,805 patients (23.7%) underwent EUS compared to 9,031 (76.3%) without. However, only 19.7% of all patients also had PET-CT for staging. Reported change of management by EUS varied widely from 0% to 56%.

EUS use in oesophageal cancer patients across the NHS is also reported to vary widely. Considerable variation in EUS practice was found in a survey of oesophageal cancer multi-disciplinary team (MDT) leads across the UK. Eighty-seven of 97 UK NHS trusts responded. 29% recommended EUS for all potentially curable patients whereas 46% requested EUS after PET-CT on a case-by-case basis. 20% reported both a lack of utility and concerns about treatment delay. Overall, 63% and 43% routinely use EUS for radiotherapy and surgical planning, respectively. Further, data from the National Oesophago-Gastric Cancer Audit (NOGCA) all describe the reported decline in EUS use from 62% of all patients in 2013, to 39% in 2019, and 18.6% to 2021. In 2020/21, EUS was used in 23.6% of patients who had a curative treatment plan.

The Cancer of Oesophagus or Gastricus-New Assessment of Technology of Endosonography (COGNATE) trial randomised patients between EUS with CT, and CT alone. EUS led to improved quality-adjusted survival. However, since COGNATE, oesophageal cancer staging has been transformed by PET-CT, a cross-sectional nuclear imaging test usually performed prior to EUS. PET-CT has greater sensitivity for distant metastases than CT, and therefore identifies more patients unsuitable for radical treatment, meaning that local staging with EUS becomes less critical in these patients.

This conclusion is supported by data from a large retrospective cohort study by Findlay et al which included 953 patients, of which 798 had EUS, and 918 had PET-CT. The authors found that patient management was changed by EUS in 11% of cases, but when probability thresholds were calculated, the utility of EUS in the majority of patients (71.8% staged T2-T4a) was minimal (0.4%), concluding that the risk of EUS exceeded its benefit. However, these data have not been validated outside of this single-centre study but does question the value of EUS in the modern staging pathway.

In summary, the use of PET-CT for oesophageal cancer staging is increasing, and use of EUS declining, which supports the modern tendency of clinicians to favour non-invasive cross-sectional imaging. However, evidence supporting the basis for this recent change in practice is limited.

There will also be a qualitative part of the trial where a qualitative researcher will interview 30 patients who consent to this in the patient information sheet and 30 clinicians who can carry out EUS, and ask both for their opinions and thoughts on the procedure.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 16 or above with first diagnosis of biopsy-confirmed oesophageal cancer.
2. Referred for EUS examination as part of standard of care investigations.
3. Tumour location in the oesophagus, or gastro-oesophageal junction (Siewert types I-III)
4. MDT decision that patient is potentially curable with radical treatment (e.g., endoscopic treatment, surgery +/- neoadjuvant therapy, or definitive chemoradiotherapy)
5. Prior staging with CT and PET-CT
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
7. Clinical staging of T1-T4, N0-N3, M0 disease
8. Adenocarcinoma or squamous cell carcinoma (SCC) histopathological cell type

   Exclusion Criteria:
9. Recurrent or residual disease
10. Distant metastatic disease detected before EUS.
11. Previous oesophagectomy or oesophageal radiotherapy
12. Unable to undergo EUS examination.
13. Concurrent malignancy e.g., second primary tumour
14. Other histopathological cell type

Primary outcomes:
measure: Number of patients who change treatment management
timeFrame: this decision will be made at baseline.
Secondary outcomes:
measure: Number of clinicians and patients who will share their opinions on EUS by a one to one interview with a qualitative researcher.
timeFrame: This will take place up to 6 weeks following the EUS at one to one interviews.
measure: Number of patients who changed their treatment management following EUS.
timeFrame: this decision will be made at baseline.
measure: Number of patients who decided on their treatment.
timeFrame: this decision will be made at baseline.
Other outcomes:
Locations:
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge University NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Velindre University NHS Trust
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Chief Investigator, based at Velindre University NHS Trust
name: Kieran Foley
role: PRINCIPAL_INVESTIGATOR
References: