Wait-and-see Policy for Complete Responders After Chemoradiotherapy for Rectal Cancer

Study Overview
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Brief Summary
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The aim of this prospective observational cohort study is to provide short and long term oncological and functional outcome data on organ preserving treatment in good responders after a standard indication for neoadjuvant (chemo)radiation for rectal cancer.

Detailed Description
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Standard treatment for patients with locally advanced rectal cancer consists of a long course of (CRT) followed by surgical resection. Although the aim of neoadjuvant treatment in these patients is not organ preservation, but rather to provide improved local control, in the tumour disappears completely. Studies from Maastricht, the UK and Brazil have shown that in selected patients with a clinical complete response after CRT, a wait-and-see policy without any surgery could be a safe alternative with comparable long-term outcome and better functional outcome compared to patients who had surgery. The main objective of the study is to provide short and long term oncological and functional outcome data on organ preserving treatment in good responders after a standard indication for neoadjuvant (chemo)radiation. Additional aims are: to set up a national network with expertise centres in the 'wait-and-see' treatment of rectal cancer; to set up a national registry for organ preservation treatment that will generate more evidence on the management and oncological outcome of patients evaluated and treated with organ preservation and [3] to offer through this network to all patients who are considered good candidates this 'wait-and-see' approach using the most up to date tools for selection and follow-up. Study design: multicenter prospective observational cohort study and implementation study. Study population: The population will consist of patients, aged 18 years or older, with rectal cancer who after a long course of CRT or a short course of radiation with a long waiting interval have a clinical complete response (ycT0N0). The main study endpoint is 2-year non-regrowth disease-free survival. Secondary endpoints are [1] the number of fully operational centres who can deliver high quality organ preserving care in rectal cancer in the Netherlands, [2] 2-year regrowth rate, [3] 2-year local control, [4] 2-year overall survival, [5] determination of the optimal follow-up schedule and [6] quality of life. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: In the majority of patients who participate in the study, major surgery and the associated morbidity can be avoided. Although scientific proof shows wait-and-see only comes with a small risk with adequate selection and follow up, the exact risk is not yet well established and needs to be confirmed by this study. The benefit-risk ratio for this study is regarded as favourable.

Official Title
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Multicentre Evaluation of the Wait-and-see Policy for Complete Responders After Chemoradiotherapy for Rectal Cancer

Conditions
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Rectal Neoplasms

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older Primary rectal cancer (pathologically confirmed) Treated with neoadjuvant (chemo)radiotherapy Clinical complete response (ycT0N0) to neoadjuvant treatment, as determined clinically (digital rectal examination, endoscopy) and radiologically (diffusion weighted imaging-MRI). Informed consent and capability of giving informed consent; before informed consent is obtained the patient will be extensively informed about the fact that 'wait-and-see' instead of conventional surgery is not accepted yet by most physicians and that the risks and benefits from these strategies have not been fully determined yet. These issues will be discussed in the patient information form as well. Comprehension of the alternative strategies and risks are clear to the patient (in other words that the patient understands the experimental base of the study). Exclusion Criteria: Recurrent rectal cancer Contra-indications for MRI. If MRI is not possible because of contra-indications (e.g. pacemaker) patients will be excluded. MRI is crucial for response evaluation and follow-up and cannot be omitted in patients that follow the 'wait-and-see policy'. Unable to understand or read Dutch Unable or unwilling to comply to the intensive follow-up schedule

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study population<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year non-regrowth disease-free survival | Absence of non-regrowth local or distant recurrence or death within 2 years of follow-up | 2 years after start of wait-and-see protocol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of fully operational centres | Number of operational centres who can deliver high quality organ preserving care in rectal cancer in the Netherlands | 2 years after start of wait-and-see protocol | 
| 2-year local regrowth rate | The proportion of local regrowth | 2 years after start of wait-and-see protocol | 
| 2-year local control | Absence of local recurrence(unresectable regrowth, resected with R1, or requiring more extensive than TME surgery) or death | 2 years after start of wait-and-see protocol | 
| 2-year overall survival | Absence of death | 2 years after start of wait-and-see protocol | 
| Determination of the optimal follow-up schedule | A balance between early detection of recurrence and compliance to follow-up | 2 years after start of wait-and-see protocol | 
| Quality of life | Quality of life (general health, disease specific and functional outcomes) | At 3 months, 1 year, 2 years and 5 years after the start of wait-and-see protocol | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Complete response, Organ preservation, Wait-and-See, Watch-and-Wait, Watchful Waiting