Local Excision for Organ Preservation in Early REctal Cancer With No Adjuvant Treatment

Study Overview
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Brief Summary
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Rectal cancer is one of the most frequent malignant tumors nowadays. There are several possible treatment options including chemotherapy, radiotherapy and surgery. Surgery for early stage rectal cancer can be either a radical surgery (RS) or a local excision (LE). A radical surgery removes the rectum including the tumor and the lymph nodes through which it spreads, improving survival but with a possible impact in the patients quality of life (QoL). A local excision only removes the tumor and a safety margin of healthy rectum. This has the potential to avoid the possible complications and QoL decrease. However there are some complications after a LE and also poor prognostic factors inherent to the tumor biology that can lead the surgical team to perform a RS after LE with worse outcomes. These are impossible to know before the procedure. The goal of this registry is to determine the frequency of these poor prognostic biological factors and complications in patients undergoing LE for early rectal cancer. The main question it aims to answer are: • How frequently does LE allow for rectum preservation? Participants will undergo LE for early rectal cancer when it is considered the best treatment by their surgeons according to their expertise and protocols. Patients will follow the standard treatment that would be given to them, and the biological prognostic factors and the appearance of complications will be recorded.

Detailed Description
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Registry´s main hypothesis: Exclusive LE is insufficient for in situ rectum preservation in cT1N0M0 extraperitoneal rectal adenocarcinoma in ≥20% of the patients treated with this approach in real everyday´s clinical practice. A database will be design recording demographics, tumor details, type of intervention, complications, histological details and further necessity of treatments and rectal preservation along time. It will be hosted online through the REDCap system. Data entry will be done baseline, after surgical procedure, and at different follow-up periods, at 30 postoperative day and at 6, 12, 18, 24 and 36 months after surgical intervention. Sample size calculation: Previous evidence states that most patients would be willing to assume a recurrence risk of 20% (IQR 10-35%) in locally advanced rectal cancer after chemo-radiotherapy in order to join the watch and wait strategy for organ preservation. In the project the investigators propose a salvage TME rate of less than 20% at three years to be acceptable. With this approach, accepting a risk α of 0.05 and a risk β of 0.2, a two-tailed test would require a total of 145 patients to identify a difference of 0.1 units. A proportion in the reference group of 0.2 and a loss rate of 5% has been estimated. Clinical variables Clinical and demographic data will be collected from each patient, using their computerised clinical history, and a data collection notebook will be prepared. Centre code: Each participating centre will receive a unique code that will be the first variable in the database in order to identify the participation of each centre in the study. Patient code: Each patient included in each centre will receive a consecutive numerical code to identify the different cases registered in the study. Demographic variables: Sex, date of birth, weight (kg), height (cm). Comorbidities and cardiovascular risk factors: ASA classification, diabetes mellitus, hypertension, dyslipidaemia, smoking, heart disease, immunosuppression. Preoperative laboratory values: haemoglobin (mg/dl), albumin (mg/dl), carcinoembryonic antigen (mg/dl). Preoperative clinical staging: Tests performed (MRI, endoanal ultrasound, endoscopic techniques), distance of the tumour to the ano-rectal ridge, distance of the tumour to the external anal margin, tumour size (cranial-caudal axis), percentage of rectal circumference occupation (<25%, 25-50%, >50%). Operative data: Date of resection, resection approach (endoscopic vs. surgical), transanal resection devices (TEM, TEO, TAMIS, Robot-TAMIS), technique used (local full-wall resection vs. submucosal dissection), intraoperative complications (bleeding, vaginal perforation, tumour perforation/rupture), medical complications). Postoperative complications: Clavien-Dindo classification, wound dehiscence, surgical site infection, bleeding. Pathological data: pT classification, histological grade, circumferential margins, vascular, lymphatic and perineural infiltration, micron infiltration of submucosa and tumour budding. Need to complete treatment: Reason (local resection complication, high risk factors, inadequate surgical margins, piecemeal resection, local recurrence, final pathological staging greater than pT1), radical surgery (dichotomous), technique used (total mesorectal excision, abdominoperineal amputation of rectum), time from local excision to radical surgery (date), stoma preparation (dichotomous), type of stoma (ileostomy vs. Colostomy, temporary vs. definitive), transit reconstruction within the study period (in temporary stomas), adjuvant radiotherapy, adjuvant radio-chemotherapy, Follow-up: complications recorded prospectively at 60 days by means of periodic visits to the coloproctology clinic, with the end of follow-up for the patient within the study being the annual check-up. The number of consultations during the first year, recurrence (indicating date and management) and death will be assessed. Oncological follow-up will be carried out with control of tumour markers (CEA), control imaging tests (CAT scan associated with PET/CT in the case of recurrence), and selected biopsies according to the results. Statistical method: The data obtained from each patient will be entered into a database and the analysis will be performed with a statistical programme Stata 13.1 (StataCorp, Texas, USA). A descriptive analysis of demographic and clinical variables will be performed. Categorical variables will be presented as percentages and frequencies. Qualitative variables will be presented as percentages and frequencies. Quantitative variables will be described as mean and standard deviation (SD) if they follow a normal distribution or as median and interquartile range (IQR), in case of skewness. The association between the variables collected and the target variables of the study will be performed by Pearson's Chi-square test or Fisher's exact test, as appropriate, in the case of categorical variables and, for continuous variables, by Student's t-test for independent samples or Mann-Whitney U-test, respectively, depending on whether or not their distribution conforms to the normal distribution. Overall survival, disease-free survival, local recurrence-free survival and overall mesorectal resection-free survival will be estimated using the Kaplan-Meier method and the Cox proportional hazards model. Patients lost to follow-up will be censored. Chronogram and study´s stages: March - September, 2023: Study´s protocol design and approval by the promoter center´s local ethics committee. Recruitment period for other participant centers. September - October, 2023: Unique registry database design in the REDCap platform. November, 2023 - December, 2024: Anticipated patient´s recruitment period. January - December, 2025: First year follow-up. January - April, 2026: Intermediate analysis after first year´s follow-up, measuring the study´s main outcome, in situ preservation of the rectum, as well as secondary outcomes. April, 2026 - December 2027: Complete follow-up period for the primary and secondary outcome measures. Ethical and legal aspects: The investigation will be conducted according to the 2013 Fortaleza´s update of the the Helsinki Declaration, and to each participant´s country law.

Official Title
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Local Excision for Organ Preservation in Early REctal Cancer With No Adjuvant Treatment (LORENA Trial).

Conditions
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Rectal Cancer, Rectum Neoplasm

Intervention / Treatment
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* Procedure: Transanal local excision


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rectal cancer diagnosed patients with clinical staging cT1N0M0. Tumor´s inferior verge must be no farther than 2 cm proximal to the anorectal rim. Patients receiving Local Excision as surgical treatment. Exclusion Criteria: Patients younger than 18 years old. Patients scheduled to receive adjuvant chemotherapy. Patients with a clinical TNM staging different to T1N0M0. Tumor´s inferior verge farther than 2cm proximal to the anorectal rim.

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 |
| --- | --- |
| Local excision<br>Patients older than 18 years Diagnosis of rectal cancer Inferior edge of the tumour not further than 2 cm above the anorectal ring Clinical TNM staging T1N0M0 | Procedure: Transanal local excision<br>* Transanal full thickness local excision<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate | Rate of patients with no need of Total Mesorectal Excision after follow-up | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity rate | Postoperative complication rate, description, and severity according to Clavien Dindo classification | 2 months | 
| Radicality of resection | Describe the rate of margin tumor infiltration | 1 month | 
| Histological poor outcome predictor rate | Describe the rate of lymphatic, vascular and perineural invasion, histological grade, mean submucosal invasion depth | 1 month | 
| Radical rescue surgery specimen quality | Describe the quality of Total Mesorectal Excision specimen in terms of mesorectal fascia integrity | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early rectal cancer, Local excision, Total Mesorectal Excision, Organ preservation