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.
October,- December 2023: Unique registry database design in the REDCap platform.
January 2024 - December 2024: Recruitment of the necessary cases according to the
sample size calculation.
January - December 2025: 1-year follow-up of patients included in the study.
January - April 2026: Interim analysis after the first year of oncologic follow-up
for assessment of the primary endpoint of the study (organ preservation with
exclusive local resection) as well as some of the secondary endpoints.
December 2027: Follow-up period to complete the study at 3 years.
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.
