Trial Title:
Local Excision for Organ Preservation in Early REctal Cancer With No Adjuvant Treatment
NCT ID:
NCT05927584
Condition:
Rectal Cancer
Rectum Neoplasm
Conditions: Official terms:
Rectal Neoplasms
Conditions: Keywords:
Early rectal cancer
Local excision
Total Mesorectal Excision
Organ preservation
Study type:
Observational [Patient Registry]
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Procedure
Intervention name:
Transanal local excision
Description:
Transanal full thickness local excision
Arm group label:
Local excision
Summary:
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:
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.
Criteria for eligibility:
Study pop:
Adults diagnosed with early stage rectal cancer, meaning clinical TNM staging cT1N0M0,
programmed to receive Local Excision as an exclusive therapy according to each center´s
standard practice.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
- Patients age 18 years or older.
- Histologic proof of infiltrating rectal adenocarcinoma. or
- Preoperative biopsy compatible with rectal adenoma or intramucous adenocarcinoma
with endoscopic or radiological suspicion of infiltrating adenocarcinoma.
1. Endoscopic criteria: Kudo´s crypt pattern of V or higher, despite non
confirmatory preoperative histology. endoscópicos: patrón de criptas V o
superior según la clasificación de Kudo, que define lesiones infiltrantes, a
pesar de que la histología preoperatoria no sea confirmatoria .
2. Ultrasonographic criteria: hipoecogenic rectal tumor invading the intermediate
hyperecogenic layer (submucosal), but does not infiltrate the hypoecogenic
outer layer (muscularis propia).
3. Radiological criterio in MR: tumor invades the submucosal layer without
infiltration of the rectal muscularis propia. The usual low signal submucosal
image is substituted with an aberrant signal, meaning the loss of the zebra
pattern in a normal rectal wall.
- Rectal neoplasm with an inferior limit no further than 2cm proximal to the anorectal
verge, both in digital rectal examination and in radiology examinations, ideally
magnetic resonance (MR).
- Rectal neoplasms up to 3 cm of major diameter.
- Clinical preoperative staging of cT1N0M0, based on endoscopy, MR, +/- endorectal
ultrasound.
- Cases in which LE as exclusive treatment with curative intent is prescribed after
MDT discusión, regardless of the approach both via flexible endoscopy and transanal
endoscopic microsurgery and its variations.
- Neoplasms with low risk histologic criteria known preoperatively or lack of
information regarding this aspect:
1. Submucosal infiltration of less than 1000µm (sm1 in the Kikuchi classification)
.
2. Tumor budding absent.
3. En bloc resection in patients with a previous endoscopic resection.
4. Vascular, lymphatic and perineural invasión absent.
5. Low histologic grade.
Exclusion Criteria:
- Patients younger than 18 years old.
- Rectal neoplasms different from adenocarcinoma.
- Neoplasms in which the inferior edge is farther than 2cm proximal to the anorectal
verge in the preoperative MR.
- Any other clinical stage other than cT1N0M0 (any T>1, N+, or M+).
- Neoplasms larger than 3cm.
- Preoperatively demonstration of PPHF:
1. Submucosal infiltration deeper than 1000µm (sm2 and sm3 in the Kikuchi
classification)
2. Tumor budding present.
3. Piecemeal resection in cases with previous endoscopic resection.
4. Vascular, lymphatic and perineural invasión presence.
5. High histologic grade.
- Any patient with planned systemic treatment with RTQT combined with the LE after MDT
discusión, regardless of the preoperative clinical or postoperative pathological
stage.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital Universitario de la Princesa
Address:
City:
Madrid
Zip:
28028
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Carlos Cerdán Santacruz, PhD
Phone:
+34639638156
Email:
carloscerdansantacruz@hotmail.com
Start date:
May 13, 2024
Completion date:
May 1, 2027
Lead sponsor:
Agency:
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Agency class:
Other
Collaborator:
Agency:
Hospital Alemão Oswaldo Cruz
Agency class:
Other
Collaborator:
Agency:
Hospital Universitario La Fe
Agency class:
Other
Collaborator:
Agency:
Complejo Hospitalario Universitario de Vigo
Agency class:
Other
Source:
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05927584
