REsults of LOw Anterior Resections With or Without Preventive Stoma in Nonemergency Department

Official title

Results of Anastomotic Leak After Low Anterior Resection With or Without Preventive Stoma for Rectal Cancer in Low-risk Patients in Nonemergency Departments (RELOAD): Protocol of Multicenter Randomized Controlled Non-inferiority Trial

Overview

The purpose of this multicenter randomized non-inferiority trial is to evaluate the safety of low anterior resection for rectal cancer performed with versus without a diverting stoma in patients with a low predicted risk of colorectal anastomotic leakage. The primary objective is to determine whether the rate of anastomotic leakage within 30 days after surgery in the no-stoma group is non-inferior to that in the diverting stoma group. The secondary objectives include comparison between groups regarding: Stoma rate at 1 year after surgery; Quality of life at 30 days and 1 year (EORTC QLQ-C30, EORTC QLQ-CR29, and LARS score); Short-term postoperative outcomes, including postoperative day metrics, length of hospital stay, and complications graded according to the Clavien-Dindo classification; Reoperation rates within 30 days and 1 year. Participants will include adult patients with mid- or low-rectal adenocarcinoma who are scheduled for radical minimally invasive total mesorectal excision and have a predicted risk of anastomotic leakage \<10% according to the study risk model.

Detailed description

This study is a multicenter randomized controlled non-inferiority trial evaluating the safety of omitting routine diverting stoma formation in low-risk patients undergoing total mesorectal excision (TME) for mid- and low-rectal cancer.

Patients with a predicted risk of colorectal anastomotic leakage (AL) ≤10% will be enrolled across 7 accredited centers. Local Ethics Committee approval has been obtained at each site. The protocol follows the SPIRIT 2025 recommendations.

After informed consent, patients will be randomized 1:1 to "with preventive stoma" and "without preventive stoma". Stratified block randomization (block sizes 2, 4, or 6) will be used, stratified by center and sex. Allocation will be computer-generated (R software). No blinding will be performed. Cross-over to stoma formation in the no-stoma group is permitted in case of intraoperative safety concerns.

All patients will undergo minimally invasive TME according to oncological principles (sharp dissection within embryological planes, adequate vascular control, stapled tension-free colorectal anastomosis).

In the stoma group, a diverting ileostomy or colostomy will be created. Closure is planned ≥2-3 months postoperatively if clinically appropriate.

Postoperative care follows institutional standards. Complications will be graded according to the Clavien-Dindo classification. Patients will be followed for 1 year with clinical visits (or telephone follow-up) at 30 days and every 3 months. Imaging and colonoscopy will be performed according to clinical guidelines. Quality-of-life assessments and LARS score will be obtained at 30 days and 1 year.

Risk Prediction Model. To include the patient in the study, the risk of anastomotic leaks will be assessed on the AFOR scale. If the value is 0-1 (6-10%), the patient will be invited to participate.

Sample Size and Statistical Analysis. Assuming a baseline AL rate of 15% in the stoma group, a non-inferiority margin of 10%, one-sided α=2.5%, 80% power, and 10% dropout rate, 442 patients (221 per group) are required. The primary analysis will follow the intention-to-treat (ITT) principle. A binomial logistic regression model will estimate risk difference with 95% confidence intervals using clustered robust standard errors by center. Non-inferiority will be concluded if the upper bound of the confidence interval does not cross the predefined margin. Sensitivity analyses will include per-protocol and instrumental variable approaches. Missing data for secondary outcomes will be handled using multiple imputation (MCAR assumption).

Interim Safety Analysis. A safety analysis will be conducted after enrollment of 50 patients per group. If unacceptable differences in AL rates are observed, early termination may be considered.

Interventions

• Procedure Without a preventive stoma
  At the conclusion of total mesorectal excision (TME), a diverting ileostomy or transverse colostomy will be created at the discretion of the operating surgeon. The pelvic peritoneum over the anastomotic site will be closed, and a pelvic drain will be placed (the type of drain will be determined by the operating surgeon).
• Procedure With a preventive stoma
  The operating surgeon will follow the standard practice adopted at the respective center and will create either a diverting ileostomy or transverse colostomy at their discretion. The pelvic peritoneum will not be closed. Placement of a percutaneous pelvic drain adjacent to the anastomotic site is mandatory.

Primary outcome measures

• Colorectal anastomotic leak [Time frame: 30 days after main surgery]

Secondary outcome measures (8)

• Postoperative complications [Time frame: 30 days after main surgery]
• Reoperation rate [Time frame: 30 days and 1 year after main surgery]
• Stoma rate [Time frame: 1 year after main surgery]
• Hospital readmissions [Time frame: 30 days after main surgery]
• Quality of life by European Organization for Research and Treatment of Cancer-Cancer30 (EORTC-C30) [Time frame: 30 days and 1 year after surgery]
• Quality of life by European Organization for Research and Treatment of Cancer-ColoRectal 29 (EORTC-CR29) [Time frame: 30 days and 1 year after surgery]
• Low Anterior Resection Syndrome (LARS) [Time frame: 1 year after main surgery]
• Length of hospital stay [Time frame: until discharge within 90 days]

Eligibility criteria

Inclusion criteria

• Age >18 years;
• Primary rectal cancer staged as cT1-4aN0-3M0 (or ycT0-4aN0-2M0);
• Histologically confirmed rectal adenocarcinoma based on endoscopic biopsy;
• Tumor located ≤12 cm from the dentate line (based on endoscopy, digital rectal examination, and/or pelvic MRI);
• Planned radical minimally invasive (laparoscopic/robot-assisted) intervention with TME and formation of primary colorectal/colonanal anastomosis;
• Adequate hematologic function: hemoglobin ≥100 g/L, leukocytes >4 × 10\^9/L, platelets >100 × 10\^9/L;
• Adequate renal function: serum creatinine <150 µmol/L;
• Adequate hepatic function: AST/ALT <100 U/L;
• Predicted risk of anastomotic leakage ≤10% (AFOR 0-1).

Exclusion criteria

• Age ≥80 years;
• Presence of a pre-existing diverting ileostomy or colostomy;
• Peritumoral abscess or tumor perforation;
• Distant metastases (M1) identified preoperatively and/or intraoperatively;
• Synchronous or metachronous malignancy;
• Prior pelvic irradiation for another condition (e.g., cervical or prostate cancer);
• Evidence of malnutrition (serum albumin <34 g/L);
• Severe uncontrolled comorbid conditions (e.g., acute myocardial infarction, uncontrolled hypertension, decompensated heart failure, immunosuppression, systemic corticosteroid therapy, severe chronic obstructive pulmonary disease, chronic kidney disease stage 4-5), type 1 or type 2 diabetes mellitus, or psychiatric/neurological disorders impairing the ability to provide informed consent;
• Tumor invasion into adjacent structures or organs (cT4b) identified preoperatively and/or intraoperatively;
• Predicted risk of anastomotic leakage >10% (AFOR 2-6).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Russia · 7 centers

• Moscow City Oncology Hospital No. 62 of the Moscow Department of Health — Moscow
• Central Clinical Hospital of the Administrative Directorate of the President of the Russia — Moscow
• State Budgetary Institution of Healthcare of the city of Moscow "Moscow Clinical Scientifi — Moscow
• State Autonomous Healthcare Institution of Nizhny Novgorod Region "Research Institute of C — Nizhny Novgorod
• Leningrad Regional Clinical Hospital — Saint Petersburg
• Republican clinical oncological center — Ufa
• Sverdlovsk Regional Oncological Center — Yekaterinburg

Identifiers

NCT: NCT07463261 · 07/25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗