Local Advanced Rectal Cancer, Low Rectal Cancer, Middle Rectal Cancer, Rectal Cancer Surgery, TME
Conditions
Keywords
rectal cancer, preventive stoma, randomized trial, low-risk patients, anastomotic leak
Brief summary
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
PROCEDUREWithout 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).
PROCEDUREWith 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.
Sponsors
ANO Scientific and Practical Club for the Development of Modern Medical Technologies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Colorectal anastomotic leak | 30 days after main surgery | If anastomotic leakage is suspected in the postoperative period defined by worsening abdominal pain (\>5-point increase on the Visual Analog Scale), signs of peritonitis, drain output containing fibrin or intestinal content, or radiologic findings suggestive of leakage on contrast-enhanced CT of the abdomen and pelvis (with or without proctography) and/or findings at diagnostic laparoscopy. Diagnostic and/or therapeutic measures will be undertaken to confirm or rule out the complication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative complications | 30 days after main surgery | Postoperative complications will be classified according to the Clavien-Dindo classification |
| Reoperation rate | 30 days and 1 year after main surgery | During a clinic visit or by telephone interview |
| Stoma rate | 1 year after main surgery | During a clinic visit or by telephone interview |
| Hospital readmissions | 30 days after main surgery | The frequency of repeated admissions to this or other hospitals after the patient's discharge |
| Quality of life by European Organization for Research and Treatment of Cancer-Cancer30 (EORTC-C30) | 30 days and 1 year after surgery | EORTC-C30 domain scores in scales 0-100 points, a high score for the global health status /quality of life represents a high quality of life, but a high score for a symptom scale / item represents a high level of symptomatology / problems. |
| Quality of life by European Organization for Research and Treatment of Cancer-ColoRectal 29 (EORTC-CR29) | 30 days and 1 year after surgery | EORTC-CR29 domain scores in scales 0-100 points, a high score for the global health status /quality of life represents a high quality of life, but a high score for a symptom scale / item represents a high level of symptomatology / problems. |
| Low Anterior Resection Syndrome (LARS) | 1 year after main surgery | At 1 year, assessment of Low Anterior Resection Syndrome (LARS) will be performed during a clinic visit or by telephone interview. |
| Length of hospital stay | until discharge within 90 days | total days in hospital |
Countries
Russia
Contacts
CONTACTVladislava S Goncharova, Ms.
CONTACTNikita N Burlov, Dr.
Outcome results
None listed