A Phase III Randomized Trial Evaluating the Tailored Versus the Systematic Use of Defunctioning Stoma After Total Mesorectal Excision for Rectal Cancer
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 212
- Locations
- 28
- Primary Endpoint
- Quality of life over the 12 months after surgery
Study Overview
Brief Summary
GRECCAR 17 will be the first prospective and randomized trial to assess a tailored policy in the use of defunctioning stoma after TME according to the personalized risk of anastomotic leakage. The tailored use of defunctioning stoma after TME for rectal cancer should improve both the quality of life of patients and the anorectal function, without any impact on anastomotic leakage. Moreover, for the healthcare system, this new approach could be a cost-effective strategy, leading to a decrease in healthcare expenses.
The main objective is to compare the impact of tailored defunctioning stoma after TME for rectal cancer versus the systematic use of defunctioning stoma on the evolution of the specific Quality Of Life (QLQC30) during the 12 months after surgery.
Detailed Description
The introduction of Total Mesorectal Excision (TME) as the surgical procedure of choice for low and mid rectal cancer has led to decrease local recurrence and improved oncological results. Postoperative morbidity remains a major issue, and the most feared complication is anastomotic leakage. The systematic use of a defunctioning stoma during 3 months to protect low colorectal anastomosis (below than 7 cm from the anal verge) is the standard of practice after TME surgery in order to decrease risks of anastomotic leakage and urgent re-operations.
However, there have been a lot of controversies surrounding the role of defunctioning stoma mainly due to stoma-related complications, ranked from 20% to 60%, which may lead to prolonged inpatient care, urgent re-operation and devastating effects on quality of life (QOL) and healthcare expenses. Moreover, it has been reported that patients either without defunctioning stoma, or with early stoma closure (days 8-12 after TME) have a better functional outcomes than patients with systematic defunctioning stoma for 3 months.
The experimental arm (arm A) will benefit from a tailored use of defunctioning stoma after TME based on a 2-step process: i) to perform or not a defunctioning stoma according to the personalized risk of anastomotic leakage (defunctioning stoma only if Anastomotic Failure Observed Risk Score=[2-6]), ii) to perform an early stoma closure at day 8-12, according to clinical (fever), biological (CRP level days 2 and 4 postoperatively) and radiological postoperative assessment (CT-scan with colonic contrast retrograde enema day 7-8 postoperatively). The control arm (arm B) will benefit from systematic use of defunctioning stoma for 2-3 months after TME, according to French national and international guidelines.
Patients will be followed at 1, 4, 8 and 12 months after surgery, with chest, abdominal and pelvic scan and tumour markers.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18-80 years;
- •Rectal adenocarcinoma (histologically proven)
- •No metastasis or medical history of colorectal metastasis (M0)
- •Patients with rectal cancer < 12 cm from the anal verge (determined by rectal examination or MRI)
- •Patients operated on by mini-invasive TME (laparoscopic, robotic or TaTME);
- •With or without neo adjuvant treatment
- •Realize a stapling anastomosis < 7 cm from the anal verge (determined by rectal examination or MRI)
- •Patients with expected defunctioning ileostomy
- •Appropriate hematologic function: hemoglobin ≥ 10.5 g/dL, leukocytes > 4000/mm3, blood platelets > 100,000/mm3);
- •Appropriate renal function (serum creatinine < 15 mg/dL);
- •Effective contraception of childbearing age : Male patients and premenopausal women should agree to use two medically validated contraceptive methods (one for the patient et one for the partner) during the study
- •Patient affiliated or beneficiary to a health security system;
- •Patient and doctor have signed informed consent
Exclusion Criteria
- •Patients with rectal cancer requiring TME surgery with handsewn anastomosis;
- •Patients operated on by open approach;
- •Previous pelvic irradiation for reasons other than rectal cancer
- •Concomitant cancer or medical history of cancer within 5 years other than cancers treated in situ (cervical carcinoma or basocellular carcinoma or spinocellular carcinoma)
- •Patients with expected defunctioning colostomy;
- •Patients with perforated rectal cancer or preoperative pelvic sepsis;
- •Patients with inflammatory bowel disease and/or bowel obstruction,
- •Patients operated on in emergency;
- •Patients with poor nutrition (Albumin < 34 g/L, pre-Alb < 0.14 g/L)
- •Patients with extended-TME or pelvic exenteration (prostate);
- •Patients with history of heart or vascular ischemia;
- •Severe heart disease or congestive heart disease;
- •Patients with immunodeficiency and/or under corticotherapy;
- •Severe lung disease or respiratory failure;
- •Severe kidney disease;
- •Previous disease or disability expected to influence the assessment of postoperative QOL;
- •Pregnancy or breast feeding;
- •Persons deprived of liberty or under guardianship (curatorship or tutorship) or incapable of giving consent;
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up scheduled.
Outcomes
Primary Outcomes
Quality of life over the 12 months after surgery
Time Frame: At 1, 4, 8, and 12 months of follow-up
The QLQ-C30 is a patient self-rating questionnaire (30 questions) that measures physical, role, social, emotional, and cognitive functions as well as overall QoL. Scores can be linearly transformed to provide a score from 0 to 100 REF. Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales. The area under the quality of life curve will be measured over the 12 months after rectal surgery, with measurement time points at 1, 4, 8 and 12 months.
Secondary Outcomes
- Proportion of anastomotic leakage(At 1 and 4 months after the rectal surgery)
- Rate of defunctioning stoma(At 1 month after the rectal surgery)
- Low Anterior Resection Syndrome score (LARS score)(At 1, 4, 8 and 12 months after the rectal surgery)
- Anal Incontinence (Wexner score)(At 1, 4, 8 and 12 months after the rectal surgery)
- Urinary symptom profil (USP)(At 1, 4, 8, 12 months after the rectal surgery)
- Postoperative morbidity (Clavien-Dindo score I-IV)(At 1 and 4 months after the rectal surgery)
- Proportion to work return after TME in active workers(Through study completion, an average of 1 year)
- The PF, RF, CF, EF, SF, FA, PA, NV, QL Dimensions of the QLQ-C30 questionnaire(At 1, 4, 8 and 12 months after the rectal surgery)
- The urinary frequency(At 1, 4, 8, and 12 months post-surgery)
- Blood or mucus in stools(At 1, 4, 8, and 12 months post-surgery)
- Stool frequency(At 1, 4, 8, and 12 months post-surgery)
- Body image dimensions of the QLQ-CR29 questionnaire(At 1, 4, 8, and 12 months post-surgery)
- International Index of Erectile Function (IIEF)-5(At 1, 4, 8 and 12 months after the rectal surgery)
- Female Sexual Function Index (FSFI) scale scores(At 1, 4, 8 and 12 months after the rectal surgery)
- Time to work return after TME in active workers(Through study completion, an average of 1 year)
- Incremental cost-utility ratio defined as an incremental cost / Quality-Adjsuted Life Year (QALY) gained(From surgery to 12 months after surgery)
- Postoperative mortality (Clavien-Dindo score V)(At 1 and 4 months after the rectal surgery)
- Quality of life over the 12 months after surgery(QLQ-C30 is assessed at 1, 4, 8 and 12 months after the rectal surgery)
- Changes in microbiome composition and diversity from baseline to 1 month(From baseline to Month 1)
- Total budgetary impact for French healthcare insurance system of spreading selective ostomy practice in France(From surgery to 12 months after surgery)
- Indirect Costs (€) for French Healthcare insurance scheme of sickness leaves(From surgery to 12 months after surgery)