Cost-utility of Two Strategies of Perineal Reconstruction After Abdominoperineal Resection for Anorectal Carcinoma

Study Overview
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Brief Summary
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Abdominoperineal resection performed for anorectal tumors leaves a large pelvic and perineal defect causing a high rate of morbidity of the perineal wound (40 - 60 %). Biological meshes offer possibility for a new standard of perineal wound reconstruction. Perineal filling with biological mesh is expected to increase quality of life by reducing perineal morbidity.

Detailed Description
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Perineal wound problems after abdominoperineal resection (APR) in the context of cancer are frequent. These types of resection problems occur because of wound complications caused by large perineal defects. Indeed, perineal wound complications, perineal abscess, wound dehiscences, chronic fistulas and sinuses lengthen the hospital stays. Futhermore, the standardization of the surgery since the late 2000s and the extralevator technique lead a larger defect and increase i perineal complications. Several strategies are used to decrease the complication rate. Closure by direct approximation of the pelvic muscles leads to a rate of major complication up to 57% depending on the series. Musculocutaneous flaps help to reduce this rate (16- 65%) but they generate their own morbidity, require experience and increase the costs of care. Finally, the use of biologic meshes since the beginning of 2010 seems to have improve the healing process. However, results are still variable and the only randomized study comparing direct closure and mesh closure showed no significant results at one year. Another ongoing randomized trial is comparing gluteus maximus flap to mesh closure and focusing on physical performances. This increase in post-operative complications and their consequences causes an increase in costs. In addition, they affect the patients' quality of life and lead to a loss of productivity. From an oncological point of view, perineal scarring problems can cause a delay in the adjuvant therapeutic sequence. Few studies have highlighted the efficiency of perineal wound complications, using cost-effectiveness analyses. In order to clarify the best strategy comparing primary and mesh closure in term of cost effectiveness on perineal healing after ELAPE, we designed this randomized controlled trial.

Official Title
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Cost-utility Evaluation of Two Strategies of Perineal Reconstruction After Abdominoperineal Resection for Anorectal Carcinoma: Perineal Filling With Biological Meshes vs. Primary Perineal Wound Closure

Conditions
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Abdominoperineal Resection

Intervention / Treatment
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* Procedure: Biological mesh
* Procedure: Primary perineal wound closure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Eastern Cooperative Oncology Group performance status score of 2 or less Histologically proven rectal adenocarcinoma or anal canal epidermoïd carcinoma Abdominoperineal resection indication after multidisciplinary team discussion: for rectal adenocarcinoma: circumferential MRI margin equal or less than 1 mm from closest tumoral structure and a striated muscular layer (levator ani or external anal sphincter) for epidermoid carcinoma: residual or recurrent tumour after chemoradiotherapy. Voluntary written informed consent Patients with social security insurance or equivalent social protection Exclusion Criteria: T4 tumour needing a surgical extensive resection with reconstruction by a musculocutaneous flap Metastasis disease deemed unresectable with curative intent Previous pelvic radiotherapy for another disease than the rectal or anal cancer Immunosuppressive drugs treatment Uncontrolled diabetes (glycosylated hemoglobin (HbA1c) > 8 % despite adequate therapy) Patient under juridical protection. Sensitivity to porcine derived products. Enrolment in trial with overlapping primary endpoint. Pregnant women Breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm with biological mesh<br>The intervention consists of perinal reconstruction using biological mesh (Cellis prosthesis from Meccellis Biotech, reference C1015E size 10x15cm) | Procedure: Biological mesh<br>* The intervention consists of suturing a biological mesh in the pelvic floor defect. The mesh will be sutured at each side of the coccyx or distal sacrum and directly to the residual pelvic floor muscle and fascia by using interrupted or continuous hand-sewn sutures with an appropriate amount of tension. The mesh that will be used is the Cellis prosthesis from Meccellis Biotech, reference C1015E which size is 10x15cm.<br>|
| Active Comparator: Arm with primary perineal wound closure<br>The intervention consists of perinal reconstruction by primary perineal wound closure | Procedure: Primary perineal wound closure<br>* The intervention consists of stitching the ischioanal and subcutaneous fat using interrupted Vicryl sutures in one or two layers similar to primary perineal closure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental Cost-Utility Ratio (ICUR) | The primary endpoint in this study is based on the assessment of the incremental cost-utility ratio at 1 year, from the collective perspective between biological mesh perineal reconstructions versus. primary perineal closure in patients operated for anorectal carcinoma with proven rectal adenocarcinoma or anal canal epidermoid carcinoma. | At 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perineal wound healing | The perineal wound healing will be assessed using the Southampton wound assessment scale (6-point scale ranging from 0=normal healing to V=deep or severe wound infection) | At 1, 3, 6, 9 and 12 months | 
| Pain intensity | assessed on an 11-point Numeric Rating Scale (NRS) at baseline before surgical procedure and at least 3 times a day during hospital stay. Thereafter, patients will rate their pain intensity in a patient subject diary every day and immediately before each use of pain medication | From date of randomization until the date of study participation end of patient, assessed up to 12 months | 
| Health related Quality of life | Health related quality of life will be assessed using the EuroQOL EQ-5D-5L questionnaire | 1 month, 3 months, 6 months, 9 months, 12 months | 
| Perineal complications | Perineal complications include: Perineal wound infection defined as a swelling of the wound or surrounding tissues with purulent discharge Breakdown of the perineal wound included any wound dehiscence, sinus or ulcer Pelvic abscess included a fluid collection in the pelvis Perineal evisceration defined by exposure of the pelvic cavity through the perineal wound Perineal hernia symptomatic or not Perineal sinus defined as an incomplete healing after 6 months | Daily during hospitalization and at 1, 3, 6, 9 and 12 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anorectal carcinoma, perineal filling, cost-utility analysis, biological meshes, primary perineal wound closure