Biological Mesh Closure of the Pelvic Floor After Extralevator Abdomino Perineal Resection for Rectal Cancer (BIOPEX)

Long-term Results of Biological Mesh Closure of the Pelvic Floor After Extralevator Abdominoperineal Resection for Rectal Cancer

Rationale: Approximately 800 abdominoperineal resections (APR) are performed for rectal cancer each year in the Netherlands. The extralevator approach (eAPR) reduces the rate of positive margins and improves oncological outcome in distal rectal cancer. However, wider excisions increase wound healing problems and development of perineal hernia. This has resulted in a progressive increase of the use of musculocutaneous flaps and biological meshes associated with a substantial increase of costs, which is not supported by proper data.

Objective: The aim of this study is to determine the cost-effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo)radiotherapy.

Study design: This is a multicenter study in which patients undergoing an eAPR are randomized between standard care using primary closure of the perineum and the experimental arm with assisted closure using a biological mesh.

Study population: Patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo)radiotherapy. A total number of 104 patients will be randomized.

Intervention: The intervention in the experimental arm consists of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm.

Main study parameters/endpoints: The primary endpoint is the percentage of uncomplicated perineal wound healing (Souphampton wound score less than II at day 30). Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Both primary perineal closure and biological mesh assisted closure are being performed in daily clinical practise. The potential benefit resulting from participation of the study in patients randomized for biological mesh assisted closure may be a higher chance of uncomplicated perineal wound healing and lower perineal hernia rate. On the other hand, the use of a biological mesh has been associated with increased postoperative pain and seroma formation.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Procedure: Biological mesh assisted perineal closure; Procedure: Primary perineal closure

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Noord-holland
    • Amsterdam, Noord-holland, Netherlands, 1105AZ
      • Academic Medical Cener

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age of 18 years or higher.
2. Planned for eAPR for primary rectal cancer.
3. Life expectancy of more than 2 years.
4. Ability to return for all scheduled and required study visits.
5. Preoperative (chemo)radiotherapy.
6. Written informed consent for study participation.

Exclusion Criteria:

1. Previous pelvic irradiation for other cancers (i.e. prostate cancer).
2. Total exenteration or sacral resection above level S4/S5.
3. Sensitivity to porcine derived products or polysorbate.
4. Severe systemic diseases affecting wound healing (i.e. renal failure requiring dialysis, liver cirrhosis, and immune compromised status like HIV).
5. Collagen disorders (i.e. Marfan).
6. Enrolment in trials with overlapping primary endpoint or otherwise expected influence on wound healing (i.e. biological therapy like antiangiogenic agents).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biological mesh closure; Biological mesh reconstruction of the pelvic floor after extralevator abdomino perineal resection	Procedure: Biological mesh assisted perineal closure; The eAPR procedure will be performed in an identical way as described for the control arm of the study, and this is preferably followed by an omental plasty. The intervention in the experimental arm consists of suturing an acellular biological mesh derived from porcine dermis in the pelvic floor defect (Strattice™, 6x10 cm). The mesh will be sutured at each side of the coccyx or distal sacrum with Prolene or PDS to the discretion of the surgeon. Laterally, the mesh is attached to the remainings of the levator complex and, anteriorly, to the transverse perineal muscle or posterior vaginal wall. A suction drain will be inserted and positioned on top of the mesh. The perineal subcutaneous fat and skin will be subsequently closed in layers similar to primary simple closure as performed in the standard arm.; Other Names: Biological Mesh; Strattice™; Strattice® Reconstructive Tissue Matrix; Lifecell; Porcine dermal Mesh
Active Comparator: Primary perineal closure; Primary perineal closure after extralevator abdomino perineal resection	Procedure: Primary perineal closure; The perineal phase of the APR will be performed according to the principles of an extralevator APR, which means that the levator muscles will be laterally transected in order to leave a muscular cuff around the tumour. The coccyx will not be routinely resected, but only if indicated based on surgical exposure or oncological principles. The extent of excision of perineal skin and ischioanal fat will be as limited as oncologically justified. Preferably, an omental plasty is positioned in the pelvic cavity following resection. Closure of the perineum in the control arm consists of stitching the perineal subcutaneous fat together using interrupted Vicryl sutures in one or two layers. Subsequently, the skin will be closed using interrupted sutures according to the preference of the surgeon. Placement of a transabdominal or transperineal drain will be at the discretion of the surgeon.; Other Names: Primary closure; Perineal wound closure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day Uncomplicated Perineal Wound Healing	uncomplicated perineal wound healing is defined as a Souphampton wound score less than II	From operation to 30 days after the operation

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: LifeCell
• Investigators: Study Chair: Gijsbert D. Musters, M.D., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Principal Investigator: Willem A. Bemelman, Prof, PhD, M.D., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Principal Investigator: Harm J. Rutten, M.D. PhD, Catharina Ziekenhuis Eindhoven; Principal Investigator: Baljit Singh, M.D. PhD, Leicester hospital, Leicester; Principal Investigator: Marcel G.W. Dijkgraaf, M.D., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• Musters GD, Bemelman WA, Bosker RJ, Burger JW, van Duijvendijk P, van Etten B, van Geloven AA, de Graaf EJ, Hoff C, de Korte N, Leijtens JW, Rutten HJ, Singh B, van de Ven A, Vuylsteke RJ, de Wilt JH, Dijkgraaf MG, Tanis PJ. Randomized controlled multicentre study comparing biological mesh closure of the pelvic floor with primary perineal wound closure after extralevator abdominoperineal resection for rectal cancer (BIOPEX-study). BMC Surg. 2014 Aug 27;14:58. doi: 10.1186/1471-2482-14-58.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 19, 2013
• First Submitted That Met QC Criteria: August 20, 2013
• First Posted (Estimate): August 22, 2013

Study Record Updates

• Last Update Posted (Actual): August 17, 2021
• Last Update Submitted That Met QC Criteria: July 23, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Rectal cancer; Extralevator abdominoperineal resection; Biological Mesh; Primary closure
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: METC 2012_360; NTR3717 (Other Identifier: Nederlands Trial register)