Understanding and Tailored Treatment of Low Anterior Resection Syndrome

Overview

The goal of this observational study is to learn why some patients develop low anterior resection syndrome (LARS) after colorectal cancer treatment. The study also aims to identify different subtypes of LARS and understand which patients may respond to specific treatments. The main questions it aims to answer are: * What physiological and imaging changes are associated with LARS? * How do patients with LARS differ from patients without LARS after colorectal cancer surgery? * Are there measurable differences between LARS, patients treated with organ-preserving chemoradiotherapy, and patients with fecal incontinence? Participants will: * Complete advanced physiological and imaging assessments related to bowel function * Be compared with four control groups: * patients without LARS after colorectal cancer surgery * patients treated with organ-preserving chemoradiotherapy * patients with fecal incontinence and urge fecal incontinence * Take part in a single study visit where all measurements are performed

Detailed description

Low anterior resection syndrome (LARS) is a common long-term complication after colorectal cancer surgery. Up to 80% of patients experience symptoms such as urgency, frequent bowel movements, clustering, and fecal incontinence. These symptoms can severely affect quality of life, and the underlying causes are not fully understood. LARS appears to result from several interacting mechanisms, including sensory changes, altered motility, reduced reservoir function, sphincter dysfunction, and effects of chemotherapy or radiotherapy. Because different patients may have different dominant mechanisms, treatment responses vary widely.

This observational study aims to investigate the physiological and imaging characteristics of LARS using advanced assessment methods. The goal is to better understand the mechanisms behind LARS, identify distinct patient subtypes, and support development of more targeted treatment strategies.

The study will include 50 patients with minor or major LARS after rectal cancer surgery. Their results will be compared with four control groups:

* patients who had rectal cancer surgery but did not develop LARS, * patients with fecal incontinence (before/after sacral nerve stimulation), * patients with urge fecal incontinence (before/after dorsal genital nerve stimulation), and * patients treated with organ-preserving chemoradiotherapy ("watch-and-wait"), whose rectum has not been surgically removed.

All participants will attend a single study visit that includes advanced physiological measurements, Magnetic Resonance Imaging (MRI)-based assessments, and standardized questionnaires. These methods are not part of routine clinical care but are used to explore mechanisms such as motility, sensory function, sphincter activity, and rectal reservoir function.

Patients with LARS will also be followed during their standard stepwise treatment pathway. They will complete questionnaires before and during each treatment step, which may include dietary advice, medication, pelvic floor training (biofeedback), and rectal emptying techniques such as mini-enemas or transanal irrigation. This follow-up will help determine how different physiological patterns relate to treatment response.

The study is conducted in collaboration between Aarhus University Hospital and Aalborg University Hospital, with expert input from The Royal London Hospital (UK) and Motilis SA (Switzerland).

Primary outcome measures

• EuroQol 5-Dimension, 5-Level quality-of-life questionnaire [Time frame: From baseline visit to the end of each standardized treatments at 4 weeks]
• Low Anterior Resection Syndrome Score [Time frame: From baseline visit to the end of each standardized treatments at 4 weeks]

Secondary outcome measures (12)

• St Mark's Incontinence score [Time frame: • Applied at baseline and four weeks into all treatment periods]
• Colostomy Impact Score [Time frame: From baseline visit to the end of each standardized treatments at 4 weeks]
• Bristol Stool Form Scale [Time frame: From baseline visit to the end of each standardized treatments at 4 weeks]
• Patient Assessment of Constipation Symptoms (PAC-SYM) [Time frame: From baseline visit to the end of each standardized treatments at 4 weeks]
• Wexner Incontinence Score [Time frame: From baseline visit to the end of each standardized treatments at 4 weeks]
• Hospital Anxiety and Depression Scale (HADS) [Time frame: From baseline visit to the end of each standardized treatments at 4 weeks]
• Whole gut and segmental transit times as measured with 3D-Transit [Time frame: At baseline]
• Colonic and segmental colonic volumes [Time frame: At baseline]
• Resting Anal Pressure Measured by High-Resolution Anorectal Manometry [Time frame: At baseline]
• Maximal Voluntary Anal Squeeze Pressure Measured by High-Resolution Anorectal Manometry [Time frame: At baseline]
• Rear-Front Pressure Gradient Measured by the Fecobionics Device [Time frame: At baseline]
• Compare the physiological findings in LARS patients with controls [Time frame: At baseline]

Eligibility criteria

Inclusion criteria

General:

• Must be able to read and understand Danish.
• All participants must be adults and >18 years and have full legal capacity.
• Assessed by study personnel to have understood the research protocol, being able to comply with investigation procedures as well as ability to come to the hospital at the agreed timepoints, and to complete the trial.

Specific inclusion criteria for LARS patients:

• Patients operated for rectal cancer with a rectal resection and sphincter preserving surgery at a minimum of three months postop.
• If patients have received a temporary protective ileostomy, this should have been reversed for a minimum of three months postop.

Specific inclusion criteria for fecal incontinence patients and urge fecal incontinence patients

• Patients planned for neuromodulation.
• Satisfactory interoperative test results leading to permanent implantation of a pacemaker for sacral nerve modulation.

Specific inclusion criteria for "watch and wait" patients:

• Rectum/colon cancer patients treated with organ-preserving treatment, i.e., chemotherapy and radiotherapy with a complete clinical and radiological response at a minimum of 12 months posttreatment.

Exclusion criteria

General exclusion criteria

• Persons that are not able to understand information
• Connective tissue disorders
• Parkinson's disease
• Non-MRI compatible pacemaker, clips or other metal objects in the body. Patients implanted with a pacemaker for sacral nerve modulation will not undergo MRI postoperatively.
• Piercings that cannot be removed before MRI
• Claustrophobia
• Allergic to latex
• Abdominal diameter equal or more than 140 cm
• Have other individual factors, in the opinion of the physician/healthcare professional, in which participating is contraindicated
• Participation in concomitant clinical trial
• Known intestinal obstruction, significant intestinal strictures or perforation. If in doubt about intestinal stricture, the patient will be examined with MRI of the small intestine, colonoscopy or other supplementing examination
• Disorders of swallowing
• Pregnant women

Specific exclusion criterias for LARS patients

• History of anastomotic leakage following rectal resection and sphincter preserving therapy
• Evidens of local recurrence or dessimination of the cancer

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

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

Denmark · 3 centers

• Aalborg University Hospital — Aalborg
• Aarhus University Hospital — Aarhus
• Vejle Hospital — Vejle

Identifiers

NCT: NCT07573371 · R325-A19027

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗