Clinical trial NCT05671809: Effects of Different Treatment for Anorectal Function of Patients With Rectal Cancer
Official title: Effects of Different Treatment for Anorectal Function of Patients With Rectal Cancer: a Study Protocol for a Prospective, Observational, Controlled, Multicentre Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Rectal Cancer
Keywords: Anorectal function, Rectal cancer, NCRT, Surgery
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Nanfang Hospital, Southern Medical University
First posted: 2023-01-05
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with rectal cancer at The Sixth Affiliated Hospital, Sun Yat-sen University and Nanfang Hospital, Southern Medical University will be assessed for suitability for inclusion.

Brief summary: Background

Neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision are standard treatments for patients with locally advanced rectal cancer. These sphincter-saving operations may be accompanied by a series of functional disorders. Prospective studies dynamically evaluating the different roles of surgery and NCRT on anorectal function are lacking.

Methods/design

The study is a prospective, observational, controlled, multicentre study. After screening for eligibility and obtaining informed consent, a total of 402 rectal cancer patients aged from 18 to 75 years old undergoing sphincter preservation treatments at The Sixth Affiliated Hospital, Sun Yat-sen University and Nanfang Hospital, Southern Medical University are included in the trial. The primary outcome measure is the average resting pressure of anal sphincter. The secondary outcome measures are maximum anal sphincter contraction pressure and Wexner continence score. Evaluations will be carried out at the following stages: baseline (T1), after radiotherapy or chemotherapy (before surgery, T2), after surgery (before closing the temporary stoma, T3), and at follow-up visits (every 3 to 6 months, T4, T5......). Follow-up for each patient will be at least 2 years.

Discussion

We expect the program to provide more information on therapeutical options and strategies to reduce anorectal dysfunction of rectal cancer patients who have been undergone sphincter preservation treatments.

Detailed description: Study design and setting

The study is a prospective, observational, controlled, multicentre study of patients diagnosed with rectal cancer. The eligible patients will be informed about the study in detail. After providing written informed consent, these patients will undergo sphincter-preserving therapies including either NCRT with surgery, or NCT with surgery or surgery. All patients will receive anorectal manometry and Wexner continence score before and after therapies and at follow-up visits.

Participants

Patients diagnosed with rectal cancer at The Sixth Affiliated Hospital, Sun Yat-sen University and Nanfang Hospital, Southern Medical University will be assessed for suitability for inclusion.

Inclusion criteria

18-75 years of age. Rectal cancer with pathological diagnosis. Patient will undergo sphincter-preserving therapies. ECOG score for performance status is 0-2. Written informed consent.

Exclusion criteria

Patients who have undergone rectal cancer surgery. Patients who have received pelvic radiotherapy. Patients with other active malignant tumors. Recently (less than 4 weeks) received surgery or patients with recent severe trauma.

Significant cardiac disease: congestive heart failure of New York Heart Association class ≥2; patients with recent (less than 12 months) active coronary artery disease (unstable angina or myocardial infarction).

Recent (less than 6 months) thrombosis or embolism events, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism and deep vein thrombosis.

Patients with toxicity (CTCAE Grade ≥ 2) caused by previous treatment that has not subsided.

Pregnant or lactating women.

Interventions

The eligible patients who voluntarily sign the consent form will undergo either NCRT with surgery, or NCT with surgery, or surgery according to treatment guidelines.

Outcomes

Evaluations will take place at baseline (T1), after radiotherapy or chemotherapy (before surgery, T2), after surgery (before closing the temporary stoma, T3), and at follow-up visits (every 3 to 6 months, T4, T5......). Follow-up for each patient will be at least 2 years.

The primary outcome is the average resting pressure (ARP) of anal sphincter. The secondary outcomes are maximum anal sphincter contraction pressure and Wexner continence score. High-resolution anorectal manometry will be used to assess the average resting pressure and maximal contraction pressure. We will use high-resolution anorectal manometry with a 24-channel water-perfused catheter (Multiplex, Alacer, Biomedica, Sao Paulo, Brazil), which has proven to be adequate for clinical use. This test will be performed by a trained physician. In addition, we will use Wexner continence score to assess fecal incontinence symptoms and their impact on the quality of life of patients following sphincter-preserving rectal cancer surgery.

Recruitment

Patients aged 18-75 years who have been diagnosed with rectal cancer and consider sphincter-preserving therapies are eligible for the study. The study physicians will inform the patients about the study in detail. After obtaining informed consent, the patient is recruited to the study.

Allocation

The study is a prospective, observational, controlled study without randomization. Treatment decisions will be made by multidisciplinary team for eligible patients who voluntarily sign the consent form. All patients will receive evaluation of the anorectal function through anorectal manometry and Wexner continence score before and after therapies and at follow-up visits.

Participant timeline

Recruitment started in December 2022 at The Sixth Affiliated Hospital, Sun Yat-sen University and Nanfang Hospital, Southern Medical University.

Sample size

The sample size calculation was performed considering the results of a previous case-control study with rectal cancer patients undergoing chemoradiotherapy and/or surgery. In this study, RP was significantly lower in the chemoradiotherapy group than in the surgery group (32.7 +/- 17 vs 45.3 +/- 18 mmHg; P =.03) at the time of ileostomy closure. These values were introduced at PASS v11 software (NCSS, LLC. Kaysville, Utah, USA) with a power of 80%, alpha 0.05, and an enrollment ratio of 1/1, resulting in an estimated sample size of 122 participants in each group. Then, considering the need of lost to follow-up, which is estimated at around 10.0% of the cases, we will require a total of 134 patients in each group.

Data management, collection and monitoring

All protocol-required information collected during the study will be entered by the investigator in the electronic case report forms (CRF). The investigator should complete the CRF as soon as possible after information is collected. An explanation should be given for all missing data. The completed CRF will be reviewed and signed by the investigator. The main investigator will continuously monitor data. Data will be stored in the secured network of Sun Yat-sen University and for security reasons, in an external hard drive which will be used to back up regularly the database.

Statistical methods

For statistical analysis of the quantitative variables with normal distribution, the mean, standard deviation (SD), median and interquartile range will be calculated. Group comparisons will be made using t tests or Mann-Whitney U test for continuous variables. Associations between the categorical variables will be tested with the Chi-Square-test or the Fisher exact test, when appropriate. Paired values (before and after therapies) will be compared for each patient using a paired t test or a Wilcoxon test. The data will be analyzed using IBM SPSS Statistics for Windows, version 27.0 (IBM Corporation, Armonk, NY, USA). A significance threshold of p \< 0.05 will be adopted for all tests.

Research ethic approval

The study adheres to the Declaration of Helsinki on medical research protocols and ethics. The protocol was reviewed and approved by the Human Medical Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (number 2022ZSLYEC-614).

Eligibility criteria: Inclusion Criteria:

18-75 years of age. Rectal cancer with pathological diagnosis. Patient will undergo sphincter-preserving therapies. ECOG score for performance status is 0-2. Written informed consent.

Exclusion Criteria:

Patients who have undergone rectal cancer surgery. Patients who have received pelvic radiotherapy. Patients with other active malignant tumors. Recently (less than 4 weeks) received surgery or patients with recent severe trauma.

Significant cardiac disease: congestive heart failure of New York Heart Association class ≥2; patients with recent (less than 12 months) active coronary artery disease (unstable angina or myocardial infarction).

Recent (less than 6 months) thrombosis or embolism events, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism and deep vein thrombosis.

Patients with toxicity (CTCAE Grade ≥ 2) caused by previous treatment that has not subsided.

Pregnant or lactating women.

Primary outcomes:
measure: ARP
timeFrame: Baseline (T1), after radiotherapy or chemotherapy (before surgery, T2), after surgery (before closing the temporary stoma, T3), follow-up visits (every 3 to 6 months, T4, T5……)
Secondary outcomes:
measure: MASCP and Wexner
timeFrame: Baseline (T1), after radiotherapy or chemotherapy (before surgery, T2), after surgery (before closing the temporary stoma, T3), follow-up visits (every 3 to 6 months, T4, T5……)
Other outcomes:
Locations:
Study officials:
affiliation: The Sixth Affiliated Hospital, Sun Yat-sen University
name: Xin-juan Fan, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: The Sixth Affiliated Hospital, Sun Yat-sen University
name: Xiang-Bo Wan, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: The Sixth Affiliated Hospital, Sun Yat-sen University
name: Hong-Cheng Lin, Ph.D
role: PRINCIPAL_INVESTIGATOR
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