The Efficacy of Primary Total Mesorectal Excision (TME) Surgery Versus Neoadjuvant Chemotherapy Combined With TME Surgery in Low-risk Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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Comparative analysis of the clinical efficacy between primary Total Mesorectal Excision (TME) surgery and neoadjuvant chemotherapy combined with TME surgery for low-risk locally advanced rectal cancer. Randomly enrolling eligible patients into either the control group receiving neoadjuvant chemotherapy combined with TME surgery or the experimental group receiving primary TME surgery, and subsequently comparing the clinical outcomes of the two groups

Official Title
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TME vs TME+nCT in Low-risk LARC

Conditions
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Rectal Cancer

Intervention / Treatment
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* Procedure: neoadjuvant chemotherapy plus total mesorectal excision
* Procedure: total mesorectal excision


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed patients, aged 18 to 75 years; Pathologically confirmed rectal adenocarcinoma; Distance of the lower margin of the rectal tumor lesion from the anal margin <15cm; High-resolution MRI indicates low-risk locally advanced rectal cancer: T1-3bN1-2 or T3aN0 or T3bN0; no involvement of the anal sphincter; negative mesorectal fascia (MRF) status; negative extramural vascular invasion (EMVI); no cancer nodules; Exclusion of patients with non-local recurrence or distant metastases; Absence of synchronous colorectal multiple primary cancers; Adequate physical condition to tolerate surgery and neoadjuvant chemotherapy, including cardiac, pulmonary, hepatic, and renal functions; The study physician assessed no difficulty in sphincter preservation; patients and their families will be willing to participate in this study and provide written informed consent. Exclusion Criteria: Patients with concurrent other malignancies or a history of malignant tumors in the past; Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, or other conditions requiring emergency surgery; Patients with tumor invasion into the external sphincter or levator ani muscles, or involvement of adjacent organs necessitating combined organ resection; Patients with poor anal function or fecal incontinence before surgery; Patients with a history of inflammatory bowel disease or familial adenomatous polyposis; Patients recently diagnosed with other malignancies; Patients with ASA grade ≥ IV and/or ECOG performance status score > 2; Patients with severe liver or kidney dysfunction, significant cardiopulmonary impairment, coagulation disorders, or those with extreme underlying conditions unable to tolerate surgery; Patients with a history of severe mental illness; Pregnant or lactating women; Patients with uncontrolled infections before surgery; Patients with other clinical or laboratory conditions, as determined by the investigator, that render them unsuitable for participation in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: Primary TME neoadjuvant chemotherapy plus TME
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary total mesorectal excision<br>Patients with low-risk locally advanced rectal cancer received total mesorectal excision alone. | Procedure: total mesorectal excision<br>* Standard total mesorectal excision<br>|
| Active Comparator: Neoadjuvant chemotherapy plus TME<br>Patients with low-risk locally advanced rectal cancer received neoadjuvant chemotherapy and total mesorectal excision. | Procedure: neoadjuvant chemotherapy plus total mesorectal excision<br>* Neoadjuvant chemotherapy regimen recommended FOLFOX6, XELON, FOLFOX, mFOLFOX for 4-6 courses, and TME surgical treatment after preoperative tumor restaging 1-2 weeks after neoadjuvant chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Disease Free Survival | Defined as the proportion of patients who did not experience any of the following events from the beginning of the randomized subgroup to the end of the third year, which included disease progression, local recurrence, distant metastasis, or second primary colorectal cancer, or death from any cause. | 3 years after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distance from the inferior resection margin to the tumor | The length between inferior resection margin and the tumor. | Immediately after the surgery | 
| The status of circumferential margin | When the distance from the tumor or malignant lymph node to the circumferential margin was ≤ 1 mm, it was recorded as a positive circumferential margin. | Immediately after the surgery | 
| The status of distal resection margin | When the distance from the tumor to the distal resection margin was ≤ 10 mm, it was recorded as a positive distal resection margin. | Immediately after the surgery | 
| Postiveoperative stay | The days after surgery in the hospital | 1 months after surgery | 
| Time to Postoperative first feed | The duration after surgery to first feed | 1 months after surgery | 
| Time to Postoperative first gas | The duration after surgery to first gas | 1 months after surgery | 
| Postoperative pain | Postoperative pain according to pain socres | 1 months after surgery | 
| Postoperative anal function | Anal function would be based on wexner Incontinence score. A total score of less than ten is considered good, and a score of more than ten is considered poor. | 3 years after the surgery | 
| Quality of life score | Quality of life score would be based on EORTC QoL C30 scale. | 3 years after the surgery | 
| 3-year overall survival |  | 3 years after the surgery | 
| 5-year Disease Free Survival |  | 5 years after the surgery | 
| 5-year overall survival |  | 5 years after the surgery | 
| Number of participants with treatment-related adverse events | It would be assessed by CTCAE v4.0 | 1 month after neoadjuvant chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal cancer, total mesorectal excision, neoadjuvant chemotherapy