Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy

Study Overview
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Brief Summary
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Treatment for Low rectal cancer, especially in patients with regional lymph node metastasis are quite different between Japanese guideline (JSCCR) and western countries' guideline (NCCN, ESMO). While Japanese scholars advocate total mesorectal excision (TME) plus lateral lymph node dissection (LLND), European and American scholars advocate TME alone after Neoadjuvant Chemo-radiotherapy (nCRT), without the need of LLND. Accordingly, this clinical trial is designed to directly compare the efficacy and safety of these two treatment strategies for low rectal cancer with regional lymph node metastasis. It will provide high-level clinical evidence for the treatment of low rectal cancer with suspected local lymph node metastasis

Detailed Description
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There are significant differences between Japanese guidelines (JSCCR) and Western guidelines (NCCN, ESMO) in the treatment of low rectal cancer, especially in patients with regional lymph node metastasis. Japanese scholars advocated total meso rectal resection (TME) + Lateral lymph node dissection (LLND), However, European and American scholars advocate that only TME is used after new adjuvant chemo-radiation (nCRT), without LLND. Therefore, the purpose of this clinical trial was to directly compare the efficacy and safety of these two treatment strategies for low rectal cancer with regional lymph node metastasis. This will provide a high level of clinical evidence for the treatment of low rectal cancer with suspected local lymph node metastasis

Official Title
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Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy of Lower Rectal Cancer With Suspected Local Lymph Node Metastasis

Conditions
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Rectal Neoplasm Malignant

Intervention / Treatment
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* Procedure: TME+LLND
* Procedure: TME+nCRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma(below the peritoneal reflection) Clinical stage Ⅲ Tumor is capable of performing radical recession No past history of chemotherapy, pelvic radiation of other cancers. Written informed consent Lower tumor margin is confirmed below the peritoneal reflection Clinical state T(1-3)N(1-2)M0 is confirmed by the multiple disciplines team(MDT) including surgeons,diagnostic radiologist,radiation oncologist and medical oncologists base on MRI and endorectal ultrasound - Exclusion Criteria: Past history of other cancers Multiple Primary Colorectal Cancers or Familial adenomatous polyposis(FAP) Combine with inflammatory bowl disease(IBD) Recurrence tumor or invade other organs Combine with obstruction,perforation or bleeding which need emergency surgery. Local tumor invade the external sphincter, levator ani muscle or adjacent organs Participant join other clinical trials in 4 weeks. American Society of Anesthesiologists(ASA) ≥Ⅳ and/or Eastern Cooperative Oncology Group(ECOG) ≤2 Pregnant or lactating patients Severity infection before operation Psychological disorder Severe dysfunction of organs or other contraindications Cardiac infarction within six months Severe pulmonary emphysema and pulmonary fibrosis Doctor's decision for exclusion Operative findings: Tumor invade other organs Lower tumor margin is above the peritoneal reflection

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: TME+LLND group<br>Total Mesorectal Excision plus Lateral Lymph Node Dissection for low rectal cancer with regional lymph node metastasis. | Procedure: TME+LLND<br>* patients in TME+LLND group receive Lateral Lymph Node Dissection (LLND) after Total Mesorectal Excision(TME)<br>|
| Other: TME+nCRT group<br>Total Mesorectal Excision After Neoadjuvant Chemo-radiotherapy for low rectal cancer with regional lymph node metastasis. | Procedure: TME+nCRT<br>* patients in TME+nCRT group receive Neoadjuvant Chemo-radiotherapy (nCRT) before Total Mesorectal Excision(TME)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease-free survival | 36 months after surgery | From date of operation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Operative time | Operation day | Operation day | 
| Blood loss | in the perioperative period | Operation day | 
| Incidence of sexual dysfunction | From the date of operation until the date of complication,assessed up to 3 years | 3 years | 
| Incidence of urinary dysfunction | From the date of operation until the date of complication,assessed up to 3 years | 3 years | 
| Incidence of defecation dysfunction | From the date of operation until the date of complication,assessed up to 3 years | 3 years | 
| incidence of Postoperative complications | From the date of operation until the date of complication,assessed up to 3 months | 3 months | 
| overall survival | 60 months after surgery | From the date of operation until the date of death,assessed up to 5 years | 
| 3-year local recurrence rate | 36 months after surgery | From date of operation until the date of local-recurrence (up to 3 years) | 
| 5-year disease-free survival | 60 months after surgery | From date of operation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years | 
| the score of quality of life | The study investigate the quality of life using the WHOQOL Scale | 3 months after operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low rectal cancer, Total Mesorectal Excision (TME), neoadjuvant Chemo-radiotherapy (nCRT), lateral lymph node dissection (LLND)