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Lateral Lymph Node Dissection After Neoadjuvant Chemo-radiation in Advanced Low Rectal Cancer

Primary Purpose

Rectal Cancer

Status
Terminated
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
LLND
labeled line
Sponsored by
West China Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring rectal cancer, lateral lymph node dissection, neoadjuvant chemoradiation, total mesorectal excision, surgery, recurrence, metastasis, overall survival

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed rectal cancer (below the peritoneal reflection) Clinical stage I, II, or III
  • No extramesorectal lymph node swelling (shorter diameter is less than 10 mm)
  • No invasion to other organ (s)
  • PS: 0, 1
  • No past history of chemotherapy, pelvic surgery or radiation
  • Written informed consent operative criteria:
  • Mesorectal excision is performed
  • Operative findings:
  • Main lesion of the tumor is located at the rectum
  • Lower tumor margin is below the peritoneal reflection
  • R0 after resection

Exclusion Criteria:

  • High rectal cancer
  • Multiple cancer patients
  • Pregnant patients
  • Psychological disorder
  • Steroid administration
  • Cardiac infarction within six months
  • Severe pulmonary emphysema and pulmonary fibrosis
  • Doctor's decision for exclusion

Sites / Locations

  • West China Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

LLND+TME group

TME group

Arm Description

advanced rectal cancer patients after neoadjuvant chem-radiation with suspicious lateral lymph nodes involvement undergo lateral lymph node dissection and total mesorectal excision(LLND+TME)

advanced rectal cancer patients after neoadjuvant chem-radiation with suspicious lateral lymph nodes involvement undergo total mesorectal excision (TME)solely, without LLND

Outcomes

Primary Outcome Measures

3-year local recurrence

Secondary Outcome Measures

overall survival
disease free survival
Incidence of sexual and urinary dysfunction
postoperative complications

Full Information

First Posted
November 23, 2015
Last Updated
January 27, 2021
Sponsor
West China Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02614157
Brief Title
Lateral Lymph Node Dissection After Neoadjuvant Chemo-radiation in Advanced Low Rectal Cancer
Official Title
Lateral Pelvic Lymph Node Dissection After Neoadjuvant Chemo-radiation for Preoperative Enlarged Lateral Nodes in Advanced Low Rectal Cancer: a Phase III Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Terminated
Why Stopped
The enrollment was too low
Study Start Date
May 2016 (undefined)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
West China Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Lateral lymph nodes (LLD) metastasis is a major cause of local recurrence for advanced rectal cancer. As for the treatment strategies on LLN metastasis, there are huge controversies on whether lateral pelvic lymph nodes dissection (LLND) after neoadjuvant chemo-radiotherapy (nCRT) between Western and Eastern countries. Retrospective cohort evidences indicate that LLND following total mesorectal excision (TME) will bring benefit from cT3-4 rectal cancer, not regular predictive LLND, which will bring more side effects on the contrary. Existing reports tend to recommend LLND for specific individual with suspicious LLN metastasis. Moreover, there is a blank strict prospective randomized control study on the comparison of LLND+TME and LLND after nCRT. Therefore, our trial will compare the efficacy and safety of the two strategies for mid/low rectal cancer with suspicious LLN metastasis. The risk factors (such as radiologic factors, pathologic factors, and serum protein) to predict local recurrence and overall survival will be further investigated.
Detailed Description
Recently, the incidence and mortality of colorectal cancer have increased, leading the second prevalence after lung cancer. Local recurrence of mid/low rectal cancer is not only the poor prognostic factor but also the threat of terrible quality of life. Although universal usage of neoadjuvant chemo-radiotherapy (nCRT) and total mesorectal excision (TME) have decreased local recurrence to 5%-10%, the ratio of local recurrence has occupied almost 30% of total metastasis and recurrence incidences, which limited the therapeutic effect of rectal cancer. Increasing evidences have demonstrated lateral pelvic lymph nodes (LLN) metastasis as one of the prominent causes of local recurrence, accompanied with 10%-25% advanced rectal cancer. Published researches also reminder us preoperative LLN involvement may lead to high local recurrence and poor overall survival. As for the treatment strategies on LLN metastasis, there are huge controversies on whether lateral pelvic lymph nodes dissection (LLND) or LLND+TME after nCRT: Eastern countries especially Japan favors LLND following TME with the reasons: 1) the incidence of LLN metastasis reaches as high as 10%-25% and 27% of rectal patients who undergo TME solely (without LLND) will develop into local recurrence. And the predictive pelvic recurrence rate will decrease 50%; corresponding 5-year overall survival will increase 8%-9%. 2) efficacy of LLND equals to resection of "local lymph nodes metastases". A large cohort of 11567 cases from Japan demonstrates resection of iliac lymph nodes metastasis does not show any difference from TME of cTxN2aM0 and resection of obturator and external iliac lymph nodes favors that of liver metastasis. 3) Japanese Guidelines for treatment of colorectal in 2014 also recommends mid/low II/III rectal cancer under peritoneal reflex undergo regular TME+LLND. On the contrary, western countries favor sole TME after nCRT for LLN metastasis, holding that: 1) rate of lymph nodes metastasis is relatively low and LLN metastasis is regarded as systemic metastasis. 2) LLND experiences longer operative time, higher postoperative complications, and poor quality of life. 3) American NCCN and European ESMO guidelines recommend single TME for rectal cancer, if necessary, LLDN is added when LLN is indeed metastasis. However, there is a blank strict prospective randomized control study on the comparison of nCRT and LLND. Present existing retrospective cohort mainly focus on all the mid/low advanced cancer, not the specific individual of suspicious LLN metastasis. In fact, the results almost indicate no differences on local recurrence and overall survival, except for less operation time, blood loss, and perioperative complications in LLND. Although the latest researches start to report their preliminary outcomes, the patients sample sizes are small and they achieve varied recurrence and overall survival. In conclusion, the treatment strategy for colorectal cancer has focused on individual and precision. Massive of retrospective reports have indicated that rectal cancer patients with LLN metastasis will benefit from LLND, however, there is hot controversy on the treatment of whether TME+LLND or TME+nCRT for specific rectal patients with suspicious LLN metastasis. Therefore, our trial will compare the efficacy and safety of the two strategies for mid/low rectal cancer with suspicious LLN metastasis. The risk factors (such as radiologic factors, pathologic factors, and serum protein) to predict local recurrence and overall survival will be further investigated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
rectal cancer, lateral lymph node dissection, neoadjuvant chemoradiation, total mesorectal excision, surgery, recurrence, metastasis, overall survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LLND+TME group
Arm Type
Experimental
Arm Description
advanced rectal cancer patients after neoadjuvant chem-radiation with suspicious lateral lymph nodes involvement undergo lateral lymph node dissection and total mesorectal excision(LLND+TME)
Arm Title
TME group
Arm Type
No Intervention
Arm Description
advanced rectal cancer patients after neoadjuvant chem-radiation with suspicious lateral lymph nodes involvement undergo total mesorectal excision (TME)solely, without LLND
Intervention Type
Procedure
Intervention Name(s)
LLND
Other Intervention Name(s)
Lateral Lymph Node Dissection
Intervention Description
advanced rectal cancer patients whose lymph nodes are suspiciously enlarged after neoadjuvant chemoradiation will undergo lateral lymph node dissection (LLND) and total mesorectal excision (TME)
Intervention Type
Device
Intervention Name(s)
labeled line
Primary Outcome Measure Information:
Title
3-year local recurrence
Time Frame
until local-recurrence (up to 3 years)
Secondary Outcome Measure Information:
Title
overall survival
Time Frame
3 years
Title
disease free survival
Time Frame
3 years
Title
Incidence of sexual and urinary dysfunction
Time Frame
1 year
Title
postoperative complications
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed rectal cancer (below the peritoneal reflection) Clinical stage I, II, or III No extramesorectal lymph node swelling (shorter diameter is less than 10 mm) No invasion to other organ (s) PS: 0, 1 No past history of chemotherapy, pelvic surgery or radiation Written informed consent operative criteria: Mesorectal excision is performed Operative findings: Main lesion of the tumor is located at the rectum Lower tumor margin is below the peritoneal reflection R0 after resection Exclusion Criteria: High rectal cancer Multiple cancer patients Pregnant patients Psychological disorder Steroid administration Cardiac infarction within six months Severe pulmonary emphysema and pulmonary fibrosis Doctor's decision for exclusion
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ziqiang Wang, MD,PhD
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
West China Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China

12. IPD Sharing Statement

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Lateral Lymph Node Dissection After Neoadjuvant Chemo-radiation in Advanced Low Rectal Cancer

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