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

January 27, 2021 updated by: Ziqiang Wang,MD, West China Hospital

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • West China hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LLND+TME group
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)
Procedure: LLND
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)
Other Names:
  • Lateral Lymph Node Dissection
Device: labeled line
No Intervention: TME group
advanced rectal cancer patients after neoadjuvant chem-radiation with suspicious lateral lymph nodes involvement undergo total mesorectal excision (TME)solely, without LLND

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
3-year local recurrence
Time Frame: until local-recurrence (up to 3 years)
until local-recurrence (up to 3 years)

Secondary Outcome Measures

Outcome Measure
Time Frame
disease free survival
Time Frame: 3 years
3 years
overall survival
Time Frame: 3 years
3 years
postoperative complications
Time Frame: 1 year
1 year
Incidence of sexual and urinary dysfunction
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Investigators

  • Principal Investigator: Ziqiang Wang, MD,PhD, West China hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (Actual)

May 1, 2017

Study Completion (Actual)

May 1, 2017

Study Registration Dates

First Submitted

November 23, 2015

First Submitted That Met QC Criteria

November 24, 2015

First Posted (Estimate)

November 25, 2015

Study Record Updates

Last Update Posted (Actual)

February 1, 2021

Last Update Submitted That Met QC Criteria

January 27, 2021

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • pLNR-201501

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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