Extended Lymphadenectomy for Bile Duct Cancer

Recruiting at 13 trial locations

Overseen By Jiang-Tao LI, PHD;MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Disqualifiers: Heart, lung, brain, kidney dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best approach for removing lymph nodes during surgery for bile duct cancer in the liver. It examines whether removing more lymph nodes improves survival rates compared to removing only nearby ones. The trial involves two groups: one will undergo extended lymphadenectomy, while the other will have only nearby lymph nodes removed. Candidates for this trial include those with bile duct cancer that can be surgically removed and no evident signs of lymph node spread before surgery. As an unphased trial, this study provides patients the opportunity to contribute to important research that could enhance surgical outcomes for future patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What prior data suggests that this extended lymphadenectomy is safe for intrahepatic cholangiocarcinoma?

Research has shown that extended lymphadenectomy, a surgery that removes more lymph nodes, can offer survival benefits for certain bile duct cancer patients. However, the safety of this procedure must be considered. Studies comparing extended lymphadenectomy to regional lymphadenectomy have examined both the potential benefits and risks.

Removing more lymph nodes might help doctors better understand the cancer and could improve outcomes. However, this more involved surgery may also carry a higher risk of complications, such as longer surgery times and recovery periods.

These factors are important to consider when evaluating participation in a clinical trial for extended lymphadenectomy. Patients should always consult with healthcare providers to fully understand the potential risks and benefits for their specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard approach for bile duct cancer, which typically involves regional lymphadenectomy focusing on fewer lymph nodes, the new technique, Extended Lymphadenectomy, involves a more comprehensive removal of lymph nodes, depending on the tumor location in the liver. This expanded approach targets additional lymph node stations, potentially leading to a more thorough removal of cancerous tissue. Researchers are excited about this method because it may improve surgical outcomes and reduce the likelihood of cancer recurrence by addressing more potential sites of cancer spread.

What evidence suggests that this trial's treatments could be effective for intrahepatic cholangiocarcinoma?

Research has shown that removing more lymph nodes, known as extended lymphadenectomy, might help some patients with bile duct cancer live longer. In this trial, participants will join either the Extended Lymphadenectomy arm or the Regional Lymphadenectomy arm. Studies suggest that the extended approach could benefit patients with potential cancer spread to lymph nodes near the aorta. Examining more lymph nodes provides doctors with a clearer picture of the cancer's stage. Some research indicates that this method might lead to better outcomes than removing only nearby lymph nodes. However, the evidence remains mixed, and ongoing research aims to better understand its role in treatment. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with intrahepatic cholangiocarcinoma (ICC), a type of bile duct cancer. Candidates must have resectable tumors without obvious lymph node metastasis, adequate liver function (Child-Turcotte-Pugh score A-B), and be able to tolerate surgery. They should understand the study and consent to follow-up plans. Those with severe organ dysfunction or other cancers are excluded.

Inclusion Criteria

Sign the written informed consent form prior to the test screening

I understand the study, agree to participate, and can follow the study plan.

My liver is working well enough, not the worst.

Exclusion Criteria

I have had other types of cancer in the past.

My liver is severely impaired.

The investigator determined that it was not suitable for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo either regional or extended lymphadenectomy during resection of intrahepatic cholangiocarcinoma

1 day

1 visit (in-person)

Postoperative Recovery

Participants are monitored for postoperative complications and recovery

up to 2 months

Multiple visits (in-person)

Follow-up

Participants are monitored for disease-free survival and overall survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Extend LymphAdenectomy

Trial Overview The trial investigates whether extending lymph node removal during ICC tumor resection improves patient outcomes compared to regional lymphadenectomy alone. It aims to clarify if more extensive surgery affects survival rates, given contradictory findings in previous studies.

How Is the Trial Designed?

Group I: Extend LymphAdenectomy Experimental Treatment 1 Intervention

Expanded lymph node dissection for right liver tumors included stations 12, 8, and 13, and stations 12, 1, 3, 7, and 8 for left liver tumors

Group II: Regional LymphAdenectomy Active Control 1 Intervention

Regional lymph node dissection for intrahepatic cholangiocarcinoma included station 12.

Extend LymphAdenectomy is already approved in United States, European Union, China for the following indications:

Approved in United States as Extended Lymphadenectomy for:

• Intrahepatic cholangiocarcinoma staging and treatment

Approved in European Union as Extended Lymphadenectomy for:

• Intrahepatic cholangiocarcinoma staging and treatment

Approved in China as Extended Lymphadenectomy for:

• Intrahepatic cholangiocarcinoma staging and treatment

Who Is Running the Clinical Trial?

Second Affiliated Hospital, School of Medicine, Zhejiang University

Lead Sponsor

Trials

985

Recruited

2,050,000+

Published Research Related to This Trial

In a study of 257 patients with extrahepatic bile duct cancer, metastasis to regional lymph nodes was found in 34.6% of cases and was linked to significantly poorer survival outcomes, highlighting the importance of lymph node status in prognosis.

The research revealed that the median number of lymph nodes examined was significantly lower in hilar cholangiocarcinoma (3 nodes) compared to distal bile duct adenocarcinoma (12 nodes), suggesting that current staging guidelines may lead to understaging of tumors, particularly for hilar cholangiocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adequate lymph node assessment for extrahepatic bile duct adenocarcinoma. Ito, K., Ito, H., Allen, PJ., et al.[2010]

In a study of 110 patients with hilar cholangiocarcinoma, nearly half had no lymph node involvement, while 35.5% had regional metastases and 17.3% had both regional and paraaortic metastases, indicating a significant rate of lymphatic spread in advanced cases.

The 3-year survival rate was notably higher (55.4%) for patients without node involvement compared to those with metastases (31.8% for regional and 12.3% for paraaortic), suggesting that extended lymphadenectomy may be beneficial, although further research is needed to confirm its impact on survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymph node metastasis from hilar cholangiocarcinoma: audit of 110 patients who underwent regional and paraaortic node dissection. Kitagawa, Y., Nagino, M., Kamiya, J., et al.[2023]

In a study of 468 patients with locally advanced head and neck cancer, the number of lymph nodes removed during neck dissection was found to be less important for disease-free survival (DFS) and overall survival (OS) than factors like T classification and the number of positive nodes.

The study revealed that high-risk factors such as positive resection margins and extranodal extension (ENE) had diminished negative impacts on DFS and OS, suggesting that current risk-adapted treatment strategies may improve outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traditional risk factors and nodal yield-still relevant with high-quality risk-adapted adjuvant treatment for locally advanced head and neck cancer? Butt, Y., Tennstedt, P., Busch, CJ., et al.[2023]

Lymph node status is crucial in head and neck cancer prognosis, as involvement can reduce overall survival by 50%, highlighting the importance of managing regional lymphatics.

Performing a neck dissection not only minimizes patient morbidity but also provides essential staging information and helps determine the need for additional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neck dissection: nomenclature, classification, and technique. Holmes, JD.[2011]

In a study of 42 patients who underwent neck dissection after chemo-radiotherapy for head and neck cancer, only 26% showed positive pathologic findings, suggesting that extensive neck dissection may be unnecessary for many patients.

The study indicates that a more limited neck dissection, targeting only the clinically or radiologically identified areas of disease, could reduce treatment-related complications while still effectively controlling cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role and extent of neck dissection for persistent nodal disease following chemo-radiotherapy for locally advanced head and neck cancer: how much is enough? Sandhu, A., Rao, N., Giri, S., et al.[2009]

In a study of 192 patients with clinically node-negative intrahepatic cholangiocarcinoma, those who underwent lymphadenectomy during liver resection had significantly better long-term survival rates, with 3-year overall survival at 78% compared to 52% for those without lymphadenectomy.

Lymphadenectomy also improved disease-free survival, with rates of 46% at 3 years versus 31% for patients who did not have the procedure, suggesting that lymphadenectomy may be beneficial for improving outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of lymphadenectomy for long-term outcomes in node-negative intrahepatic cholangiocarcinoma: A multicenter study. Yoh, T., Cauchy, F., Le Roy, B., et al.[2020]

In a study of 27 patients with distal bile duct cancer who underwent pancreatoduodenectomy with extended lymphadenectomy, the procedure showed a 65% survival rate at one year and 37% at three and five years, indicating its potential effectiveness.

Factors such as having up to 2 positive lymph nodes, negative resection margins, and the use of postoperative adjuvant chemotherapy were associated with better survival outcomes, supporting the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors after pancreatoduodenectomy with extended lymphadenectomy for distal bile duct cancer. Yoshida, T., Matsumoto, T., Sasaki, A., et al.[2022]

In a study of 136 patients with perihilar cholangiocarcinoma, the classification of regional lymph nodes significantly impacted survival outcomes, with 5-year disease-specific survival rates decreasing from 61.4% for patients with no positive nodes to 17.6% for those with four or more positive nodes.

The study suggests that the common hepatic artery (no. 8) and posterior superior pancreaticoduodenal (no. 13a) node groups should be included as regional nodes alongside the hepatoduodenal ligament (no. 12), as this classification improves prognostic stratification for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational Extent of Regional Lymphadenectomy and the Prognostic Impact of the Number of Positive Lymph Nodes for Perihilar Cholangiocarcinoma. Sakata, J., Takizawa, K., Miura, K., et al.[2023]

The Relay-HC trial is a large, prospective, multicenter study involving 734 patients with resectable hilar cholangiocarcinoma, aiming to compare the overall survival rates between extended lymphadenectomy and regional lymphadenectomy.

This trial will also assess the safety of the procedures by evaluating perioperative mortality and postoperative complications, providing crucial data on the risks associated with extended lymphadenectomy for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional lymphadenectomy vs. extended lymphadenectomy for hilar cholangiocarcinoma (Relay-HC trial): study protocol for a prospective, multicenter, randomized controlled trial. He, M., Xu, X., Feng, H., et al.[2020]

The study analyzed 10 retrospective studies and found that patients with para-aortic lymph node metastasis had significantly lower survival rates compared to those without, with 1-, 3-, and 5-year survival rates of 2.30, 1.70, and 1.42 times higher, respectively, for the negative group.

For patients with both para-aortic and regional lymph node metastasis, the survival rates were still lower, indicating that while extended lymphadenectomy may be performed, careful consideration is needed based on intraoperative biopsy results, highlighting the need for further prospective studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical prognostic significance of regional and extended lymphadenectomy for biliary cancer with para-aortic lymph node metastasis: A systematic review and meta-analysis. Gu, J., Xia, L., Xu, B., et al.[2022]

A review of 15 studies involving 607 patients suggests that up-front neck dissection (UFND) may lead to fewer surgical complications and reduced acute radiation toxicity compared to salvage neck dissection and (C)RT alone.

However, due to the overall variability in the data and the absence of well-designed randomized trials, the definitive role of UFND in the treatment of head and neck cancer remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Up-front neck dissection followed by definitive (chemo)-radiotherapy in head and neck squamous cell carcinoma: Rationale, complications, toxicity rates, and oncological outcomes - A systematic review. Elicin, O., Nisa, L., Dal Pra, A., et al.[2019]

Selective neck dissection in 80 patients with lymph node-positive head and neck squamous cell carcinoma achieved a high regional control rate of 90% and a disease-specific survival rate of 93.4%.

The study found that factors like T stage, N stage, and extracapsular spread did not significantly affect survival rates, indicating that selective neck dissection is a safe and effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Selective Neck Dissection in Lymph Node-Positive Squamous Cell Carcinoma of the Head and Neck. Polat, M., Celenk, F., Baysal, E., et al.[2018]

Extended surgical procedures, such as hemihepatectomy and pancreatoduodenectomy, can lead to long-term survival in patients with extrahepatic bile duct cancer while maintaining acceptable surgical risks, especially when performed with curative intent.

For effective local disease control and accurate staging, it is crucial for surgeons to examine at least 10 lymph nodes during these surgeries, as the benefits of radical procedures are primarily seen in patients without nodal metastasis and with negative surgical margins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical resection of biliary tract cancers and the role of extended lymphadenectomy. Seyama, Y., Kokudo, N., Makuuchi, M.[2009]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7327786/

Extended lymphadenectomy in hilar cholangiocarcinoma Extended lymphadenectomy can bring some survival benefits for patients with potential para-aortic lymph node metastasis and more lymph nodes can be obtained.

2. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-019-3605-z

Regional lymphadenectomy vs. extended ... - Trials Journal The aim of this study is to explore the clinical effect and safety of extended lymphadenectomy compared to regional lymphadenectomy in patients with hilar ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1590865815301274

Clinical prognostic significance of regional and extended ... The purpose of our study was to conduct a meta-analysis of the published literature concerning the efficacy and safety of extended lymphadenectomy in patients ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31147975/

Extended Lymphadenectomy Versus Regional ... The aim of this study is to compare the effects of extended lymphadenectomy (E-LD) and regional lymphadenectomy (R-LD) on outcome after radical resection of ...

5. wjgnet.com wjgnet.com/1007-9327/full/v18/i22/2775.htm

Regional lymphadenectomy for gallbladder cancer This paper provides detailed description of their surgical technique for gallbladder cancer, “extended” portal lymph node dissection.

6. surgonc.org surgonc.org/wp-content/uploads/2019/03/National-Video-Conference-April-2016-Article-8.pdf

Lymph node dissection in resectable perihilar ... A median lymph node count greater than or equal to 15 was reported in 9% of perihilar cholangiocarcinoma patients and could only be achieved in extended ...