Extended Lymphadenectomy for Bile Duct Cancer

Recruiting at 12 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

Trial Summary

What is the purpose of this trial?

Intrahepatic cholangiocarcinoma (ICC) is one of the common malignant tumors. Lymph node metastasis is an important factor affecting the poor prognosis of intrahepatic cholangiocarcinoma. The eighth edition of the AJCC guidelines recommends at least 6 lymph nodes to be used for staging. The American Hepatobiliary and Pancreatic Association also recommends the removal of hilar lymph nodes as part of the radical surgery for intrahepatic cholangiocarcinoma. However, some scholars have found that patients with regional lymph nodes have similar survival rates. This contradictory result has prompted more scholars to conduct clinical research to explore the necessity and standardization of lymph node dissection in intrahepatic cholangiocarcinoma.

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 data supports the idea that Extended Lymphadenectomy for Bile Duct Cancer is an effective treatment?

The available research shows that Extended Lymphadenectomy can help achieve long-term survival in patients with extrahepatic bile duct cancer when combined with other surgical procedures. It is particularly effective for patients without cancer spread to the lymph nodes and when the surgery successfully removes all cancerous tissue. This treatment also helps in accurately determining the stage of the cancer, which is crucial for planning further treatment. However, the benefits are more pronounced in selected patients, and the overall impact on long-term survival varies. ^{1 2 3 4 5}

What safety data exists for extended lymphadenectomy in bile duct cancer?

The provided research focuses on neck dissection in head and neck cancers, not bile duct cancer. However, it highlights that extensive lymph node surgery can lead to complications such as lymphedema, nerve damage, and sensory issues. These findings suggest that similar risks might be considered for extended lymphadenectomy in bile duct cancer, but specific safety data for this treatment in bile duct cancer is not provided in the research. ^{6 7 8 9 10}

Is the treatment Extended Lymphadenectomy a promising treatment for bile duct cancer?

Extended Lymphadenectomy, which involves removing more lymph nodes during surgery, is being studied to see if it helps people with bile duct cancer. Some research suggests it might be beneficial, especially for certain types of bile duct cancer, but more studies are needed to fully understand its advantages. ^{1 2 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prognostic factors after pancreatoduodenectomy with extended lymphadenectomy for distal bile duct cancer. [2022]

2. Netherlands 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Rational Extent of Regional Lymphadenectomy and the Prognostic Impact of the Number of Positive Lymph Nodes for Perihilar Cholangiocarcinoma. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Radical resection of biliary tract cancers and the role of extended lymphadenectomy. [2009]

5. United States pubmed.ncbi.nlm.nih.gov

Prognostic value of lymphadenectomy for long-term outcomes in node-negative intrahepatic cholangiocarcinoma: A multicenter study. [2020]

6. Ireland 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. [2019]

7. Germany 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? [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Selective Neck Dissection in Lymph Node-Positive Squamous Cell Carcinoma of the Head and Neck. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

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

10. England 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? [2009]

11. United States pubmed.ncbi.nlm.nih.gov

Adequate lymph node assessment for extrahepatic bile duct adenocarcinoma. [2010]

12. United States pubmed.ncbi.nlm.nih.gov

Lymph node metastasis from hilar cholangiocarcinoma: audit of 110 patients who underwent regional and paraaortic node dissection. [2023]

13. England 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. [2020]