Nephroureterectomy With and Without Lymph Node Removal for Bladder Cancer

Recruiting at 3 trial locations

Overseen By Rebecca Campbell, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Case Comprehensive Cancer Center

Disqualifiers: Metastases, Bladder cancer, Psychiatric disorder, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Surgical procedure

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether removing lymph nodes during surgery for upper tract urothelial cell carcinoma (a type of bladder cancer) improves cancer outcomes. Participants will undergo surgery either with or without lymph node removal. Researchers aim to determine if removing lymph nodes helps patients remain cancer-free longer and affects overall survival. The trial seeks individuals diagnosed with this specific cancer who are scheduled for nephroureterectomy (kidney and ureter surgery). As an unphased trial, it offers participants the chance to contribute to important research that could enhance future cancer treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nephroureterectomy, the removal of a kidney and ureter, is generally a safe procedure for treating upper tract urothelial carcinoma, a type of bladder cancer. Removing some lymph nodes during the surgery helps doctors understand the cancer's stage and may aid in treatment if the cancer hasn't spread extensively.

Previous studies found that lymph node removal did not significantly extend patient survival, but it provides valuable information for planning further treatment. Importantly, adding this step to the surgery is safe and does not significantly increase risk for patients.

Overall, both nephroureterectomy and lymph node removal are considered safe procedures with a manageable risk of complications. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they offer new insights into managing bladder cancer. Nephroureterectomy, a surgical procedure typically used for upper tract urothelial carcinoma (UTUC), is being evaluated both with and without lymph node dissection (LND). While standard treatment often includes nephroureterectomy combined with LND to potentially improve outcomes, this trial seeks to determine if omitting LND can be just as effective, potentially minimizing surgical risks and recovery time for patients. This could lead to a more personalized approach to treating bladder cancer, refining how surgery is utilized based on patient needs.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

This trial will compare nephroureterectomy with and without lymph node dissection for bladder cancer. Research has shown that removing lymph nodes during kidney cancer surgery can extend life for some patients. One study found this particularly true when following a specific surgical method. However, other research suggests that while lymph node removal provides valuable information about the cancer, it doesn't always extend patient survival. Thus, while the procedure can enhance understanding of the cancer, it may not prolong life for every patient. For those considering this treatment, these findings highlight both potential benefits and limitations. ^{1 3 4 6 7}

Who Is on the Research Team?

Mohamed Eltemamy, MD

Principal Investigator

Cleveland Clinic, Glickman Urological and Kidney Institute, Case Comprehensive Cancer Center

Adam Calaway, MD, MPH

Principal Investigator

University Hospitals Cleveland Medical Center, Urology Institute, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with upper tract urothelial cell carcinoma, a type of bladder cancer. The study is looking to include people who are candidates for surgery called nephroureterectomy. Specific eligibility criteria were not provided.

Inclusion Criteria

I am scheduled for surgery to remove my kidney and ureter.

I have been diagnosed with upper tract urothelial cancer through a biopsy.

My cancer is localized and has not spread to lymph nodes or other parts of the body.

Exclusion Criteria

The participant has a psychiatric disorder that precludes them from understanding the consent process.

My lymph nodes are enlarged and need to be removed.

My cancer has spread to distant parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo nephroureterectomy with or without lymph node dissection for upper tract urothelial cell carcinoma

Surgical procedure

Follow-up

Participants are monitored for oncologic outcomes, including recurrence-free survival, cancer-specific survival, and overall survival

2 years

Adjuvant Therapy Evaluation

Evaluation of the use of adjuvant therapies post-surgery

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Lymph Node Dissection
• Nephroureterectomy

Trial Overview The study tests the effectiveness of lymph node dissection during nephroureterectomy in improving cancer outcomes like recurrence-free survival over two years and overall survival rates. Participants will be randomly assigned to undergo surgery with or without lymph node dissection.

How Is the Trial Designed?

Group I: Nephroureterectomy With Lymph Node Dissection Experimental Treatment 2 Interventions

Participants will undergo nephroureterectomy for UTUC and will receive LND.

Group II: Nephroureterectomy Without Lymph Node Dissection Active Control 1 Intervention

Participants will undergo nephroureterectomy for UTUC and will not receive LND.

Nephroureterectomy is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Radical Nephroureterectomy for:

• Upper Tract Urothelial Cell Carcinoma

Approved in United States as Radical Nephroureterectomy for:

• Upper Tract Urothelial Cell Carcinoma

Approved in Canada as Radical Nephroureterectomy for:

• Upper Tract Urothelial Cell Carcinoma

Approved in Japan as Radical Nephroureterectomy for:

• Upper Tract Urothelial Cell Carcinoma

Approved in China as Radical Nephroureterectomy for:

• Upper Tract Urothelial Cell Carcinoma

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Published Research Related to This Trial

Radical nephroureterectomy (RNU) is the standard treatment for non-metastatic upper tract urothelial cancer, showing long-term oncologic outcomes that are comparable across open, laparoscopic, and robotic techniques.

Factors such as perioperative chemotherapy, patient health conditions (like chronic kidney disease and diabetes), and tumor characteristics (like stage and grade) significantly influence survival outcomes, highlighting the importance of personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncologic outcomes following radical nephroureterectomy for upper tract urothelial carcinoma: a literature review. Grob, G., Rogers, D., Pandolfo, SD., et al.[2023]

In a study of 28 patients with upper tract carcinoma in situ (UT-CIS), BCG instillations showed a complete response in 58.8% of renal units, indicating that it can be an effective conservative treatment option.

There were no significant differences in recurrence-free survival or cancer-specific survival between patients treated with radical nephroureterectomy (RNU) and those treated with BCG, suggesting that BCG can be a viable alternative to RNU for managing UT-CIS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of primary upper urinary tract carcinoma in situ diagnosed by ureteroscopic biopsy: Is bacillus Calmette-Guerin an alternative to nephroureterectomy? Territo, A., Fontanet, S., Meneghetti, I., et al.[2023]

In a study of 451 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy, patients aged 80 years and older showed similar recurrence-free survival (RFS) and cancer-specific survival (CSS) rates compared to younger patients, indicating that the surgery is effective regardless of age.

However, overall survival (OS) was significantly poorer in patients aged 80 and older, with age being identified as an independent risk factor for decreased OS, suggesting that while surgery is beneficial, older patients may face other health challenges affecting their long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninferior oncological outcomes in adults aged 80 years or older compared with younger patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma. Yamada, Y., Ikeda, M., Hirayama, T., et al.[2023]

In a study of 27 patients undergoing concurrent radical cystectomy (RC) and radical nephroureterectomy (RNU) for bladder and upper tract urothelial carcinoma, the five-year overall survival rate was 42%, indicating that this combined procedure can be a viable treatment option for select patients.

The procedure carries significant perioperative risks, with 30% of patients experiencing major complications and 7% facing early postoperative mortality, highlighting the need for careful patient selection, especially among those with multiple health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of patients undergoing concurrent radical cystectomy and nephroureterectomy: A single-institution series. Carpinito, GP., Cook, GS., Tverye, AN., et al.[2022]

In a study of 714 patients with non-metastatic upper urinary tract urothelial carcinoma who underwent radical nephroureterectomy, lymph node status (LNS) was found to be significant for survival stratification, with 5-year cancer-specific survival rates of 81% for negative lymph nodes compared to only 47% for positive lymph nodes.

Despite the association between lymph node involvement and lower survival rates, LNS did not serve as an independent prognostic factor for cancer-specific survival, overall survival, or metastasis-free survival, indicating the need for further research in larger, prospective studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of lymph node status and features on oncological outcomes in urothelial carcinoma of the upper urinary tract (UTUC) treated by nephroureterectomy. Ouzzane, A., Colin, P., Ghoneim, TP., et al.[2021]

Radical nephroureterectomy (RNU) for upper urinary tract cancer must include the removal of a bladder-cuff and lymphadenectomy to improve oncological outcomes and reduce the risk of bladder recurrence.

The study confirms that both laparoscopic and open surgical approaches yield similar oncological results, emphasizing the importance of adhering to specific surgical techniques to ensure effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surgical treatment of upper tract urothelial carcinomas by nephroureterectomy: state of the art review for the yearly scientific report of the French National Association of Urology]. Neuzillet, Y., Colin, P., Phé, V., et al.[2018]

In a study of 242 patients who underwent radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma, there was an average decrease in renal function of 19.7% one month after surgery.

Key predictors of diminished renal function post-RNU included being over 65 years old, having a body mass index greater than 25 kg/m², a contralateral kidney length of less than 10 cm, and the absence of hydronephrosis on the affected side.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors associated with ineligibility of adjuvant cisplatin-based chemotherapy after nephroureterectomy. Shao, IH., Lin, YH., Hou, CP., et al.[2021]

The laparoscopic nephroureterectomy (LNU) technique for treating upper tract urothelial cancer was performed on 50 patients with a mean operative time of 168 minutes and a short hospital stay of 3 days, indicating a quicker recovery compared to traditional methods.

There were no intraoperative complications, and while four late complications were reported, the overall safety profile was strong, with long-term oncological outcomes comparable to existing literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laparoscopic radical nephroureterectomy with only three trocars: Results of a prospective single centre study. Al Salhi, Y., Fuschi, A., Martoccia, A., et al.[2022]

Radical nephroureterectomy (RNU) is the standard treatment for upper tract urothelial carcinoma (UTUC), but it comes with significant risks of morbidity and mortality.

There is a lack of high-quality data on RNU due to the low incidence of the disease and limited randomized studies, highlighting the need for better preoperative tools and understanding of potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative complications and adverse sequelae of radical nephroureterectomy. Levy, A., Canes, D.[2020]

In a study of 1,266 patients undergoing radical nephroureterectomy (RNU), nearly 10% experienced major complications, highlighting the surgical risks associated with this procedure for upper-tract urothelial carcinoma.

Preoperative factors such as poor performance status (ECOG ≥2), high comorbidity index (CCI >5), and advanced chronic kidney disease (CKD stage ≥3) were significantly linked to an increased risk of major complications, suggesting these factors should be carefully evaluated before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and preoperative predictors for major complications following radical nephroureterectomy. Kocher, NJ., Canes, D., Bensalah, K., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8987284/

Lymph Node Dissection During Radical Nephro- ... The aim of this study was to summarize the current knowledge concerning the indication, anatomical template, prognostic, and therapeutic roles of lymph node ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35377778/

Analysis of the ROBUUST Registry LND during nephroureterectomy in patients with positive lymph nodes provides prognostic data, but is not associated with improved OS.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2405456917302365

Potential Benefit of Lymph Node Dissection During Radical ... LND improves survival in patients with high-stage disease of the renal pelvis, if it is performed according to an anatomical template-based approach.

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-019-6364-z

Effect of lymph node dissection on stage-specific survival in ... We aimed to estimate the stage-specific impact of lymph node dissection (LND) on survival for upper urinary tract urothelial carcinoma ...

5. link.springer.com link.springer.com/article/10.1007/s11912-023-01460-y

Lymph Node Dissection in Upper Tract Urothelial Carcinoma This narrative review aims to evaluate the role of lymph node dissection (LND) in upper tract urothelial carcinoma (UTUC) and its implications ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0302283811007469

Urothelial Cancer Lymphadenectomy at the Time of ... An extended LND can provide better disease staging and may be curative in patients with limited nodal disease.

7. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.791140/full

Prospective Clinical Trial of the Oncologic Outcomes and ... Purpose: To determine the safety and feasibility of extraperitoneal laparoscopic extended lymph node dissection (LND) at the time of ...