Nephroureterectomy With and Without Lymph Node Removal for Bladder Cancer

Recruiting at 1 trial location

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

Trial Summary

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.

What data supports the effectiveness of the treatment Nephroureterectomy With and Without Lymph Node Removal for Bladder Cancer?

Radical nephroureterectomy (RNU) is considered the standard treatment for upper tract urothelial carcinoma, which is a type of cancer similar to bladder cancer. It has been shown to provide good cancer control, although it can lead to complications and reduced kidney function. ^{1 2 3 4 5}

Is nephroureterectomy with or without lymph node removal generally safe for humans?

Radical nephroureterectomy (RNU) is a common treatment for certain types of cancer, but it can lead to complications and decreased kidney function. Patients often have other health issues that increase the risk of surgical complications. ^{1 2 3 6 7}

How is the treatment nephroureterectomy unique for bladder cancer?

Nephroureterectomy (RNU) is a surgical treatment that involves removing the kidney, ureter, and part of the bladder, and is typically used for upper tract urothelial cancer. It is unique because it is considered the gold standard for non-metastatic cases, providing effective cancer control, although it comes with significant risks and complications. ^{1 2 8 9 10}

What is the purpose of this trial?

The goal of this study is to conduct the first randomized-controlled trial to determine the oncologic efficacy of lymph node dissection in participants with upper tract urothelial cell carcinoma. The main questions it aims to answer are: * To determine oncologic outcomes, specifically 2-year recurrence-free survival * To determine other oncologic outcomes including treatment-free, cancer-specific and overall survival * To determine time to recurrence and recurrence patterns * To determine use of adjuvant therapies * To determine perioperative complications Participants will undergo nephroureterectomy with or without lymph node dissection. Researchers will compare these two groups to determine the oncologic efficacy of performing lymph node dissection.

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

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 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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

Oncologic outcomes following radical nephroureterectomy for upper tract urothelial carcinoma: a literature review. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Perioperative complications and adverse sequelae of radical nephroureterectomy. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Risk factors associated with ineligibility of adjuvant cisplatin-based chemotherapy after nephroureterectomy. [2021]

4. Germany 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. [2021]

5. Australia 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. [2023]

6. China pubmed.ncbi.nlm.nih.gov

Incidence and preoperative predictors for major complications following radical nephroureterectomy. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

Outcomes of patients undergoing concurrent radical cystectomy and nephroureterectomy: A single-institution series. [2022]

8. France 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]. [2018]

9. Spain 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? [2023]

10. Italy pubmed.ncbi.nlm.nih.gov

Laparoscopic radical nephroureterectomy with only three trocars: Results of a prospective single centre study. [2022]