Surgical Techniques for Bladder Cancer

Recruiting at 6 trial locations

Overseen By Alvin Goh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Opioids

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

530 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to look at two standard surgical techniques used during a radical cystectomy and see whether they influence outcomes such as length of stay in the hospital and infections after surgery. This trial will evaluate whether the following surgical methods influence outcomes: A ureteral stent is a thin tube that is placed in the ureter to drain urine from the kidney. Ureteral stents are often used to promote urine drainage after radical cystectomy, but may come at risk of urinary tract infection. Alvimopan is a standard drug used to promote return of bowel function following surgery. Doctors do not know whether alvimopan is beneficial in current clinical practice. The surgeon will decide whether participants will receive a stent and/or alvimopan, but if they are unsure what the best approach is, a surgical technique has been assigned by chance to them.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on chronic opioid therapy, you cannot receive alvimopan as part of the trial.

What data supports the effectiveness of the treatment involving ureteral stent placement for bladder cancer?

Ureteral stent placement is effective in managing ureteral obstruction and improving quality of life in patients with widespread malignancy, as it avoids the need for more invasive surgery and reduces associated risks. ^{1 2 3 4 5}

Is the use of ureteral stents generally safe for humans?

Ureteral stents are generally safe for humans, but they can cause discomfort, pain, and other symptoms that affect quality of life. Complications are rare, and the procedure is less risky than other methods for managing blocked ureters. ^{1 6 7 8 9}

How does the drug alvimopan differ from other treatments for bladder cancer surgery?

Alvimopan is unique because it helps speed up the recovery of bowel function after bladder cancer surgery, specifically radical cystectomy, by preventing postoperative ileus (a condition where the intestines don't work properly after surgery). This is different from other treatments that may not focus on bowel recovery. ^{3 10 11 12 13}

Research Team

Alvin Goh, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for individuals undergoing radical cystectomy, a surgery for bladder cancer. Participants must be suitable candidates for the surgical procedure. The study excludes those who have conditions or circumstances that might interfere with the trial procedures or outcomes.

Inclusion Criteria

I am 21 or older and will have surgery for bladder cancer at MSK.

I am 21 or older and will have surgery for bladder cancer at MSK.

Exclusion Criteria

No exclusion criteria Alvimopan vs. no alvimopan

I am not on long-term opioid pain medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Immediate Postoperative Care

Participants undergo radical cystectomy with potential use of ureteral stents and/or alvimopan as per randomization

1 week

In-hospital stay

Postoperative Monitoring

Participants are monitored for length of hospital stay and symptomatic urinary tract infections

4 weeks

In-hospital and follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Alvimopan
• Stent placement

Trial Overview The study compares two standard surgical techniques during cystectomy: ureteral stent placement to aid urine drainage and Alvimopan use to speed up bowel function recovery post-surgery. Surgeons may assign these methods by chance if there's uncertainty about which is best.

Participant Groups

Group I: Stent vs No Stent Experimental Treatment 1 Intervention

For patients treated by a surgeon randomized to use ureteral stents, the operating surgeon may choose to use a single or double J ureteral stent (6- to 8.5-fr in size) or an alternative ureteral stent of the surgeon's choice to be placed across the ureteroenteric anastomosis intraoperatively. Because there is no standard ureteral stent size or type, the surgeon will select a stent type and size according to their experience and will document the stent size and type used. This is already routinely recorded as part of the standard of care at MSK.

Group II: Alvimopan vs No Alvimopan Experimental Treatment 1 Intervention

For patients randomized to receive alvimopan, the patient will receive alvimopan as a fixed 12-mg dose, with the first dose administered 0.5 to 5 h before the start of surgery; administration will be continued with twice daily oral doses postoperatively until hospital discharge or a maximum of 7 days (15 in-hospital doses), as indicated on the medication's FDA label. This is the current standard of care for most cases at MSK.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

The endoscopic placement of the Gibbons indwelling stent in obstructed ureters is safer and associated with lower morbidity and mortality compared to traditional methods like supravesical diversion, making it a better option for high-risk patients.

In a study involving 16 patients aged 25 to 74, the Gibbons stent not only preserves quality of life better than other methods but is also reversible and does not interfere with future surgeries, although some technical challenges may arise during placement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ureteral drainage with the Gibbons indwelling ureteral stent (author's transl)]. Schreiber, B.[2006]

Ureteral stenting in patients with bladder cancer significantly increases the risk of developing metachronous upper tract urothelial carcinoma, with a likelihood 3.49 times higher compared to those with no stents.

In cases of hydronephrosis, both nephrostomy and ureteral stenting are viable drainage options, as they do not differ in their risk of metachronous upper tract urothelial carcinoma, suggesting that stenting should be avoided when possible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Ureteral Stenting Increase the Risk of Metachronous Upper Tract Urothelial Carcinoma in Patients with Bladder Tumors? A Systematic Review and Meta-analysis. Sountoulides, P., Pyrgidis, N., Brookman-May, S., et al.[2021]

The study introduces a new transurethral stent placement technique during robot-assisted radical prostatectomy (RARP) to prevent ureteral damage, especially in patients with large median lobes or prior surgeries.

This technique is presented as a simple and feasible alternative to preoperative stenting, addressing potential anatomical challenges encountered during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is ureteral stent placement by the transurethral approach during robot-assisted radical prostatectomy an effective option to preoperative technique? Molinari, A., Simonelli, G., De Concilio, B., et al.[2016]

Endoscopically placed ureteral stents are a safe and effective method for managing ureteral obstruction and can improve the quality of life for high-risk patients with malignancies without the need for surgery.

The technique described allows for customized stent fitting using readily available graduated ureteral catheters, minimizing preparation time and eliminating the need for a wide range of catheter sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Useful technique for long-term urinary drainage by inlying ureteral stent. Six-year experience. Kearney, GP., Mahoney, EM., Brown, HP.[2019]

The migration of indwelling ureteral stents out of the bladder presents a significant challenge for urologists, often requiring innovative solutions to avoid invasive surgery.

A new transurethral technique has been successfully employed to remove a migrated catheter, potentially offering a less invasive option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transurethral removal of migrated indwelling ureteral stents: a new technique. Berman, D., Donovan, J., Assimos, D., et al.[2019]

The newly designed 'Yoticurl' stent showed promising results in a preliminary in vivo evaluation in a pig model, demonstrating normal urine flow and no significant complications over a 25-day period.

Histological analysis revealed only mild inflammation in the ureter, suggesting that this innovative stent design may be a safer and more effective alternative to traditional ureteral stents for facilitating urine drainage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of a fully intraureteral stent and proof-of-concept in vivo evaluation. Shilo, Y., Willenz, U., Berkowitz, B.[2022]

Routine placement of stents after uncomplicated ureteroscopy is no longer considered necessary, as it leads to increased pain and irritative voiding symptoms for patients.

While stents add to the overall cost of the procedure, there is a specific subgroup of patients who may still benefit from them, indicated by higher readmission rates, suggesting a need for future research to identify these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stenting after ureteroscopy: pros and cons. Knudsen, BE., Beiko, DT., Denstedt, JD.[2014]

In a study of 60 patients with double-J ureteral stents, tamsulosin therapy significantly reduced various measures of stent-related discomfort, including pain and urinary symptoms, compared to a placebo after 4 weeks.

Tamsulosin was well tolerated with no reported discontinuations due to side effects, suggesting it is a safe and effective option to minimize morbidity associated with ureteral stenting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of tamsulosin hydrochloride in relieving "double-J ureteral stent-related morbidity": a randomized placebo controlled clinical study. Singh, I., Tripathy, S., Agrawal, V.[2021]

In a systematic review of 14 randomized clinical trials involving 2,842 patients, alpha antagonists, antimuscarinics, and phosphodiesterase (PDE) inhibitors were all found to significantly reduce symptoms related to ureteric stents compared to placebo.

Combination therapy using both alpha antagonists and antimuscarinics was more effective in improving symptoms than using either drug alone, while PDE inhibitors showed comparable effectiveness to alpha antagonists and provided additional benefits for sexual health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Ureteral Stent-Related Symptoms. Pecoraro, A., Peretti, D., Tian, Z., et al.[2023]

In a study of 573 patients undergoing radical cystectomy, alvimopan significantly improved recovery outcomes for those who had open radical cystectomy (ORC), reducing postoperative ileus rates and hospital length of stay.

However, in patients undergoing robot-assisted radical cystectomy (RARC), alvimopan did not show any significant benefits for recovery, suggesting that its use may need to be more selective based on the surgical approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How the Beneficial Effects of Alvimopan Differ With Surgical Approach for Radical Cystectomy. Faraj, KS., Judge, NZ., Rose, KM., et al.[2022]

Alvimopan significantly accelerates gastrointestinal recovery in patients undergoing radical cystectomy, as evidenced by faster toleration of clear liquids, solid food, and bowel movements, based on a meta-analysis of 5 studies involving 613 patients.

The use of alvimopan also reduces the length of hospital stay for these patients, indicating its potential to improve postoperative recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of alvimopan on accelerates gastrointestinal recovery after radical cystectomy: A systematic review and meta-analysis. Cui, Y., Chen, H., Qi, L., et al.[2018]

The study estimates that using alvimopan for all patients undergoing radical cystectomy can lead to cost savings by reducing the costs associated with postoperative ileus (POI), especially if POI occurs in more than 14% of patients or leads to an extended hospital stay of 3.5 days or more.

Routine administration of alvimopan, which costs $700 per hospitalization, is associated with a lower mean cost of $1495 per patient for POI management, compared to $1597 for patients not treated with the drug, indicating its potential cost-effectiveness in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alvimopan for prevention of postoperative paralytic ileus in radical cystectomy patients: a cost-effectiveness analysis. Hilton, WM., Lotan, Y., Parekh, DJ., et al.[2022]

In patients undergoing radical cystectomy, alvimopan significantly reduced the time to reach solid food tolerance and hospital discharge, with moderate-quality evidence showing a hazard ratio of 1.77 for food tolerance and 1.67 for discharge, indicating faster recovery compared to standard care.

Alvimopan was associated with a lower risk of major adverse events (risk ratio 0.28), suggesting it may enhance safety during recovery, while not affecting readmission rates or narcotic pain medication use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alvimopan for recovery of bowel function after radical cystectomy. Sultan, S., Coles, B., Dahm, P.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Ureteral drainage with the Gibbons indwelling ureteral stent (author's transl)]. [2006]

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

Does Ureteral Stenting Increase the Risk of Metachronous Upper Tract Urothelial Carcinoma in Patients with Bladder Tumors? A Systematic Review and Meta-analysis. [2021]

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

Is ureteral stent placement by the transurethral approach during robot-assisted radical prostatectomy an effective option to preoperative technique? [2016]

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

Useful technique for long-term urinary drainage by inlying ureteral stent. Six-year experience. [2019]

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

Transurethral removal of migrated indwelling ureteral stents: a new technique. [2019]

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

Design of a fully intraureteral stent and proof-of-concept in vivo evaluation. [2022]

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

Stenting after ureteroscopy: pros and cons. [2014]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of tamsulosin hydrochloride in relieving "double-J ureteral stent-related morbidity": a randomized placebo controlled clinical study. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of Ureteral Stent-Related Symptoms. [2023]

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

How the Beneficial Effects of Alvimopan Differ With Surgical Approach for Radical Cystectomy. [2022]

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

Effect of alvimopan on accelerates gastrointestinal recovery after radical cystectomy: A systematic review and meta-analysis. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Alvimopan for prevention of postoperative paralytic ileus in radical cystectomy patients: a cost-effectiveness analysis. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Alvimopan for recovery of bowel function after radical cystectomy. [2023]