Decision Tool for Organ-Sparing Surgery in Bladder Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Live virus vaccines

Disqualifiers: Metastatic disease, Non-urothelial cancer, 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)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

147 Participants Needed

Trial Summary

What is the purpose of this trial?

Currently, the standard of care for female patients undergoing radical cystectomy includes the removal of the bladder, pelvic lymph nodes, anterior vagina, uterus, fallopian tubes and ovaries. Removal of female ancillary organs, both in pre and post-menopausal stages is associated with reduction in various quality of life metrics, including sexual health, cognitive decline and depression. Furthermore, removal of ovaries has been associated with increased cardiovascular events, metabolic acidosis, osteoporosis and bone fractures. In premenopausal women, the removal of the ovaries is associated with increased all-cause mortality. From an oncologic standpoint, multi institutional retrospective reviews have demonstrated certain pre-operative radiographic and cystoscopic risk factors that are associated with bladder cancer involvement of female reproductive organs. The absence of these unfavorable risk factors may provide an opportunity to spare women from undergoing unnecessary reproductive organ removal during RC. In doing so, this may eliminate the associated sequelae of removing these additional organs while also providing acceptable oncologic care. The investigators thus propose a decision tool to stratify women undergoing radical cystectomy as favorable and unfavorable for reproductive organ sparing radical cystectomy. This decision tool classification will be used to decide which patients will undergo reproductive organ sparing radical cystectomy versus radical cystectomy in this study.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that you cannot have received a live virus vaccine within 30 days before the study intervention.

Is organ-sparing surgery for bladder cancer safe for humans?

Organ-sparing surgery for bladder cancer, including techniques like reproductive organ-sparing and nerve-sparing radical cystectomy, has been shown to be safe in terms of cancer control and can improve sexual and urinary function in select patients. ^{1 2 3 4 5}

How is reproductive organ-sparing radical cystectomy different from standard treatments for bladder cancer?

Reproductive organ-sparing radical cystectomy is unique because it aims to preserve pelvic organs, which can improve sexual and urinary functions in women without compromising cancer treatment outcomes, unlike standard radical cystectomy that often involves removing these organs. ^{1 5 6 7 8}

Research Team

Tarik Benidir, MD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for women aged 18 or older with urothelial carcinoma of the bladder who are candidates for radical cystectomy. They must have at least one reproductive organ, be physically able to undergo surgery and an MRI, and not have received certain treatments recently.

Inclusion Criteria

I am eligible for major bladder surgery.

I am a woman aged 18 or older.

You are able to have a pelvic MRI.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either radical cystectomy or reproductive organ sparing radical cystectomy based on the decision tool classification

4-6 weeks

Follow-up

Participants are monitored for safety, effectiveness, and recurrence rates after treatment

15 months

Quality of Life Assessment

Evaluate quality of life using the FACT-G questionnaire and sexual function using the FSFI

15 months

Treatment Details

Interventions

• Radical cystectomy
• Reproductive organ sparing radical cystectomy

Trial Overview The study compares traditional radical cystectomy (removal of bladder and reproductive organs) with a sparing approach that preserves reproductive organs when possible. A decision tool will help determine which procedure each participant should receive.

Participant Groups

Group I: Reproductive organ sparing radical cystectomy Experimental Treatment 1 Intervention

Group II: Radical cystectomy Active Control 1 Intervention

Radical cystectomy is already approved in United States, European Union for the following indications:

Approved in United States as OPDIVO for:

• Metastatic non-small cell lung cancer (NSCLC)
• Unresectable malignant pleural mesothelioma (MPM)
• Intermediate or poor risk advanced renal cell carcinoma (RCC)
• Advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy
• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC)
• Hepatocellular carcinoma (HCC) who have been previously treated with sorafenib
• Unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC)
• Adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease
• Advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma
• Urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection

Approved in European Union as OPDIVO for:

• Advanced (unresectable or metastatic) melanoma
• Adjuvant treatment of adults and adolescents 12 years of age and older with Stage IIB or IIC melanoma, or melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection
• Metastatic NSCLC in adults whose tumours have no sensitising EGFR mutation or ALK translocation
• Locally advanced or metastatic NSCLC after prior chemotherapy in adults
• Neoadjuvant treatment of resectable NSCLC at high risk of recurrence in adult patients whose tumours have PD-L1 expression ≥ 1%
• Unresectable malignant pleural mesothelioma
• Intermediate/poor-risk advanced RCC
• Advanced RCC after prior therapy in adults
• First-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥ 1%
• Urothelial carcinoma

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Findings from Research

In a study of 123 women undergoing radical cystectomy for bladder cancer, 15% had reproductive organ involvement, with 4% specifically showing ovarian involvement, indicating a significant risk associated with advanced disease stages.

The study suggests that women with organ-confined bladder cancer (≤T2) may safely undergo ovary-sparing radical cystectomy without compromising oncologic safety, as the risk of incomplete resection of malignancy is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gynecologic Organ Involvement During Radical Cystectomy for Bladder Cancer: Is It Time to Routinely Spare the Ovaries? Taylor, BL., Matrai, CE., Smith, AL., et al.[2019]

In a study of 180 women with bladder cancer who underwent orthotopic neobladder reconstruction, the rate of urethral recurrence and overall oncological failure was found to be low, supporting the continued use of this surgical approach.

The research indicated that if preoperative imaging shows no malignancy in the internal genitalia, the risk of secondary cancer in these organs after cystectomy is very low, justifying the preservation of healthy gynecological organs during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncological outcome after radical cystectomy and orthotopic bladder substitution in women. Ali-El-Dein, B.[2022]

A survey of 101 urologists revealed that while many routinely perform radical cystectomy (RC) with organ-sparing techniques in premenopausal patients, there is a significant decrease in the use of these techniques for postmenopausal patients, despite their oncological safety and potential to improve sexual function outcomes.

The study highlights a gap in the adoption of female reproductive organ-sparing and nerve-sparing techniques, suggesting a need for enhanced training and education among urologists to optimize postoperative outcomes for female patients with organ-confined bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice Patterns Regarding Female Reproductive Organ-Sparing and Nerve-Sparing Radical Cystectomy Among Urologic Oncologists in the United States. Gupta, N., Kucirka, L., Semerjian, A., et al.[2023]

Reproductive organ-sparing radical cystectomy (ROSRC) may improve sexual and urinary function for patients, but careful patient selection is crucial to avoid oncologic risks, as current evidence is based on small cohorts with only intermediate-term follow-up.

While ROSRC shows promising functional benefits, the extent of these advantages is uncertain, and further long-term studies are needed to ensure oncologic safety and effective candidate selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Female reproductive organ-sparing radical cystectomy: contemporary indications, techniques and outcomes. Niver, BE., Daneshmand, S., Satkunasivam, R.[2015]

Pelvic organ-preserving radical cystectomy (POPRC) may improve sexual and urinary function outcomes compared to standard radical cystectomy (RC), with 86% of patients resuming sexual activity within 6 months and high satisfaction scores.

Oncological outcomes for POPRC appear comparable to standard RC, with cancer-specific survival rates ranging from 70-100% at 3 and 5 years, but further research is needed due to high risk of bias and variability in the studies reviewed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of the oncological and functional outcomes of pelvic organ-preserving radical cystectomy (RC) compared with standard RC in women who undergo curative surgery and orthotopic neobladder substitution for bladder cancer. Veskimäe, E., Neuzillet, Y., Rouanne, M., et al.[2018]

In a study of 273 female bladder cancer patients, those who underwent pelvic organ preserving-radical cystectomy (POPRC) showed no significant difference in overall survival compared to those who had standard radical cystectomy (SRC) after a median follow-up of 38.6 months.

Both surgical methods resulted in similar cancer-specific survival and recurrence-free survival rates, indicating that POPRC is a viable alternative to SRC without compromising long-term oncological outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival after female pelvic organ-sparing radical cystectomy versus standard radical cystectomy: a multi-institutional propensity score-matched analysis. Zhong, W., Xia, K., Liu, L., et al.[2023]

Women who underwent reproductive organ-sparing cystectomy (ROSC) with orthotopic bladder substitution (OBS) experienced significantly higher daytime and nighttime urinary continence rates compared to those who had standard cystectomy (SC), with rates of 87.5% versus 63.5% and 87.5% versus 57.7%, respectively.

Despite the improved continence rates, there were no significant differences in oncological outcomes, such as local recurrence rates and overall survival rates, between the ROSC and SC groups, indicating that ROSC can be a safe and effective option for women undergoing OBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproductive organ-sparing cystectomy significantly improves continence in women after orthotopic bladder substitution without affecting oncological outcome. Gross, T., Furrer, M., Schorno, P., et al.[2019]

Radical cystectomy combined with neoadjuvant chemotherapy is the standard treatment for muscle-invasive bladder cancer, particularly in postmenopausal women, with a median diagnosis age of 73 in Sweden.

The traditional practice of performing oophorectomy alongside radical cystectomy may not be justified, as recent literature suggests that preserving the ovaries could reduce postoperative functional impairment without increasing cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should we Refrain from Performing Oophorectomy in Conjunction with Radical Cystectomy for Bladder Cancer? Liedberg, F., Jancke, G., Sörenby, A., et al.[2018]

References

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

Gynecologic Organ Involvement During Radical Cystectomy for Bladder Cancer: Is It Time to Routinely Spare the Ovaries? [2019]

2. England pubmed.ncbi.nlm.nih.gov

Oncological outcome after radical cystectomy and orthotopic bladder substitution in women. [2022]

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

Practice Patterns Regarding Female Reproductive Organ-Sparing and Nerve-Sparing Radical Cystectomy Among Urologic Oncologists in the United States. [2023]

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

Female reproductive organ-sparing radical cystectomy: contemporary indications, techniques and outcomes. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Systematic review of the oncological and functional outcomes of pelvic organ-preserving radical cystectomy (RC) compared with standard RC in women who undergo curative surgery and orthotopic neobladder substitution for bladder cancer. [2018]

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

Long-term survival after female pelvic organ-sparing radical cystectomy versus standard radical cystectomy: a multi-institutional propensity score-matched analysis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Reproductive organ-sparing cystectomy significantly improves continence in women after orthotopic bladder substitution without affecting oncological outcome. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Should we Refrain from Performing Oophorectomy in Conjunction with Radical Cystectomy for Bladder Cancer? [2018]