PURPOSE: There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across disease settings in UC, the Society for Immunotherapy of Cancer (SITC) and the International Bladder Cancer Group (IBCG) convened a multidisciplinary, international consensus panel. METHODS: Through open communication and scientific debate in small- and whole-group settings, surveying, and responses to clinical questionnaires, the consensus panel developed recommendations on optimal definitions of the disease state, end points, trial design, evaluations, sample size calculations, and pathology considerations for definitive studies in low- and intermediate-risk nonmuscle-invasive bladder cancer (NMIBC), high-risk NMIBC, muscle-invasive bladder cancer in the neoadjuvant and adjuvant settings, and metastatic UC. The expert panel also solicited input on the recommendations through presentations and public discussion during an open session at the 2021 Bladder Cancer Advocacy Network (BCAN) Think Tank (held virtually). RESULTS: The consensus panel developed a set of stage-specific bladder cancer clinical trial design recommendations, which are summarized in the table that accompanies this text. CONCLUSION: These recommendations developed by the SITC-IBCG Bladder Cancer Clinical Trial Design consensus panel will encourage uniformity among studies and facilitate drug development in this disease.

• MeSH
• Adjuvants, Immunologic therapeutic use   MeSH
• Immunotherapy MeSH
• Carcinoma, Transitional Cell * MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH

BACKGROUND AND OBJECTIVE: Standard radical cystectomy (RC) in women includes the removal of the bladder, urethra, uterus with the adnexa, and the anterior vaginal wall, thereby severely affecting the urinary, sexual, and reproductive system. To limit these detrimental effects, organ-sparing, including nerve-sparing approaches, have been developed. Health-related quality of life (HRQOL) and functional outcomes are, indeed, becoming increasingly central to the shared decision-making with the patient. The objectives of this narrative review are: (I) to review the current status of RC in women, including the use of different urinary diversions (UDs); (II) to discuss organ-sparing approaches and their impact on oncological and functional outcomes in women; (III) to discuss the impact of RC on HRQOL and sexual function in women. METHODS: We performed a non-systematic literature review of the available publications in the PubMed database. KEY CONTENT AND FINDINGS: Over the past years, gender differences in oncological and functional outcomes after RC have received increased attention. According to the currently available literature, organ-sparing approaches can be safely performed in well-selected women without negatively impacting oncological outcomes. The orthotopic neobladder is feasible and oncologically safe in well-selected and informed women. The choice of the UD should be based on comprehensive counseling and the patient's comorbidities and preferences. There still is a lack of data on sexual recovery after the different surgical approaches aimed to mitigate sexual dysfunction in women undergoing RC. CONCLUSIONS: Pre-and post-operative counseling and support of females undergoing RC regarding their expectations and experiences in terms of quality of life and functional and sexual outcomes are currently insufficient. Well-designed studies in this field are necessary to further improve outcomes of women treated with RC with an overarching aim to close the gender gap in managing women with bladder cancer.

• Keywords
• Radical cystectomy (RC), functional outcomes, nerve-sparing, organ-sparing, women,
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Radical cystectomy (RC) is indicated in primary or secondary muscle-invasive bladder cancer (primMIBC, secMIBC) and in primary or recurrent high- or very high-risk non-muscle-invasive bladder cancer (primHR-NMIBC, recHR-NMIBC). The optimal timing for RC along the disease spectrum of nonmetastatic urothelial carcinoma remains unclear. OBJECTIVE: To compare outcomes after RC between patients with primHR-NMIBC, recHR-NMIBC, primMIBC, and secMIBC. DESIGN SETTING AND PARTICIPANTS: This retrospective, multicenter study included patients with clinically nonmetastatic bladder cancer (BC) treated with RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed oncological outcomes for patients who underwent RC according to the natural history of their BC. primHR-NMIBC and primMIBC were defined as no prior history of BC, and recHR-NMIBC and secMIBC as previously treated NMIBC that recurred or progressed to MIBC, respectively. Log-rank analysis was used to compare survival outcomes, and univariable and multivariable Cox and logistic regression analyses were used to identify predictors for survival. RESULTS AND LIMITATIONS: Among the 908 patients included, 211 (23%) had primHR-NMIBC, 125 (14%) had recHR-NMIBC, 404 (44%) had primMIBC, and 168 (19%) had secMIBC. Lymph node involvement and pathological upstaging were more frequent in the secMIBC group than in the other groups (p < 0.001). The median follow-up was 37 mo. The 5-year recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were 77.9%, 83.2%, and 72.7% in primHR-NMIBC, 60.0%, 59%, and 48.9% in recHR-NMIBC, 60.9%, 64.5%, and 54.8% in primMIBC, and 41.3%, 46.5%, and 39% in secMIBC, respectively, with statistically significant differences across all survival outcomes except between recHR-NMIBC and primMIBC. On multivariable Cox regression, recHR-NMIBC was independently associated with shorter RFS (hazard ratio [HR] 1.64; p = 0.03), CSS (HR 1.79; p = 0.01), and OS (HR 1.45; p = 0.03), and secMIBC was associated with shorter CSS (HR 1.77; p = 0.01) and OS (HR 1.57; p = 0.006). Limitations include the biases inherent to the retrospective study design. CONCLUSIONS: Patients with recHR-NMIBC and primHR-MIBC had similar survival outcomes, while those with sec-MIBC had the worst outcomes. Therefore, early radical intervention may be indicated in selected patients, and potentially neoadjuvant systemic therapies in some patients with recHR-NMIBC. PATIENT SUMMARY: We compared cancer outcomes in different bladder cancer scenarios in a large, multinational series of patients who underwent removal of the bladder with curative intent. We found that patients who experienced recurrence of non-muscle-invasive bladder cancer (NMIBC) had similar survival outcomes to those with initial muscle-invasive bladder cancer (MIBC), while patients who experienced progression of NMIBC to MIBC had the worst outcomes. Selected patients with non-muscle-invasive disease may benefit from early radical surgery or from perioperative chemotherapy or immunotherapy.

• Keywords
• Disease progression, Mycobacterium bovis, Recurrence, Survival, Urinary bladder neoplasms,
• Publication type
• Journal Article MeSH