Non-muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the most common urinary tract cancer and the 6th most common cancer in the US. Yet bladder cancer research is underfunded relative to other common cancers. As a result, bladder cancer care is prone to evidence gaps that produce decision uncertainty for both patients and clinicians. The Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer Study 2 (CISTO2) has the potential to fill these critical evidence gaps, change care pathways for the management of NMIBC (non-muscle-invasive bladder cancer), and provide for personalized, patient-centered care. The purpose of CISTO2 is to conduct a large prospective study that directly compares the impact of bladder sparing therapies versus bladder removal in recurrent high-grade NMIBC patients on financial toxicity, clinical outcomes and patient and caregiver experience using standardized patient-reported outcomes (PROs).

This study aims to evaluate the efficacy and safety of intravenous administration of vedacitinib combined with intravesical instillation of mitomycin in treating patients with high-risk NMIBC with HER2 expression. The goal is to provide a new treatment option for NMIBC patients, reduce the risk of tumor recurrence, decrease the proportion of radical bladder surgery, and improve the quality of life of patients.

The goal of this clinical trial is to learn whether a combination of two chemotherapy drugs, Gemcitabine and Docetaxel, can treat high-grade non-muscle-invasive bladder cancer (HG-NMIBC) in adults whose cancer failed conventional BCG therapy. The drugs are given directly into the bladder (intravesically), one immediately after the other. The study will also assess the safety of this treatment. The main questions it aims to answer are: Can this drug combination effectively treat HG-NMIBC that did not respond to BCG and help prevent the cancer from coming back, offering long-term protection? What side effects or medical issues do participants experience during treatment? Researchers will evaluate this non-surgical approach as a potential alternative to bladder removal surgery (radical cystectomy), with the goal of validating it as a bladder-sparing option in this setting. Participants will: * Go through a screening process, including tumor removal and imaging tests * Receive weekly bladder treatments with Gemcitabine followed by Docetaxel for 6 weeks * If the cancer responds, continue with similar once monthly treatments (maintenance therapy) for up to 2 years * Attend regular check-ups, including bladder exams, urine tests, biopsies, and optional quality-of-life surveys * Possibly receive a second 6-week treatment cycle if the cancer returns early * Be followed for up to 5 years to monitor long-term outcomes

Bladder cancer is a significant global and local health concern, and predicting how aggressive a patient's tumor will behave is critical for guiding treatment. This observational study aims to evaluate two specific microscopic features of urothelial bladder carcinoma to see if they can reliably predict patient outcomes: the depth of early tumor invasion (T1 substaging) and the presence of small clusters of cancer cells at the tumor's edge (Tumor Budding). Researchers will retrospectively analyze tissue samples (paraffin blocks) from at least 100 patients who were diagnosed with urothelial bladder carcinoma and underwent transurethral resection (TUR) at the South Egypt Cancer Institute between 2018 and 2024. The tissue samples will be analyzed in two main ways: * Early-stage tumors (pT1 cases): Researchers will carefully measure the exact depth the tumor has invaded the bladder lining using anatomical and micrometric sub-classification systems. * More advanced tumors (pT2 cases): Researchers will examine the invasive edge of the tumors under a microscope to count "tumor buds" (single cells or small clusters of cells). By comparing these detailed microscopic measurements with the patients' historical medical records, the study hopes to determine if T1 substaging and Tumor Budding are strong predictors of disease recurrence, disease progression, and overall patient survival.

Despite increasing recognition of sexual dysfunction and sexual distress as important survivorship issues in oncology, research and clinical attention remain uneven across cancer types. This imbalance is particularly evident in bladder cancer, where sexual health has received limited research and clinical attention. However, existing studies demonstrate substantial sexual dysfunction and reduced intimacy among patients following disease and treatment. The treatment of bladder cancer is a multimodal and multidisciplinary discipline. Low-risk non-muscle-invasive bladder cancer (NMIBC) is treated by transurethral resection of the bladder (TURB) alone, while recurrent intermediate- and high-risk NMIBC undergo a combination of TURB and adjuvant intravesical instillation therapy. For patients with muscle-invasive bladder cancer (MIBC) and specific high-risk NMIBC cases, the first-line treatment option is radical cystectomy with urinary diversion, with or without neoadjuvant chemotherapy. These treatment modalities are known to have a negative impact on sexual function, and studies in both men and women demonstrate profound impairments in sexual function, intimacy, and body image after treatment. Among men, erectile and ejaculatory dysfunction are prevalent for this patient group and frequently associated with diminished sexual satisfaction and body-image concerns. Likewise, women experience loss of sexual desire, orgasmic disorders, dyspareunia, and vaginal dryness following cystectomy. A targeted literature search further identified no contemporary sexology-focused interventional or feasibility trials specifically in bladder cancer (neither MIBC or NMIBC). Existing evidence on the topic is largely descriptive or addresses non-sexological rehabilitation, demonstrating a evidence gap\[1\]. Qualitative research has also explored informational and psychosocial needs among bladder cancer patients, revealing limited communication about sexual health and unmet needs for professional support. Such studies provide valuable insight into patient experiences but have not yet translated this knowledge into the development of structured, sexological interventions. Evidence from other cancer populations demonstrates that counselling and psychoeducational programmes addressing intimacy and sexuality are both feasible and beneficial, suggesting that similar interventions could be adapted for bladder cancer care. To develop a relevant and acceptable intervention, it is essential to understand how patients themselves perceive their sexual health challenges, informational needs, and preferences for professional support regarding sexual health. This project therefore consists of two sequential sub-studies: * Study 1a (Development phase): A qualitative, exploratory study to develop a sexological intervention with patient and clinician involvement. * Study 1b (Feasibility phase): A one-armed feasibility trial assessing the implementation and acceptability of the intervention among patients with muscle-invasive bladder cancer (MIBC).

This is an open-label, phase 2, randomized study of intravesical N-803 plus BCG (experimental arm A) and intravesical N-803 plus gemcitabine (experimental arm B) in participants who have intermediate-risk Ta/T1 papillary disease. The primary objective of this study is to evaluate the efficacy of these experimental therapies without the need for surgical intervention by CR rate at month 3 or month 6 (for re-inducted participants).

The goal of this clinical trial is to use urine tumor DNA (utDNA) as an indicator for non-muscle invasive bladder cancer to identify patients suitable for less frequent cystoscopy surveillance.

This is an open label, multi-center study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of RAG-01 in patients with NMIBC who have failed BCG therapy.

The study is to evaluate the safety and tolerability of intravesical FL115 alone or in combination with BCG in the patients with NMIBC, and to determine the RP2D of FL115 in combination with BCG. To evaluate the preliminary efficacy of FL115 alone or in combination with BCG in the treatment of NMIBC. The study consists of three parts: FL115 monotherapy dose escalation (Phase Ia), FL115 combined with BCG dose escalation (Phase Ib), and FL115 combined with BCG cohort expansion (Phase II). Each subject will receive FL115 alone or in combination with intravesical BCG, administered over three treatment periods: induction, enhanced induction/maintenance 1, and maintenance 2.

The goal of this clinical trial is to learn if neoadjuvant intravesical instillation of mitomycin C combined with en-bloc surgery works to treat high-risk non-muscle-invasive bladder cancer (NMIBC) patients. It will also learn about the safety of neoadjuvant intravesical instillation of mitomycin C. The main questions it aims to answer are: Does neoadjuvant intravesical instillation of mitomycin C heighten the 1-year recurrence-free survival (RFS) rate for high-risk non-muscle-invasive bladder cancer (NMIBC) patients? What medical problems do participants have when taking neoadjuvant intravesical instillation of mitomycin C? Researchers will compare neoadjuvant intravesical instillation of mitomycin C to a placebo (normal saline) to see if neoadjuvant intravesical instillation of mitomycin C works to treat high-risk NMIBC. Participants will: Take neoadjuvant intravesical instillation of mitomycin C or a placebo twice，1 day and 4 hours before en-bloc surgery Visit the clinic once every 8 weeks for checkups and tests Keep track of the recurrence and progression of the tumor.

This is an open-label, multicenter phase 1 study to evaluate the safety, efficacy, and pharmacokinetics (PK) characteristics of SIM0237 alone or in combination with bacillus Calmette-Guerin (BCG) in participants with Non-Muscle-Invasive Bladder Cancer (NMIBC)