Muscle Invasive Bladder Cancer (MIBC)

This prospective, multicenter, open-label phase II study will evaluate a response-guided bladder-preservation strategy in patients with HER2-expressing muscle-invasive bladder cancer. Participants will receive maximal transurethral resection of the bladder tumor, trastuzumab rezetecan plus adebrelimab, and concurrent bladder radiotherapy. Treatment response will be assessed by cystoscopic biopsy or diagnostic transurethral resection at 8 weeks (±2 weeks) after radiotherapy. Participants with a pathological stage of T1 or lower may continue bladder-preserving management, whereas radical cystectomy will be recommended for participants with disease above T1. The primary outcome is the major pathological response rate.

This is a multicenter, non-interventional, prospective and retrospective observational patient registry study of adults with muscle-invasive bladder cancer receiving perioperative systemic therapy as part of routine clinical care. The registry includes patients treated with perioperative systemic therapies such as Enfortumab Vedotin plus Pembrolizumab as well as cisplatin-based combinations including Gemcitabine/Cisplatin/Durvalumab and other standard perioperative treatment approaches in the neoadjuvant and adjuvant setting. The study aims to evaluate real-world feasibility, treatment tolerability, pathologic response, and oncologic outcomes of perioperative systemic treatment strategies. Key outcomes include event-free survival (EFS), pathologic complete response (pCR), pathologic downstaging, disease-free survival (DFS), overall survival (OS), perioperative complications, and treatment-related adverse events. Patient-reported neurotoxicity symptoms will also be assessed using standardized neuropathy questionnaires. All treatments, surgeries, and follow-up procedures are performed according to routine clinical practice. No study-specific interventions are assigned. Clinical data are collected pseudonymized through participating GUARDIANS centers using standardized electronic case report forms. Both prospective and retrospective data collection are included.

The main purpose of Part A of the study is to evaluate safety, tolerability and tracer uptake after a single intravenous (IV) administration of \[68Ga\]Ga-DPI-4452 for each tumor type such as clear cell renal cell cancer (ccRCC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC); Part B: is to determine the recommended phase 2 dose (RP2D) \[maximum tolerated dose (MTD) or lower dose\] for \[177Lu\]Lu-DPI-4452 for each tumor type such as ccRCC, PDAC, CRC, and urothelial carcinoma (UC); Part C: is to evaluate the preliminary antitumor activity of \[177Lu\]Lu-DPI-4452 as monotherapy for each tumor type such as ccRCC, PDAC, CRC, and UC; Part D: is to assess the diagnostic concordance between \[68Ga\]Ga-DPI-4452 Positron Emission Tomography (PET) and the histopathology result of the Indeterminate Renal Mass (IDRM); Part E: is to assess \[68Ga\]Ga-DPI-4452 uptake in each tumour type such as UC, muscle invasive bladder cancer (MIBC), head and neck cancer (H\&N), triple negative breast cancer (TNBC), squamous non-small cell lung cancer (NSCLC), and any other tumor with locally confirmed carbonic anhydrase (CA) IX expression except ccRCC, CRC and PDAC.

This prospective observational study evaluates a blood-based circulating tumor DNA (ctDNA) test in patients with muscle-invasive bladder cancer or upper tract urothelial cancer. ctDNA consists of small fragments of tumor DNA that can sometimes be detected in the blood. In this study, DNA from tumor tissue obtained during routine diagnostic or surgical procedures will be analyzed to identify tumor-specific mutations. Blood samples collected during routine clinical care will then be tested to determine whether the same mutations can be detected in plasma ctDNA. The main purpose is to assess how well the internally developed ctDNA assay detects tumor-specific mutations compared with tumor tissue sequencing. The study will also explore whether ctDNA results after treatment are associated with recurrence or remission during two years of follow-up, and whether changes in ctDNA levels during treatment are associated with pathological response. This study does not assign participants to a treatment and does not require additional blood draws beyond routine care. Treating physicians will remain blinded to ctDNA results during the study, so the test results will not influence clinical decisions.

Removal of the urinary bladder (radical cystectomy) is a major surgical procedure that can have a permanent impact on a patient's quality of life. Consequently, some patients, despite having received comprehensive counseling and completing systemic therapy, decide against subsequent surgery or alternative radiotherapy. Recent scientific studies suggest that, for selected patients, an attempt at bladder preservation may be a medically justifiable option. However, it remains unclear which patients are truly suitable candidates for bladder-preserving management and which are not. The aim of this registry is therefore to collect and analyze clinical data from this specific patient population.

The purpose of this Phase II, open-label, multicenter, randomized controlled study is to evaluate the efficacy and safety of Enfortumab Vedotin in combination with Toripalimab compared to Gemcitabine plus Cisplatin. This regimen is evaluated as a neoadjuvant treatment for patients with locally advanced or high-risk muscle-invasive bladder cancer. Participants will be randomly assigned in a 1:1 ratio to one of two cohorts. Cohort A will receive Enfortumab Vedotin and Toripalimab for 3 treatment cycles. Cohort B will receive Gemcitabine and Cisplatin for 3 treatment cycles. Following the neoadjuvant treatment phase, patients will undergo radical cystectomy and pelvic lymph node dissection. The primary endpoint of the study is the 1-year Event-Free Survival (EFS) rate. Secondary endpoints include pathological downstaging rate (pDR), pathological complete response (pCR), Disease-Free Survival (DFS), Overall Survival (OS), and the assessment of adverse events. Additionally, the study will evaluate the relationship between treatment efficacy and the expression of PD-L1 and Nectin-4 in tumor tissues.

For patients with HER2-expressing muscle-invasive bladder cancer (MIBC), current neoadjuvant therapies dominated by platinum-based chemotherapy remain unsatisfactory with respect to improved clinical efficacy, pathological complete response (pCR) rates, and the achievement rate of tumor downstaging for bladder preservation; in addition, a subset of patients have limited tolerance or eligibility to chemotherapy. Therefore, this study aims to evaluate the neoadjuvant regimen of Ruikang Trastuzumab combined with Camrelizumab, to determine whether this regimen can, with acceptable safety profiles: elevate pCR rate and the proportion of patients downstaged to ≤T1 disease, enable bladder preservation based on TURBT for eligible patients, and explore predictive biomarkers to identify the population most likely to derive clinical benefits.

This study aims to evaluate the efficacy and safety of neoadjuvant trastuzumab rezetecan combined with adebrelimab for the treatment of HER2-positive muscle-invasive bladder cancer.

This prospective diagnostic accuracy study compares computed tomography (CT) and multiparametric magnetic resonance imaging (MRI) using the Vesical Imaging-Reporting and Data System (VI-RADS) for local staging of newly diagnosed bladder cancer. All participants undergo both imaging modalities prior to transurethral resection of the bladder tumor (TURBT) or cystectomy. Histopathology serves as the reference standard.

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.

The goal of this clinical trial is to learn if oral probiotics (Clostridium butyricum) work to improve the efficacy of targeted therapy plus immunotherapy in bladder preservation setting for cisplatin-ineligible T2-3N0M0 bladder cancer patients with low serum butyrate. The main questions it aims to answer are: Do oral probiotics elevate serum butyrate levels and enhance the duation of bladder preservation interval with targeted therapy plus immunotherapy? Researchers will compare oral probiotics combined with targeted therapy plus immunotherapy to standard regimens (targeted therapy plus immunotherapy) to see if oral probiotics can improve its efficacy. Participants will: 1. Take oral probiotics and/or Disitamab Vedotin (HER2-ADC) and Toripalimab (PD-L1 inhibitor) for one year in total, which is divided into induction treatment period, intensive treatment period and maintenance treatment period. 2. Return to the hospital for evaluation of tumor residual burden according to the follow-up plan, which will include urine cytology, imaging, surgical biopsy, and urine DNA methylation detection.

This is a multicenter, open-label, prospective, single-arm, phase II study designed to evaluate the efficacy and safety of neoadjuvant zanidatamab combined with tislelizumab and chemotherapy, followed by selective bladder preservation, in patients with HER2-positive muscle-invasive bladder cancer (MIBC) staged cT2-4aN0-1M0.

Radical cystectomy is the standard of care for muscle invasive bladder cancer, however despite advances, it is still associated with high morbidity. Many complications may be driven by dehydration and it is unclear if a home intravenous fluid (IVF) infusion program post-operatively, which is an accepted standard practice, is beneficial. This study is a single institution randomized controlled trial where patients who choose to undergo radical cystectomy for bladder cancer will be randomized to an Enhanced Recovery After Surgery (ERAS) protocol with a home IVF program, consisting of 1 liter (L) of crystalloid fluid three times per week for four weeks, or ERAS protocol alone. The primary outcome will be 90-day hospital re-admissions, with secondary outcomes including 30 and 90 day complications.

This is a phase II clinical study to evaluate the efficacy of RC48-ADC combined with toripalimab bladder-sparing therapy. The RC48-ADC dose in this study is 2.0 mg/kg Q2W and toripalimab is 3 mg/kg Q2W. This study plans to enroll 59 participants. The participants will start drug therapy within 2 weeks after the first diagnostic resection in the first stage, receiving RC48-ADC combined with toripalimab 3 times. At the 8th week after enrollment, the second stage of cystectomy was performed, and RC48-ADC combined with toripalimab was treated every two weeks thereafter for a total of 3 treatments. After the completion of the two-stage treatment, the participants should be discharged from the group by cystoscopy or other imaging examinations. On the contrary, if the participants have complete remission or partial remission, continue to the third stage of treatment, that is, receive RC48-ADC combined with toripalimab every two weeks for a total of 6 treatments, followed by cystoscopy, imaging, or a third cystectomy. If the participants achieve complete remission of the disease, maintenance immunotherapy will be given for 12 months. If the participants show that there is still a tumor, the participants will be discharged from the group for other treatments. Due to disease progression, death, participants voluntarily requested termination of study treatment, toxicity intolerance, initiation of new anti-tumor therapy, pregnancy, serious violation of the study process stipulated by the protocol, termination of study treatment determined by the investigator based on the best interests of the participants, loss to follow-up, whichever occurred first. During the study, the first and second electrotoxic tissues were sequenced using RNA and single-cell sequencing, and ctDNA was tested in urine before treatment, in the third month, and in the sixth month.

The goal of this clinical trial is to learn if the use of MRI-guided irradiation increases the rates of bladder preservation as well as to decrease complications in patients with muscle invasive bladder cancer who wish to retain their bladders

The TEMPO-MIBC trial is a phase III, single-center, two-arm, randomized, controlled trial. Its primary objective is to evaluate the efficacy of a simplified diagnostic and treatment pathway for muscle-invasive bladder cancer (MIBC). This study investigates the role of multiparametric bladder MRI (mpMRI) in patients with biopsy proven cancer of the bladder with clinical features of detrusor muscle invasion. In the experimental arm, enrolled patients will receive a bladder mpMRI, if this exam will confirm the high suspicion of muscle invasion a conventional endoscopic transurethral resection of bladder tumour (TURBt) for staging purposes will be foregone and patients will immediately access the next step of their clinical management. Experimental arm outcomes will be compared to a control arm in which all enrolled patients will be receiving TURBt as part of the standard management of bladder cancer. The aim of this study is demonstrating a significant reduction of the time needed to offer patients the definitive treatment for their disease, possibly ensuring better long-term oncological outcomes. A blood sample will be collected from each patient enrolled in the study at pre-planned time points to measure the levels of circulating tumour (ctDNA), a primer will be built from bladder cancer biopsies performed at enrolment. ctDNA has been shown to be a proxy measure of tumour burden and residual molecular disease after treatment. The ctDNA levels in the experimental arm will be compared to those of the control arm to investigate wether foregoing endoscopic resection of the tumour and reducing time to definitive cancer treatment might be associated to lower ctDNA levels.