Bladder cancer research is continuously advancing, from new developments to best standards of care. Explore the links and research highlights below to stay informed and learn more about the latest advancements in the field.
Bladder Cancer Research & Studies
Summaries
Sasanlimab plus BCG in BCG-naive, high-risk non-muscle invasive bladder cancer: the randomized phase 3 CREST trial
Researchers from an international consortium led by Dr. Neal D. Shore have reported promising results from the phase 3 CREST trialâa global study testing a new combination treatment for patients newly starting Bacillus CalmetteâGuĂ©rin (BCG) therapy for bladder cancer. The trial evaluated sasanlimab, a novel subcutaneous PDâ1 inhibitor, given together with standard BCG immunotherapy after tumor resection. More than 1,000 patients with highârisk nonâmuscle invasive bladder cancer (NMIBC) were enrolled across 14 countries. Results published in Nature Medicine show that patients receiving sasanlimab plus BCG induction and maintenance therapy had a 32% lower risk of recurrence, progression, or death compared to those receiving BCG alone. After three years, 82% of combinationâtreated patients remained free from disease events, compared with 75% receiving BCG alone. The benefit was seen across key patient groups, including those with carcinoma in situ (CIS) or T1 tumors. Importantly, the combination-maintained patientsâ quality of life, with manageable side effects typical of immuneâbased therapies. No new safety concerns were identified. The addition of sasanlimab could represent a significant advance toward more durable, bladderâpreserving disease control for individuals facing earlyâstage highârisk bladder cancer.
Note: This summary was based on research and findings from the following published paper in Nature Medicine by Shore N., et al (May 2025; https://www.nature.com/articles/s41591-025-03738-z)
Modulating the PPARÎł pathway upregulates NECTIN4 and enhances chimeric antigen receptor (CAR) T cell therapy in bladder cancer
A new study published in Nature Communications by researchers from the University of California, San Francisco, and collaborators worldwide has uncovered a promising way to make CARâT cell therapy more effective in bladder cancer. The team found that activating a cellular metabolism regulator called PPARÎł increases the expression of NECTIN4, a protein found on many bladder cancer cells. NECTIN4 is already targeted by existing antibodyâdrug conjugates such as enfortumab vedotin. By upregulating NECTIN4, the cancer cells effectively âlight upâ and become easier for engineered immune cellsâCARâT cellsâto recognize and destroy. In preclinical models, combining PPARÎłâactivating drugs with NECTIN4âdirected CARâT therapy led to stronger tumor control and improved survival. The results suggest that metabolic modulation could be a powerful way to broaden CARâT cell therapy to more solid tumors, including bladder cancer, which has historically been difficult to treat with immunotherapy alone. Dr. Kevin Chang and colleagues note that the next steps will involve testing this combination strategy in earlyâphase clinical trials to determine safety and efficacy in patients.
Note: This summary was based on research and findings from the following published paper in Nature Communications by Chang K., et al (Sep 2025; https://www.nature.com/articles/s41467-025-62710-0).
Members of the Urinary Microbiota as Modulators of BCG-Induced Immunotherapy
Non-muscle invasive bladder cancer (NMIBC) is a form of cancer where the tumour remains in the inner lining of the bladder. Immunotherapy in the form of Bacillus Calmette-Guerin (BCG) therapy is a common adjuvant treatment of NMIBC which activates the innate and adaptive immune system to promote an anti-tumour immune response. Urinary microbiota has been shown to regulate local and systemic immune responses, and studies have demonstrated a disturbance in urinary microbiota in bladder cancer patients compared to healthy individuals. Enriching specific members of urinary microbiota (Actinomycetota and Pseudomonadota) in combination with BCG therapy has the potential to change host immunity and affect treatment response in NMIBC, improving patient outcomes. Additionally, the secondary metabolites of these bacteria have been shown to possess anti-tumour activity. Dr. Dirk Lange and his team seek to identify secondary metabolites produced by bacteria of interest that have anti-bladder cancer activity and investigate how the co-administration of the whole bacteria and BCG affect anti-bladder cancer activity. Secondary metabolites will be isolated from bacterial suspensions of members of Actinomycetota and Pseudomonadota and their cytotoxic effects on bladder cancer cells will be assessed. Mice studies will be used to analyze anti-bladder cancer activity of whole bacteria and BCG combined therapy. This research could ultimately lead to the determination of a bacterial cocktail with maximal BCG response and anti-tumour activity to improve clinical outcomes.
Note: This summary was written from the research proposal titled ‘Members of the Urinary Microbiota as Modulators of BCG-Induced Immunotherapyâ, by Dr. Dirk Lange, a research study funded with support from Bladder Cancer Canada.
Predictive Power of IgA Responses for Sex Differences in Muscle-Invasive Bladder Cancer
New research led by Dr. Eva Michaud aims to bridge the gap between immune responses in the bladder and sex differences in muscle-invasive bladder cancer (MIBC). Females are more likely to be affected by MIBC and have less response to treatment and higher rates of tumour reoccurrence. Researchers have identified the antibody, Immunoglobulin A (IgA), as compound of interest that could explain sex differences in bladder cancer. IgA is a blood protein in mucous membranes that helps protects the body from germs, and differences in IgA levels have been observed between males and females. Researchers determined that increased IgA2 secretion was associated with improved survival outcomes in female MIBC patients that were not seen in males. Dr. Michaudâs team seeks to understand how IgA expression is controlled by hormones and genes in MIBC and predict MIBC reoccurrence in females based on hormonal features, tumour tissue characteristics, and IgA secretion. The study uses transcriptomic analyses (to observe gene expression differences), immunohistochemical staining (to analyze microscopic differences in tumour tissue), and mice studies, to uncover the relationship between IgA expression and hormonal and autosomal sex differences. Further analyses contribute to creating an artificial intelligence system that can predict MIBC reoccurrence in females. By analyzing the significance of IgA changes in MIBC, this research takes advantage of sex-based differences in bladder cancer to predict outcomes and lead to better strategies in cancer treatment.
Note: This summary was written from the research proposal titled Predictive Power of IgA Responses for Sex Differences in Muscle-Invasive Bladder Cancerâ, by Dr. Eva Michaud, a research study funded with support from Bladder Cancer Canada.
High-Resolution Characterization of the Scar-Like Subtype Post-Systemic Therapy Using Spatial Transcriptomics and Digital Pathology
Muscle-invasive bladder cancer (MIBC) is a difficult form of bladder cancer with a 5-year survival rate of 55% even after optimal treatment with chemotherapy and radial cystectomy (bladder removal). Residual tumours after chemotherapy are associated with poor prognoses, highlighting the need for improved therapeutic management. Analysis of bladder tumours post-treatment has identified distinct subtypes, including a âscar-likeâ transcriptomic subtype that has been associated with favourable outcomes. The characterization of this subtype could help uncover new potential therapeutic targets and a deeper understanding of the biological processes underlying treatment response. Dr. Ewan Gibb and his team seek to profile this subtype by examining the cellular composition and organization of scar-like tumours to identify and predict their occurrence in clinical settings. RNA-sequencing of bladder tumours will be used to gather gene expression information to perform spatial transcriptomics and determine the genetic landscape of this bladder cancer subtype. To assist with identification, the team also aims to develop an image-based classifier of scar-like tumours using digital pathology and machine-learning techniques. This research supports a tailored approach to bladder cancer management by allowing the identification of patients who would most benefit from adjuvant therapy, reducing unnecessary treatment exposure and improving health outcomes.
Note: This summary was written from the research proposal titled ‘High-Resolution Characterization of the Scar-Like Subtype Post-Systemic Therapy Using Spatial Transcriptomics and Digital Pathologyâ, by Dr. Ewan Gibb, a research study funded with support from Bladder Cancer Canada.
Epigenetic regulation of neuroendocrine differentiation in urothelial bladder cancers
A new study led by Dr. Amina Zoubeidi, is investigating how changes in gene regulation – known as epigenetic alterations – may drive the transformation of conventional bladder cancer into its aggressive neuroendocrine form. Although neuroendocrine bladder cancer (NEBC) makes up only about 3% of bladder cancers, it is associated with earlier spread and worse outcomes. This project, is using advanced techniques like ATAC-seq and RNA-seq to study tumor samples from four groups of patients, including those with pure NEBC and those with conventional bladder cancer that shows NE-like features. By mapping changes in chromatin (the structure that organizes DNA) and linking them to gene activity, the research team hopes to uncover what triggers this dangerous transformation. Understanding these processes could lead to new treatment strategies – especially for patients who do not respond well to current therapies. This study is an important step toward more personalized and effective treatments for bladder cancer, especially in its most difficult-to-treat forms.
Note: This summary was written from the research proposal titled âEpigenetic regulation of neuroendocrine differentiation in urothelial bladder cancersâ, by Dr. Amina Zoubeidi, and research funded thanks to support from Bladder Cancer Canada.
Systemic immune reprogramming and response to BCG therapy in patients with bladder cancer
Patients with non-muscle invasive bladder cancer (NMIBC) often face high recurrence rates despite treatment with Bacillus Calmette-GuĂ©rin (BCG) immunotherapy, the gold standard for high-risk disease. This project focuses on understanding why some bladder cancer patients respond well to BCG therapy while others do not. Emerging research suggests that differences in the immune system, particularly in a type of white blood cell called monocytes, may influence treatment outcomes. Preliminary single-cell RNA and ATAC sequencing (scRNA-seq and scATAC-seq) revealed differences in the composition and chromatin accessibility of monocyte subsets post-BCG therapy. Patients with better-trained innate immune responses appear to have more favorable results. The author has already found differences in the monocyte function after BCG treatment. Next, they plan to analyze blood samples collected before BCG therapy. The goal is to identify early immune signatures that can predict a patient’s response to BCG, ultimately guiding more personalized and effective treatment strategies.
Note: This summary was written from the research proposal titled âSystemic immune reprogramming and response to BCG therapy in patients with bladder cancerâ, by Dr. Charles Graham, a research study funded with support from Bladder Cancer Canada.
Boosting the response to BCG immunotherapy: Harnessing the gut microbiota for bladder cancer treatment
Bacillus Calmette-Guérin (BCG) remains the gold standard treatment for non-muscle invasive bladder cancer (NMIBC), yet it fails in up to 40% of patients, highlighting the need for improved therapeutic strategies. Recent findings suggest that distinct gut microbiota profiles may be linked to BCG response, with certain bacterial signatures correlating with better treatment outcomes. Dr. Vincent Fradet and his team are exploring how gut microbiota influences the effectiveness of BCG immunotherapy in treating NMIBC.
Their study involves analyzing stool samples from patients undergoing BCG treatment to identify microbial differences between responders and non-responders, followed by fecal microbiota transplants (FMT) in preclinical models to assess causal relationships. By using these models, scientists have demonstrated a potential link between gut microbes and BCG efficacy, showing enhanced anti-tumor immune responses. This research aims to uncover key mechanisms driving this interaction, potentially leading to microbiome-based interventions to improve BCG therapy and patient outcomes.
Note: This summary was written from the research proposal titled âBoosting the response to BCG immunotherapy: Harnessing the gut microbiota for bladder cancer treatmentâ, by Dr. Vincent Fradet, a research study funded with support from Bladder Cancer Canada.
Tumor microenvironment transcriptional heterogeneity in neoadjuvant therapy response prediction in MIBC
Bladder cancer remains a challenging disease, especially for patients with muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma (mUC). Enfortumab Vedotin (EV), an antibody-drug conjugate, has shown promise, especially when combined with pembrolizumab, reducing cancer progression and mortality compared to chemotherapy. However, while many patients respond well initially, some experience treatment resistance, limiting its long-term effectiveness. Dr. Peter Black and his team are leading a critical research project to better understand this resistance – why some bladder cancers stop responding to EV and pembrolizumab, and to develop tools that help predict which patients are most likely to benefit from this treatment. Specifically, the team will investigate how bladder cancer cells adapt to evade treatment. A key focus is NECTIN-4, the protein targeted by EV, which some tumors lose, reducing treatment response. Using patient tumor samples and advanced mouse models, the team aims to identify biomarkers predicting treatment success and uncover mechanisms of resistance. By identifying biomarkers and mechanisms of resistance, this research could lead to better patient selection for therapy, new drug combinations to overcome resistance, and more effective strategies to manage bladder cancer.
Note: This summary was written from the research proposal titled âTumor microenvironment transcriptional heterogeneity in neoadjuvant therapy response prediction in MIBCâ, by Dr. Peter Black, a research study funded with support from Bladder Cancer Canada.
BCG: Beyond Bladder Cancer â Exploring Potential Benefits for Alzheimerâs and Dementia
Emerging research suggests that the Bacillus CalmetteâGuĂ©rin (BCG) vaccine may have potential protective effects against Alzheimerâs disease (AD) and dementia. Originally developed to prevent tuberculosis and widely used in non-muscle invasive bladder cancer treatment, studies have observed that patients receiving BCG therapy show significantly lower rates of AD compared to those who do not.
This effect may stem from BCG’s ability to modulate the immune system, promoting resilience and possibly reducing the inflammation associated with neurodegenerative diseases. Other vaccines, such as Shingrix, which includes a potent adjuvant system, have also demonstrated reductions in dementia risk. However, these findings are based on retrospective studies and remain preliminary.
Ongoing clinical trials are investigating BCGâs impact on AD biomarkers and cognitive health to determine its efficacy. While promising, further research is required to confirm whether BCG or similar interventions can reliably prevent or delay dementia, potentially offering a novel approach to addressing this growing public health challenge.
Note: This summary was based on research and findings from the following sources:
- PubMed article: “A study on BCG vaccine effects” (https://pubmed.ncbi.nlm.nih.gov/38393913/)
- PubMed article: “Exploring the use of BCG in new therapeutic areas” (https://pubmed.ncbi.nlm.nih.gov/37693645/)
- The Guardian article: “Is the 100-year-old TB vaccine a new secret weapon against Alzheimer’s?” (https://www.theguardian.com/society/2024/feb/25/is-the-100-year-old-tb-vaccine-a-new-secret-weapon-against-alzheimers-dementia-bcg)