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Open research questions in Bladder and Urothelial Cancer Treatments

699 gap statements mined from Bladder and Urothelial Cancer Treatments papers in our 7.9M-paper local library, which holds 4,009 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The low incidence of bladder neuroendocrine carcinoma, resulting in limited data for model development and validation. The complexity of the disease, requiring the consideration of numerous factors such as patient characteristics and treatment modalities.

    Development and validation of a machine learning-based model for predicting survival in patients with bladder neuroendocrine carcinoma: a large retrospective study · 2026 · DOI

  • Limited understanding of the reproducibility of tumor-associated transcriptional alterations across independent cohorts. Limited knowledge of the localization of these alterations at single-cell resolution. Need for validation of the findings using in vitro qRT-PCR.

    Inflammation- and regulated-cell-death–relevant transcriptomic signatures in bladder urothelial carcinoma: cross-cohort reproducibility, exploratory single-cell localization, and in vitro qRT-PCR validation · 2026 · DOI

  • The paper highlights the need for more clinical trials to ensure the bio-efficacy of phytochemicals in humans.

    Phytochemicals as Chemo-Preventive and Therapeutic Agents Against Bladder Cancer: A Comprehensive Review · 2025 · DOI

  • Most studies on phytochemicals have been conducted in cell cultures and animal models. There is a need for more clinical trials to ensure the bio-efficacy of phytochemicals in humans.

    Phytochemicals as Chemo-Preventive and Therapeutic Agents Against Bladder Cancer: A Comprehensive Review · 2025 · DOI

  • The paper identifies technical challenges in evaluating DSC3 protein expression, including the need for accurate immunohistochemistry techniques. The study highlights domain challenges, such as the complexity of bladder cancer and the need for further research on the relationship between DSC3 expression and pathological classification.

    Desmocollin-3 and Bladder Cancer · 2025 · DOI

  • The mechanisms underlying Fucoxanthin's cytotoxic effects and its potential to potentiate the efficacy of Cisplatin on human bladder TCC cells are not well understood. The role of the STAT3/BCL-xL axis in Fucoxanthin's proapoptotic and cytotoxic actions is not clearly defined.

    Blockade of the STAT3/BCL-xL Axis Leads to the Cytotoxic and Cisplatin-Sensitizing Effects of Fucoxanthin, a Marine-Derived Carotenoid, on Human Bladder Urothelial Carcinoma Cells · 2025 · DOI

  • The potential of PDT for the treatment of urothelial carcinoma has not been thoroughly investigated. There is a lack of clinical data on the use of PDT in the treatment of bladder cancer. The current evidence on the preclinical and clinical application of PDT for urothelial carcinoma is limited.

    Photodynamic Therapy: Current Trends and Potential Future Role in the Treatment of Bladder Cancer · 2024 · DOI

  • A substantial unmet need persists as a majority of bladder cancer patients do not respond adequately to immunotherapy. The mechanisms of immune evasion in bladder cancer are not fully understood. There is a need to identify viable therapeutic targets to improve immunotherapy.

    Strategies for Overcoming Immune Evasion in Bladder Cancer · 2024 · DOI

  • However, the relative contribution of each agent remains unclear, and high PD-L1 expression alone could explain part of the response.

    HER2-low metastatic urothelial carcinoma with liver metastases responding to antibody–drug conjugate therapy: a case report · 2026 · DOI

  • Sarcopenia and altered body composition are established prognostic markers in several malignancies, but their relevance in non-muscle-invasive bladder cancer (NMIBC) remains unclear.

    Sarcopenia and recurrence risk in high-risk non–muscle-invasive bladder cancer: a nonlinear modeling approach · 2026 · DOI

  • Response assessment after NAT in MIBC remains insufficiently standardised.

    Response evaluation of neoadjuvant therapy in MIBC : clinical trial‐derived evidence to guide practice · 2026 · DOI

  • Overexpression of N-RAS has been previously reported, although its clinical implication remains uncertain.

    Association Between Proto-Oncogene N-RAS Transcript Level and Overall Survival in Node-Negative Muscle-Invasive Bladder Cancer · 2026 · DOI

  • Introduction Urothelial carcinoma with trophoblastic differentiation (TUC) is a rare, aggressive variant reported in the upper and lower urinary tract, but its genomic landscape remains poorly defined.

    Trophoblastic-Differentiated Urothelial Carcinoma: Real-World Sequencing and Clinical Implications · 2026 · DOI

  • Systemic inflammation may further influence prognosis, yet combined muscle and inflammation assessment has not been evaluated.

    Baseline Sarcopenia is Associated With Overall Survival but Not Toxicity in Patients Receiving Enfortumab Vedotin Plus Pembrolizumab for Locally Advanced or Metastatic Urothelial Carcinoma · 2026 · DOI

  • There is limited data evaluating their safety when combined with radiation therapy (RT).

    Safety of Combining Radiation Therapy and Antibody Drug Conjugates in Advanced Urothelial and Other Cancers · 2025 · DOI

  • In high-risk patients, routine imaging remains warranted, although the optimal frequency and duration are yet to be determined.

    Risk of metachronous upper tract urothelial carcinoma following non‐muscle‐invasive bladder cancer · 2025 · DOI

  • Limitations of this study include its retrospective design, heterogeneity in chemotherapy regimens, and the absence of clearly defined patient selection criteria for treatment.

    Response to neoadjuvant chemotherapy leads to better survival outcomes in upper tract urothelial carcinoma · 2025 · DOI

  • To describe the oncological outcomes for patients with newly diagnosed bladder cancer, as long-term oncological outcomes and natural history of different initial subtypes of diagnoses of bladder cancer are understudied.

    Long‐term oncological outcomes of bladder cancer: a population‐based study with a 25‐year follow‐up · 2025 · DOI

  • The understanding of the prognosis and survival trends of upper tract urothelial carcinoma remains incomplete. The importance of age in prognostic assessment remains contentious. Prior research has not developed a prognostic nomogram specifically for early-onset upper tract urothelial carcinoma.

    Development and validation of a SEER-based prognostic nomogram for patients with early-onset upper tract urothelial carcinoma · 2026 · DOI

  • The study was limited to patients with pathologically confirmed BNEC, - The study used a retrospective design, - The study did not include patients with missing…

    Development and validation of a machine learning-based model for predicting survival in patients with bladder neuroendocrine carcinoma: a large retrospective study · 2026 · DOI

  • Investigate the mechanisms of DSC3 expression in bladder cancer, - Evaluate the potential of DSC3 as a therapeutic target for bladder cancer, - Conduct larger studies to confirm the association between DSC3 expression…

    Desmocollin-3 and Bladder Cancer · 2025 · DOI

  • Further investigation of PDT in the treatment landscape of BC is needed, - Clinical trials to demonstrate the efficacy of PDT in urothelial carcinoma are required, - Research on the combination of PDT with other therapeutic modalities…

    Photodynamic Therapy: Current Trends and Potential Future Role in the Treatment of Bladder Cancer · 2024 · DOI

  • Investigating the role of TLR polymorphisms in bladder cancer, - Exploring novel pathways and molecular targets that might circumvent resistance to immunotherapy, - Studying the effects of LDH-A inhibition on anti-tumor immune response to immune checkpoint…

    Strategies for Overcoming Immune Evasion in Bladder Cancer · 2024 · DOI

  • Sarcopenia prevalence varied widely across definitions (6-66%) with low-to-moderate concordance…

    Sarcopenia and recurrence risk in high-risk non–muscle-invasive bladder cancer: a nonlinear modeling approach · 2026 · DOI

  • First, regarding the reduced number of evaluable samples (271/652), we agree that this represents an important limitation of the study.

    Response to: “Caution in interpreting the diagnostic superiority of digital Uromonitor in NMIBC surveillance” · 2026 · DOI

Most-cited papers in Bladder and Urothelial Cancer Treatments

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Open questions raised by papers listed on this page include: (1) The relative contribution of each agent remains unclear, and high PD-L1 expression alone could explain part of the response (“HER2-low metastatic urothelial carcinoma with liver metastases responding to…”, 2026); (2) Sarcopenia and altered body composition are established prognostic markers in several malignancies, but their relevance in non-muscle-invasive bladder cancer (NMIBC) remains unclear (“Sarcopenia and recurrence risk in high-risk non–muscle-invasive bladder cancer:…”, 2026); (3) Systemic inflammation may further influence prognosis, yet combined muscle and inflammation assessment has not been evaluated (“Baseline Sarcopenia is Associated With Overall Survival but Not Toxicity in…”, 2026); (4) There is a need for more clinical trials to ensure the bio-efficacy of phytochemicals in humans (“Phytochemicals as Chemo-Preventive and Therapeutic Agents Against Bladder…”, 2025); (5) The mechanisms underlying Fucoxanthin's cytotoxic effects and its potential to potentiate the efficacy of Cisplatin on human bladder TCC cells are not well understood (“Blockade of the STAT3/BCL-xL Axis Leads to the Cytotoxic and…”, 2025). 699 gap statements have been mined from Bladder and Urothelial Cancer Treatments papers in our 7.9M-paper local library, which holds 4,009 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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