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Prehabilitation in patients undergoing bladder cancer surgery - A systematic review and meta-analysis.

The evidence on the effectiveness of prehabilitation in patients undergoing bladder cancer surgery remains lacking. Thus, the aim of this study is to determine the effectiveness of prehabilitation on reducing postoperative morbidity and length of hospital stay in patients undergoing bladder cancer surgery.

Adherence to First-Line Intravesical Bacillus Calmette-Guérin Therapy in the Context of Guideline Recommendations for US Patients With High-Risk Non-muscle Invasive Bladder Cancer.

Background: Bacillus Calmette-Guérin (BCG) can reduce recurrence and delay progression among patients with high-risk non-muscle invasive bladder cancer (NMIBC), but is associated with a substantial emotional, physical, and social burden.

Mortality rates in radical cystectomy patients with bladder cancer after radiation therapy for prostate cancer.

To conduct a population-based study examining cancer-specific mortality (CSM) and other-cause mortality (OCM) differences in patients with radiation-induced secondary bladder cancer (RT-BCa) vs those with primary bladder cancer (pBCa) undergoing radical cystectomy (RC).

HLA-G expression associates with immune evasion muscle-invasive urothelial cancer and drives prognostic relevance.

Urothelial bladder cancer is frequent and exhibits diverse prognoses influenced by molecular subtypes, urothelial subtype histology, and immune microenvironments. HLA-G, known for immune regulation, displays significant membranous expression in tumor tissues.

The interplay of mutagenesis and ecDNA shapes urothelial cancer evolution

Advanced urothelial cancer is a frequently lethal disease characterized by marked genetic heterogeneity1. In this study, we investigated the evolution of genomic signatures caused by endogenous and external mutagenic processes and their interplay with complex structural variants (SVs). We superimposed mutational signatures and phylogenetic analyses of matched serial tumours from patients with urothelial cancer to define the evolutionary dynamics of these processes. We show that APOBEC3-induced mutations are clonal and early, whereas chemotherapy induces mutational bursts of hundreds of late subclonal mutations. Using a genome graph computational tool2, we observed frequent high copy-number circular amplicons characteristic of extrachromosomal DNA (ecDNA)-forming SVs. We characterized the distinct temporal patterns of APOBEC3-induced and chemotherapy-induced mutations within ecDNA-forming SVs, gaining new insights into the timing of these mutagenic processes relative to ecDNA biogenesis. We discovered that most CCND1 amplifications in urothelial cancer arise within circular ecDNA-forming SVs. ecDNA-forming SVs persisted and increased in complexity, incorporating additional DNA segments and contributing to the evolution of treatment resistance. Oxford Nanopore Technologies long-read whole-genome sequencing followed by de novo assembly mapped out CCND1 ecDNA structure. Experimental modelling of CCND1 ecDNA confirmed its role as a driver of treatment resistance. Our findings define fundamental mechanisms that drive urothelial cancer evolution and have important therapeutic implications.

Duy D Nguyen # 1, William F Hooper # 2, Weisi Liu # 1, Timothy R Chu 2, Heather Geiger 2, Jennifer M Shelton 2, Minita Shah 2, Zoe R Goldstein 2, Lara Winterkorn 2, Adrienne Helland 2, Michael Sigouros 3, Jyothi Manohar 3, Jenna Moyer 3, Majd Al Assaad 3, Alissa Semaan 3, Sandra Cohen 3 4, Florencia Madorsky Rowdo 3 5, David Wilkes 3, Mohamed Osman 1, Rahul R Singh 1, Andrea Sboner 3 4 5, Henkel L Valentine 6, Phillip Abbosh 6 7, Scott T Tagawa 1 3 8 9, David M Nanus 1 3 8 9, Jones T Nauseef 1 3 8, Cora N Sternberg 1 3 8, Ana M Molina 1 3 8, Douglas Scherr 8 9, Giorgio Inghirami 3 4 8, Juan Miguel Mosquera 3 4 8, Olivier Elemento 3 4 5 8 10, Nicolas Robine 2, Bishoy M Faltas 11,12,13,14,15

  1. Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  2. New York Genome Center, New York, NY, USA.
  3. Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
  4. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
  5. Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
  6. Nuclear Dynamics and Cancer program, Fox Chase Cancer Center, Philadelphia, PA, USA.
  7. Department of Urology, Einstein Healthcare Network, Philadelphia, PA, USA.
  8. Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  9. Department of Urology, Weill Cornell Medicine, New York, NY, USA.
  10. Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
  11. Department of Medicine, Weill Cornell Medicine, New York, NY, USA. 
  12. Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA. 
  13. Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. 
  14. Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. 
  15. Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, USA. 
Source: Duy D Nguyen, William F Hooper, Weisi Liu et al. The interplay of mutagenesis and ecDNA shapes urothelial cancer evolution. Nature. 2024 Oct 9. doi: 10.1038/s41586-024-07955-3.

Efficacy and safety of pembrolizumab in patients with advanced urothelial carcinoma deemed potentially ineligible for platinum-containing chemotherapy: Post hoc analysis of KEYNOTE-052 and LEAP-011.

First-line pembrolizumab monotherapy is a standard of care for platinum-ineligible patients with advanced urothelial carcinoma (UC). No global standardized definition of platinum ineligibility exists.

Sex Disparity in Non-muscle-invasive Bladder Cancer: Pitfalls of Large Population-based Data Sets and Lessons from an Integrated Analysis.

The impact of sex on non-muscle-invasive bladder cancer (NMIBC) remains uncertain and current evidence is conflicting. To address this uncertainty, we conducted an integrative analysis using Surveillance, Epidemiology and End Results (SEER)-Medicare and UROMOL data sets to explore sex disparities in NMIBC oncological outcomes.

Sensitive Detection of Urothelial Cancer via High-volume Urine DNA Analysis.

European urology. 2024 Oct 22 [Epub ahead of print]

Jussi Nikkola, Lauri Ryyppö, Juuso Vuorinen, Heini Kallio, Hanna Selin, Pyry Jämsä, Jonne Åkerla, Tuomo Virtanen, Tarmo Pekkarinen, Antti Kaipia, Johanna Pulkkinen, Gillian Vandekerkhove, David C Müller, Alexander W Wyatt, Peter C Black, Matti Nykter, Thea Veitonmäki, Matti Annala

Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, Tampere, Finland; Department of Urology, Tampere University Hospital, Tampere, Finland; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, Canada.

Altered immunophenotypic expression in the peripheral bladder cancer immune landscape.

Treatments targeting the immune system only benefit a subset of patients with bladder cancer (BC). Biomarkers predictive of BC progression and response to specific therapeutic interventions are required.

Long-term recurrence risk, metastatic potential and length of cystoscopic surveillance of low-grade non-muscle invasive bladder cancer.

Patients with Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) rarely develop metastases or die from it. Long-term data are scant and length of follow-up poorly defined.

This retrospective study included 521 patients diagnosed with primary TaLG (n=491) or papillary urothelial neoplasm of low malignant potential (PUNLMP, n=30) from 1989-2019 at an Academic center.

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