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Nature Reviews. Disease Primers Oct 2023Bladder cancer is a global health issue with sex differences in incidence and prognosis. Bladder cancer has distinct molecular subtypes with multiple pathogenic pathways... (Review)
Review
Bladder cancer is a global health issue with sex differences in incidence and prognosis. Bladder cancer has distinct molecular subtypes with multiple pathogenic pathways depending on whether the disease is non-muscle invasive or muscle invasive. The mutational burden is higher in muscle-invasive than in non-muscle-invasive disease. Commonly mutated genes include TERT, FGFR3, TP53, PIK3CA, STAG2 and genes involved in chromatin modification. Subtyping of both forms of bladder cancer is likely to change considerably with the advent of single-cell analysis methods. Early detection signifies a better disease prognosis; thus, minimally invasive diagnostic options are needed to improve patient outcomes. Urine-based tests are available for disease diagnosis and surveillance, and analysis of blood-based cell-free DNA is a promising tool for the detection of minimal residual disease and metastatic relapse. Transurethral resection is the cornerstone treatment for non-muscle-invasive bladder cancer and intravesical therapy can further improve oncological outcomes. For muscle-invasive bladder cancer, radical cystectomy with neoadjuvant chemotherapy is the standard of care with evidence supporting trimodality therapy. Immune-checkpoint inhibitors have demonstrated benefit in non-muscle-invasive, muscle-invasive and metastatic bladder cancer. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics.
Topics: Humans; Female; Male; Treatment Outcome; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms; Urinary Bladder; Prognosis
PubMed: 37884563
DOI: 10.1038/s41572-023-00468-9 -
CA: a Cancer Journal For Clinicians Sep 2020Bladder cancer accounts for nearly 170,000 deaths worldwide annually. For over 4 decades, the systemic management of muscle-invasive and advanced bladder cancer has... (Review)
Review
Bladder cancer accounts for nearly 170,000 deaths worldwide annually. For over 4 decades, the systemic management of muscle-invasive and advanced bladder cancer has primarily consisted of platinum-based chemotherapy. Over the past 10 years, innovations in sequencing technologies have led to rapid genomic characterization of bladder cancer, deepening our understanding of bladder cancer pathogenesis and exposing potential therapeutic vulnerabilities. On the basis of its high mutational burden, immune checkpoint inhibitors were investigated in advanced bladder cancer, revealing durable responses in a subset of patients. These agents are now approved for several indications and highlight the changing treatment landscape of advanced bladder cancer. In addition, commonly expressed molecular targets were leveraged to develop targeted therapies, such as fibroblast growth factor receptor inhibitors and antibody-drug conjugates. The molecular characterization of bladder cancer and the development of novel therapies also have stimulated investigations into optimizing treatment approaches for muscle-invasive bladder cancer. Herein, the authors review the history of muscle-invasive and advanced bladder cancer management, highlight the important molecular characteristics of bladder cancer, describe the major advances in treatment, and offer future directions for therapeutic development.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Biomarkers; Clinical Trials as Topic; Combined Modality Therapy; Cystectomy; Humans; Immune Checkpoint Inhibitors; Muscle, Smooth; Neoplasm Invasiveness; Organ Sparing Treatments; Receptors, Fibroblast Growth Factor; Urinary Bladder Neoplasms
PubMed: 32767764
DOI: 10.3322/caac.21631 -
Cell Reports Aug 2019Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased...
Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models, which fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology as cachectic patients. We envision that the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia.
Topics: Animals; Cachexia; Disease Models, Animal; Disease Progression; Female; Gene Ontology; Heterografts; Humans; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Neoplasm Transplantation; Pancreatic Neoplasms; RNA-Seq; Transcriptome
PubMed: 31390573
DOI: 10.1016/j.celrep.2019.07.016 -
Seminars in Nuclear Medicine Jul 2022In the urinary tract, bladder cancer is the most common malignancy. It is a heterogenous cancer type with approximately 30% presenting as muscle invasive bladder cancer... (Review)
Review
In the urinary tract, bladder cancer is the most common malignancy. It is a heterogenous cancer type with approximately 30% presenting as muscle invasive bladder cancer with a high risk of metastatic spread associated with risk of death from distant metastases. The other 70% of bladder cancer patients present with superficial tumors with tendency of recurrence but in general not life-threatening. Like in other malignancies, accurate and precise staging of bladder cancer is one of the mainstays at the time of diagnosis to select the optimal treatment for each patient. The detection of metastatic spread is of utmost importance for selection of treatment strategy. Hybrid imaging med with FDG PET/CT is widely used in the clinical management of a variety of malignancies. FDG PET/CT is increasingly used for primary staging of muscle invasive bladder cancer and for detection of recurrence after radical cystectomy. Few studies have used FDG PET/CT for response evaluation of neoadjuvant, induction chemotherapy or immunotherapy. Furthermore, small studies have tested non-FDG PET agents with little or no urinary excretions of the tracer. This review provides an update on PET/CT in bladder cancer.
Topics: Fluorodeoxyglucose F18; Humans; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Urinary Bladder Neoplasms
PubMed: 34996595
DOI: 10.1053/j.semnuclmed.2021.12.004 -
Current Oncology Reports Feb 2023The treatment options for high-risk non-muscle invasive bladder cancer (NMIBC), particularly following BCG, remain limited. We highlight recent, promising therapies for... (Review)
Review
PURPOSE OF REVIEW
The treatment options for high-risk non-muscle invasive bladder cancer (NMIBC), particularly following BCG, remain limited. We highlight recent, promising therapies for high-risk NMIBC.
RECENT FINDINGS
Several therapies utilizing different mechanisms of action have demonstrated favorable results in the BCG-naïve and BCG-unresponsive settings. These treatments include intravenous and intravesical immunotherapy, viral- and bacterial-based intravesical therapies, combination intravesical chemotherapy regimens, and novel intravesical chemotherapy administration. Overall, the efficacy and tolerability of emerging treatments for NMIBC appear promising and provide potential alternatives to radical cystectomy. As the landscape of managing BCG-unresponsive disease evolves, clinical trials will explore future options and determine effective alternatives.
Topics: Humans; BCG Vaccine; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Urinary Bladder; Immunotherapy; Neoplasm Invasiveness
PubMed: 36571706
DOI: 10.1007/s11912-022-01350-9 -
International Journal of Cancer Dec 2021Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell... (Observational Study)
Observational Study
Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet-based single-cell RNA sequencing (scRNA-seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial-mesenchymal transition (EMT) and mainly located at the tumor-stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle-invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single-cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease Progression; Epithelial Cells; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Muscle, Smooth; Neoplasm Invasiveness; RNA-Seq; Single-Cell Analysis; Tomography, X-Ray Computed; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 34480339
DOI: 10.1002/ijc.33794 -
International Braz J Urol : Official... 2020Standard management of muscle-invasive bladder cancer involves radical cystectomy with pelvic lymph node dissection. However, patients may be ineligible for surgery or... (Review)
Review
BACKGROUND
Standard management of muscle-invasive bladder cancer involves radical cystectomy with pelvic lymph node dissection. However, patients may be ineligible for surgery or may wish to avoid the morbidity of cystectomy due to quality of life concerns. Bladder preservation therapies have emerged as alternatives treatment options that can provide comparable oncologic outcomes while maintaining patients' quality of life.
OBJECTIVE
To review bladder preservation therapies, patient selection criteria, and functional and oncologic outcomes for BPT in muscle-invasive bladder cancer.
MATERIALS AND METHODS
We conducted a comprehensive literature review of bladder preservation therapies in Pubmed and Embase.
DISCUSSION
The ideal patient for BPT has low-volume T2 disease, absence of CIS, absence of hydronephrosis, and a maximal TURBT with regular surveillance. Technological advancements involving cancer staging, TURBT technique, and chemotherapy and radiation therapy regimens have improved BPT outcomes, with oncologic outcomes now comparable to those of radical cystectomy. Advancements in BPT also includes a heightened focus on improving quality of life for patients undergoing bladder preservation. Preservation strategies with most evidence for use include trimodality therapy and partial cystectomy with pelvic lymph node dissection.
CONCLUSIONS
This review highlights the breadth of strategies that aim to preserve a patient's bladder while still optimizing local tumor control and overall survival. Future areas for innovation include the use of predictive biomarkers and implementation of immunotherapy, moving the field towards patient-tailored care.
Topics: Combined Modality Therapy; Cystectomy; Humans; Neoplasm Invasiveness; Neoplasm Staging; Organ Sparing Treatments; Urinary Bladder Neoplasms
PubMed: 31961624
DOI: 10.1590/S1677-5538.IBJU.2020.99.01 -
Journal of Experimental & Clinical... Sep 2021Ovarian cancer (OC) progression is an unmet medical challenge. Since omental metastases were palpated harder than their primary counterparts during cytoreductive surgery...
BACKGROUND
Ovarian cancer (OC) progression is an unmet medical challenge. Since omental metastases were palpated harder than their primary counterparts during cytoreductive surgery of patients with epithelial ovarian cancer (EOC), we were inspired to investigate OC progression from the perspective of biomechanics.
METHODS
Atomic Force Microscope (AFM) was used to measure the Young's modulus of tissues. The collagen-coated polyacrylamide hydrogel (PA gel) system was prepared to mimic the soft and stiff substrates in vitro. The effect of TAGLN was evaluated both in vitro and in vivo using transwell assay, immunofluorescence, western blot analysis and immunohistochemistry.
RESULTS
We quantitatively confirmed that omental metastases were stiffer and more abundant in desmoplasia compared with paired primary tumors, and further demonstrated that matrix stiffness could notably regulate OC progression. Remarkably, TAGLN, encoding an actin cross-linking/gelling protein, was identified as a potent mechanosensitive gene that could form a regulation loop with Src activation reacting to environmental stiffness, thus mediating stiffness-regulated OC progression through regulating RhoA/ROCK pathway.
CONCLUSIONS
These data demonstrate that targeting extra-cellular matrix (ECM) stiffness could probably hamper OC progression, and of note, targeting TAGLN might provide promising clinical therapeutic value for OC therapy.
Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Disease Progression; Extracellular Matrix; Female; Fluorescent Antibody Technique; Gene Expression; Gene Expression Profiling; Humans; Mice; Microfilament Proteins; Models, Biological; Muscle Proteins; Neoplasm Metastasis; Ovarian Neoplasms; Prognosis; Signal Transduction; Tumor Microenvironment; rho-Associated Kinases; rhoA GTP-Binding Protein; src-Family Kinases
PubMed: 34538264
DOI: 10.1186/s13046-021-02091-6 -
Molecular Biology Reports Sep 2023Urothelial bladder carcinoma (UC) ranks among the top ten most commonly diagnosed cancers worldwide on an annual basis. The standardized classification system for... (Review)
Review
Urothelial bladder carcinoma (UC) ranks among the top ten most commonly diagnosed cancers worldwide on an annual basis. The standardized classification system for urothelial bladder tumors is the Tumor, Node, Metastasis classification, which reflects differences between non-muscle-invasive bladder carcinoma (NMIBC) and muscle-invasive bladder carcinoma (MIBC) and it depends on the extent to which tumor has infiltrated the bladder wall and other tissues and organs. NMIBC and MIBC exhibit great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. In recent years, studies based on mRNA expression profiling revealed the existence of biologically relevant molecular subtypes of UC, which show variant molecular features that can provide more precise stratification of UC patients. Here, we present a complex classification of UC based on mRNA expression studies and molecular subtypes of NMIBC and MIBC in detail with regard to different mRNA expression profiles, mutational signatures, and infiltration by non-tumor cells. The possible impact of molecular subtyping on treatment decisions and patients' outcomes is outlined, too.
Topics: Humans; Urinary Bladder; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Mutation; Neoplasm Invasiveness
PubMed: 37525073
DOI: 10.1007/s11033-023-08689-7 -
International Braz J Urol : Official... 2019Radical prostatectomy (RP) can result in urinary incontinence (UI) and erectile dysfunction (ED), which negatively impact quality of life (QoL). This study aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of perioperative pelvic floor muscle training on early recovery of urinary continence and erectile function in men undergoing radical prostatectomy: a randomized clinical trial.
AIMS
Radical prostatectomy (RP) can result in urinary incontinence (UI) and erectile dysfunction (ED), which negatively impact quality of life (QoL). This study aimed to evaluate the effects of a perioperative pelvic floor muscle training (PFMT) program versus usual care on early recovery of urinary continence and erectile function after RP.
MATERIALS AND METHODS
Of 59 eligible men, 31 were randomly allocated into 2 groups: Group 1 (Control, N=15) received usual post-RP care; and Group 2 (Physical therapy, N=16) received two pre-RP physical therapist-guided PFMT sessions, including exercises and electromyographic biofeedback, and verbal and written instructions to continue PFMT until RP, which was then resumed after urethral catheter removal. The International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire were used to evaluate UI and ED, respectively.
RESULTS
Demographic characteristics were similar in both groups. Three months after RP, the UI rate was 72.7% and 70.0% in Groups 1 and 2, respectively (P >0.05). The severity and frequency of UI and its impact on QoL were evaluated by the ICIQ-Short Form, with scores of 6.9±6.26 in Group 1 and 7.0±5.12 in Group 2 (P >0.05). The IIEF-5 scores were similar in Groups 1 and 2 (5.73±7.43 vs. 6.70±6.68, respectively) (P >0.05).
CONCLUSION
Our pre-RP protocol of two physical therapist-assisted sessions of PFMT plus instructions did not signifi cantly improve urinary continence or erectile function at 3 months after RP.
Topics: Adenocarcinoma; Aged; Erectile Dysfunction; Humans; Male; Middle Aged; Muscle Contraction; Muscle Stretching Exercises; Neoplasm Grading; Neoplasm Staging; Neurofeedback; Pelvic Floor; Perioperative Care; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Urinary Incontinence
PubMed: 31808408
DOI: 10.1590/S1677-5538.IBJU.2019.0238