|
1
|
Munavvir M, M M, Khan A, Debashish GD. TAR-200: Investigational intravesical drug delivery system for bladder cancer. Urologia 2025; 92:243-251. [PMID: 39930602 DOI: 10.1177/03915603251319133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2025]
Abstract
Bladder cancer is second among the most common urothelial malignancy and one of the most expensive in terms of treatment. Localized bladder cancer is classified into non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). First line approach for treatment of NMIBC is transurethral resection of bladder tumor (TURBT) followed by intravesical instillation of immuno/chemotherapeutic agents to prevent or delay recurrence or progression. Historically intravesical Bacillus Calmette Geurin (BCG) instillation has been a mainstay of therapy for NMIBC post-TURBT. Commonly followed drug delivery is intravesical instillation that maximizes exposure of the drug to the lesion and minimizes systemic side effects. Gemcitabine used in bladder cancer due to its pharmacological properties making it appropriate for intravesical instillation. Limitations of intravesical instillation is low bladder permeability leading to decreased drug concentration in bladder tissues and frequent urination causing drug wash out or dilution reducing the effect of treatment. Effective intravesical therapy depends on the penetration of the drug into the tumor. TAR200 is a novel drug delivery system that facilitates sustained release of continuous low dose gemcitabine over an indwelling period providing a uniform concentration of drug after each voiding cycle and exposure of drug to the bladder tumor. There are completed and ongoing clinical trials to evaluate the efficacy of TAR200 alone or in combination with other chemotherapeutic agents in NMIBC and MIBC. FDA has granted breakthrough therapy designation (BTD) for TAR-200 in December 2023. This review highlights the potential of TAR-200 and clinical trials that improve bladder cancer treatment outcome.
Collapse
Affiliation(s)
- Muhammed Munavvir
- Department of Urology, Yenepoya Medical College Hospital, Derlakatte, Mangalore, Karnataka, India
| | | | | | | |
Collapse
|
|
2
|
Banegas MP, O'Keeffe Rosetti M, Gilbert SM, Kwan ML, Leo MC, Danforth KN, Bulkley J, Weinmann S, Yi DK, Lee VS, McMullen C. Comparing direct medical care costs of patients with bladder cancer who received an ileal conduit vs. neobladder in the year following cystectomy. Urol Oncol 2025; 43:267.e1-267.e7. [PMID: 39406639 DOI: 10.1016/j.urolonc.2024.09.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 08/05/2024] [Accepted: 09/20/2024] [Indexed: 02/26/2025]
Abstract
PURPOSE Bladder cancer is 1 of the most costly cancers, however there is limited research on medical care costs by type of urinary diversion. The objective of our study was to compare medical care costs of the 2 most common urinary diversions in the year following radical cystectomy. METHODS The Bladder Cancer Quality of Life Study included patients diagnosed with bladder cancer who underwent radical cystectomy and received an ileal conduit (IC, n = 821) or neobladder (NB, n = 181) in 3 integrated health systems. Medical care costs per patient per quarter were estimated for the year following cystectomy. Multivariable generalized linear models with a gamma distribution and log link were used to estimate mean monthly medical care costs (2022 USD$), adjusted for patient demographic and clinical characteristics. RESULTS In multivariable analysis, mean monthly costs per quarter were not significantly different between IC and NB patients in the 12 months following cystectomy. Overall, mean monthly costs in IC and NB patients were highest during the first quarter and decreased thereafter. Factors associated with higher mean costs across all quarters included presence of any complications and advanced tumor stage at cystectomy (all P < 0.001). CONCLUSION Our study addresses an important knowledge gap by quantifying the medical costs of bladder cancer patients by urinary diversion type and comparing costs of different treatment approaches. Studies that assess patient-reported outcomes and out-of-pocket costs, by urinary diversion type, are warranted to inform treatment decision-making and cost conversations.
Collapse
Affiliation(s)
- Matthew P Banegas
- University of California San Diego, La Jolla, CA; Kaiser Permanente Northwest Center for Health Research, Portland, OR.
| | | | - Scott M Gilbert
- H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
| | | | - Michael C Leo
- Kaiser Permanente Northwest Center for Health Research, Portland, OR
| | - Kim N Danforth
- Kaiser Permanente Department of Research & Evaluation, Pasadena, CA; RTI International, Research Triangle Park, NC
| | - Joanna Bulkley
- Kaiser Permanente Northwest Center for Health Research, Portland, OR
| | - Sheila Weinmann
- Kaiser Permanente Northwest Center for Health Research, Portland, OR
| | - David K Yi
- Kaiser Permanente Department of Research & Evaluation, Pasadena, CA
| | | | - Carmit McMullen
- Kaiser Permanente Northwest Center for Health Research, Portland, OR
| |
Collapse
|
|
3
|
Ahmad S, Almanaa TN, Khan S, Aljahdali SM, Waheed Y, Aljasir MA, Al-Megrin WAI, Aziz A, Ateeq M, Amin F, Khattak SU, Sanami S. Identification of potential drug molecules against fibroblast growth factor receptor 3 (FGFR3) by multi-stage computational-biophysics correlate. J Biomol Struct Dyn 2025; 43:1240-1248. [PMID: 38064307 DOI: 10.1080/07391102.2023.2291541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 11/21/2023] [Indexed: 12/06/2024]
Abstract
The fibroblast growth factor receptor 3 (FGFR3) is warranted as a promising therapeutic target in bladder cancer as it is described in 75% of papillary bladder tumors. Considering this, the present study was conducted to use different approaches of computer-aided drug discovery (CADD) to identify the best binding compounds against the active pocket of FGFR3. Compared to control pyrimidine derivative, the study identified three promising lead structures; BDC_24037121, BDC_21200852, and BDC_21206757 with binding energy value of -14.80 kcal/mol, -12.22 kcal/mol, and -11.67 kcal/mol, respectively. The control molecule binding energy score was -9.85 kcal/mol. The compounds achieved deep pocket binding and produced balanced interactions of hydrogen bonds and van der Waals. The FGFR3 enzyme residues such as Leu478, Lys508, Glu556, Asn562, Asn622, and Asp635. The molecular dynamic (MD) simulation studies additionally validated the docked conformation stability with respect to FGFR3 with a mean root mean square deviation (RMSD) value of < 3 Å. The root mean square fluctuation (RMSF) complements the complexes structural stability and the residues showed less fluctuation in the presence of compounds. The Poisson-Boltzmann or generalized Born and surface area continuum solvation (MM/PBSA and MM/GBSA) methods revalidated compounds better binding and highlighted van der Waals energy to dominate the overall net energy. The docked stability was additionally confirmed by WaterSwap and AMBER normal mode entropy energy analyses. In a nutshell, the compounds shortlisted in this study are promising in term of theoretical binding affinity for FGFR3 but experimental validation is needed.Communicated by Ramaswamy H. Sarma.
Collapse
Affiliation(s)
- Sajjad Ahmad
- Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan
- Department of Natural Sciences, Lebanese American University, Beirut, Lebanon
- Department of Computer Science, Virginia Tech, Blacksburg, VA, USA
| | - Taghreed N Almanaa
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Saifullah Khan
- Institute of Biotechnology and Microbiology, Bacha Khan University, Charsadda, Pakistan
| | | | - Yasir Waheed
- Office of Research, Innovation and Commercialization, Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad, Pakistan
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon
| | - Mohammad Abdullah Aljasir
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Wafa Abdullah I Al-Megrin
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Aamir Aziz
- Sarhad Institute of Allied health Sciences, Sarhad University of Science and Information Technology, Peshawar, Pakistan
| | - Muhammad Ateeq
- Sarhad Institute of Allied health Sciences, Sarhad University of Science and Information Technology, Peshawar, Pakistan
| | - Fazli Amin
- Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan
| | - Saeed Ullah Khattak
- Center of Biotechnology and Microbiology, University of Peshawar, KPK, Peshawar, Pakistan
| | - Samira Sanami
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
| |
Collapse
|
|
4
|
Pham J, Alzubaidi AN, Raman JD, Garg T. Rural Versus Urban Genitourinary Cancer Incidence and Mortality in Pennsylvania: 1990-2019. Curr Oncol 2024; 31:8110-8117. [PMID: 39727720 DOI: 10.3390/curroncol31120597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/17/2024] [Accepted: 12/19/2024] [Indexed: 12/28/2024] Open
Abstract
Our aim was to describe the incidence and mortality of genitourinary (GU) cancers in rural and urban Pennsylvania counties. We calculated age-adjusted incidence and mortality rates of GU (prostate, bladder, and kidney) cancers from 1990 to 2019 in the Pennsylvania Cancer Registry. We defined rurality using the Center for Rural Pennsylvania's population density-based definition. We modeled average annual percent changes (AAPC) in age-adjusted incidence and mortality rates using joinpoint regression. Overall GU cancer incidence decreased in rural and urban counties (AAPC -7.5%, p = 0.04 and AAPC -6.6%, p = 0.02, respectively). Prostate cancer incidence decreased in rural and urban counties by -10.5% (p = 0.02) and -9.1% (p = 0.01), respectively. Kidney cancer incidence increased in both rural and urban counties, respectively (AAPC = +11.2, p = 0.002 and +9.3%, p = 0.01). GU cancer mortality decreased in rural and urban counties (AAPC = -11.6, p = 0.047 and AAPC -12.2, p = 0.01, respectively). Prostate cancer mortality decreased at similar rates in rural and urban counties (AAPC -15.5, p = 0.03 and -15.4, p = 0.02, respectively). Kidney cancer mortality decreased in urban (AAPC -6.9% p = 0.03) but remained stable in rural counties. Bladder cancer incidence and mortality were unchanged in both types of counties. Over three decades, GU cancer incidence and mortality decreased across Pennsylvania counties.
Collapse
Affiliation(s)
- Jonathan Pham
- Department of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA
| | - Ahmad N Alzubaidi
- Department of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA
| | - Jay D Raman
- Department of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA
| | - Tullika Garg
- Department of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA
| |
Collapse
|
|
5
|
Choudry MM, Murray N, Dindinger-Hill K, Ambrose J, Hunt T, Horns J, Martin C, Haaland B, Lowrance W, Hanson HA, Matern R, Cartwright PC, O’Neil B. Genitourinary cancer and family: The reverberating psychological and cardiovascular effects of a genitourinary cancer diagnosis on first-degree relatives and spouses. Cancer 2024; 130:4061-4070. [PMID: 39246024 PMCID: PMC11560680 DOI: 10.1002/cncr.35486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 05/22/2024] [Accepted: 06/04/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND The psychological and cardiovascular health impacts on family members of patients who have been diagnosed with cancer have not been well characterized. The purpose of this study is to determine whether a family member's cancer diagnosis influences the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients affected by cancer. METHODS This retrospective cohort analysis evaluated the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients diagnosed with a genitourinary cancer between 1990 and 2015 compared to relatives of those not diagnosed with a genitourinary cancer. The Utah Population Database was used and familial linkage was determined. Follow-up included 1-, 3-, and 5-year intervals. Patients residing outside of Utah and first-degree relatives and spouses with psychological or cardiovascular disease diagnosed before a family member's cancer diagnosis were excluded. RESULTS A total of 49,284 patients with a genitourinary cancer were identified with 77,938 first-degree relatives and spouses. A matched control group included 246,775 patients with 81,022 first-degree relatives and spouses. Via Cox proportional hazards models, a 10% increased risk of developing a psychological illness (hazard ratio [HR], 1.10; 95% CI, 1.00-1.20) and a 28% increased risk of developing cardiovascular disease (HR, 1.28; 95% CI, 1.17-1.41) at 1 year after a family member's cancer diagnosis were found. CONCLUSIONS This study provides population-level evidence to support the hypothesis that cancer diagnoses will lead to adverse health outcomes for family members of patients with cancer. Increased clinical attention and support are needed to reduce the harm to families caused by cancer.
Collapse
Affiliation(s)
| | - Nicole Murray
- Division of Urology, University of Utah, Salt Lake City, Utah, USA
| | | | - Jacob Ambrose
- Departments of Surgery and Population Sciences, University of Utah, Salt Lake City, Utah, USA
| | - Trevor Hunt
- Department of Urology, University of Rochester Medical Center, Rochester, New York, USA
| | - Joshua Horns
- Department of Urology, Mayo Clinic, Phoenix, Arizona, USA
| | | | - Benjamin Haaland
- Departments of Surgery and Population Sciences, University of Utah, Salt Lake City, Utah, USA
| | | | - Heidi A. Hanson
- Division of Urology, University of Utah, Salt Lake City, Utah, USA
- Departments of Surgery and Population Sciences, University of Utah, Salt Lake City, Utah, USA
| | | | - Patrick C. Cartwright
- Division of Urology, University of Utah, Salt Lake City, Utah, USA
- Intermountain Healthcare, Salt Lake City, Utah, USA
| | - Brock O’Neil
- Division of Urology, University of Utah, Salt Lake City, Utah, USA
| |
Collapse
|
|
6
|
Kayama E, Uemura M, Onagi A, Meguro S, Ogawa S, Yaginuma K, Matsuoka K, Hoshi S, Koguchi T, Hata J, Sato Y, Akaihata H, Honma R, Watanabe S, Kojima Y. A Novel Gene Expression Scoring System Predicts Recurrence in Non-Muscle-Invasive Bladder Cancer Patients. Cancer Med 2024; 13:e70349. [PMID: 39540204 PMCID: PMC11561421 DOI: 10.1002/cam4.70349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 10/05/2024] [Accepted: 10/07/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Despite the high recurrence rate of non-muscle-invasive bladder cancer (NMIBC), there are limitations in accurately predicting recurrence after transurethral resection of bladder tumor (TURBT) based on clinicopathological factors alone. However, prediction of recurrence using biomolecular characteristics of bladder tumors has not been applied to clinical practice. The objective of this study was to establish a new gene expression scoring system for identifying patients at high risk of recurrence. METHODS NMIBC and normal bladder samples were subjected to microarray analysis to obtain gene expression profiles. We identified 6 genes that were specifically upregulated in bladder cancer and also in recurrent cases. All patients were randomly grouped into a discovery cohort (n = 59) and a validation cohort (n = 30). Gene expression score (GES) was defined as the mean Z-score of the 6 genes specific for recurrent bladder cancer. RESULTS The intravesical recurrence rate of the high GES group (n = 38) was higher than the low GES group (n = 21). GES was significantly associated with recurrence-free survival in the validation cohort as well. In prognostic analysis, the European Organization for Research and Treatment of Cancer (EORTC) risk classification was not related to recurrence after TURBT in either univariate or multivariate analysis. On the other hand, the GES we developed was an independent factor for recurrence in NMIBC. CONCLUSIONS A novel gene expression scoring system was shown to predict recurrence in NMIBC patients after TURBT and might be helpful in clinical decision-making for NMIBC patients.
Collapse
Affiliation(s)
- Emina Kayama
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Motohide Uemura
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
- Department of UrologyIwase General HospitalFukushimaJapan
| | - Akifumi Onagi
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Satoru Meguro
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Soichiro Ogawa
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Kei Yaginuma
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Kanako Matsuoka
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Seiji Hoshi
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Tomoyuki Koguchi
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Junya Hata
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Yuichi Sato
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | - Hidenori Akaihata
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| | | | - Shinya Watanabe
- Translational Research CenterFukushima Medical UniversityFukushimaJapan
| | - Yoshiyuki Kojima
- Department of UrologyFukushima Medical University School of MedicineFukushimaJapan
| |
Collapse
|
|
7
|
Clark O, Sarmento T, Eccleston A, Brinkmann J, Picoli R, Daliparthi V, Voss J, Chandrasekar S, Thompson A, Chang J. Economic Impact of Bladder Cancer in the USA. PHARMACOECONOMICS - OPEN 2024; 8:837-845. [PMID: 39154309 PMCID: PMC11499469 DOI: 10.1007/s41669-024-00512-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/15/2024] [Indexed: 08/19/2024]
Abstract
INTRODUCTION Incidence and mortality for bladder cancer has changed very little over the past 20 years. Approximately 40% of patients with high-risk nonmuscle invasive bladder cancer eventually recur/progress. It is important to understand the economic impact of disease recurrence/progression in bladder cancer. Our aim was to estimate and understand the direct costs associated with the treatment of bladder cancer from the payer's perspective in the USA, in the year of 2021, including costs for both newly diagnosed bladder cancer (stages 0a-IV) and recurrent patients. METHODS An economic model was constructed to calculate the number of patients receiving each treatment modality at every stage of disease and their respective costs. Epidemiological data were based on the CancerMPact Patient Metrics (PM) database and treatment modality data retrieved from CMP Treatment Architecture (TA), 2021 version. Resource utilization and costs were obtained from medical literature and public data sources. Only direct costs were considered. RESULTS There were an estimated 83,532 newly diagnosed patients with bladder cancer of all stages in 2021 with a projected total cost of treatment of ~$2.6 billion. Average cost per newly diagnosed patient varied from $19,521 (stage 0a) to $169,533 (metastatic disease). Cost profile differed substantially among the stages of disease. For the 75,760 patients that were expected to have a recurrence in 2021, an additional cost of ~$3.9 billion was estimated at an average cost per patient of $52,179. The expected total cost to treat newly diagnosed and newly recurrent patients is reported in this model, with the total cost in 2021 estimated to exceed $6.5 billion. CONCLUSIONS Treatment and resource costs increase for bladder cancer as the disease recurs/progresses. More effective treatments that can delay recurrence/progression may reduce the economic burden associated with bladder cancer.
Collapse
|
|
8
|
Kurnot JA, Kaye DR. Reducing financial toxicity in bladder cancer care. Curr Opin Urol 2024; 34:484-488. [PMID: 39219372 PMCID: PMC11560494 DOI: 10.1097/mou.0000000000001218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
PURPOSE OF REVIEW Financial toxicity is a significant concern for many individuals with bladder cancer, which is, overall, the most expensive malignancy, per patient. Financial toxicity, defined as the harmful effects of treatment costs on an individual's quality of life, is associated with worse outcomes and decreased quality of life. Awareness of the objective and subjective factors that contribute to financial toxicity, and ways to mitigate their effects on patients, is essential to reduce the burden of bladder cancer care. This commentary aims to discuss the elements contributing to financial toxicity amongst bladder cancer patients, identify at-risk populations, and review current and potential strategies for mitigating financial burden. RECENT FINDINGS Bladder cancer is becoming more expensive as the use of novel therapies increases. Early data suggest how some of these novel treatments or changes in treatment delivery may impact costs. Potential innovative strategies for cost reduction include blue light cystoscopy, intravesical gemcitabine-docetaxel rather than BCG for high-risk nonmuscle-invasive patients, home BCG therapy, and surveillance guideline optimization. However, there is still much work to be done on the potential impacts of these treatment on financial toxicity. While there is a paucity of data on treatment changes to reduce financial toxicity, and cost data can be hard to access, clinicians can still reduce the financial burden of cancer care. Awareness, financial toxicity screening, cost communication, and/or early referral to financial navigators or other similar resources have the potential to reduce financial burden. Despite mounting evidence, these tools/techniques are largely underutilized. SUMMARY Many individuals with bladder cancer face significant financial toxicity, with the potential for this to worsen in the setting of rising treatment costs. Novel diagnostic and treatment modifications may reduce financial toxicity. However, awareness, screening, cost discussions, and utilization of financial navigators are tools/techniques that are currently available and should be used to reduce financial burden.
Collapse
Affiliation(s)
| | - Deborah R Kaye
- Department of Urology
- Duke-Margolis Center for Public Policy, Duke University
- Duke Cancer Institute
- Duke Clinical Research Institute, Durham, North Carolina, USA
| |
Collapse
|
|
9
|
Fan Y, Hao Y, Zhu C, Hu B, Ma R, Liu Y, Li G. PLCε promotes the Warburg effect and tumorigenesis through AKT/GSK3β/Cdc25a in bladder cancer. Biotechnol Genet Eng Rev 2024; 40:2155-2169. [PMID: 37018449 DOI: 10.1080/02648725.2023.2199188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 03/23/2023] [Indexed: 04/07/2023]
Abstract
Phospholipase C epsilon (PLCε) is a oncogene in various malignancies and regulates diverse cellular functions. But understanding of the relation between PLCε and glycolytic pathways has not been clearly identified. In the present study, we explored the effect of PLCε on the Warburg effect and tumorigenesis in bladder cancer (BCa). In our study, we showed that PLCε expression was elevated in BCa samples compared with matched adjacent nonmalignant bladder tissues. PLCε depletion using Lentivirus-shPLCε (LV-shPLCε) dramatically decreased cell growth, glucose consumption and lactate production, arresting T24 and BIU cells in the S phase of the cell cycle. We also observed that PLCε was correlated with the activation of protein kinase B (AKT) and cell division cycle 25 homolog A (Cdc25a) overexpression. In addition, we demonstrated that AKT/glycogen synthase kinase 3 beta (GSK3β)/Cdc25a signaling pathways are involved in the PLCε-mediated Warburg effect in BCa. Moreover, we showed that PLCε had an effect on tumorigenesis in in vivo experiments. In summary, our findings demonstrate that AKT/GSK3β/Cdc25a is critical for the effect PLCε on Warburg effect and tumorigenesis.
Collapse
Affiliation(s)
- Yanru Fan
- Clinical Lab department, Henan Provincial People's Hospital, Zhengzhou, China
| | - Yanni Hao
- Clinical Lab department, Jiaocheng County maternal and Child Health and Family Planning Service Centre, Taiyuan, China
| | - Chunkai Zhu
- Clinical Lab department, Henan Provincial People's Hospital, Zhengzhou, China
| | - Biao Hu
- Clinical Lab department, Henan Provincial People's Hospital, Zhengzhou, China
| | - Rufei Ma
- Clinical Lab department, Henan Provincial People's Hospital, Zhengzhou, China
| | - Yanhong Liu
- Clinical Lab department, Henan Provincial People's Hospital, Zhengzhou, China
| | - Gang Li
- Clinical Lab department, Henan Provincial People's Hospital, Zhengzhou, China
| |
Collapse
|
|
10
|
Sharan KC, Srinivasan R, Uppal R, Rohilla M, Dey P, Kakkar N, Mavuduru RS. Utility of UroVysion Fluorescence in situ Hybridization in Improving the Diagnostic Performance of Urine Cytology. Acta Cytol 2024; 68:423-435. [PMID: 39047715 DOI: 10.1159/000540070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 06/18/2024] [Indexed: 07/27/2024]
Abstract
INTRODUCTION The atypical urothelial cell (AUC) category in The Paris System (TPS) in urine cytology (UrCy) is a challenging area. This study aimed to evaluate the UroVysion fluorescence in situ hybridization (U-FISH) assay in predicting the outcome of AUC. Additionally, we explored the association of abnormal U-FISH results in high-grade urothelial carcinoma (HGUC) concerning muscularis propria invasion (MPI). METHODS This is a retrospective study, and U-FISH was done on archived Papanicolaou-stained smears. Four cohorts were included: non-neoplastic AUC (AUC-NN), neoplastic AUC (AUC-N), muscle-invasive HGUC (HGUC-MI), and muscle-free HGUC (HGUC-MF) outcome on histopathology (HPE) and with clinical follow-up of 12-29 months. U-FISH was evaluated for diagnostic purposes, and MPI and tumor stage prediction by urine FISH score (UFS; high vs. low) based on copy number gain of chromosomes (Chr). RESULTS U-FISH was performed on 70 cases (20 AUC-NN, 20 AUC-N, 15 HGUC-MI, and 15 HGUC-MF) and was successful in 58/70 (82.85%) cases. All UC cases showed polysomy of ≥2Chr, and all the AUC-NN cases reported non-neoplastic on HPE were negative for U-FISH. U-FISH picked up all carcinoma cases in the AUC-N cohort. Chr 3 polysomy was statistically significant in differentiating HGUC-MI from HGUC-MF and low-grade urothelial carcinoma cases. Chr 3 signals with a cut-off of 6 signals could identify MPI with a sensitivity of 80.95% and specificity of 41.94%. The UFS of the HGUC-MI group was significantly higher than HGUC-MF. CONCLUSIONS U-FISH successfully identified all cases of AUC with neoplastic outcomes. In the HGUC group, there was a difference in cases with and without MPI, which requires further confirmation in a larger prospective cohort.
Collapse
Affiliation(s)
- K C Sharan
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radhika Srinivasan
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha Uppal
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manish Rohilla
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pranab Dey
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nandita Kakkar
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ravimohan S Mavuduru
- Department of Urology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
11
|
Sharan KC, Rohilla M, Dey P, Srinivasan R, Kakkar N, Mavuduru RS. Utility of Image Morphometry in the Atypical Urothelial Cells and High-Grade Urothelial Carcinoma Categories of the Paris System for Reporting Urinary Cytology. J Cytol 2024; 41:137-142. [PMID: 39239321 PMCID: PMC11373713 DOI: 10.4103/joc.joc_177_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 04/10/2024] [Accepted: 05/07/2024] [Indexed: 09/07/2024] Open
Abstract
Introduction Urinary cytology (UrCy) is highly sensitive to diagnosing high-grade urothelial carcinoma (HGUC) but cannot predict muscularis propria invasion. Further, the atypical urothelial cell category (AUC) may have variable outcomes. Image morphometry (IM) may be a valuable adjunct technique in this setting. Hence, we evaluated IM in the AUC and HGUC categories to improve the diagnostic performance. Materials and Methods The following six nuclear parameters were evaluated by IM on 3150 cells: nucleo-cytoplasmic (N:C) ratio, nuclear area, diameter, perimeter, standard deviation of the nuclear area (SDNA; pleomorphism) and integrated density (ID; nuclear chromasia), using the ImageJ software, in three cohorts based on the histopathology outcome: 20 cases of AUC - benign non-neoplastic outcome (AUC-B); 22 cases of HGUC Muscle invasive (HGUC-MI) and 21 cases of HGUC non-muscle invasive (HGUC-MF). Results A retrospective analysis of urine cytology. The patient's ages ranged from 36 to 85 years, with a mean age of 60.6. The male-to-female ratio was 5.4:1. A total of 20 cases of AUC-B and 43 cases of HGUC were selected for IM analysis. HGUC cases had higher nuclear parameters than AUC-B, and HGUC-MI had higher SDNA, ID, diameter, and area than HGUC-MF. SDNA and ID predict muscularis propria invasion in HGUC. Conclusions Image morphometry successfully differentiates HGUC cases from benign non-neoplastic ones and might help to identify muscularis propria invasion in HGUC using a combination of nuclear parameters.
Collapse
Affiliation(s)
- K C Sharan
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manish Rohilla
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pranab Dey
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radhika Srinivasan
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nandita Kakkar
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ravimohan S Mavuduru
- Department of Urology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
12
|
Satyal U, Valentine H, Liu D, Slifker M, Lallas CD, Trabulsi EJ, Bukavina L, Szeto L, Hoffman-Censits JH, Mouw KW, Faltas BM, Grivas P, Ibragimova I, Porten SP, Van Allen EM, Geynisman DM, Parker DC, O’Neill JP, Drevik J, Christianson SS, Ginzburg S, Correa AF, Uzzo RG, Ross EA, Zibelman MR, Ghatalia P, Plimack ER, Kutikov A, Abbosh PH. Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates. JCO Precis Oncol 2024; 8:e2300362. [PMID: 38865671 PMCID: PMC11671773 DOI: 10.1200/po.23.00362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 11/30/2023] [Accepted: 03/01/2024] [Indexed: 06/14/2024] Open
Abstract
PURPOSE There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer. METHODS Urine samples from 20 and 44 patients with bladder cancer undergoing RC were prospectively collected for retrospective analysis for molecular correlate analysis from two clinical trials, respectively. The first cohort was used to benchmark the assay, and the second was used to determine the performance characteristics of the test as it correlates to responder status as measured by pathologic examination. RESULTS First, to benchmark the assay, known mutations identified in the tissue (MT) of patients from the Accelerated Methotrexate, Vinblastine, Doxorubicin, Cisplatin trial (ClinicalTrials.gov identifier: NCT01611662, n = 16) and a cohort from University of California-San Francisco (n = 4) were cross referenced against mutation profiles from urine (MU). We then determined the correlation between MU persistence and residual disease in pre-RC urine samples from a second prospective clinical trial (The pT0 trial; ClinicalTrials.gov identifier: NCT02968732). Residual MU status correlated strongly with residual disease status (pT0 trial; n = 44; P = .0092) when MU from urine supernatant and urine pellet were assessed separately and analyzed in tandem. The sensitivity, specificity, PPV, and NPV were 91%, 50%, 86%, and 63% respectively, with an overall accuracy of 82% for this second cohort. CONCLUSION MU are representative of MT and thus can be used to enhance clinical staging of urothelial carcinoma. Urine biopsy may be used as a reliable tool that can be further developed to identify complete response to NAC in anticipation of safe RC avoidance.
Collapse
Affiliation(s)
| | | | - David Liu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA
| | | | - Costas D. Lallas
- Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, USA
| | - Edouard J. Trabulsi
- Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, USA
- Department of Urology, Albert Einstein Medical Center, Philadelphia, PA, USA
| | | | - Lauren Szeto
- Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, USA
| | - Jean H. Hoffman-Censits
- Department of Urology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA
| | - Kent W. Mouw
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA
| | - Bishoy M. Faltas
- Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Petros Grivas
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Division of Oncology, Department of Medicine, University of Washington, WA, USA
| | | | - Sima P. Porten
- Department of Urology, University of California, San Francisco, CA, USA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Eliezer M. Van Allen
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA
| | | | - Daniel C. Parker
- Department of Urology, University of Oklahoma Health Sciences Center & The Stephenson Cancer Center, Oklahoma City, OK, USA
| | | | - Johnathan Drevik
- Department of Urology, Albert Einstein Medical Center, Philadelphia, PA, USA
| | | | - Serge Ginzburg
- Department of Urology, Albert Einstein Medical Center, Philadelphia, PA, USA
| | | | | | | | | | | | | | | | - Philip H. Abbosh
- Fox Chase Cancer Center, Philadelphia, PA, USA
- Department of Urology, Albert Einstein Medical Center, Philadelphia, PA, USA
| |
Collapse
|
|
13
|
Huelster HL, Mason NT, Davaro F, Naqvi SMH, Kim Y, Gilbert SM. Cost-utility of Initial Management of High-grade T1 Bladder Cancer With Intravesical BCG vs Immediate Radical Cystectomy. Urology 2024; 187:106-113. [PMID: 38467285 DOI: 10.1016/j.urology.2024.02.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/27/2024] [Accepted: 02/21/2024] [Indexed: 03/13/2024]
Abstract
OBJECTIVE To compare the cost-utility of initial management of high-grade T1 non-muscle invasive bladder cancer (HGT1 NMIBC) with intravesical BCG vs immediate radical cystectomy. High-risk NMIBC patients may climb a costly ladder of treatments, culminating in radical cystectomy for oncologic or symptomatic benefit in up to one-third. This high healthcare resource utilization presents a challenging dilemma in balancing sufficiently aggressive management with cost, toxicity, and quality-of-life. METHODS Cost-utility of initially managing HGT1 with intravesical BCG and early radical cystectomy with ileal conduit urinary diversion was compared using decision-analytic Markov models. Five-year oncologic outcomes, adverse event rates, and published utility values were extracted from literature. Costs were calculated from a US Medicare perspective in 2021 US dollars. Sensitivity analysis identified drivers of cost and break-even points for recurrence and progression. RESULTS Mean costs were $26,093 for intravesical BCG and $39,720 for immediate radical cystectomy, though cystectomy generated a gain of 2.2 quality-adjusted life years (QALYs) compared to intravesical BCG. Immediate cystectomy was a more cost-effective management strategy for HGT1 NMIBC with an incremental CE ratios (ICER) of $7120/QALY. The costs associated with cystectomy, TURBT, and BCG toxicity had the greatest impact on ICER. One-way sensitivity analysis demonstrated that intravesical BCG became a cost-effective management strategy if the 5-year recurrence rate of HG T1 was less than 56% or the 5-year progression rate to MIBC was less than 4%. CONCLUSION At current prices, treatment of high-grade T1 NMIBC with early radical cystectomy is more cost-effective management strategy than initial treatment with intravesical BCG.
Collapse
Affiliation(s)
- Heather L Huelster
- Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Department of Urology, Indiana University Health, Indianapolis, IN.
| | - Neil T Mason
- Department of Individualized Cancer Medicine, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
| | - Facundo Davaro
- Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
| | | | - Youngchul Kim
- Department of Biostatistics, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
| | - Scott M Gilbert
- Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
| |
Collapse
|
|
14
|
Dave P, Patel RD, Desai K, Davila J, Sankin A. A Procedural Checklist for Transurethral Resection of Bladder Tumors (TURBT) Enhances Operative Dictation and Assesses Surgeon Accuracy of Tumor Characteristic Predictions. Bladder Cancer 2023; 9:335-344. [PMID: 38174124 PMCID: PMC10759802 DOI: 10.3233/blc-230074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 10/28/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND A lack of standardization is pervasive in procedural application and reporting templates for TURBT with the use of a surgical checklist proposed as a means for quality improvement. OBJECTIVE To introduce a TURBT checklist to assess surgeon prediction accuracy and the impact of standardized documentation on quality of resection and oncologic outcomes. METHODS Nine critical elements of a high-quality TURBT identified by literature review were incorporated into a prospectively implemented checklist for operative reports. The checklist included both visualized and predicted tumor characteristics. A retrospective single-institution analysis compared quality of dictation pre- and post-checklist implementation. Surgeon predictions were compared to final pathology reports to determine rates of concordance. Kaplan-Meier curves examined the association of checklist use with recurrence free survival (RFS). RESULTS 333 operative reports were included in this analysis, of which 107 (32.1%) were completed pre-checklist implementation. The average number of critical elements reported was 8.69 with checklist use compared to 4.99 without (p < 0.001). There was no significant difference in RFS between the pre- and post-checklist cohorts (log-rank test p = 0.53). Surgeons were least and most accurate in predicting low grade tumor (43.5%) and absence of muscle invasion (96.6%), respectively. CONCLUSIONS Incorporation of a TURBT surgical checklist improves operative dictation and quality of reporting but did not directly impact RFS. With quality of initial resection a proven correlate to recurrence rates, checklist implementation to improve surgical performance and long-term oncologic outcomes reveals an interesting area of exploration highlighting the need for more standardized methodology when performing these procedures.
Collapse
Affiliation(s)
- Priya Dave
- Department of Urology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Rutul D. Patel
- Department of Urology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Kush Desai
- Department of Urology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Jonathan Davila
- Smith Institute for Urology, Northwell Health, Lake Success, NY, USA
| | - Alex Sankin
- Department of Urology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| |
Collapse
|
|
15
|
Stone BV, Labban M, Filipas DK, Beatrici E, Lipsitz SR, Reis LO, Feldman AS, Kibel AS, Cole AP, Morgans AK, Trinh QD. The Risk of Catastrophic Healthcare Expenditures Among Prostate and Bladder Cancer Survivors in the United States. Clin Genitourin Cancer 2023; 21:617-625. [PMID: 37316413 DOI: 10.1016/j.clgc.2023.05.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 05/24/2023] [Accepted: 05/25/2023] [Indexed: 06/16/2023]
Abstract
INTRODUCTION Little is known about the rates of catastrophic health care expenditures among survivors of prostate and bladder cancer or the factors that place patients at highest risk for undue cost. MATERIALS AND METHODS The Medical Expenditure Panel Survey was utilized to identify prostate and bladder cancer survivors from 2011 to 2019. Rates of catastrophic health care expenditures (out-of-pocket health care spending >10% household income) were compared between cancer survivors and adults without cancer. A multivariable regression model was used to identify risk factors for catastrophic expenditures. RESULTS Among 2620 urologic cancer survivors, representative of 3,251,500 (95% CI 3,062,305-3,449,547) patients annually after application of survey weights, there were no significant differences in catastrophic expenditures among respondents with prostate cancer compared to adults without cancer. Respondents with bladder cancer had significantly greater rates of catastrophic expenditures (12.75%, 95% CI 9.36%-17.14% vs. 8.33%, 95% CI 7.66%-9.05%, P = .027). Significant predictors of catastrophic expenditures in bladder cancer survivors included older age, comorbidities, lower income, retirement, poor health status, and private insurance. Though White respondents with bladder cancer had no significantly increased risk of catastrophic expenditures, among Black respondents the risk of catastrophic expenditures increased from 5.14% (95% CI 3.95-6.33) without bladder cancer to 19.49% (95% CI 0.84-38.14) with bladder cancer (OR 6.41, 95% CI 1.28-32.01, P = .024). CONCLUSIONS Though limited by small sample size, these data suggest that bladder cancer survivorship is associated with catastrophic health care expenditures, particularly among Black cancer survivors. These findings should be taken as hypothesis-generating and warrant further investigation with larger sample sizes and, ideally, prospective investigation.
Collapse
Affiliation(s)
- Benjamin V Stone
- Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Muhieddine Labban
- Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Dejan K Filipas
- Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Edoardo Beatrici
- Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Stuart R Lipsitz
- Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Leonardo O Reis
- UroScience, School of Medical Sciences, University of Campinas, UNICAMP, and Pontifical Catholic University of Campinas, PUC-Campinas, Campinas, Sao Paulo, Brazil
| | - Adam S Feldman
- Department of Urology, Massachusetts General Hospital, Boston, MA
| | - Adam S Kibel
- Division of Urological Surgery, Brigham and Women's Hospital, Boston, MA
| | - Alexander P Cole
- Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Alicia K Morgans
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Quoc-Dien Trinh
- Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
| |
Collapse
|
|
16
|
Jindal T, Sarwal A, Jain P, Koju R, Mukherjee S. A retrospective analysis of the factors associated with increased risk of readmission within 30 days after primary transurethral resection of bladder tumor. Curr Urol 2023; 17:257-261. [PMID: 37994339 PMCID: PMC10662801 DOI: 10.1097/cu9.0000000000000160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 01/16/2022] [Indexed: 11/26/2022] Open
Abstract
Background Transurethral resection of bladder tumor (TURBT) is associated with perioperative morbidity of 5% to 10%, which can lead to unplanned readmissions. In this study, we aimed to identify the factors that lead to an increased risk of unplanned readmissions within 30 days of primary TURBT. Materials and methods A retrospective study was conducted to identify patients who underwent primary TURBT at our institute from 2011 to 2019. Clinical and demographic factors, history of smoking, antiplatelet drugs intake, comorbidities, tumor size (<3 or >3 cm), multifocality, and histopathological type were abstracted. Patients who were readmitted were identified, and reasons for admission were recorded. Results A total of 435 patients were identified. The median age of the patients was 66 years. From 378 male patients (86.9%), 110 (25.3%) and 37 (8.5%) had a history of smoking and antiplatelet agents intake, respectively. In the cohort, 166 patients (38.2%) were diabetic, 239 (54.9%) were hypertensive, 72 (16.6%) had chronic obstructive pulmonary disease, and 78 (7.9%) had hypothyroidism. A total of 206 patients (47.4%) had a tumor >3 cm; multifocality was seen in 140 (32.2%) patients, whereas muscle invasive tumors were present in 161 patients (37%). A total of 22 patients (5.06%) had readmissions within 30 days, with hematuria being the most common etiology. On univariate and multivariate analyses, a history of smoking (p = 0.006 and p = 0.008, respectively) or antiplatelet agents intake (p < 0.001 and p < 0.001, respectively) was significantly associated with increased unplanned readmission. Conclusions Our study revealed smoking and antiplatelet agents intake as factors leading to an increased risk of unplanned readmissions.
Collapse
Affiliation(s)
- Tarun Jindal
- Department of Uro-oncologyy, Tata Medical Centre, Kolkata, India
- Department of Uro-Oncology, NH Narayana Superspeciality Hospital, Howrah, India
| | - Ankush Sarwal
- Department of Uro-oncologyy, Tata Medical Centre, Kolkata, India
| | - Prateek Jain
- Department of Head and Neck Surgery, Tata Medical Centre, Kolkata, India
| | - Rajan Koju
- Department of Uro-oncologyy, Tata Medical Centre, Kolkata, India
| | | |
Collapse
|
|
17
|
Ranti D, Dey L, Bieber C, Grauer R, Rich J, Rosenzweig S, Koskela LR, Steineck G, Hosseini A, Egevad L, Patrakka J, Attalla K, Wiklund P, Sfakianos J, Waingankar N. Surveillance for Nonmuscle Invasive Bladder Cancer: Identifying the Point of Diminishing Returns. Urology 2023; 181:84-91. [PMID: 37604253 DOI: 10.1016/j.urology.2023.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 08/04/2023] [Accepted: 08/07/2023] [Indexed: 08/23/2023]
Abstract
OBJECTIVE To characterize first and second recurrence patterns using 26years of cohort-level follow-up and microsimulation modeling. METHODS Patients diagnosed with nonmuscle-invasive bladder cancer in Stockholm County between 1995 and 1996 were included. Clinical, pathological, and longitudinal follow-up data were gathered. Logistic regressions, Kaplan Meier curves, and Cox proportional hazards models were run to generate assumptions for a microsimulation model, simulating first and second recurrence and progression for 10,000 patients. RESULTS Three hundred eighty-six patients were included: 67.4% were male; >50% were TaLG; and 37.5% were American Urological Association high-risk. Median time to recurrence was 300days. Three patients had missing data. Cohort follow-up has been carried out for 26years. For simulated first-recurrences, low-risk patients recurred at 56.6% over 15years of follow-up, with 2.2% muscle-invasive (MI) progression; intermediate-risk patients recurred at 62.8%, with 4.3% MI progression; high-risk patients recurred at 48.7% over 15years, with MI progression at 14.3%. For second recurrences, 70.7%, 75.7%, and 84.7% of low, medium, and high-risk patients recurred. No patients were seen to have first recurrences after 9years, with low, but notable, rates beyond 5years. CONCLUSION These data suggest that low-, intermediate-, and high-risk patients without recurrence at 5years may be potentially transitioned to less invasive monitoring.
Collapse
Affiliation(s)
- Daniel Ranti
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY.
| | - Linda Dey
- Department of Pelvic Cancer, Karolinska University Hospital, Solna, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden
| | - Christine Bieber
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Ralph Grauer
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Jordan Rich
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Shoshana Rosenzweig
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Lotta Renström Koskela
- Department of Pelvic Cancer, Karolinska University Hospital, Solna, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden
| | - Gunnar Steineck
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden; Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Abolfazl Hosseini
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden
| | - Lars Egevad
- Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden
| | - Jaakko Patrakka
- Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Sweden
| | - Kyrollis Attalla
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Peter Wiklund
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Pelvic Cancer, Karolinska University Hospital, Solna, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden
| | - John Sfakianos
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Nikhil Waingankar
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| |
Collapse
|
|
18
|
Chang S, Giannico GA, Haugen E, Jardaneh A, Baba J, Mahadevan-Jansen A, Chang SS, Bowden AK. Multiparameter interferometric polarization-enhanced imaging differentiates carcinoma in situ from inflammation of the bladder: an ex vivo study. JOURNAL OF BIOMEDICAL OPTICS 2023; 28:102907. [PMID: 37576611 PMCID: PMC10415042 DOI: 10.1117/1.jbo.28.10.102907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 08/15/2023]
Abstract
Significance Successful differentiation of carcinoma in situ (CIS) from inflammation in the bladder is key to preventing unnecessary biopsies and enabling accurate therapeutic decisions. Current standard-of-care diagnostic imaging techniques lack the specificity needed to differentiate these states, leading to false positives. Aim We introduce multiparameter interferometric polarization-enhanced (MultiPIPE) imaging as a promising technology to improve the specificity of detection for better biopsy guidance and clinical outcomes. Approach In this ex vivo study, we extract tissue attenuation-coefficient-based and birefringence-based parameters from MultiPIPE imaging data, collected with a bench-top system, to develop a classifier for the differentiation of benign and CIS tissues. We also analyze morphological features from second harmonic generation imaging and histology slides and perform imaging-to-morphology correlation analysis. Results MultiPIPE enhances specificity to differentiate CIS from benign tissues by nearly 20% and reduces the false-positive rate by more than four-fold over clinical standards. We also show that the MultiPIPE measurements correlate well with changes in morphological features in histological assessments. Conclusions The results of our study show the promise of MultiPIPE imaging to be used for better differentiation of bladder inflammation from flat tumors, leading to a fewer number of unnecessary procedures and shorter operating room (OR) time.
Collapse
Affiliation(s)
- Shuang Chang
- Vannderbilt University, Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Nashville, Tennessee, United States
| | - Giovanna A. Giannico
- Vanderbilt University Medical Center, Department of Pathology, Microbiology, and Immunology, Nashville, Tennessee, United States
| | - Ezekiel Haugen
- Vannderbilt University, Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Nashville, Tennessee, United States
| | - Ali Jardaneh
- Vanderbilt University Medical Center, Department of Urology, Nashville, Tennessee, United States
| | - Justin Baba
- Vannderbilt University, Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Nashville, Tennessee, United States
| | - Anita Mahadevan-Jansen
- Vannderbilt University, Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Nashville, Tennessee, United States
| | - Sam S. Chang
- Vanderbilt University Medical Center, Department of Urology, Nashville, Tennessee, United States
| | - Audrey K. Bowden
- Vannderbilt University, Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Nashville, Tennessee, United States
- Vanderbilt University, Department of Electrical and Computer Engineering, Nashville, Tennessee, United States
| |
Collapse
|
|
19
|
Chin FW, Chan SC, Veerakumarasivam A. Homeobox Gene Expression Dysregulation as Potential Diagnostic and Prognostic Biomarkers in Bladder Cancer. Diagnostics (Basel) 2023; 13:2641. [PMID: 37627900 PMCID: PMC10453580 DOI: 10.3390/diagnostics13162641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/07/2023] [Accepted: 07/10/2023] [Indexed: 08/27/2023] Open
Abstract
Homeobox genes serve as master regulatory transcription factors that regulate gene expression during embryogenesis. A homeobox gene may have either tumor-promoting or tumor-suppressive properties depending on the specific organ or cell lineage where it is expressed. The dysregulation of homeobox genes has been reported in various human cancers, including bladder cancer. The dysregulated expression of homeobox genes has been associated with bladder cancer clinical outcomes. Although bladder cancer has high risk of tumor recurrence and progression, it is highly challenging for clinicians to accurately predict the risk of tumor recurrence and progression at the initial point of diagnosis. Cystoscopy is the routine surveillance method used to detect tumor recurrence. However, the procedure causes significant discomfort and pain that results in poor surveillance follow-up amongst patients. Therefore, the development of reliable non-invasive biomarkers for the early detection and monitoring of bladder cancer is crucial. This review provides a comprehensive overview of the diagnostic and prognostic potential of homeobox gene expression dysregulation in bladder cancer.
Collapse
Affiliation(s)
- Fee-Wai Chin
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia;
| | - Soon-Choy Chan
- School of Liberal Arts, Science and Technology, Perdana University, Kuala Lumpur 50490, Malaysia
| | - Abhi Veerakumarasivam
- School of Medical and Life Sciences, Sunway University, Bandar Sunway 47500, Selangor, Malaysia
| |
Collapse
|
|
20
|
Leow JJ, Yong DZ, Chong YL. Value-based healthcare for bladder cancer patients undergoing robot-assisted radical cystectomy. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:1329-1330. [PMID: 37550011 DOI: 10.1016/j.ejso.2023.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 07/09/2023] [Indexed: 08/09/2023]
Affiliation(s)
- Jeffrey J Leow
- Department of Urology, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
| | - Daniel Zp Yong
- Department of Urology, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yew-Lam Chong
- Department of Urology, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| |
Collapse
|
|
21
|
Glynn D, Nikolaidis G, Jankovic D, Welton NJ. Constructing Relative Effect Priors for Research Prioritization and Trial Design: A Meta-epidemiological Analysis. Med Decis Making 2023; 43:553-563. [PMID: 37057388 PMCID: PMC10336712 DOI: 10.1177/0272989x231165985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 03/01/2023] [Indexed: 04/15/2023]
Abstract
BACKGROUND Bayesian methods have potential for efficient design of randomized clinical trials (RCTs) by incorporating existing evidence. Furthermore, value of information (VOI) methods estimate the value of reducing decision uncertainty, aiding transparent research prioritization. These methods require a prior distribution describing current uncertainty in key parameters, such as relative treatment effect (RTE). However, at the time of designing and commissioning research, there may be no data to base the prior on. The aim of this article is to present methods to construct priors for RTEs based on a collection of previous RCTs. METHODS We developed 2 Bayesian hierarchical models that captured variability in RTE between studies within disease area accounting for study characteristics. We illustrate the methods using a data set of 743 published RCTs across 9 disease areas to obtain predictive distributions for RTEs for a range of disease areas. We illustrate how the priors from such an analysis can be used in a VOI analysis for an RCT in bladder cancer and compare the results with those using an uninformative prior. RESULTS For most disease areas, the predicted RTE favored new interventions over comparators. The predicted effects and uncertainty differed across the 9 disease areas. VOI analysis showed that the expected value of research is much lower with our empirically derived prior compared with an uninformative prior. CONCLUSIONS This study demonstrates a novel approach to generating informative priors that can be used to aid research prioritization and trial design. The methods can also be used to combine RCT evidence with expert opinion. Further work is needed to create a rich database of RCT evidence that can be used to form off-the-shelf priors. HIGHLIGHTS Bayesian methods have potential to aid the efficient design of randomized clinical trials (RCTs) by incorporating existing evidence. Value-of-information (VOI) methods can be used to aid research prioritization by calculating the value of current decision uncertainty.These methods require a distribution describing current uncertainty in key parameters, that is, "prior distributions."This article demonstrates a methodology to estimate prior distributions for relative treatment effects (odds and hazard ratios) estimated from a collection of previous RCTs.These results may be combined with expert elicitation to facilitate 1) value-of-information methods to prioritize research or 2) Bayesian methods for research design.
Collapse
Affiliation(s)
- David Glynn
- Centre for Health Economics, University of York, UK
| | | | | | | |
Collapse
|
|
22
|
Teixeira-Marques A, Lourenço C, Oliveira MC, Henrique R, Jerónimo C. Extracellular Vesicles as Potential Bladder Cancer Biomarkers: Take It or Leave It? Int J Mol Sci 2023; 24:ijms24076757. [PMID: 37047731 PMCID: PMC10094914 DOI: 10.3390/ijms24076757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 03/22/2023] [Accepted: 03/29/2023] [Indexed: 04/09/2023] Open
Abstract
Bladder cancer (BC) is the 10th most frequently diagnosed cancer worldwide. Although urine cytology and cystoscopy are current standards for BC diagnosis, both have limited sensitivity to detect low-grade and small tumors. Moreover, effective prognostic biomarkers are lacking. Extracellular vesicles (EVs) are lipidic particles that contain nucleic acids, proteins, and metabolites, which are released by cells into the extracellular space, being crucial effectors in intercellular communication. These particles have emerged as potential tools carrying biomarkers for either diagnosis or prognosis in liquid biopsies namely urine, plasma, and serum. Herein, we review the potential of liquid biopsies EVs’ cargo as BC diagnosis and prognosis biomarkers. Additionally, we address the emerging advantages and downsides of using EVs within this framework.
Collapse
Affiliation(s)
- Ana Teixeira-Marques
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal
| | - Catarina Lourenço
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- INEB—Instituto Nacional de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal
- Doctoral Programme in Biomedical Sciences, School Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
| | - Miguel Carlos Oliveira
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal
| | - Rui Henrique
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal
- Department of Pathology, Portuguese Oncology Institute of Porto (IPOPorto), 4200-072 Porto, Portugal
- Department of Pathology and Molecular Immunology, School of Medicine & Biomedical Sciences, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
| | - Carmen Jerónimo
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal
- Department of Pathology and Molecular Immunology, School of Medicine & Biomedical Sciences, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
| |
Collapse
|
|
23
|
Daza J, Grauer R, Chen S, Lavallèe E, Razdan S, Dey L, Steineck G, Renström-Koskela L, Li Q, Hussein AA, Mehrazin R, Waingankar N, Guru K, Wiklund P, Sfakianos JP. Development of a predictive model for recurrence-free survival in pTa low-grade bladder cancer. Urol Oncol 2023; 41:256.e9-256.e15. [PMID: 36941190 DOI: 10.1016/j.urolonc.2023.01.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 01/04/2023] [Accepted: 01/27/2023] [Indexed: 03/23/2023]
Abstract
BACKGROUND Data on Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) have shown that follow-up cystoscopies are normal in 82% and 67% of patients with single and multiple tumors, respectively. OBJECTIVE To develop a predictive model associated with recurrence-free survival (RFS) at 6, 12, 18 and 24 months in TaLG cases that consider the patients' risk aversion. MATERIALS AND METHODS Data from a prospectively maintained database of 202 newly diagnosed TaLG NMIBC patients treated at Scandinavian institutions were used for the analysis. To identify risk groups associated with recurrence, we performed a classification tree analysis. Association between risk groups and RFS was evaluated by Kaplan Meier analysis. A Cox proportional hazard model selected significant risk factors associated with RFS using the variables defining the risk groups. The reported C index for the Cox model was 0.7. The model was internally validated and calibrated using 1000 bootstrapped samples. A nomogram to estimate RFS at 6, 12, 18, and 24 months was generated. The performance of our model was compared to EUA/AUA stratification using a decision curve analysis (DCA). RESULTS The tree classification found that tumor number, tumor size and age were the most relevant variables associated with recurrence. The patients with the worst RFS were those with multifocal or single, ≥ 4cm tumors. All the relevant variables identified by the classification tree were significantly associated with RFS in the Cox proportional hazard model. DCA analysis showed that our model outperformed EUA/AUA stratification and the treat all/none approaches. CONCLUSION We developed a predictive model to identify TaLG patients that benefit from less frequent follow-up cystoscopy schedule based on the estimated RFS and personal recurrence risk aversion.
Collapse
Affiliation(s)
- Jorge Daza
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Urology, Roswell Park Cancer Institute, Buffalo, NY
| | - Ralph Grauer
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Sophie Chen
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Etienne Lavallèe
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Shirin Razdan
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Linda Dey
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Gunnar Steineck
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | | | - Qiang Li
- Department of Urology, Roswell Park Cancer Institute, Buffalo, NY
| | - Ahmed A Hussein
- Department of Urology, Roswell Park Cancer Institute, Buffalo, NY
| | - Reza Mehrazin
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Nikhil Waingankar
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Khurshid Guru
- Department of Urology, Roswell Park Cancer Institute, Buffalo, NY
| | - Peter Wiklund
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - John P Sfakianos
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY.
| |
Collapse
|
|
24
|
Impact of an optimized surveillance protocol based on the European Association of Urology substratification on surveillance costs in patients with primary high-risk non-muscle-invasive bladder cancer. PLoS One 2023; 18:e0275921. [PMID: 36763567 PMCID: PMC9916549 DOI: 10.1371/journal.pone.0275921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 09/26/2022] [Indexed: 02/11/2023] Open
Abstract
OBJECTIVES The optimal frequency and duration of surveillance in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) remain unclear. The aim of the present study is to develop an optimal surveillance protocol based on the European Association of Urology (EAU) substratification in order to improve surveillance costs after transurethral resection of bladder tumor (TURBT) in patients with primary high-risk NMIBC. MATERIALS AND METHODS We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. Patients were substratified into the highest-risk and high-risk without highest-risk groups based on the EAU guidelines. An optimized surveillance protocol that enhances cost-effectiveness was then developed using real incidences of recurrence after TURBT. A recurrence detection rate ([number of patients with recurrence / number of patients with surveillance] × 100) of ≥ 1% during a certain period indicated that routine surveillance was necessary in this period. The 10-year total surveillance cost was compared between the EAU guidelines-based protocol and the optimized surveillance protocol developed herein. RESULTS Among the 428 patients with primary high-risk NMIBC, 97 (23%) were substratified into the highest-risk group. Patients in the highest-risk group had a significantly shorter recurrence-free survival than those in the high-risk without highest-risk group. The optimized surveillance protocol promoted a 40% reduction ($394,990) in the 10-year total surveillance cost compared to the EAU guidelines-based surveillance protocol. CONCLUSION The optimized surveillance protocol based on the EAU substratification could potentially reduce over investigation during follow-up and improve surveillance costs after TURBT in patients with primary high-risk NMIBC.
Collapse
|
|
25
|
Kiełbik A, Sowa PW, Pakhomov AG, Gudvangen E, Mangalanathan U, Kulbacka J, Pakhomova ON. Urine protects urothelial cells against killing with nanosecond pulsed electric fields. Bioelectrochemistry 2023; 149:108289. [DOI: 10.1016/j.bioelechem.2022.108289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 10/01/2022] [Accepted: 10/05/2022] [Indexed: 11/07/2022]
|
|
26
|
Raadabadi M, Daroudi R, Zendehdel K, Haghdoost AA, Ebadzadeh MR, Rashidian H. Direct and indirect medical costs of bladder cancer in Iran. Cost Eff Resour Alloc 2023; 21:5. [PMID: 36647054 PMCID: PMC9841712 DOI: 10.1186/s12962-023-00416-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 01/03/2023] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Bladder cancer is one of the most prevalent and costly cancers in the world. Estimating the economic burden of bladder cancer is essential for allocating resources to different sectors of health systems and determining the appropriate payment mechanisms. The present study aimed at estimating the economic burden of bladder cancer in Iran. METHODS In this study, we used a prevalence-based approach for estimating the economic burden of bladder cancer. Direct and indirect costs of bladder cancer were calculated using the cost of illness and human capital approaches. Data were collected using a researcher-made checklist obtained from several sources including Iran bladder cancer clinical practice guideline, the Statistical Center of Iran, Iran's Ministry of Cooperatives, Labor, and Social Welfare, Relative Value of Health Services (RVHS) book and Iranian Food and Drug Administration organization. The analyses were done by Microsoft Excel 2013 and Stata 13. RESULTS The number of the cases of 5-year prevalence of bladder cancer in Iran was estimated as 21,807 people in 2018. The economic burden of bladder cancer in Iran was estimated at US$ 86,695,474. Indirect medical costs constituted about two-third of the economic burden of bladder cancer, and mostly related to productivity loss due to mortality. Most of the direct medical costs (29.7%) were related to the stage T2-T3 and transurethral resection of bladder (31.01%) and radical cystectomy (19.99%) procedures. CONCLUSION Our results showed that the costs of bladder cancer, imposed on the healthcare system, were significant and mostly related to lost production costs. The implementation of screening and diagnostic programs can improve the survival rate and quality of life of patients and reduce the cost of lost productivity due to mortality in these patients.
Collapse
Affiliation(s)
- Mehdi Raadabadi
- grid.412505.70000 0004 0612 5912Health Policy and Management Research Center, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Rajabali Daroudi
- grid.411705.60000 0001 0166 0922Department of Health Management, Policy and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Kazem Zendehdel
- grid.414574.70000 0004 0369 3463Cancer Research Center, Cancer Institute of Iran, Imam Khomeini Hospital, Tehran University of Medical Sciences, Keshavarz Bulvard, PoBox: 13145-158, Tehran, Iran ,grid.411705.60000 0001 0166 0922Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Akbar Haghdoost
- grid.412105.30000 0001 2092 9755 HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Reza Ebadzadeh
- grid.412105.30000 0001 2092 9755Department of Urology, Bahonar Hospital, Kerman University of Medical Sciences, Kerman, Iran
| | - Hamideh Rashidian
- grid.414574.70000 0004 0369 3463Cancer Research Center, Cancer Institute of Iran, Imam Khomeini Hospital, Tehran University of Medical Sciences, Keshavarz Bulvard, PoBox: 13145-158, Tehran, Iran
| |
Collapse
|
|
27
|
Li K, Raveendran A, Xie G, Zhang Y, Wu H, Huang Z, Jia Z, Yang J. Prediction for recurrent non-muscle invasive bladder cancer. Cancer Biomark 2023; 38:275-285. [PMID: 37661872 DOI: 10.3233/cbm-220373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Non-muscle invasive bladder cancer (NMIBC) has a high recurrence rate, which places a significant burden on both patients and the healthcare system. Hence, it holds significant importance to predict the recurrence risk following treatment for individuals diagnosed with non-muscle invasive bladder cancer (NMIBC). As new generation technologies continue to emerge, an increasing number of recurrence risk prediction tools are being developed and discovered. This article provides an overview of the primary recurrence risk prediction tools currently available, including the liquid biopsy, tissue biopsy, and risk prediction tables. Each of these tools is described in detail and illustrated with relevant examples. Furthermore, we conduct an analysis of the advantages and disadvantages of these tools. This article aims to enhance the reader's understanding of the current progress in recurrence prediction tools and encourage their practical utilization in the fields of precision medicine and public health.
Collapse
Affiliation(s)
- Keqiang Li
- Laboratory Urology, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan, China
- Academy of Medical Sciences, Zhengzhou University, Henan, China
| | - Aravind Raveendran
- Laboratory Urology, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Guoqing Xie
- Laboratory Urology, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan, China
- Academy of Medical Sciences, Zhengzhou University, Henan, China
| | - Yu Zhang
- Laboratory Urology, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan, China
- Academy of Medical Sciences, Zhengzhou University, Henan, China
| | - Haofan Wu
- Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Zhenlin Huang
- Laboratory Urology, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Zhankui Jia
- Laboratory Urology, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Jinjian Yang
- Laboratory Urology, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan, China
| |
Collapse
|
|
28
|
Dong Y, Cheng Y, Guo H, Sun J, Han J, Zhong F, Li Q, Wang D, Chen W, Fan X, Zhao J. Association of obesity and different metabolic status with prognosis in patients with bladder cancer: a retrospective cohort study. Ther Adv Urol 2023; 15:17562872231213720. [PMID: 38033708 PMCID: PMC10685784 DOI: 10.1177/17562872231213720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 10/25/2023] [Indexed: 12/02/2023] Open
Abstract
Background and objectives Patients with bladder cancer (BC) are at high risk for recurrence rates and readmission costs. However, the evidence about obesity and metabolic abnormalities on the BC prognosis was inconsistent. Our primary aim was to determine the impact of obesity and different metabolic status on the readmission risk in patients with BC. Design and methods We identified 16,649 patients with BC using the 2018 Nationwide Readmissions Database who were hospitalized from January to June 2018 and followed for 180 days. The primary outcome was 180-day readmission. The multivariate Cox regression analysis and ordered logistic regression were performed to analyze data. Results Obesity and metabolic abnormalities were associated with an increased readmission risk in patients with BC [obesity: adjusted hazard ratio (aHR) = 1.08, 95% confidence interval (CI): 1.01-1.16; hyperglycemia: aHR = 1.11, 95% CI: 1.05-1.17; hypertension: aHR = 1.09, 95% CI: 1.03-1.15]. Compared with non-obese and no metabolic abnormalities, the risk of readmission was significantly increased in patients with metabolic abnormalities, irrespective of obesity (non-obese and metabolic abnormalities: aHR = 1.07, 95% CI: 1.02-1.13; obese and metabolic abnormalities: aHR = 1.20, 95% CI: 1.10-1.31), but not in obese and no metabolic abnormalities. These associations were consistent in patients aged 60 years or older and the surgery group. Moreover, hyperglycemia, hypertension, and a graded increment of metabolic risk were associated with an increased readmission risk. We also found increased length of stay for readmission in patients with obesity and metabolic abnormalities (aOR = 1.17, 95% CI: 1.00-1.36). Conclusion Obesity with metabolic abnormalities and metabolic abnormalities alone were associated with higher readmission risks in patients with BC. It is suggested that prevention should focus not only on obesity but also on metabolic abnormalities to decrease the risk of readmission.
Collapse
Affiliation(s)
- Yingchun Dong
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Yiping Cheng
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Honglin Guo
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Jiaxing Sun
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Junming Han
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Fang Zhong
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Qihang Li
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Dawei Wang
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Wenbin Chen
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| | - Xiude Fan
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| | - Jiajun Zhao
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| |
Collapse
|
|
29
|
Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention. J Clin Med 2022; 11:jcm11195827. [PMID: 36233691 PMCID: PMC9571552 DOI: 10.3390/jcm11195827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/13/2022] [Accepted: 09/27/2022] [Indexed: 11/15/2022] Open
Abstract
The clinical standard of care for urothelial carcinoma (UC) relies on invasive procedures with suboptimal performance. To enhance UC treatment, we developed a urinary comprehensive genomic profiling (uCGP) test, UroAmplitude, that measures mutations from tumor DNA present in urine. In this study, we performed a blinded, prospective validation of technical sensitivity and positive predictive value (PPV) using reference standards, and found at 1% allele frequency, mutation detection performs at 97.4% sensitivity and 80.4% PPV. We then prospectively compared the mutation profiles of urine-extracted DNA to those of matched tumor tissue to validate clinical performance. Here, we found tumor single-nucleotide variants were observed in the urine with a median concordance of 91.7% and uCGP revealed distinct patterns of genomic lesions enriched in low- and high-grade disease. Finally, we retrospectively explored longitudinal case studies to quantify residual disease following bladder-sparing treatments, and found uCGP detected residual disease in patients receiving bladder-sparing treatment and predicted recurrence and disease progression. These findings demonstrate the potential of the UroAmplitude platform to reliably identify and track mutations associated with UC at each stage of disease: diagnosis, treatment, and surveillance. Multiple case studies demonstrate utility for patient risk classification to guide both surgical and therapeutic interventions.
Collapse
|
|
30
|
Hashemi M, Mirzaei S, Barati M, Hejazi ES, Kakavand A, Entezari M, Salimimoghadam S, Kalbasi A, Rashidi M, Taheriazam A, Sethi G. Curcumin in the treatment of urological cancers: Therapeutic targets, challenges and prospects. Life Sci 2022; 309:120984. [PMID: 36150461 DOI: 10.1016/j.lfs.2022.120984] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 09/09/2022] [Accepted: 09/17/2022] [Indexed: 11/26/2022]
Abstract
Urological cancers include bladder, prostate and renal cancers that can cause death in males and females. Patients with urological cancers are mainly diagnosed at an advanced disease stage when they also develop resistance to therapy or poor response. The use of natural products in the treatment of urological cancers has shown a significant increase. Curcumin has been widely used in cancer treatment due to its ability to trigger cell death and suppress metastasis. The beneficial effects of curcumin in the treatment of urological cancers is the focus of current review. Curcumin can induce apoptosis in the three types of urological cancers limiting their proliferative potential. Furthermore, curcumin can suppress invasion of urological cancers through EMT inhibition. Notably, curcumin decreases the expression of MMPs, therefore interfering with urological cancer metastasis. When used in combination with chemotherapy agents, curcumin displays synergistic effects in suppressing cancer progression. It can also be used as a chemosensitizer. Based on pre-clinical studies, curcumin administration is beneficial in the treatment of urological cancers and future clinical applications might be considered upon solving problems related to the poor bioavailability of the compound. To improve the bioavailability of curcumin and increase its therapeutic index in urological cancer suppression, nanostructures have been developed to favor targeted delivery.
Collapse
Affiliation(s)
- Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Maryamsadat Barati
- Department of Biology, Faculty of Basic (Fundamental) Science, Shahr Qods Branch, Islamic Azad University, Tehran, Iran
| | - Elahe Sadat Hejazi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Amirabbas Kakavand
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Alireza Kalbasi
- Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States of America
| | - Mohsen Rashidi
- Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
| |
Collapse
|
|
31
|
Active surveillance for non-muscle-invasive bladder cancer: fallacy or opportunity? Curr Opin Urol 2022; 32:567-574. [DOI: 10.1097/mou.0000000000001028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
32
|
Williams SB, Shan Y, Fero KE, Movva G, Baillargeon J, Tyler DS, Chamie K. Comparing costs of renal preservation versus radical nephroureterectomy management among patients with non-metastatic upper tract urothelial carcinoma. Urol Oncol 2022; 40:345.e1-345.e7. [DOI: 10.1016/j.urolonc.2022.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/14/2022] [Accepted: 02/26/2022] [Indexed: 10/18/2022]
|
|
33
|
Deng L, Chao H, Deng H, Yu Z, Zhao R, Huang L, Gong Y, Zhu Y, Wang Q, Li F, Liu L, He L, Tang Z, Liao C, Qi Y, Wang X, Zeng T, Zou H. A novel and sensitive DNA methylation marker for the urine-based liquid biopsies to detect bladder cancer. BMC Cancer 2022; 22:510. [PMID: 35524222 PMCID: PMC9077853 DOI: 10.1186/s12885-022-09616-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 04/25/2022] [Indexed: 11/15/2022] Open
Abstract
Background Better prognostic outcome is closely correlated with early detection of bladder cancer. Current non-invasive urianalysis relies on simultaneously testing multiple methylation markers to achieve relatively high accuracy. Therefore, we have developed an easy-to-use, convenient, and accurate single-target urine-based DNA methylation test for the malignancy. Methods By analyzing TCGA data, 344 candidate markers with 424 primer pairs and probe sets synthesized were systematically screened in cancer cell lines, paired tissue specimens, and urine sediments from bladder cancer patients and normal controls. The identified marker was further validated in large case-control cohorts. Wilcoxon rank sum tests and c2 tests were performed to compare methylation levels between case-control groups and correlate methylation levels with demographic and clinical characteristics. In addition, MSP, qMSP, RT-PCR, western blot analysis, and immunohistochemistry were performed to measure levels of DNA methylation, mRNA transcription, and protein expression in cancer cell lines and tissues. Results A top-performing DMRTA2 marker identified was tested in both discovery and validation sets, showing similar sensitivity and specificity for bladder cancer detection. Overall sensitivity in the aggregate set was 82.9%(179/216). The specificity, from a control group consisting of patients with lithangiuria, prostatoplasia, and prostatitis, is 92.5%(468/506). Notably, the methylation assay had the highest sensitivities for tumors at stages of T1(90.4%) and T2(95.0%) compared with Ta (63.0%), T3(81.8%), and T4(81.8%). Furthermore, the test showed admirable detection rate of 80.0%(24/30) for recurring cancers. While methylation was observed in 39/54(72.2%) urine samples from patients with carcinomas of renal pelvis and ureter, it was detected at extremely low rate of 6.0%(8/133) in kidney and prostate cancers. Compared with SV-HUC-1, the normal bladder epithelial cell line, DMRTA2 was hypermethylated in 8/9 bladder cancer cell lines, consistent with the results of MSP and qMSP, but not correlated with mRNA and protein expression levels in these cell lines. Similarly, DMRTA2 immunostaining was moderate in some tissues but weak in others. Further studies are needed to address functional implications of DMRTA2 hypermethylation. Conclusions Our data demonstrated that a single-target DNA methylation signature, mDMRTA2, could be highly effective to detect both primary and recurring bladder cancer via urine samples. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09616-y.
Collapse
Affiliation(s)
- Leihong Deng
- The First Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006, Jiangxi, China
| | - Haichao Chao
- The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi, China
| | - Huanhuan Deng
- Donghu Campus, Medical College of Nanchang University, 461 Bayi Dadao, Nanchang, 330006, Jiangxi, China
| | - Zhaojun Yu
- Donghu Campus, Medical College of Nanchang University, 461 Bayi Dadao, Nanchang, 330006, Jiangxi, China
| | - Rongsong Zhao
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Longwu Huang
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Yun Gong
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Yueting Zhu
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Qingping Wang
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Feng Li
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Lirong Liu
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Lei He
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Zhimin Tang
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Caizhi Liao
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Yan Qi
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Xianshu Wang
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China
| | - Tao Zeng
- The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi, China.
| | - Hongzhi Zou
- Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, 510530, Guangdong, China.
| |
Collapse
|
|
34
|
Korkes F, Timóteo F, Soledade LCB, Bugalho LS, Peixoto GA, Teich VD, Glina S. Stage-Related Cost of Treatment of Bladder Cancer in Brazil. PHARMACOECONOMICS - OPEN 2022; 6:461-468. [PMID: 35165828 PMCID: PMC9043045 DOI: 10.1007/s41669-022-00325-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 01/16/2022] [Indexed: 06/14/2023]
Abstract
PURPOSE Bladder cancer is the ninth most frequent cancer worldwide with the twelfth highest incidence. However, its treatment has financial impacts that directly affect health burden. There is a scarcity of data about the costs related to healthcare in Brazil, especially in the public setting. As previously demonstrated, despite not being one of the most frequent cancers, bladder cancer appears to be one of the most expensive. The present study aimed to assess the costs related to the treatment of bladder cancer in the public setting in Brazil. PATIENTS AND METHODS Retrospective data of patients treated for urothelial bladder carcinoma from 2019 to 2020 were retrieved at a single center. All charts were reviewed, with the assessment of clinical data, exams, surgical data, and post-procedure outcomes. The hospital finance department calculated the costs for outpatient evaluation, inpatient procedures, complementary exams, materials, drugs, and professionals' fees throughout all operations. RESULTS A total of 107 patients with bladder cancer were analyzed, representing a total expenditure of BRL 5,671,042.70 and a mean cost of BRL 53,000.04 per patient (US$1.00 = BRL 5.60). Median costs were progressively higher for patients with stages I, II, III, and IV. Patients who underwent radical cystectomy (n = 14) had a median treatment cost of BRL 136,606.25 ± 96,059.08, during a mean follow-up of 9.2 months. Hospitalization costs represented 25% (range 20-43% according to the stage) of all expenditure. Medications and medical supplies represented 18% (16-23% according to the stage) of expenditure. Medical fees represented 31% of costs for stage I disease, but only 4% in stage II, III, and IV. Costs associated with emergency room visits were only observed in stage III and IV disease, representing 1% of all expenditure. CONCLUSIONS The management of bladder cancer resulted in a significant economic burden on our public health system. The costs associated with stage I bladder cancer were 4-12 times higher than those related to the treatment of other common malignancies at initial stages. Treatment was also expensive during the first months with more advanced stages.
Collapse
Affiliation(s)
- Fernando Korkes
- Faculdade de Medicina do ABC, Rua Iguatemi, 192, cj 23, São Paulo, SP, Brazil.
- Hospital Municipal da Vila Santa Catarina, São Paulo, Brazil.
- Hospital Israelita Albert Einstein, São Paulo, Brazil.
| | - Frederico Timóteo
- Faculdade de Medicina do ABC, Rua Iguatemi, 192, cj 23, São Paulo, SP, Brazil
- Hospital Municipal da Vila Santa Catarina, São Paulo, Brazil
- Hospital Israelita Albert Einstein, São Paulo, Brazil
| | | | | | - Guilherme A Peixoto
- Faculdade de Medicina do ABC, Rua Iguatemi, 192, cj 23, São Paulo, SP, Brazil
- Hospital Israelita Albert Einstein, São Paulo, Brazil
| | | | - Sidney Glina
- Faculdade de Medicina do ABC, Rua Iguatemi, 192, cj 23, São Paulo, SP, Brazil
- Hospital Israelita Albert Einstein, São Paulo, Brazil
| |
Collapse
|
|
35
|
Ortiz-Bonilla CJ, Uccello TP, Gerber SA, Lord EM, Messing EM, Lee YF. Bladder Cancer Extracellular Vesicles Elicit a CD8 T Cell-Mediated Antitumor Immunity. Int J Mol Sci 2022; 23:ijms23062904. [PMID: 35328324 PMCID: PMC8949613 DOI: 10.3390/ijms23062904] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/24/2022] [Accepted: 02/27/2022] [Indexed: 11/25/2022] Open
Abstract
Tumor-derived extracellular vesicles (TEVs) play crucial roles in mediating immune responses, as they carry and present functional MHC-peptide complexes that enable them to modulate antigen-specific CD8+ T-cell responses. However, the therapeutic potential and immunogenicity of TEV-based therapies against bladder cancer (BC) have not yet been tested. Here, we demonstrated that priming with immunogenic Extracellular Vesicles (EVs) derived from murine MB49 BC cells was sufficient to prevent MB49 tumor growth in mice. Importantly, antibody-mediated CD8+ T-cell depletion diminished the protective effect of MB49 EVs, suggesting that MB49 EVs elicit cytotoxic CD8+ T-cell-mediated protection against MB49 tumor growth. Such antitumor activity may be augmented by TEV-enhanced immune cell infiltration into the tumors. Interestingly, MB49 EV priming was unable to completely prevent, but significantly delayed, unrelated syngeneic murine colon MC-38 tumor growth. Cytokine array analyses revealed that MB49 EVs were enriched with pro-inflammatory factors that might contribute to increasing tumor-infiltrating immune cells in EV-primed MC-38 tumors. These results support the potential application of TEVs in personalized medicine, and open new avenues for the development of adjuvant therapies based on patient-derived EVs aimed at preventing disease progression.
Collapse
Affiliation(s)
- Carlos J. Ortiz-Bonilla
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA;
| | - Taylor P. Uccello
- Department of Immunology, Microbiology and Virology, University of Rochester Medical Center, Rochester, NY 14642, USA; (T.P.U.); (S.A.G.); (E.M.L.)
| | - Scott A. Gerber
- Department of Immunology, Microbiology and Virology, University of Rochester Medical Center, Rochester, NY 14642, USA; (T.P.U.); (S.A.G.); (E.M.L.)
- Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Edith M. Lord
- Department of Immunology, Microbiology and Virology, University of Rochester Medical Center, Rochester, NY 14642, USA; (T.P.U.); (S.A.G.); (E.M.L.)
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA;
| | - Edward M. Messing
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA;
- Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Yi-Fen Lee
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA;
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA;
- Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA
- Correspondence: ; Tel.: +1-(585)-275-9702
| |
Collapse
|
|
36
|
Emerging treatment options for bacillus Calmette–Guérin-unresponsive non-muscle invasive bladder cancer. Curr Opin Support Palliat Care 2022; 16:48-53. [DOI: 10.1097/spc.0000000000000587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
37
|
Wroński P, Wroński S, Kurant M, Malinowski B, Wiciński M. Curcumin May Prevent Basement Membrane Disassembly by Matrix Metalloproteinases and Progression of the Bladder Cancer. Nutrients 2021; 14:32. [PMID: 35010907 PMCID: PMC8746354 DOI: 10.3390/nu14010032] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 12/18/2021] [Accepted: 12/19/2021] [Indexed: 12/25/2022] Open
Abstract
Authors present a review of crucial mechanisms contributing to the invasion of the basement membrane (BM) of the urothelium by cancer cells and to the progression of bladder cancer (BC). The breeching of the urothelial BM, facilitated by an aberrant activation of matrix metalloproteinases (MMP) is particularly perilous. Inhibition of activation of these proteinases constitutes a logic opportunity to restrain progression. Because of limited efficacy of current therapeutic methods, the search for the development of alternative approaches constitutes "the hot spot" of modern oncology. Recent studies revealed significant anticancer potential of natural phytochemicals. Especially, curcumin has emerged as a one of the most promising phytochemicals and showed its efficacy in several human malignancies. Therefore, this article addresses experimental and clinical data indicating multi-directional inhibitory effect of curcumin on the growth of bladder cancer. We particularly concentrate on the mechanisms, by which curcumin inhibits the MMP's activities, thereby securing BM integrity and alleviating the eventual cancer invasion into the bladder muscles. Authors review the recently accumulating data, that curcumin constitutes a potent factor contributing to the more effective treatment of the bladder cancer.
Collapse
Affiliation(s)
- Paweł Wroński
- Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland; (P.W.); (B.M.)
- Department of Oncological Urology, The Franciszek Lukaszczyk Oncology Center, Romanowskiej 2, 85-796 Bydgoszcz, Poland
| | - Stanisław Wroński
- Department of Urology, Jan Biziel Memorial University Hospital, Ujejskiego 75, 85-168 Bydgoszcz, Poland;
| | - Marcin Kurant
- Department of Urology, District Hospital, 10 Lesna Street, 89-600 Chojnice, Poland;
| | - Bartosz Malinowski
- Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland; (P.W.); (B.M.)
| | - Michał Wiciński
- Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland; (P.W.); (B.M.)
| |
Collapse
|
|
38
|
Serum irisin is a novel biomarker for bladder cancer detection. Int Urol Nephrol 2021; 54:55-61. [PMID: 34807348 DOI: 10.1007/s11255-021-03074-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 11/17/2021] [Indexed: 01/10/2023]
Abstract
BACKGROUND This study intended to investigate irisin levels in bladder cancer patients and healthy controls. OBJECTIVE Our aim was to evaluate if serum irisin could be used as a diagnostic tool in bladder cancer and further, if it could differentiate muscle-invasive and non-muscle-invasive bladder cancer patients. METHODS In this study, 90 primary bladder cancer patients in addition to 30 age-matched healthy individuals for the control group were prospectively included. Bladder cancer patients were divided into two subgroups as non-muscle-invasive (60 patients) and muscle-invasive (30 patients). Blood samples were obtained before the diagnosis of the disease. Serum irisin levels were measured using ELISA. Demographic data as well as tumor grade and stage were noted. RESULTS Mean serum irisin level was significantly lower in the bladder cancer patients compared to the control group (4.53 ± 2.55 vs. 16.5 ± 5.67, p < 0.001). Also, serum irisin level was statistically lower in the muscle-invasive bladder cancer group compared to the non-muscle-invasive counterparts (3.19 ± 1.47 vs. 5.18 ± 2.73, p < 0.001). Serum irisin could differentiate bladder cancer patients from healthy individuals with a sensitivity of 86.2% and a specificity of 89.7% at a cut-off value of 8.689 (AUC = 0.859). Moreover, to discriminate between NMIBC and MIBC, the sensitivity was 75% and the specificity was 73.7% at a cut-off value of 3.97 (AUC = 0.732). CONCLUSION Our results showed that serum irisin levels can be used for the diagnosis of bladder cancer. Also, it can help distinguish high-grade and stage tumor.
Collapse
|
|
39
|
Mahran A, Miller A, Calaway A, Prunty M, Arenas-Gallo C, Isali I, Ginsburg KB, Ponsky L, Markt S, Schumacher F, Bukavina L. The Impact of Race and Sex on Metastatic Bladder Cancer Survival. Urology 2021; 165:98-105. [PMID: 34813833 DOI: 10.1016/j.urology.2021.08.049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 07/28/2021] [Accepted: 08/19/2021] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To characterize the epidemiological profile of metastatic bladder cancer (BC) and assess mortality rate with respect to race and gender across the three most common histologies of bladder cancer-Transitional Cell Carcinoma, Adenocarcinoma, and SCC (Squamous Cell Carcinoma). MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results Program database (2000-2017) was queried for all metastatic bladder cancer patients at presentation. Our primary exposure consists of four race/gender combinations. One-way ANOVA and Chi-square tests compared categorical and continuous variables across the exposure variable, respectively. Univariable and multivariable Cox proportional hazards regression analyses were used to examine the association between race/gender combinations and the overall and cancer specific survival adjusting for the other variables. RESULTS A total of 312,846 bladder cancer patients, 6337 with distant metastases and 11,446 with regional metastases were evaluated. Black female cancer specific survival in metastatic disease was disproportionally lower compared to all race/gender for Transitional Cell Carcinoma 4.3% (95% CI: 1.6-8.9), SCC 2.6% (95% CI: 0.2-11.8), and Adenocarcinoma 6.4% (0.4%-25%). In regional metastastatic disease, worse cancer specific mortality was associated with identifying as a Black Female (aHR 1.17, P = .023), SCC (aHR 1.8, P <.001), increasing age (aHR 1.3, P <.001), and poorly differentiated grade (aHR 2.01, P <.001). CONCLUSION Black females experience excess mortality in overall and cancer oncologic outcomes in metastatic BC. Our findings contribute to the body of research warranting examination of the impact of social determinants of health and provider decisions on BC survivorship and contribute to physician decision making in the treatment and surveillance of bladder cancer.
Collapse
Affiliation(s)
- Amr Mahran
- Case Western Reserve University School of Medicine, Cleveland, OH; University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, OH
| | - April Miller
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Adam Calaway
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Megan Prunty
- Case Western Reserve University School of Medicine, Cleveland, OH; University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, OH
| | - Camilo Arenas-Gallo
- Case Western Reserve University School of Medicine, Cleveland, OH; University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, OH
| | - Ilaha Isali
- Case Western Reserve University School of Medicine, Cleveland, OH; University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, OH; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH
| | | | - Lee Ponsky
- Case Western Reserve University School of Medicine, Cleveland, OH; University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, OH; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH; Fox Chase Cancer Center, Philadelphia, PA
| | - Sarah Markt
- Case Western Reserve University School of Medicine, Cleveland, OH; University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, OH; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH; Fox Chase Cancer Center, Philadelphia, PA
| | - Fredrick Schumacher
- Case Western Reserve University School of Medicine, Cleveland, OH; University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, OH; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH; Fox Chase Cancer Center, Philadelphia, PA
| | - Laura Bukavina
- Case Western Reserve University School of Medicine, Cleveland, OH; University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, OH; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH; Fox Chase Cancer Center, Philadelphia, PA.
| |
Collapse
|
|
40
|
Arthuso FZ, Fairey AS, Boulé NG, Courneya KS. Bladder cancer and exeRcise trAining during intraVesical thErapy-the BRAVE trial: a study protocol for a prospective, single-centre, phase II randomised controlled trial. BMJ Open 2021; 11:e055782. [PMID: 34561265 PMCID: PMC8475156 DOI: 10.1136/bmjopen-2021-055782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
INTRODUCTION Non-muscle invasive bladder cancer (NMIBC) accounts for about 75% of newly diagnosed bladder cancers. The treatment for NMIBC involves surgical removal of the tumour followed by 6 weekly instillations of immunotherapy or chemotherapy directly into the bladder (ie, intravesical therapy). NMIBC has a high rate of recurrence (31%-78%) and progression (15%). Moreover, bladder cancer and its treatment may affect patient functioning and quality of life. Exercise is a safe and effective intervention for many patient with cancer groups, however, no studies have examined exercise during intravesical therapy for NMIBC. The primary objective of the Bladder cancer and exeRcise trAining during intraVesical thErapy (BRAVE) trial is to examine the safety and feasibility of an exercise intervention in patients with bladder cancer undergoing intravesical therapy. The secondary objectives are to investigate the preliminary efficacy of exercise on health-related fitness and patient-reported outcomes; examine the social cognitive predictors of exercise adherence; and explore the potential effects of exercise on tumour recurrence and progression. METHODS AND ANALYSIS BRAVE is a phase II randomised controlled trial that aims to include 66 patients with NMIBC scheduled to receive intravesical therapy. Participants will be randomly assigned to the exercise intervention or usual care. The intervention consists of three supervised, high-intensity interval training sessions per week for 12 weeks. Feasibility will be evaluated by eligibility, recruitment, adherence and attrition rates. Preliminary efficacy will focus on changes in cardiorespiratory fitness and patient-reported outcomes from baseline (prior to intravesical therapy) to pre-cystoscopy (3 months). Cancer outcomes will be tracked at 3 months, and 1-year follow-up by cystoscopy. Analysis of covariance will compare between-group differences at post-intervention (pre-cystoscopy) for all health-related fitness and patient-reported outcomes. ETHICS AND DISSEMINATION The study was approved by the Health Research Ethics Board of Alberta-Cancer Committee (#20-0184). Dissemination will include publication and presentations at scientific conferences and public channels. TRIAL REGISTRATION NUMBER NCT04593862; Pre-results.
Collapse
Affiliation(s)
- Fernanda Z Arthuso
- Faculty of Kinesiology, Sport, and Recreation, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Adrian S Fairey
- Division of Urology, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Normand G Boulé
- Faculty of Kinesiology, Sport, and Recreation, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Kerry S Courneya
- Faculty of Kinesiology, Sport, and Recreation, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada
| |
Collapse
|
|
41
|
Sun K, Wang D, Wu G, Ma J, Wang T, Wu J, Wang J. Mirabegron improves the irritative symptoms caused by BCG immunotherapy after transurethral resection of bladder tumors. Cancer Med 2021; 10:7534-7541. [PMID: 34547193 PMCID: PMC8559481 DOI: 10.1002/cam4.4278] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 08/18/2021] [Accepted: 08/26/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This study aims to explore the efficacy and safety of mirabegron in treating irritative symptoms induced by intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) after transurethral resection of bladder tumors (TURBT). METHODS A total of 160 patients subjected to TURBT was randomly divided into the mirabegron group and placebo group with 80 patients in each group. Then, the patients were administered 25 mg mirabegron or placebo daily, starting the first day after BCG infusion. The first BCG perfusion was conducted at least 2 weeks after TURBT. The 3-day bladder diaries were completed in all patients, 1 day before BCG perfusion, and on the 1st, 6th, and 13th days after the first BCG perfusion. Overactive bladder symptom scores were completed 1 day before BCG perfusion, and on the 6th and 13th days after the first BCG perfusion. RESULTS Symptom scores of bladder hyperactivity were significantly different between the two groups (p < 0.001). Also, the frequency of nocturia, pollakiuria, micturition urgency, urinary incontinence and was significantly lower in group 1 than that in group two (p < 0.05). CONCLUSION Our findings demonstrate that mirabegron is a valuable clinical drug for the management of irritative symptoms after TURBT with subsequent intravesical BCG perfusion.
Collapse
Affiliation(s)
- Kai Sun
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China
| | - Di Wang
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China
| | - Gang Wu
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China
| | - Jian Ma
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China
| | - Tianqi Wang
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China
| | - Jitao Wu
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China
| | - Jipeng Wang
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China
| |
Collapse
|
|
42
|
Yeary KHK, Clark N, Saad-Harfouche F, Erwin D, Kuliszewski MG, Li Q, McCann SE, Yu H, Lincourt C, Zoellner J, Tang L. Cruciferous Vegetable Intervention to Prevent Cancer Recurrence in Non-Muscle Invasive Bladder Cancer Survivors: Development using a Systematic Process (Preprint). JMIR Cancer 2021; 8:e32291. [PMID: 35166681 PMCID: PMC8889476 DOI: 10.2196/32291] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 11/30/2021] [Accepted: 01/05/2022] [Indexed: 11/18/2022] Open
Abstract
Background Bladder cancer is one of the top 10 most common cancers in the United States. Most bladder cancers (70%-80%) are diagnosed at early stages as non–muscle-invasive bladder cancer (NMIBC), which can be removed surgically. However, 50% to 80% of NMIBC cases recur within 5 years, and 15% to 30% progress with poor survival. Current treatments are limited and expensive. A wealth of preclinical and epidemiological evidence suggests that dietary isothiocyanates in cruciferous vegetables (Cruciferae) could be a novel, noninvasive, and cost-effective strategy to control NMIBC recurrence and progression. Objective The aim of this study is to develop a scalable dietary intervention that increases isothiocyanate exposure through Cruciferae intake in NMIBC survivors. Methods We worked with a community advisory board (N=8) to identify relevant factors, evidence-based behavior change techniques, and behavioral theory constructs used to increase Cruciferae intake in NMIBC survivors; use the PEN-3 Model focused on incorporating cultural factors salient to the group’s shared experiences to review the intervention components (eg, the saliency of behavioral messages); administer the revised intervention to community partners for their feedback; and refine the intervention. Results We developed a multicomponent intervention for NMIBC survivors consisting of a magazine, tracking book, live telephone call script, and interactive voice messages. Entitled POW-R Health: Power to Redefine Your Health, the intervention incorporated findings from our adaptation process to ensure saliency to NMIBC survivors. Conclusions This is the first evidence-based, theoretically grounded dietary intervention developed to reduce bladder cancer recurrence in NMIBC survivors using a systematic process for community adaptation. This study provides a model for others who aim to develop behavioral, community-relevant interventions for cancer prevention and control with the overall goal of wide-scale implementation and dissemination.
Collapse
Affiliation(s)
- Karen H Kim Yeary
- Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Nikia Clark
- Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Frances Saad-Harfouche
- Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Deborah Erwin
- Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Margaret Gates Kuliszewski
- New York State Cancer Registry, New York State Department of Health, Albany, NY, United States
- Department of Epidemiology and Biostatistics, University at Albany School of Public Health, Albany, NY, United States
| | - Qiang Li
- Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
- Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Susan E McCann
- Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Han Yu
- Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Catherine Lincourt
- Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Jamie Zoellner
- Department of Public Health Science, University of Virginia, Charlottesville, VA, United States
| | - Li Tang
- Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| |
Collapse
|
|
43
|
Slovacek H, Zhuo J, Taylor JM. Approaches to Non-Muscle-Invasive Bladder Cancer. Curr Oncol Rep 2021; 23:105. [PMID: 34269918 DOI: 10.1007/s11912-021-01091-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/20/2021] [Indexed: 12/20/2022]
Abstract
PURPOSE OF REVIEW Non-muscle-invasive bladder cancer (NMIBC) is a heterogenous malignancy with high recurrence and progression rates, which necessitate uniform recommendations for diagnosis and management. Herein, we review the literature, with an emphasis on guidelines and contemporary diagnostic techniques and interventions. RECENT FINDINGS Guidelines around the world have adopted a schema which risk-stratify cases at diagnosis, to offer evidence-based treatment and surveillance recommendations. Enhanced endoscopic technologies can improve detection of NMIBC and reduce recurrence. The present Bacillus Calmette-Guerin (BCG) shortage in the USA has led to new strategies to prioritize the most high-risk cases. The entity of BCG-unresponsive high-risk NMIBC remains a challenge to manage, with multiple novel treatments under investigation; fortunately, new therapies have been approved, such as immune checkpoint inhibitors, and others are showing tremendous promise. The standardization of NMIBC management, with evolving detection techniques and therapeutics, offers great potential to improve patient outcomes and survivorship.
Collapse
Affiliation(s)
- Hannah Slovacek
- Loyola University Chicago Stritch School of Medicine, Chicago, IL, USA
| | - Jerry Zhuo
- Department of Urology, Baylor College of Medicine, 7200 Cambridge St, Ste 10B, Houston, TX, 77030, USA
| | - Jennifer M Taylor
- Department of Urology, Baylor College of Medicine, 7200 Cambridge St, Ste 10B, Houston, TX, 77030, USA.
| |
Collapse
|
|
44
|
Chang YH, Tam HL, Lu MC, Huang HS. Gemcitabine-induced Gli-dependent activation of hedgehog pathway resists to the treatment of urothelial carcinoma cells. PLoS One 2021; 16:e0254011. [PMID: 34237099 PMCID: PMC8266077 DOI: 10.1371/journal.pone.0254011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 06/17/2021] [Indexed: 01/20/2023] Open
Abstract
Patients with urothelial carcinoma (UC) experience gemcitabine resistance is a critical issue. The role of hedgehog pathway in the problem was explored. The expressions of phospho-AKTser473, phospho-GSK3βser9 and Gli2 were up-regulated in gemcitabine-resistant NTUB1 (NGR) cells. Without hedgehog ligands, Gli proteins can be phosphorylated by GSK3β kinase to inhibit their downstream regulations. Furthermore, the GSK3β kinase can be phosphorylated by AKT at its Ser9 residue to become an inactive kinase. Therefore, overexpression of AKT1, Flag-GSKS9D (constitutively inactive form) or active Gli2 (GLI2ΔN) in NTUB1 cells could activate Gli2 pathway to enhance migration/invasion ability and increase gemcitabine resistance, respectively. Conversely, overexpression of Flag-GSKS9A (constitutively active form) or knockdown of Gli2 could suppress Gli2 pathway, and then reduce gemcitabine resistance in NGR cells. Therefore, we suggest gemcitabine-activated AKT/GSK3β pathway can elicit Gli2 activity, which leads to enhanced migration/invasion ability and resistance to gemcitabine therapy in UC patients. The non-canonical hedgehog pathway should be evaluated in the therapy to benefit UC patients.
Collapse
Affiliation(s)
- Yu-Hao Chang
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hoi-Lam Tam
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Meng-Chien Lu
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Huei-Sheng Huang
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- * E-mail:
| |
Collapse
|
|
45
|
The prognostic effect of metastasis patterns on overall survival in patients with distant metastatic bladder cancer: a SEER population-based analysis. World J Urol 2021; 39:4151-4158. [PMID: 34028594 DOI: 10.1007/s00345-021-03721-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 05/03/2021] [Indexed: 10/21/2022] Open
Abstract
BACKGROUND The prognostic impact of different distant metastases pattern in bladder cancer is unexplored still now. The aim of this study is to investigate the impact of different distant metastases pattern on the survival of patients with stage IV bladder cancers. METHODS A SEER analysis was performed and the overall survival was calculated by the Kaplan-Meier method. Multivariable Cox regression models were used to further analyze survival outcome and other prognostic factors. RESULTS A total of 90,382 eligible cases were retrieved in the Surveillance, Epidemiology, and End Results database. Among these patients, stage of IV bladder cancer accounted for 7.03% (6354/90382) at initial diagnosis. Patients who suffered metastasis occupied 35.51% (2256/6354). Comparing with other three single metastases, the patients with liver metastasis exhibited worst OS whose mean of survival was 7.118 months. Multivariate analysis with Cox hazard regression model showed that metastatic site was an independent prognostic factor of OS in patients with single metastasis (P < 0.05). The results of univariate survival analysis showed that metastatic pattern, sex, age, race, tumor stage, N-classification, differentiated grade, histological type, chemotherapy, radiotherapy and insurance status were not significantly correlated with overall survival of patients with two or three metastatic sites (all, P > 0.05). CONCLUSIONS Bone was the most common site of single metastasis for bladder cancers. Patients with liver metastasis had worse survival outcome comparing with other three distant metastases. Knowledge of these differences in metastatic patterns might help to better guide pre-treatment evaluation of bladder cancer and make determination regarding curative-intent interventions.
Collapse
|
|
46
|
Yang M, Georgieva MV, Bocharova I, Vembusubramanian M, Qian K, Guo A, Kamat AM. The Impact of Progression on Healthcare Resource Utilization and Costs Among Patients with High-Grade Non-Muscle Invasive Bladder Cancer After Bacillus Calmette-Guérin Therapy: A Retrospective SEER-Medicare Analysis. Adv Ther 2021; 38:1584-1600. [PMID: 33543424 DOI: 10.1007/s12325-020-01616-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 12/23/2020] [Indexed: 10/22/2022]
Abstract
INTRODUCTION We evaluated the real-world healthcare resource utilization (HRU) and costs among patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC) following Bacillus Calmette-Guérin (BCG) therapy. METHODS Patients aged ≥ 65 years diagnosed with HG-NMIBC between 2008 and 2015 who received adequate BCG induction and were identified in the SEER-Medicare database. Those who received intravesical chemotherapy or radical cystectomy within 12 months of the last BCG induction dose, and had ≥ 6 months of data availability after treatment (index date), were included. Annualized HRU and mean medical costs (2020 United States dollars) were estimated and compared between patients with versus without progression. Inverse probability of treatment weighting was used to adjust for differences in baseline characteristics. RESULTS Of 986 patients diagnosed with HG-NMIBC who met the inclusion criteria, 257 (26.1%) progressed; the mean ages were similar between patients who did and did not progress (77.6 vs. 77.0 years). The overall population had a mean of 0.96 [standard deviation (SD): 1.18] inpatient admissions, 6.47 (11.40) hospitalization days, 1.38 (2.19) emergency department (ED) visits, and 48.03 (44.97) outpatient visits per patient-year during the study period; total annualized costs per patient post-BCG were $39,102 ($44,244). Patients experiencing progression had significantly higher mean numbers of inpatient admissions [1.61 (SD 1.40) vs. 0.72 (0.99)], hospitalization days [11.77 (14.96) vs. 4.59 (9.29)], ED visits [2.34 (2.92) vs. 1.03 (1.76)], and outpatient visits [65.97 (44.72) vs. 41.63 (43.09)] per patient-year compared with patients without progression (all p < 0.05). Total mean annualized costs per patient after BCG among those who progressed [$65,668 (SD $53,943)] were more than double compared with patients who did not [$29,780 ($36,425)]. CONCLUSIONS Existing treatments for HG-NMIBC after BCG therapy are associated with substantial HRU and medical costs, particularly after progression. Novel treatments and earlier detection are needed to reduce progression rates and associated costs in this difficult-to-treat population.
Collapse
|
|
47
|
Tang Y, Kortum A, Vohra I, Schwarz RA, Carns J, Kannady CR, Clavell-Hernandez J, Hu Z, Dhanani N, Richards-Kortum R. Initial Results of First In Vivo Imaging of Bladder Lesions Using a High-Resolution Confocal Microendoscope. J Endourol 2021; 35:1190-1197. [PMID: 33307957 DOI: 10.1089/end.2020.0757] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
Purpose: Conventional cystoscopy plays an important role in detection of bladder cancer; however, it is difficult to differentiate benign and neoplastic lesions based on cystoscopic appearance alone. Advanced microscopic modalities, such as confocal laser endomicroscopy and optical coherence tomography, have been shown to provide critical histopathologic information to help identify neoplastic bladder lesions in real time, but their availability and clinical adoption are limited due to a high cost. In this study, we present the first use of a novel and low-cost ($ <5000) confocal high-resolution microendoscope (confocal HRME) for in vivo imaging of bladder lesions. Materials and Methods: In a cohort of 15 patients undergoing white light cystoscopy as part of their standard of care, high-resolution images of proflavine-stained bladder lesions were acquired in vivo using the confocal HRME. Based on these images, we evaluated the ability of the confocal HRME to visualize uroepithelium with subcellular resolution and high contrast. Furthermore, we analyzed the cellular architecture and staining patterns of benign and neoplastic bladder lesions in confocal HRME images and compared results to that of standard cystoscopy and histopathology. Results: In vivo imaging in the pilot study demonstrates that the confocal HRME resolved subcellular structures of bladder uroepithelium with high contrast. In a wide range of clinical conditions from normal bladder wall to benign and neoplastic lesions, confocal HRME images revealed important diagnostic features that correlated to histopathology. Conclusions: The confocal HRME provides an affordable, portable, and easy-to-use tool to allow real-time and high-contrast subcellular characterization of bladder lesions, well suited for bladder cancer detection in community and resource-constrained settings. The ClinicalTrials.gov Identifier: NCT02340650.
Collapse
Affiliation(s)
- Yubo Tang
- Department of Bioengineering, Rice University, Houston, Texas, USA
| | - Alex Kortum
- Department of Bioengineering, Rice University, Houston, Texas, USA
| | - Imran Vohra
- Department of Bioengineering, Rice University, Houston, Texas, USA
| | | | - Jennifer Carns
- Department of Bioengineering, Rice University, Houston, Texas, USA
| | - Christopher R Kannady
- Department of Surgery and University of Texas Health Science Center at Houston, Houston, Texas, USA
| | | | - Zhihong Hu
- Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Nadeem Dhanani
- Department of Surgery and University of Texas Health Science Center at Houston, Houston, Texas, USA
| | | |
Collapse
|
|
48
|
Yu X, Li S, Pang M, Du Y, Xu T, Bai T, Yang K, Hu J, Zhu S, Wang L, Liu X. TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway. Front Oncol 2021; 10:613869. [PMID: 33489923 PMCID: PMC7821430 DOI: 10.3389/fonc.2020.613869] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 11/27/2020] [Indexed: 01/21/2023] Open
Abstract
The tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) has never been investigated in bladder cancer (BCa). In this study, we aimed to investigate the biological function of TSPAN7 and its therapeutic potential in human BCa. First, via reverse transcription and quantitative real-time PCR (qRT-PCR), we observed downregulation of TSPAN7 in BCa tissues samples and cell lines and found that this downregulation was associated with a relatively high tumor stage and tumor grade. Low expression of TSPAN7 was significantly correlated with a much poorer prognosis for BCa patients than was high expression. Immunohistochemistry (IHC) showed that low TSPAN7 expression was a high-risk predictor of BCa patient overall survival. Furthermore, the inhibitory effects of TSPAN7 on the proliferation and migration of BCa cell lines were detected by CCK-8, wound-healing, colony formation and transwell assays in vitro. Flow cytometry analysis revealed that TSPAN7 induced BCa cell lines apoptosis and cell cycle arrest. In vivo, tumor growth in nude mice bearing tumor xenografts could be obviously affected by overexpression of TSPAN7. Western blotting showed that overexpression of TSPAN7 activated Bax, cleaved caspase-3 and PTEN but inactivated Bcl-2, p-PI3K, and p-AKT to inhibit BCa cell growth via the PTEN/PI3K/AKT pathway. Taken together, our study will help identify a potential marker for BCa diagnosis and supply a target molecule for BCa treatment.
Collapse
Affiliation(s)
- Xi Yu
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shenglan Li
- Department of Radiography, Renmin Hospital of Wuhan University, Wuhan, China
| | - Mingrui Pang
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yang Du
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Tao Xu
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Tao Bai
- Department of Urology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kang Yang
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Juncheng Hu
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shaoming Zhu
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Lei Wang
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xiuheng Liu
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| |
Collapse
|
|
49
|
Ehlers M, Bjurlin M, Gore J, Pruthi R, Narang G, Tan R, Nielsen M, Zhu A, Deal A, Smith A. A national cross-sectional survey of financial toxicity among bladder cancer patients. Urol Oncol 2021; 39:76.e1-76.e7. [DOI: 10.1016/j.urolonc.2020.09.030] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Revised: 09/09/2020] [Accepted: 09/29/2020] [Indexed: 11/28/2022]
|
|
50
|
Loloi J, Lin YK, Camacho F, Lengerich E, Raman JD. 25-Year Trends in Stage-Specific Incidence Rates for Bladder Cancer in a Large Statewide Registry. Bladder Cancer 2020. [DOI: 10.3233/blc-200310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND: Bladder cancer (BC) is a common genitourinary malignancy with over 80,000 new cases diagnosed annually and over 17,000 associated deaths. OBJECTIVE: We review 25-years of BC incidence (1993-2017) within the state of Pennsylvania to better define incidence, geographic distribution, and trends over time. METHODS: The Pennsylvania Cancer Registry was reviewed for statewide and component county age-adjusted BC incidence rates and stage distribution. Chloropleth maps plotting statewide and county-specific incidence rates across time were created using the GeoDa statistical package. RESULTS: 93,476 cases of BC were recorded in Pennsylvania from 1993 to 2017. Age-adjusted annual rates of BC over the study interval were stable at 24.5 patients per 100,000 (range, 22.7–25.6). However, annual rates of distant disease increased from 0.5 to 1.1 patients per 100,000 (p < 0.001) with an average percent change increase of 6.6% over the study interval. The annual percent distribution of distant disease doubled from 2.3% to 5.1% (p < 0.001) with a greater increase in women compared to men. Chloropleth maps highlighted growing “hot spots” of bladder cancer incidence in the northwestern, northeastern, and southeastern portions of the state. CONCLUSIONS: While BC incidence in the state of Pennsylvania has remained relatively stable over the past 25 years, a concerning increase in distant disease was observed. Geospatial investigation implicates higher risk regions. Further studies are necessary to delineate the underlying etiologies for these observations.
Collapse
Affiliation(s)
- Justin Loloi
- Division of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Yu-Kuan Lin
- Division of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Fabian Camacho
- Department of Public Health Sciences, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Eugene Lengerich
- Department of Public Health Sciences, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Jay D. Raman
- Division of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| |
Collapse
|