Bladder Cancer最新文献

{"title":"Molecular Basis of Tumorigenesis of Bladder Cancer and Emerging Concepts in Developing Therapeutic Targets","authors":"Rana M. Abdeltwab, Elaria Yacoub, Ahmed H. Rashad, Kyrillus S. Shohdy","doi":"10.3233/blc-230025","DOIUrl":"https://doi.org/10.3233/blc-230025","url":null,"abstract":"<h4><span>Abstract</span></h4><h3><span></span>BACKGROUND:</h3><p>Advanced urothelial carcinoma (UC) is an aggressive disease whose mutagenic processes are yet to be elucidated. Targeted therapies are urgently needed, but the road from bench to bedside is slowly progressing. In this review, we discuss urothelial carcinoma etiology, along with the most recent advances in UC candidate targeted therapies.</p><h3><span></span>METHODOLOGY:</h3><p>A comprehensive database search was performed. We aimed to review the most recent updates on UC genomics and targeted therapies. Pre-clinical as well as clinical studies were included.</p><h3><span></span>RESULTS:</h3><p>Our review highlights the advances in understanding the molecular basis of urothelial tumorigenesis, including smoking, chemical parasitic carcinogens, inheritance, and APOBEC3 editing enzymes. We discussed how these factors contributed to the current mutational landscape of UC. Therapeutic options for UC are still very limited. However, several promising therapeutic approaches are in development to leverage our knowledge of molecular targets, such as targeting fibroblast growth factor receptors (FGFR), DNA damage repair pathways, and HER2.</p><h3><span></span>CONCLUSIONS:</h3><p>Blindly testing targeted therapies based on other cancer data is not sufficient. UC-specific biomarkers are needed to precisely use the appropriate drug for the appropriate population. More efforts to understand UC biology and evolution are urgently needed.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"13 8 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138531798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What is a Bladder Cancer Molecular Subtype? – Counterpoint","authors":"François Radvanyi, Francisco X. Real, David McConkey","doi":"10.3233/blc-230059","DOIUrl":"https://doi.org/10.3233/blc-230059","url":null,"abstract":"<h4><span>Abstract</span></h4><p>In an accompanying paper, Mattias Hoglund discusses on what is a bladder cancer molecular subtype. He emphasizes the need to consider the aim of tumor classification, which is obviously critical to the approach. He also focuses on considering primarily the identity features of the neoplastic cells. Here, we provide a counterpoint. While largely agreeing with his views, we underline that other parameters that may vary in a spatial or temporal scale, and the tumor microenvironment, can also provide relevant information to render tumor classifications clinically useful. Furthermore, tumor heterogeneity and evolution during the disease course - natural or under therapeutic pressure - should be considered.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"45 4","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138508186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on Novitas LCD","authors":"Yair Lotan, Daniel A. Barocas, Sam S. Chang, Siamak Daneshmand, Badrinath Konety, Joshua J. Meeks, Sima Porten, Jay D. Raman, Charles J. Rosser, Kristen R. Scarpato, Wade J. Sexton, John P. Sfakianos, Neal D. Shore, Robert S. Svatek","doi":"10.3233/blc-230057","DOIUrl":"https://doi.org/10.3233/blc-230057","url":null,"abstract":"The role of biomarkers (aka, markers) in detecting and managing cancer is an evolving field. It is crucial to develop biomarkers robustly that mirror drug development in the pharmaceutical","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135424913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer","authors":"Elaine Chang, Noah M. Hahn, Seth P. Lerner, Jaleh Fallah, Sundeep Agrawal, Ashish M. Kamat, Vishal Bhatnagar, Robert S. Svatek, Adnan A. Jaigirdar, Peter Bross, Neal Shore, Max Kates, Karen Sachse, Jamie R. Brewer, Michael A. O’Donnell, Gary D. Steinberg, Charles J. Viviano, Erik Bloomquist, Maria J. Ribal, Matthew D. Galsky, Richard Oliver, Peter C. Black, Hikmat Al-Ahmadie, Kenneth Brothers, Kamal Pohar, Colin P. Dinney, Zhou Feng, Tracy M. Downs, Sima P. Porten, Angela B. Smith, Rick Bangs, Sarah P. Psutka, Neeraj Agarwal, Laleh Amiri-Kordestani, Daniel L. Suzman, Richard Pazdur, Paul G. Kluetz, Chana Weinstock","doi":"10.3233/blc-230056","DOIUrl":"https://doi.org/10.3233/blc-230056","url":null,"abstract":"BACKGROUND: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC. OBJECTIVE: On November 18–19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies. METHODS: Representatives from various disciplines including urologists, oncologists, pathologists, statisticians, basic and translational scientists, and the patient advocacy community participated. The workshop format included invited lectures, panel discussions, and opportunity for audience discussion and comment. RESULTS: In a pre-workshop survey, 92% of urologists surveyed considered the development of alternatives to BCG as a high drug development priority for BCG-naïve high-risk patients. Key topics discussed included definitions of disease states; trial design for BCG-naïve NMIBC, BCG-unresponsive carcinoma in situ, and BCG-unresponsive papillary carcinoma; strengths and limitations of single-arm trial designs; assessing patient-reported outcomes; and considerations for assessing avoidance of cystectomy as an efficacy measure. CONCLUSIONS: The workshop discussed several important opportunities for trial design refinement in NMIBC. FDA encourages sponsors to meet with the appropriate review division to discuss trial design proposals for NMIBC early in drug development.","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135769451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Adjuvant Gemcitabine Containing Chemotherapy Following Radical Nephroureterectomy for Patients with Upper Tract Urothelial Carcinoma: Results from a Propensity-Score Matched Cohort Study","authors":"Zhao Hongda, Liu Kang, Chi-Fai Ng, Jean de la Rosette, Pilar Laguna, Paolo Gontero, Joyce Baard, Ozcan Yildiz, Jeremy Yuen-Chun Teoh","doi":"10.3233/blc-230041","DOIUrl":"https://doi.org/10.3233/blc-230041","url":null,"abstract":"BACKGROUND: The evidence regarding perioperative adjuvant chemotherapy and personalized surveillance strategies for upper tract urothelial carcinoma is limited. OBJECTIVE: To evaluate whether adjuvant gemcitabine containing chemotherapy affects the oncological outcomes of advanced upper tract urothelial carcinoma (UTUC). METHODS: The CROES-UTUC registry is an observational, international, multi-center study on patients diagnosed with UTUC. Patient and disease characteristics from 2380 patients with UTUC were collected, and finally 738 patients were included in this analysis. The primary outcome of this study was recurrence-free survival. Propensity score matching was performed. Kaplan-Meier and multivariate Cox regression analyses were performed by stratifying patients according to the treatment of adjuvant chemotherapy. RESULTS: A total of 738 patients were included in this analysis, and 59 patients received adjuvant chemotherapy (AC), including 50 patients who received gemcitabine. A propensity score matching was performed, including 50 patients who received gemcitabine containing treatment and 50 patients without adjuvant chemotherapy. Disease recurrence occurred in 34.0% of patients. The recurrence rate in the AC group was 22.0%, which was significantly lower than the non-AC group (46.0%). Kaplan-Meier analyses also showed that AC was associated with a lower likelihood of tumor recurrence (p = 0.047). However, AC was not significantly associated with a higher overall survival (OS) (p = 0.908) and cancer-specific survival (CSS) (p = 0.979). Upon multivariate Cox regression analysis, AC was associated with a lower risk of tumor recurrence (HR = 0.297, p = 0.028). CONCLUSION: The present study confirms that adjuvant gemcitabine containing chemotherapy could decrease the risk of tumor recurrence in patients with locally advanced UTUC following nephroureterectomy. However, more studies are need to draw a clearer image of the value of this treatment method.","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135769129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Robotic vs Open Cystectomy: A Systematic Review","authors":"Niranjan J. Sathianathen, Henry Y.C. Pan, Marc Furrer, Benjamin Thomas, Philip Dundee, Niall Corcoran, Christopher J. Weight, Badrinath Konety, Rajesh Nair, Nathan Lawrentschuk","doi":"10.3233/blc-220065","DOIUrl":"https://doi.org/10.3233/blc-220065","url":null,"abstract":"BACKGROUND: The benefits of a robot-assisted radical cystectomy (RARC) compared to an open approach is still under debate. Initial data on RARC were from trials where urinary diversion was performed by an extracorporeal approach, which does not represent a completely minimally invasive procedure. There are now updated data for RARC with intracorporeal urinary diversion that add to the evidence profile of RARC. OBJECTIVE: To perform a systematic review and meta-analysis of the effectiveness of RARC compared with open radical cystectomy (ORC). MATERIALS AND METHODS: Multiple databases were searched up to May 2022. We included randomised trials in which patients underwent RARC and ORC. Oncological and safety outcomes were assessed. RESULTS: Seven trials of 907 participants were included. There were no differences seen in primary outcomes: disease progression [RR 0.98, 95% CI 0.78 to 1.23], major complications [RR 0.95, 95% CI 0.72 to 1.24] and quality of life [SMD 0.05, 95% CI -0.13 to 0.38]. RARC resulted in a decreased risk of perioperative blood transfusion [RR 0.57, 95% CI 0.43 to 0.76], wound complications [RR 0.34, 95% CI 0.21 to 0.55] and reduced length of hospital stay [MD -0.62 days, 95% CI -1.11 to -0.13]. However, there was an increased risk of developing a ureteric stricture [RR 4.21, 95% CI 1.07 to 16.53] in the RARC group and a prolonged operative time [MD 70.4 minutes, 95% CI 34.1 to 106.7]. The approach for urinary diversion did not impact outcomes. CONCLUSION: RARC is an oncologically safe procedure compared to ORC and provides the benefits of a minimally invasive approach. There was an increased risk of developing a ureteric stricture in patients undergoing RARC that warrants further investigation. There was no difference in oncological outcomes between approaches.","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"66 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135769130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Y Chromosome Loss and Bladder Cancer","authors":"Edward M. Messing","doi":"10.3233/blc-239009","DOIUrl":"https://doi.org/10.3233/blc-239009","url":null,"abstract":"","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135769452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Trials Corner Issue 9(2)","authors":"Piyush K. Agarwal, Cora N. Sternberg","doi":"10.3233/blc-239007","DOIUrl":"https://doi.org/10.3233/blc-239007","url":null,"abstract":"","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"52 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135399249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypofractionated Radiation Therapy (Hypo-RT) for the Treatment of Localized Bladder Cancer","authors":"Assaf Moore, Stephanie M Lobaugh, Zhigang Zhang, Jonathan E Rosenberg, Gopa Iyer, Min Yuen Teo, Bernard Bochner, Timothy Donahue, David Aramburu Nunez, Alexandra Dreyfuss, Daniel Gorovets, Michael J Zelefsky, Marisa A. Kollmeier","doi":"10.3233/blc-220121","DOIUrl":"https://doi.org/10.3233/blc-220121","url":null,"abstract":"BACKGROUND: Various radiotherapeutic regimens are used in the treatment of bladder cancer. OBJECTIVE: We aimed to evaluate early toxicity and outcomes associated with hypofractionated radiation therapy (Hypo-RT), 55Gy in 20 fractions. MATERIAL AND METHODS: We identified 40 patients who received definitive Hypo-RT for localized bladder cancer. Most patients were men (62.5%), elderly (median age 82), had high Charlson Comorbidity Index score (median 7, range 4–9) and were nonsurgical candidates (80%). Sixty-eight percent had a macroscopically complete transurethral resection of bladder tumor (TURBT) and 33 patients (82.5%) received concurrent chemotherapy. Acute (< =3mo) and late (>3mo) toxicities were assessed according to CTCAE v4.0. Survival outcomes were estimated using the Kaplan-Meier method. Median follow up after Hypo-RT was 32 months (95% CI: 28–49 months). RESULTS: Overall rates of acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were 40% each, most commonly urinary frequency and diarrhea. Two cases of acute grade 3 GU/GI toxicity occurred. Late grade 2+ toxicity occurred in 3 patients (7.5%): 2 grade 2 GU and 1 grade 3 GI. Seventy-seven percent achieved a complete response (CR). Six patients (20%) developed disease recurrence at a median time of 9.1 months. The estimated 2-year DFS and 2-year DSS rate were 59% (95% CI, 45–78%) and 78% (95% CI, 65–93%), respectively. Receipt of concurrent chemotherapy (p = 0.003) and achieving a CR (p = 0.018) were univariably associated with improved DSS. Tis component was associated with worse DSS (p = 0.015). CONCLUSION: Hypo-RT had a favorable toxicity profile and encouraging cancer control outcomes in this mostly elderly and frail patient cohort.","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135399250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electromotive Drug Administration Chemotherapy with Mitomycin C Versus Bacillus Calmette-Guerin for the Treatment of Non-Muscle Invasive Bladder Cancer.","authors":"María Teresa Melgarejo Segura, Ana Morales Martínez, Yaiza Yáñez Castillo, Miguel Ángel Arrabal Polo, Francisco Gutiérrez Tejero, Manuel Pareja Vílchez, Miguel Arrabal Martín","doi":"10.3233/BLC-230042","DOIUrl":"10.3233/BLC-230042","url":null,"abstract":"<p><strong>Background: </strong>Devices that increase the penetrance of intravesical chemotherapeutics are emerging as alternatives to classical Bacillus Calmette Guérin (BCG) treatment.</p><p><strong>Objective: </strong>To compare the efficacy of mitomycin C applied with the electromotive drug delivery device (MMC-EMDA) versus BCG in patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ (CIS).</p><p><strong>Methods: </strong>Prospective non-randomized study in which 47 patients received MMC-EMDA (40 mg of MMC diluted in 50 mg of distilled water at 20 mA for 30 min. Regimen of 6 weekly and then 6 monthly instillations) and 48 patients received BCG (50 mg of OncoCITE® diluted in 50 ml of normal saline for 60 min. Regimen of 6 weekly instillations and then 3 weekly instillations at months 3, 6 and 12). The primary endpoint was the recurrence-free rate (RFR) at 24 months. Secondary endpoints were time to recurrence and progression-free rate (PFR) at 24 months follow-up.</p><p><strong>Results: </strong>Baseline patient assessment and mean follow-up time were similar in both groups (MMC-EMDA group: 26.4 months; BCG group: 28.4 months (<i>p</i> = 0.44)). The RFR at 24 months was 80.9% for the MMC-EMDA group and 77.1% for the BCG group (<i>p</i> = 0.969). The mean time to recurrence was 12.5 months in the MMC-EMDA group and 14 months in the BCG group (<i>p</i> = 0.681). At 24 months, PFR was 97.9% in the MMC-EMDA group and 93.8% in the BCG group (<i>p</i> = 0.419).</p><p><strong>Conclusions: </strong>No differences were found between MMC-EMDA and BCG treatments in patients with high-risk and intermediate-risk NMIBC without CIS.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"1 1","pages":"159-166"},"PeriodicalIF":1.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69809971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}