The Experts below are selected from a list of 4737 Experts worldwide ranked by ideXlab platform
Joaquim Bellmunt - One of the best experts on this subject based on the ideXlab platform.
-
erdafitinib for the treatment of Metastatic Bladder Cancer
Expert Review of Clinical Pharmacology, 2020Co-Authors: Kamaneh Montazeri, Joaquim BellmuntAbstract:Introduction: Since the approval of immune checkpoint inhibitors (ICIs), there has been continuing and significant progress in urothelial Cancer (UC) treatment. However, only about one fifth of UC patients respond to ICI. Recently, erdafitinib was developed for treating locally advanced or Metastatic UC (mUC) with FGFR3 or FGFR2 alterations, accounting for 15-20% of patients. Erdafitinib is the first targeted therapy ever approved for mUC.Areas covered: This review summarizes the preclinical and clinical data on erdafitinib for UC. PubMed search and relevant articles presented at international conferences were used for the literature search.Expert opinion: The FDA approval of erdafitinib provided a new treatment option for FGFR-altered UC progressing on platinum-based chemotherapy. It is not clear whether FGFR inhibitor is a preferred second-line treatment choice to ICI. Compared to ICI, erdafitinib has a better response rate in patients with visceral metastases. However, a shorter duration of response and toxicity profile of erdafitinib, particularly ocular toxicity, is an important consideration. Regular eye exams are recommended by the FDA. Tumor profiling during upfront therapy may help identify those who benefit at the time of progression. In summary, a high unmet need remains for new drugs in chemotherapy- and ICI-refractory UC.
-
management of Metastatic Bladder Cancer
Cancer Treatment Reviews, 2019Co-Authors: Rosa Nadal, Joaquim BellmuntAbstract:Important advances in the understanding of the biology and mechanisms of tumor progression of urothelial carcinoma (UC) have been achieved over the past decade. The treatment landscape for advanced-stage, unresectable or Metastatic UC has shifted dramatically over a short period of time, with 6 new therapeutic agents available for clinical use. The use of traditional chemotherapy and new immune checkpoints inhibitors (ICIs) directed at programmed cell-death protein 1 (PD-1) or its ligand has led to unprecedented survival benefits in selected patients with Metastatic UC. Data show that anti-PD-1 ICIs are not only improving long-term clinical benefit, but also quality of life for patients in the second-line setting. In the front-line setting, regulatory agencies have restricted the indications of atezolizumab and pembrolizumab (both ICIs) to patients with PD-L1positivity with advanced UC and who are platinum-ineligible. Very recently, erdafitinib, a pan-FGFR inhibitor, has been granted accelerated approval by FDA for platinum-pretreated advanced Metastatic UC with susceptible FGFR3 or FGFR2 genetic alterations. Enfortumab vedotin, an antibody-drug conjugate, have been granted breakthrough designation by the FDA for the treatment of Metastatic UC. Here we review the clinical trial data that have established standard-of-care treatment for advanced-stage UC. In addition, mechanisms of resistance and biomarkers of response to platinum-based chemotherapies and immunotherapies are also discussed, along with the clinical benefits and limitations of these therapies.
-
maintenance vinflunine post cisplatin chemotherapy ct in patients with advanced urothelial carcinoma uc preliminary analysis of a randomized placebo controlled phase ii trial maja trial sogug 2011 02
Journal of Clinical Oncology, 2015Co-Authors: Joaquim Bellmunt, Begona Perez Valderrama, Albert Font, Juan Antonio Virizuela, Miguel Angel Climent, Susana Hernando Polo, Begona Mellado, Nuria Lainez, Aranzazu Gonzalez Del Alba, Jose Angel ArranzAbstract:4529 Background: Vinflunine (VFL) is a microtubule inhibitor approved by EMA as treatment after platinum progression, in Metastatic Bladder Cancer. We evaluated whether maintenance VFL delays progression after response to CT. Methods: Patients (pts) with measurable disease, locally recurrent/Metastatic UC and adequate organ function with radiological response or stabilization after 4-6 cy of a cisplatin/gemcitabine chemotherapy (carboplatin allowed after cy 4) were randomized 1:1 to receive VFL 320 mg/m2 or 280mg/m2(in case of PS 1, age ≥ 75 years, prior pelvic radiotherapy or CrCl < 60ml/min) every 21 days vs best supportive care (BSC), until disease progression. The primary endpoint was progression free survival (PFS). With a median PFS considered unacceptable for the experimental arm 4 months (p0) and a very acceptable 6.5 (p1). 39 eligible pts per treatment arm were required to select better therapy with a type I error of 0.05 (α, one-tailed test), and a type II 0.1 (β) error. Results: 88 patients fro...
-
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in Metastatic Bladder Cancer
Nature, 2014Co-Authors: Tom Powles, Gregg D. Fine, Fadi S. Braiteh, Joaquim Bellmunt, Yohann Loriot, Joseph Paul Eder, Daniel P Petrylak, Howard A Burris, Cristina Cruz, Siew Leng TengAbstract:There have been no major advances for the treatment of Metastatic urothelial Bladder Cancer (UBC) in the last 30 years. Chemotherapy is still the standard of care. Patient outcomes, especially for those in whom chemotherapy is not effective or is poorly tolerated, remain poor. One hallmark of UBC is the presence of high rates of somatic mutations. These alterations may enhance the ability of the host immune system to recognize tumour cells as foreign owing to an increased number of antigens. However, these Cancers may also elude immune surveillance and eradication through the expression of programmed death-ligand 1 (PD-L1; also called CD274 or B7-H1) in the tumour microenvironment. Therefore, we examined the anti-PD-L1 antibody MPDL3280A, a systemic Cancer immunotherapy, for the treatment of Metastatic UBC. MPDL3280A is a high-affinity engineered human anti-PD-L1 monoclonal immunoglobulin-G1 antibody that inhibits the interaction of PD-L1 with PD-1 (PDCD1) and B7.1 (CD80). Because PD-L1 is expressed on activated T cells, MPDL3280A was engineered with a modification in the Fc domain that eliminates antibody-dependent cellular cytotoxicity at clinically relevant doses to prevent the depletion of T cells expressing PD-L1. Here we show that MPDL3280A has noteworthy activity in Metastatic UBC. Responses were often rapid, with many occurring at the time of the first response assessment (6 weeks) and nearly all were ongoing at the data cutoff. This phase I expansion study, with an adaptive design that allowed for biomarker-positive enriched cohorts, demonstrated that tumours expressing PD-L1-positive tumour-infiltrating immune cells had particularly high response rates. Moreover, owing to the favourable toxicity profile, including a lack of renal toxicity, patients with UBC, who are often older and have a higher incidence of renal impairment, may be better able to tolerate MPDL3280A versus chemotherapy. These results suggest that MPDL3280A may have an important role in treating UBC-the drug received breakthrough designation status by the US Food and Drug Administration (FDA) in June 2014.
-
icud eau international consultation on Bladder Cancer 2012 chemotherapy for urothelial carcinoma neoadjuvant and adjuvant settings
European Urology, 2013Co-Authors: Cora N Sternberg, Joaquim Bellmunt, Matthew I Milowsky, Dean F Bajorin, Guru Sonpavde, Arlene O Siefkerradtke, Walter M Stadler, Robert Dreicer, Daniel J George, Dan TheodorescuAbstract:Abstract Context We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of Bladder Cancer using an evidence-based strategy. Objective To review the data regarding chemotherapy in patients with clinically localized and Metastatic Bladder Cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. Evidence acquisition Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: Bladder Cancer, urothelial Cancer, Metastatic, advanced, neoadjuvant , and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included. Evidence synthesis The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed. Conclusions Cisplatin-based combination chemotherapy for advanced and Metastatic Bladder Cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.
Dan Theodorescu - One of the best experts on this subject based on the ideXlab platform.
-
icud eau international consultation on Bladder Cancer 2012 chemotherapy for urothelial carcinoma neoadjuvant and adjuvant settings
European Urology, 2013Co-Authors: Cora N Sternberg, Joaquim Bellmunt, Matthew I Milowsky, Dean F Bajorin, Guru Sonpavde, Arlene O Siefkerradtke, Walter M Stadler, Robert Dreicer, Daniel J George, Dan TheodorescuAbstract:Abstract Context We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of Bladder Cancer using an evidence-based strategy. Objective To review the data regarding chemotherapy in patients with clinically localized and Metastatic Bladder Cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. Evidence acquisition Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: Bladder Cancer, urothelial Cancer, Metastatic, advanced, neoadjuvant , and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included. Evidence synthesis The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed. Conclusions Cisplatin-based combination chemotherapy for advanced and Metastatic Bladder Cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.
-
icud eau international consultation on Bladder Cancer 2012 chemotherapy for urothelial carcinoma neoadjuvant and adjuvant settings
European Urology, 2013Co-Authors: Cora N Sternberg, Joaquim Bellmunt, Matthew I Milowsky, Dean F Bajorin, Guru Sonpavde, Arlene O Siefkerradtke, Walter M Stadler, Robert Dreicer, Daniel J George, Dan TheodorescuAbstract:Abstract Context We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of Bladder Cancer using an evidence-based strategy. Objective To review the data regarding chemotherapy in patients with clinically localized and Metastatic Bladder Cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. Evidence acquisition Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: Bladder Cancer, urothelial Cancer, Metastatic, advanced, neoadjuvant , and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included. Evidence synthesis The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed. Conclusions Cisplatin-based combination chemotherapy for advanced and Metastatic Bladder Cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.
-
profiling the evolution of human Metastatic Bladder Cancer
Cancer Research, 2004Co-Authors: Brian Nicholson, Henry F Frierson, Mark R Conaway, Jabed M Seraj, Michael A Harding, Garret M Hampton, Dan TheodorescuAbstract:Pulmonary metastases frequently develop in patients with aggressive Bladder Cancer, yet investigation of this process at the molecular level suffers from the poor availability of human Metastatic tumor tissue and the absence of suitable animal models. To address this, we developed progressively more Metastatic human Bladder Cancer cell lines and an in vivo Bladder-Cancer lung-metastasis model, and we successfully used these to identify genes of which the expression levels change according to the degree of pulmonary Metastatic potential. By initially intravenously injecting the poorly Metastatic T24T human urothelial Cancer cells into nude mice, and then serially reintroducing and reisolating the human tumor cells from the resultant mouse lung tumors, three derivative human lines with increasingly Metastatic phenotypes, designated FL1, FL2, and FL3, were sequentially isolated. To identify the genes associated with the most lung-Metastatic phenotype, the RNA complement from the parental and derivative cells was evaluated with oligonucleotide microarrays. In doing so, we found 121 genes to be progressively up-regulated during the transition from T24T to FL3, whereas 43 genes were progressively down-regulated. As expected, many of the genes identified in these groups could, according to the ascribed functions of their protein product, theoretically participate in tissue invasion and metastasis. In addition, the magnitude of gene expression changes observed during the Metastatic transition correlated with the in vivo propensity for earlier lung colonization and decreased host survival. To additionally define which genes found in the experimental system were of relevance to human Bladder Cancer lung metastasis, we evaluated gene expression profiles of 23 primary human Bladder tumors of various stages and grades, and then we compared these gene expression profiles to the altered profiles in our model cell lines. Here we found that the expression of epiregulin, urokinase-type plasminogen activator (uPA), matrix metalloproteinase (MMP)14, and tissue inhibitor of metalloproteinase (TIMP-2) were consistently and progressively up-regulated when viewed as a function of tumor stage in tissues of patients versus the Metastatic potential seen in the mouse lung model. The strong correlation of these four markers between the experimental and clinical situations helps validate this system as a useful tool for the study of lung metastasis and defines targets of therapy that may reduce the incidence of this process in patients.
Matthew I Milowsky - One of the best experts on this subject based on the ideXlab platform.
-
siu icud recommendations on Bladder Cancer systemic therapy for Metastatic Bladder Cancer
World Journal of Urology, 2019Co-Authors: Axel S Merseburger, Daniel P Petrylak, Matthew I Milowsky, Andrea B Apolo, Simon Chowdhury, Noah M Hahn, Matthew D Galsky, Thomas Powles, David I Quinn, Jonathan E. RosenbergAbstract:The SIU (Societe Internationale d’Urologie)–ICUD (International Consultation on Urologic Diseases) working group on systemic therapy for Metastatic Bladder Cancer has summarized the most recent findings on the aforementioned topic and came to conclusions and recommendations according to the evidence published. In Europe and the United States, treatment for Metastatic UC has changed a great deal recently, mainly involving a move from chemotherapy to immune checkpoint blockers. This is particularly true in platinum-refractory disease, where supportive randomized data exist. Five checkpoint blockers have been approved in this setting by the FDA: avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab. Nivolumab, pembrolizumab, and atezolizumab have been approved in Europe.
-
guideline on muscle invasive and Metastatic Bladder Cancer european association of urology guideline american society of clinical oncology clinical practice guideline endorsement
Journal of Clinical Oncology, 2016Co-Authors: Matthew I Milowsky, Bryan R Rumble, Christopher M Booth, Timothy D Gilligan, Libni J Eapen, Ralph J Hauke, Pat BoumansourAbstract:PurposeTo endorse the European Association of Urology guideline on muscle-invasive (MIBC) and Metastatic Bladder Cancer. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations.MethodsThe guideline on MIBC and Metastatic Bladder Cancer was reviewed for developmental rigor by methodologists. The ASCO Endorsement Panel then reviewed the content and recommendations.ResultsThe ASCO Endorsement Panel determined that the recommendations from the European Association of Urology guideline on MIBC and Metastatic Bladder Cancer, published online in March 2015, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorses the guideline on MIBC and Metastatic Bladder Cancer and has added qualifying statements, including highlighting the use of chemoradiotherapy for select patients with MIBC and recommending a preference for clinical trials in the treatment of met...
-
icud eau international consultation on Bladder Cancer 2012 chemotherapy for urothelial carcinoma neoadjuvant and adjuvant settings
European Urology, 2013Co-Authors: Cora N Sternberg, Joaquim Bellmunt, Matthew I Milowsky, Dean F Bajorin, Guru Sonpavde, Arlene O Siefkerradtke, Walter M Stadler, Robert Dreicer, Daniel J George, Dan TheodorescuAbstract:Abstract Context We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of Bladder Cancer using an evidence-based strategy. Objective To review the data regarding chemotherapy in patients with clinically localized and Metastatic Bladder Cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. Evidence acquisition Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: Bladder Cancer, urothelial Cancer, Metastatic, advanced, neoadjuvant , and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included. Evidence synthesis The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed. Conclusions Cisplatin-based combination chemotherapy for advanced and Metastatic Bladder Cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.
-
icud eau international consultation on Bladder Cancer 2012 chemotherapy for urothelial carcinoma neoadjuvant and adjuvant settings
European Urology, 2013Co-Authors: Cora N Sternberg, Joaquim Bellmunt, Matthew I Milowsky, Dean F Bajorin, Guru Sonpavde, Arlene O Siefkerradtke, Walter M Stadler, Robert Dreicer, Daniel J George, Dan TheodorescuAbstract:Abstract Context We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of Bladder Cancer using an evidence-based strategy. Objective To review the data regarding chemotherapy in patients with clinically localized and Metastatic Bladder Cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. Evidence acquisition Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: Bladder Cancer, urothelial Cancer, Metastatic, advanced, neoadjuvant , and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included. Evidence synthesis The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed. Conclusions Cisplatin-based combination chemotherapy for advanced and Metastatic Bladder Cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.
-
genome sequencing identifies a basis for everolimus sensitivity
Science, 2012Co-Authors: Matthew I Milowsky, Gopa Iyer, Aphrothiti J Hanrahan, Hikmat Alahmadie, Sasinya N Scott, Manickam Janakiraman, Mono Pirun, Chris SanderAbstract:Cancer drugs often induce dramatic responses in a small minority of patients. We used whole-genome sequencing to investigate the genetic basis of a durable remission of Metastatic Bladder Cancer in a patient treated with everolimus, a drug that inhibits the mTOR (mammalian target of rapamycin) signaling pathway. Among the somatic mutations was a loss-of-function mutation in TSC1 (tuberous sclerosis complex 1), a regulator of mTOR pathway activation. Targeted sequencing revealed TSC1 mutations in about 8% of 109 additional Bladder Cancers examined, and TSC1 mutation correlated with everolimus sensitivity. These results demonstrate the feasibility of using whole-genome sequencing in the clinical setting to identify previously occult biomarkers of drug sensitivity that can aid in the identification of patients most likely to respond to targeted antiCancer drugs.
Alfred J Witjes - One of the best experts on this subject based on the ideXlab platform.
-
updated 2016 eau guidelines on muscle invasive and Metastatic Bladder Cancer
European Urology, 2017Co-Authors: Alfred J Witjes, Eva Comperat, Nigel C Cowan, Maria De Santis, Thierry Lebret, Harman Maxim Bruins, V Hernandez, Estefania Linares Espinos, James Dunn, Mathieu RouanneAbstract:Abstract Context Invasive Bladder Cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. Objective To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and Metastatic Bladder Cancer. Evidence acquisition An international multidisciplinary panel of Bladder Cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. Evidence synthesis Epidemiology and aetiology of Bladder Cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including Bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. Conclusions The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with Metastatic and muscle-invasive Bladder Cancer. Patient summary Bladder Cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with Metastatic and muscle-invasive Bladder Cancer.
-
eau guidelines on muscle invasive and Metastatic Bladder Cancer summary of the 2013 guidelines
European Urology, 2014Co-Authors: Alfred J Witjes, Eva Comperat, Nigel C Cowan, Maria De Santis, Georgios Gakis, Thierry Lebret, M J Ribal, Antoine G Van Der Heijden, Amir SherifAbstract:CONTEXT: The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic Bladder Cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis o ...
-
eau guidelines on muscle invasive and Metastatic Bladder Cancer summary of the 2013 guidelines
European Urology, 2014Co-Authors: Alfred J Witjes, Eva Comperat, Nigel C Cowan, Maria De Santis, Georgios Gakis, Thierry Lebret, M J Ribal, Antoine G Van Der Heijden, Amir SherifAbstract:CONTEXT: The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic Bladder Cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis of the 2013 guidelines document, with emphasis on the latest developments. OBJECTIVE: To provide graded recommendations on the diagnosis and treatment of patients with muscle-invasive BCa (MIBC), linked to a level of evidence. EVIDENCE ACQUISITION: For each section of the guidelines, comprehensive literature searches covering the past 10 yr in several databases were conducted, scanned, reviewed, and discussed both within the panel and with external experts. The final results are reflected in the recommendations provided. EVIDENCE SYNTHESIS: Smoking and work-related carcinogens remain the most important risk factors for BCa. Computed tomography (CT) and magnetic resonance imaging can be used for staging, although CT is preferred for pulmonary evaluation. Open radical cystectomy with an extended lymph node dissection (LND) remains the treatment of choice for treatment failures in non-MIBC and T2-T4aN0M0 BCa. For well-informed, well-selected, and compliant patients, however, multimodality treatment could be offered as an alternative, especially if cystectomy is not an option. Comorbidity, not age, should be used when deciding on radical cystectomy. Patients should be encouraged to actively participate in the decision-making process, and a continent urinary diversion should be offered to all patients unless there are specific contraindications. For fit patients, cisplatinum-based neoadjuvant chemotherapy should always be discussed, since it improves overall survival. For patients with Metastatic disease, cisplatin-containing combination chemotherapy is recommended. For unfit patients, carboplatin combination chemotherapy or single agents can be used. CONCLUSIONS: This 2013 EAU Muscle-invasive and Metastatic BCa guidelines updated summary aims to increase the quality of care and outcome for patients with muscle-invasive or Metastatic BCa. PATIENT SUMMARY: In this paper we update the EAU guidelines on Muscle-invasive and Metastatic Bladder Cancer. We recommend that chemotherapy be administered before radical treatment and that Bladder removal be the standard of care for disease confined to the Bladder.
-
treatment of muscle invasive and Metastatic Bladder Cancer update of the eau guidelines
European Urology, 2011Co-Authors: Arnulf Stenzl, Nigel C Cowan, Maria De Santis, M J Ribal, Amir Sherif, Axel S Merseburger, Marcus A Kuczyk, Alfred J WitjesAbstract:Context: New data regarding treatment of muscle-invasive and Metastatic Bladder Cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. Objective: To review the new EAU guidelines for MiM-BC with a specific focus on treatment. Evidence acquisition: New literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Evidence synthesis: Current data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic Bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality Bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In Metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available. Conclusions: In the treatment of localised invasive Bladder Cancer (BCa), the standard treatment remains radical surgical removal of the Bladder within standard limits, including as-yet-unspecified regional lymph nodes. However, the addition of neoadjuvant chemotherapy must be considered for certain specific patient groups. A new drug for second-line chemotherapy (vinflunine) in Metastatic disease has been approved and is recommended.
-
the updated eau guidelines on muscle invasive and Metastatic Bladder Cancer
European Urology, 2009Co-Authors: Arnulf Stenzl, Nigel C Cowan, Maria De Santis, M J Ribal, Amir Sherif, Axel S Merseburger, Gerhard Jakse, Marcus A Kuczyk, Alfred J WitjesAbstract:CONTEXT: New data regarding diagnosis and treatment of muscle-invasive and Metastatic Bladder Cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC. EVIDENCE ACQUISITION: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS: The diagnosis of muscle-invasive Bladder Cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic Bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality Bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on (1) natural timing of recurrence, (2) probability of disease recurrence, (3) functional deterioration at particular sites, and (4) consideration of treatment of a recurrence. In Metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. CONCLUSIONS: These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.
Dean F Bajorin - One of the best experts on this subject based on the ideXlab platform.
-
first line treatment and prognostic factors of Metastatic Bladder Cancer for platinum eligible patients
Hematology-oncology Clinics of North America, 2015Co-Authors: Wassim Abida, Dean F Bajorin, Jonathan E. RosenbergAbstract:Metastatic urothelial carcinoma is primarily a disease of the elderly, with a median overall survival of approximately 15 months. Cisplatin-based combination chemotherapy is standard first-line treatment for eligible patients, with carboplatin-based regimens used as an alternative for patients considered unfit to receive cisplatin. Prognostic models incorporating clinical risk factors have been validated, and molecular characteristics that predict for treatment response are under investigation. This review summarizes the current status of first-line treatment of Metastatic urothelial carcinoma in platinum-eligible patients as well as prognostic and predictive models in this disease.
-
icud eau international consultation on Bladder Cancer 2012 chemotherapy for urothelial carcinoma neoadjuvant and adjuvant settings
European Urology, 2013Co-Authors: Cora N Sternberg, Joaquim Bellmunt, Matthew I Milowsky, Dean F Bajorin, Guru Sonpavde, Arlene O Siefkerradtke, Walter M Stadler, Robert Dreicer, Daniel J George, Dan TheodorescuAbstract:Abstract Context We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of Bladder Cancer using an evidence-based strategy. Objective To review the data regarding chemotherapy in patients with clinically localized and Metastatic Bladder Cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. Evidence acquisition Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: Bladder Cancer, urothelial Cancer, Metastatic, advanced, neoadjuvant , and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included. Evidence synthesis The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed. Conclusions Cisplatin-based combination chemotherapy for advanced and Metastatic Bladder Cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.
-
icud eau international consultation on Bladder Cancer 2012 chemotherapy for urothelial carcinoma neoadjuvant and adjuvant settings
European Urology, 2013Co-Authors: Cora N Sternberg, Joaquim Bellmunt, Matthew I Milowsky, Dean F Bajorin, Guru Sonpavde, Arlene O Siefkerradtke, Walter M Stadler, Robert Dreicer, Daniel J George, Dan TheodorescuAbstract:Abstract Context We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of Bladder Cancer using an evidence-based strategy. Objective To review the data regarding chemotherapy in patients with clinically localized and Metastatic Bladder Cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. Evidence acquisition Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: Bladder Cancer, urothelial Cancer, Metastatic, advanced, neoadjuvant , and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included. Evidence synthesis The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed. Conclusions Cisplatin-based combination chemotherapy for advanced and Metastatic Bladder Cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.
-
post chemotherapy surgery in patients with unresectable or regionally Metastatic Bladder Cancer
The Journal of Urology, 2001Co-Authors: Harry W Herr, Machele S Donat, Dean F BajorinAbstract:Purpose: We update our experience with post-chemotherapy surgery in patients with unresectable or lymph node positive Bladder Cancer.Methods: Of 207 patients with unresectable or regionally Metastatic Bladder Cancer 80 (39%) underwent post-chemotherapy surgery after treatment with a cisplatin based chemotherapy regimen. We assessed the impact of surgery on achieving a complete response to chemotherapy and on relapse-free survival.Results: No viable Cancer was present at post-chemotherapy surgery in 24 of the 80 cases (30%), pathologically confirming a complete response to chemotherapy. Of the 24 patients 14 (58%) survived 9 months to 5 years. Residual viable Cancer was completely resected in 49 patients (61%), resulting in a complete response to chemotherapy plus surgery, and 20 (41%) survived. Post-chemotherapy surgery did not benefit those who failed to achieve a major complete or partial response to chemotherapy. Only 1 of the 12 patients (8%) who refused surgery remains alive.Conclusions: Post-chemoth...