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San Francisco, CA USA (UroToday.com) FDA Update: The FDA is restricting the use of Keytruda and Tecentriq for patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing therapy.
This results from decreased survival associated with the use of Keytruda (pembrolizumab) or Tecentriq (atezolizumab) as single therapy (monotherapy) compared to platinum-based chemotherapy in clinical trials to treat patients with metastatic urothelial cancer who have not received prior therapy and who have low expression of the protein programmed death ligand 1 (PD-L1).
Published June 22, 2018
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TRUCKEE, CA (UroToday.com) The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for erdafitinib in the treatment of urothelial cancer. Urothelial cancer, most frequently in the bladder, is the sixth most common type of cancer in the U.S. A Breakthrough Therapy Designation is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition. The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.
Published March 16, 2018
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Treatment of patients with non-muscle invasive bladder cancer (NMIBC) who are unable to receive intravesical with Bacillus Calmette Guerin (BCG) remains a challenge.
Published September 10, 2020
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Non-muscle invasive bladder cancer (NMIBC) will account for 75% of the 79,000 new cases of bladder cancer expected to be diagnosed in 2017. Fortunately, most cases can be successfully treated and carry a relatively good prognosis. However, depending on the grade and stage at initial diagnosis, as many as 60% of patients with NMIBC can experience orthotopic tumor recurrence within the first year after initial resection and up to 78% can recur within five years.
Published April 20, 2017
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Objective: To investigate the clinical manifestation, diagnosis, treatment and outcome of simultaneous occurrence of renal cell carcinoma and urothelial carcinoma. Methods: Twenty-four consecutive patients with synchronous renal cell carcinoma and urothelial carcinoma treated in our center from March 2005 to December 2015 were retrospectively reviewed.
Published April 4, 2017
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There is good quality evidence that instillation of a chemotherapeutic agent such as mitomycin into the bladder within twenty-four hours of an initial transurethral bladder tumour resection reduces the rate of recurrences and prolongs recurrence-free intervals in patients with non-muscle invasive bladder cancer. Most guideline panels recommend this practice. However, despite this evidence and recommendations, there is considerable disparity in the actual use of intravesical chemotherapy amongst urologists. The reasons are manifold and include lack of awareness of the benefits, non-availability of the drug, delay in procurement from pharmacies, fear of side effects and complications, reimbursement issues and wariness of deep resections leading to extravasation.
Published April 16, 2018
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Radical cystectomy and Trimodality therapy, which combines transurethral resection of the bladder tumor (TURBT) and concurrent chemoradiation, are effective treatments for muscle-invasive bladder cancer (MIBC). A recent study investigated the outcomes of patients with MIBC who were eligible for both treatment options.
Published August 14, 2023
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Molecular subtyping of muscle-invasive bladder cancer (MIBC) tumors has the potential to guide treatment decisions and predict outcomes. However, RNA sequencing is costly and not readily available. Artificial intelligence has made its way into various clinical procedures, and recent studies have validated the use of deep learning models in the analysis of patient data for enhanced clinical management. In this study, Jiang et al. developed a deep learning model that determined subtypes based on whole slide images (stained with hematoxylin and eosin) from bladder cancer patient tumors.
Published December 8, 2022
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DNA methylation is known to be altered in many cancers, including bladder cancer, and has therefore been a promising alternative for surveillance in patients with non-muscle invasive bladder cancer (NMIBC). The Bladder EpiCheck test has been validated for detecting bladder cancer by evaluating 15 genomic biomarkers to yield a score from 0 to 100.
Published November 7, 2022
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Recent years have seen an explosive rate of transformative advances in both pre-clinical and clinical urothelial carcinoma research. With the public dissemination of comprehensive molecular data from The Cancer Genome Atlas (TCGA) urothelial carcinoma cohort, the global urothelial carcinoma research community now has the initial road map of the key biological themes that drive carcinogenesis, growth, invasion, and metastasis.1
- Written by:
Noah M. Hahn, MD
- References:
- Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507:315-22, 2014
- Bellmunt J, de Wit R, Vaughn DJ, et al: Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 376:1015-1026, 2017
- Patel MR, Ellerton J, Infante JR, et al: Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 19:51-64, 2018
- Powles T, O'Donnell PH, Massard C, et al: Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: Updated results from a phase 1/2 open-label study. JAMA Oncology 3:e172411, 2017
- Rosenberg JE, Hoffman-Censits J, Powles T, et al: Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. The Lancet 387:1909-1920, 2016
- Sharma P, Retz M, Siefker-Radtke A, et al: Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. The Lancet Oncology 18:312-322, 2017
- Rosenberg JE, Sridhar SS, Zhang J, et al: Updated results from the enfortumab vedotin phase 1 (EV-101) study in patients with metastatic urothelial cancer (mUC). Journal of Clinical Oncology 36:4504-4504, 2018
- Siefker-Radtke AO, Necchi A, Park SH, et al: First results from the primary analysis population of the phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRalt). J Clin Oncol 36, 2018
Published July 12, 2019
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There is a need for accurate nomograms for predicting oncological outcomes in intermediate-risk non–muscle-invasive bladder cancer (NMIBC) patients. Such accurate tools can be used to guide decision making for appropriate adjuvant therapy.
Published August 10, 2020
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Resistance to platinum-based chemotherapy is a significant concern in patients undergoing treatment for bladder cancer. A recent study, Jones et al. investigated the mechanisms driving chemoresistance, with the goal of discovering potential targets to improve treatment response.
Published May 29, 2024
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Enfortumab Vedotin (EV) is a novel antibody-drug conjugate targeting Nectin-4, which is overexpressed in urothelial cancer. A recent study published by Takahashi et al. in Investigational New Drugs studied EV in locally advanced/metastatic urothelial cancer in a phase I study (NCT03070990).1
Published January 6, 2020
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Patients with intermediate-risk non-muscle invasive bladder cancer (NMIBC) frequently require adjuvant therapy. The HIVEC-II study is a multi-center randomized controlled trial (RCT) that compared clinical outcomes of intermediate-risk NMIBC patients receiving hyperthermia and mitomycin C versus mitomycin C alone.
Published November 18, 2022
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Non-muscle-invasive bladder cancers (NMIBC) represent a heterogeneous group of tumors with variable clinical outcomes. Multiple risk features are incorporated in predicting the risk of recurrence and progression to muscle-invasive bladder cancer (MIBC). Intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) and chemotherapy are both considered adjuvant treatment options. However, it is challenging to define the optimum adjuvant therapy, particularly in intermediate-risk NMIBC cases. Considering the current BCG shortage, the risk-stratification tool for intermediate-risk patients is essential.
Published August 26, 2021
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Artificial intelligence (AI) models are emerging are powerful tools for the diagnosis and risk stratification of several cancers but have not been widely adopted in clinical practice. To evaluate barriers to AI integration and facilitate evaluation of new models for clinical adoption in the context of non-muscle invasive bladder cancer (NMIBC), Kwong et al. developed APPRAISE-AI, a quantitative tool for assessing the quality of AI studies in this field.
Published June 13, 2024
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Microscopic hematuria is one of the earliest clinical signs of urothelial carcinoma (UC), yet many patients do not undergo cystoscopic evaluation, thus delaying diagnosis. However, because the rate of UC in low-risk patients is 0.8%, cystoscopy is unsuitable as a screening tool. Accordingly, there has been interest in developing an accurate, safe, non-invasive urinary biomarker. A recently developed biomarker is Cxbladder Triage (CxbT), which combines the mRNA expression of five genes and four clinical questions to generate a risk score for UC. Lotan et al. recently evaluated the use of CxbT in determining whether cystoscopy was needed in lower-risk patients referred for microhematuria.
Published July 25, 2024
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Early identification of bladder cancer (BC) is critical for improving clinical outcomes. Developing urine-based molecular biomarkers is an area of active research. A recent study published in Urologic Oncology: Seminars and Original Investigations described a urine-based methylation analysis of TWIST1, NID2, RUNX3, GATA4, and FOXE1 in urinary cell pellet DNA as a biomarker.
Published June 23, 2020
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Cisplatin is frequently used in neoadjuvant, adjuvant, and systemic therapy for advanced bladder cancer. A recent study by Fu et al. characterized the effects of cisplatin on cGAS-STING activation in bladder cancer. Cisplatin treatment of the T24 bladder cancer cell lines followed by RNA sequencing showed downstream enrichment of cGAS-STING signaling with higher transcription levels of NF-KB- and IRF3-related genes. Several bladder cancer cell lines in the CLE dataset had high expression levels of cGAS. In addition, markers of canonical STING activation, including the phosphorylated STING (Ser366), TBK (Ser173), and IRF3 (Ser396), were induced by cisplatin.
Published October 19, 2022
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Neoadjuvant chemotherapy is a standard of care for patients with cisplatin-eligible muscle-invasive urothelial carcinoma. For patients who do not receive neoadjuvant chemotherapy, there is evidence of a benefit associated with cisplatin-based adjuvant chemotherapy after radical cystectomy for patients with pT3/T4 and/or pN+ bladder cancer. It is unknown whether additional adjuvant chemotherapy is beneficial for patients with adverse pathological features after neoadjuvant chemotherapy and radical cystectomy.
Published September 2, 2017
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The role of adjuvant therapy in muscle-invasive urothelial carcinoma is unclear, despite the high risk of metastatic recurrence. Adjuvant cisplatin-based chemotherapy is challenging to administer, and some patients are ineligible for or decline neoadjuvant cisplatin-based chemotherapy. Therefore, ongoing trials are designed to evaluate the efficacy of adjuvant immunotherapy.
Published February 7, 2022
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Our knowledge of the role of the gut microbiome has evolved in recent years. However, less is known about the urinary microbiome. Changes in urinary microbiota have been reported in cases of urinary incontinence, pelvic pain, and bladder cancers. However, studies have produced mixed findings on whether bladder cancer is associated with an increase or decrease in the diversity of urinary microbiota. Recently, Hrbáček et al. aimed to investigate urinary microbiota changes in males with bladder cancer.
Published January 30, 2023
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Risk factors associated with bladder cancer, such as smoking, age, and BMI, can alter metabolic profiles and can be evaluated in patients through metabolomic analysis. Recently, Jacyna et al. collected urine from ten patients (eight men and two women) with non-muscle-invasive bladder cancer at three different time points: before trans-urethral resection of bladder tumor (TURBT), the day after TURBT, and at a follow-up visit two weeks later. These samples were analyzed using high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF/MS) and gas chromatography with triple quadrupole mass spectrometry (GCQqQ/MS).
Published April 5, 2022
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The immune checkpoint inhibitor (ICI) pembrolizumab is approved for the treatment of solid tumors with a high tumor mutational burden (TMB-high ≥ 10 variants/Mb). However, measurements of TMB as a biomarker for ICI response are mainly based on studies in European populations. A recent study by Nassar et al. investigated the interplay between genetic ancestry, TMB, and tumor-only versus tumor-normal paired sequencing of solid tumors.
Published October 13, 2022
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Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm in muscle-invasive bladder cancer (MIBC). However, not all patients have consistent responses to these agents, and predictive biomarkers are still needed. Antibiotic (AB) use can potentially decrease the efficacy of ICIs in advanced stage MIBC by altering the microbiome and the antitumor immune response. This detrimental effect of AB use was not evaluated in the neoadjuvant setting.
Published December 16, 2021
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Carcinogenic agents may act by inducing genetic mutations that contribute to bladder cancer development. The most commonly mutated genes in non-muscle invasive bladder cancer (NMIBC) are FGFR3 and PIK3CA, occurring in 65% and 25% of tumors, respectively. The most common mutations in muscle-invasive bladder cancer (MIBC) are in tumor suppressor genes. Rao et al. hypothesized that recurrent mutations in these genes could be caused by environmental risk factors such as smoking and sought to determine the link between these two variables.
Published January 16, 2024
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AT-rich interactive domain-containing protein 1A Arid1a, also known as Baf250a, is the largest subunit of the SWI/SNF or BAF chromatin remodeling ATPase complex. Somatic mutations in ARID1A are common in patients with urothelial bladder carcinomas. Recently, Guo et al. set out to elucidate the function of Arid1ain bladder urothelial cells.
Published April 26, 2022
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(UroToday.com) Advanced urothelial carcinoma resulted in over 200,000 deaths across the world in 2018. Though the majority of patients eligible for such therapy respond to platinum-based chemotherapy, disease progression occurs relatively quickly and a half or less of patients receive second-line treatment. Though PD-L1/PD-1 immune checkpoint blockade (ICB) agents are standard 2nd-line therapy for disease progression after platinum, not all patients receive this therapy and only a minority of patients have a durable clinical benefit. Avelumab, an antibody against PD-L1, is approved in the second-line post-platinum treatment setting.
Published May 31, 2020
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(UroToday.com) Patients with nonmuscle-invasive bladder cancer are at high risk of recurrence and progression. In particular, patients with high-grade disease and those with carcinoma in situ are at notably elevated risk. As a result, both the European Association of Urology and the American Urological Association/Society of Urologic Oncology guidelines on nonmuscle-invasive bladder cancer recommend adjuvant treatment, typically with intravesical Bacillus Calmette-Guérin (BCG), in a risk-adapted fashion for these patients. While the use of BCG is well established and guideline-recommended, many patients either fail to initially respond or fail to maintain response to this approach. Treatment options for patients with BCG unresponsive or refractory disease are much less clear but include radical cystectomy, further intravesical therapy including intravesical chemotherapy, systemic therapy, and clinical trials.
Published May 30, 2020
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(UroToday.com) BCG therapy in non-muscle invasive bladder cancer induces cytokine release that activates NK and T immune cells and results in bladder cancer cell killing and immune memory against further tumor growth. It has been hypothesized that the IL-15 superagonist N-803 could boost the immune response to BCG, thus augmenting patient responses to BCG therapy and limit the need for cystectomy in this disease context.
Published June 4, 2022
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(UroToday.com) High-risk non-muscle invasive bladder cancers (HR-NMIBC) that are unresectable by transurethral resection or refractory to BCG treatment are managed with radical cystectomy. The Keynote-057 study1 established the safety and efficacy of pembrolizumab in the BCG-refractory HR-NMIBC setting with 41% complete response rate. In this presentation, Dr. An presented results from the TRUCE-02 study (NCT04730232) testing the combination of chemotherapy (nab-paclitaxel) with the anti-PD-1 antibody tislelizumab in HR-NMIBC.
Published June 4, 2022
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(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on optimizing treatment for your patient with urothelial cancer, and a presentation by Dr. Brent Rose discussing bladder sparing treatment strategies for localized urothelial cancer. Organ preservation is common in many other cancers, including laryngeal cancer, anal cancer, and rectal cancer.
Published May 31, 2024
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(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on bladder cancer, and a presentation by Dr. Roger Li discussing the final results of CORE-001, a phase-2, single arm study of cretostimogene grenadenorepvec in combination with pembrolizumab in patients with BCG-unresponsive, non-muscle invasive bladder cancer with CIS. Cretostimogene grenadenorepvec is a type-5 oncolytic adenovirus designed to selectively replicate in bladder cancer cells with alterations in the retinoblastoma pathway. Additionally, the virus is engineered to express the GM-CSF transgene, resulting in a potent oncolytic immunotherapy mode of action:
Published June 2, 2024
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San Francisco, CA (UroToday.com) Dr. Holzbeierlein began his discussion on the new muscle-invasive bladder cancer (MIBC) guidelines,1 a collaborative multi-disciplinary effort led by Dr. Sam Chang that involved input from all the major organizations, including AUA, ASCO, ASTRO, and patient advocates. The final analysis was built on prior work by Dr. Chou’s AHRQ systematic reviews (through 2015).
Published February 10, 2018
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San Francisco, CA (UroToday.com) Dr. Yair Lotan presented on Genomic Insights and Biomarkers for Treatment Selection in Muscle-Invasive and Non-Muscle-Invasive Bladder Cancer. He discussed the role of markers in bladder cancer and how they add independent information that can impact patient care. The markers can either be prognostic which provide information about patient’s overall cancer outcome, regardless of therapy, or predictive markers that provide information about the effect of the therapeutic intervention and can be a target for therapy.
Published February 15, 2019
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San Francisco, CA (UroToday.com) In this case panel discussion, 3 patient cases were reviewed highlighting important points in the management of bladder cancer. The text below includes a summary of each case presented and key points made by the panelists.
Case 1: Small Cell Bladder Cancer: 65-year-old man who presents feeling lethargic, 10 lb weight loss, poor appetite. He has microscopic hematuria. Cystoscopy and subsequent TURBT demonstrates small cell bladder cancer.
Published February 16, 2019
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San Francisco, CA (UroToday.com) Immune checkpoint inhibitors are approved both in the first line and second line for patients with metastatic urothelial carcinoma. In the first line, KEYNOTE 052 showed that pembrolizumab has significant anti-tumor activity for cisplatin ineligible patients with UC1, for a 38% objective response rate for patients with a combined positive score of 10% or more (PD-L1 positive). Further analysis last year found that the benefit to checkpoint inhibition in the first line was restricted to patients with a high PD-L1 expression, as defined by CPS≥10 or PD-L1 IC ≥5%. In the second line, KEYNOTE 045 improved median overall survival compared with chemo (10.3 v 7.4 months; HR, 0.70; P < 0.001)2.
Published February 20, 2019
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San Francisco, CA (UroToday.com) Sacituzumab govitecan (SG) is a humanized antibody-drug conjugate, made from anti-Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan.1 Trop-2 is transmembrane glycoprotein encoded by the Tacstd2 gene, and is differentially expressed in a wide range of tumor types, including gastric, pancreatic, triple-negative breast, colonic, prostate, and lung cancer.2 In hormone-receptor positive (HR+)/HER2- metastatic breast cancer (mBC), the overall response rate was 31% by local assessment, and the clinical benefit rate (PR+SD > 6 months) was 48%.3 In an early phase study with metastatic non-small cell lung cancer, 47 patients were treated and the objective response rate was 19% with a median response duration of 6.0 months.4
Published February 16, 2019
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San Francisco, California (UroToday.com) For patients with BCG unresponsive non-muscle invasive bladder cancer, the standard of care for patients who are operative candidates is a radical cystectomy. However, not all patients may be cystectomy candidates, often for a multitude of reasons, including coexisting comorbidities as well as personal considerations and quality of life.1 Thus, there is an unmet need in this space for better local or systemic therapies which may prevent progression of bladder cancer to muscle-invasive or metastatic disease.
Published February 14, 2020
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(UroToday.com) The optimizing personalized management of non-muscle-invasive bladder cancer session at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) included a presentation from Dr. Anne Schuckman discussing which patients with high-risk non-muscle-invasive bladder cancer may benefit from radical cystectomy. Dr. Shuckman notes that more than 70% of all newly diagnosed bladder cancers are non-muscle-invasive, including Ta (70%), T1 (20%), and CIS (10%). The natural history of non-muscle-invasive bladder cancer stratified by low-grade Ta, high-grade Ta and high-grade T1 is depicted in the following table:
Published February 17, 2021
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(UroToday.com) In this presentation, Dr. Faltas offered his perspective on how to navigate sequencing results from patients in the clinic. He first laid out several concepts that are important to understand about genomic sequencing tests:
Published February 19, 2022
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(UroToday.com) The 2022 GU ASCO Annual meeting featured a session on demystifying next-generation sequencing in urothelial carcinoma, including a presentation by Dr. Sam Chang and colleagues reporting results of a phase 3 trial assessing IL-15RαFc superagonist N-803 (Anktiva) and BCG for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). Dr. Chang notes that BCG induces (aka primes) trained immunity in the treatment of superficial bladder cancer by activating NK and T cell killing of bladder cancer cells. Furthermore, innate immune memory results in a prolonged durable complete response. Thus, the question is whether we can potentiate this innate immune response, perhaps through BCG + N-803.
Published February 19, 2022
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(UroToday.com) The 2023 GU ASCO annual meeting included a trials in progress session for bladder cancer, featuring a presentation by Dr. Massimo Lazzeri discussing the trial design of a randomized phase III clinical trial of neoadjuvant intravesical mitomycin C treatment in patients with primary treatment naïve non-muscle invasive bladder cancer (NMIBC). Approximately 75-85% of bladder urothelial carcinomas are non-muscle invasive, for which the primary treatment is transurethral resection (TUR) followed by adjuvant intravesical therapies with immunotherapy (BCG) and/or chemotherapy agents (i.e. mitomycin C). Unfortunately, the response to intravesical treatments is variable and incomplete and there is an unmet clinical need to improve its efficacy for reducing the recurrence rate and progression to muscle invasive bladder cancer. Recently, it has been shown that mitomycin C induces immunogenic cell death, determining the expression of specific damage signals, like HMGB1 molecule, that favors the phagocytosis of dying tumor cells, the activation of innate immune cells, and the presentation of tumor antigens to T lymphocytes.1
Published February 17, 2023
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(UroToday.com) The 2024 GU ASCO annual meeting featured a session on the shortage of drugs for urothelial carcinoma and a presentation by Dr. Josh Meeks discussing what is on the horizon to replace BCG. Dr. Meeks started his presentation with a case report of a 71 year old female who presented with gross hematuria and a CT scan showing a 3 cm bladder mass. A TURBT demonstrated T1 high grade urothelial carcinoma with CIS and with muscle in the specimen. A re-TURBT demonstrated only CIS. Dr. Meeks notes that in this situation the hospital has limited BCG available: there is an option to start BCG, but at only 1/3 the dose and you do not know if you can provide BCG through year 1. What do you recommend? Several options, which are all rational for this patient, include:
Published January 26, 2024
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Treatment for high-risk non-muscle invasive bladder cancer (NMIBC) typically includes intravesical administration of bacillus Calmette-Guérin (BCG) as a form of immunotherapy. BCG is thought to activate both innate and adaptive immune responses with anti-tumor effects.
Published November 15, 2022
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(UroToday.com) The 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting included a presentation by Dr. Jason Efstathiou discussing results of the NRG Oncology/RTOG 0926 trial. This trial assessed selective bladder preserving treatment by radiation therapy concurrent with radiosensitizing chemotherapy following a thorough restaging TURBT.
Published October 29, 2021
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(UroToday.com) The 2024 American Society for Radiation Oncology (ASTRO) annual meeting held in Washington D.C., between September 29 and October 2 was host to the session Presidential Symposium: Innovations in Genitourinary Cancers: Session II - Bladder Preservation - A Modern Choice for Patients. Dr. Ananya Choudhury gave a presentation titled The Dawn or Era of More Personalized Radiotherapy in Bladder Cancer.
Published September 29, 2024
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(UroToday.com) The 2024 American Society for Radiation Oncology (ASTRO) annual meeting held in Washington D.C. was host to the session Presidential Symposium: Innovations in Genitourinary Cancers: Session II - Bladder Preservation - A Modern Choice for Patients. Dr. Leslie Ballas opened this session with a talk titled: Bladder Preservation - A Modern Choice for Patients.
Published September 29, 2024
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Background: First-line chemotherapy for patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma is associated with short response duration, poor survival, and high toxicity. This study assessed
atezolizumab (anti-programmed death-ligand 1 [PD-L1]) as treatment for metastatic urothelial cancer in cisplatinineligible patients.
Methods: For this single-arm, multicentre, phase 2 study, in 47 academic medical centres and community oncology practices in seven countries in North America and Europe, we recruited previously untreated patients with locally advanced or metastatic urothelial cancer who were cisplatin ineligible. Patients were given 1200 mg intravenous atezolizumab every 21 days until progression. The primary endpoint was independently confi rmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (central review), assessed in prespecifi ed subgroups based on PD-L1 expression and in all patients. All participants who received one or more doses of atezolizumab were included in the primary and safety analyses. This study was registered with ClinicalTrials.gov, number NCT02108652.
Findings: Between June 9, 2014, and March 30, 2015, we enrolled 123 patients, of whom 119 received one or more doses of atezolizumab. At 17·2 months’ median follow-up, the objective response rate was 23% (95% CI 16 to 31), the complete response rate was 9% (n=11), and 19 of 27 responses were ongoing. Median response duration was not reached. Responses occurred across all PD-L1 and poor prognostic factor subgroups. Median progression-free survival was 2·7 months (2·1 to 4·2). Median overall survival was 15·9 months (10·4 to not estimable). Tumour mutation load was associated with response. Treatment-related adverse events that occurred in 10% or more of patients were fatigue (36 [30%] patients), diarrhoea (14 [12%] patients), and pruritus (13 [11%] patients). One treatment-related death (sepsis) occurred. Nine (8%) patients had an adverse event leading to treatment discontinuation. Immune-mediated events occurred in 14 (12%) patients.
Interpretation: Atezolizumab showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated metastatic urothelial cancer.
Funding: F Hoff mann-La Roche, Genentech.
Authors: Arjun V Balar, Matthew D Galsky, Jonathan E Rosenberg, Thomas Powles, Daniel P Petrylak, Joaquim Bellmunt, Yohann Loriot, Andrea Necchi, Jean Hoffman-Censits, Jose Luis Perez-Gracia, Nancy A Dawson, Michiel S van der Heijden, Robert Dreicer, Sandy Srinivas, Margitta M Retz, Richard W Joseph, Alexandra Drakaki, Ulka N Vaishampayan, Srikala S Sridhar, David I Quinn, Ignacio Durán, David R Shaff er, Bernhard J Eigl, Petros D Grivas, Evan Y Yu, Shi Li, Edward E Kadel III, Zachary Boyd, Richard Bourgon, Priti S Hegde, Sanjeev Mariathasan, AnnChristine Thåström, Oyewale O Abidoye, Gregg D Fine, Dean F Bajorin, for the IMvigor210 Study Group*
Go "Beyond the Abstract" - Read an article written by the authors for UroToday.com
Author Affiliations: Genitourinary Cancers Program, Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA (A V Balar MD); The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA (M D Galsky MD); Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA (J E Rosenberg MD, D F Bajorin MD); Barts Cancer Institute ECMC, Barts Health and the Royal Free NHS Trust, Queen Mary University of London, London, UK (T Powles MD); Smilow Cancer Center, Yale University, New Haven, CT, USA (D P Petrylak MD); Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA (J Bellmunt MD); Département de médecine oncologique, Université Paris-Saclay and Gustave Roussy, Villejuif, France (Y Loriot MD); Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy (A Necchi MD); Sidney Kimmel Cancer Center at Jefferson, Philadelphia, PA, USA (J Hoffman-Censits MD); Department of Oncology, Clínica Universidad de Navarra, University of Navarra, Pamplona, Navarre, Spain (J L Perez-Gracia MD); MedstarGeorgetown University Hospital, Lombardi Comprehensive Cancer Center, Washington, DC, USA (N A Dawson MD); Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands (M S van der Heijden MD); Division of Hematology/ Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA (R Dreicer MD); Division of Oncology/Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA (S Srinivas MD); Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (M M Retz MD); Department of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA (R W Joseph MD); Department of Medicine, Division of Hematology and Oncology and Institute of Urologic Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA (A Drakaki MD); Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA (U N Vaishampayan MD); Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, ON, Canada (S S Sridhar MD); University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA (D I Quinn MD); Department of Medical Oncology, Hospital Universitario Virgen del Rocío and Institute of Biomedicine of Seville, Seville, Spain (I Durán MD); New York Oncology Hematology, Albany, NY, USA (D R Shaffer MD); British Columbia Cancer Agency, British Columbia, Vancouver, Canada (B J Eigl MD); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA (P D Grivas MD); Division of Oncology, Department of Medicine, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA (E Y Yu MD); and Genentech, South San Francisco, CA, USA (S Li PhD, E E Kadel III BS,Z Boyd MSc, R Bourgon PhD, P S Hegde PhD, S Mariathasan PhD, AC Thåström PhD, O O Abidoye MD, G D Fine MD)
Published Online December 7, 2016 http://dx.doi.org/10.1016/ S0140-6736(16)32455-2
Published March 7, 2017
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BACKGROUND: First-line chemotherapy for patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma is associated with short response duration, poor survival, and high toxicity. This study assessed atezolizumab (anti-programmed death-ligand 1 [PD-L1]) as treatment for metastatic urothelial cancer in cisplatin-ineligible patients.
METHODS: For this single-arm, multicentre, phase 2 study, in 47 academic medical centres and community oncology practices in seven countries in North America and Europe, we recruited previously untreated patients with locally advanced or metastatic urothelial cancer who were cisplatin ineligible.
Published December 12, 2018