scholarly journals A húgyhólyag urothelialis daganatainak molekuláris alcsoportbeosztása és annak klinikai vonatkozásai

2019 ◽  
Vol 160 (42) ◽  
pp. 1647-1654 ◽  
Author(s):  
Tibor Szarvas ◽  
Csilla Oláh ◽  
Péter Riesz ◽  
Lajos Géczi ◽  
Péter Nyirády
Keyword(s):  
Decision Making ◽  
Bladder Cancer ◽  
Clinical Decision Making ◽  
Checkpoint Inhibitors ◽  
Clinical Decision ◽  
Molecular Techniques ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Gene And Protein Expression ◽  
Muscle Invasive

Abstract: Current advances in molecular techniques and bioinformatics allowed the analysis of complex molecular patterns in various cancers including muscle-invasive bladder cancer. As a consequence, in the last few years numerous gene- and protein expression-based molecular classifications have been recommended. Recently a comprehensive consensus classification for muscle-invasive urothelial bladder cancer has been published, distinguishing 6 subgroups with a potential impact on clinical decision-making. At the same time, the therapeutic landscape of muscle-invasive bladder cancer becomes increasingly differentiated as novel checkpoint inhibitors have been available for cisplatin-ineligible and/or resistant patients. Furthermore, promising results have been obtained with FGFR targeting agents. Therefore, molecular subtyping will probably have a crucial role in individualized therapeutic decision-making in bladder cancer. In the present work, we summarize the evolution, recent advances and potential therapeutic relevance of molecular subclassifications in bladder cancer. Orv Hetil. 2019; 160(42): 1647–1654.

scholarly journals Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives

2021 ◽  
Vol 22 (13) ◽  
pp. 7201
Author(s):  
In-Ho Kim ◽  
Hyo-Jin Lee
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Current Evidence ◽  
Future Perspectives ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

scholarly journals Management of Localized Muscle-Invasive Bladder Cancer from a Multidisciplinary Perspective: Current Position of the Spanish Oncology Genitourinary (SOGUG) Working Group

2021 ◽  
Vol 28 (6) ◽  
pp. 5084-5100
Author(s):  
Antonio Gómez Caamaño ◽  
Ana M. García Vicente ◽  
Pablo Maroto ◽  
Alfredo Rodríguez Antolín ◽  
Julián Sanz ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Working Group ◽  
Checkpoint Inhibitors ◽  
Imaging Techniques ◽  
Clinical Staging ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Selection Of Patients ◽  
Selection Of

This review presents challenges and recommendations on different aspects related to the management of patients with localized muscle-invasive bladder cancer (MIBC), which were discussed by a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group within the framework of the Genitourinary Alliance project (12GU). It is necessary to clearly define which patients are candidates for radical cystectomy and which are candidates for undergoing bladder-sparing procedures. In older patients, it is necessary to include a geriatric assessment and evaluation of comorbidities. The pathological report should include a classification of the histopathological variant of MIBC, particularly the identification of subtypes with prognostic, molecular and therapeutic implications. Improvement of clinical staging, better definition of prognostic groups based on molecular subtypes, and identification of biomarkers potentially associated with maximum benefit from neoadjuvant chemotherapy are areas for further research. A current challenge in the management of MIBC is improving the selection of patients likely to be candidates for immunotherapy with checkpoint inhibitors in the neoadjuvant setting. Optimization of FDG-PET/CT reliability in staging of MIBC and the selection of patients is necessary, as well as the design of prospective studies aimed to compare the value of different imaging techniques in parallel.

Neoadjuvant or adjuvant immunotherapy in bladder cancer: biological opportunity or clinical utility?

2021 ◽  
pp. 030089162110616
Author(s):  
Fausto Petrelli ◽  
Gianluca Perego ◽  
Ivano Vavassori ◽  
Andrea Luciani
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Cancer Of The Bladder ◽  
Muscle Invasive

In urothelial cancer of the bladder, the introduction of immunotherapy with immune checkpoint inhibitors represents progress in the management of the disease’s early and advanced stages. In particular, recent studies have implemented these drugs in the neoadjuvant and adjuvant phases to treat muscle-invasive bladder cancer. In some studies, patients received neoadjuvant immune checkpoint inhibitors alone (PURE and ABACUS) to treat muscle invasive bladder cancer, whereas other studies provided this therapy to cisplatin-ineligible patients. Furthermore, a large Phase III study (CheckMate 247) compared placebo with adjuvant nivolumab therapy in patients with high-risk urothelial cancer after neoadjuvant chemotherapy and surgery or surgery alone. Despite some uncertain niches (nonbladder, PD-L1-negative tumors, and node-negative resected cancers), certain biological opportunities (exploring new targets, evaluating in vivo pathologic response, focusing on biomarkers for response) and clinical uses (avoiding chemotherapy at all or in frail patients, attaining similar pathologic complete response rates as in cisplatin-based chemotherapy) are valid reasons for incorporating these agents into the therapeutic armamentarium of medical uro-oncologists.

Bladder preservation therapy for muscle invasive bladder cancer: the past, present and future

2020 ◽  
Vol 50 (10) ◽  
pp. 1097-1107
Author(s):  
Tomokazu Kimura ◽  
Hitoshi Ishikawa ◽  
Takahiro Kojima ◽  
Shuya Kandori ◽  
Takashi Kawahara ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
The Past ◽  
Muscle Invasive

Abstract Radical cystectomy is the gold standard treatment for muscle invasive bladder cancer, but some patients have medically inoperable disease or refuse cystectomy to preserve their bladder function. Bladder preservation therapy with transurethral resection of the bladder tumor and concurrent chemoradiotherapy, known as trimodal treatment, is regarded to be a curative-intent alternative to radical cystectomy for patients with muscle invasive bladder cancer during the past decade. After the development of immune checkpoint inhibitors, a world-changing breakthrough occurred in the field of metastatic urothelial carcinoma and many clinical trials have been conducted against non-muscle invasive bladder cancer. Interestingly, preclinical and clinical studies against other malignancies have shown that immune checkpoint inhibitors interact with the radiation-induced immune reaction. As half of the patients with muscle invasive bladder cancer are elderly, and some have renal dysfunction, not only as comorbidity but also because of hydronephrosis caused by their tumors, immune checkpoint inhibitors are expected to become part of a new therapeutic approach for combination treatment with radiotherapy. Accordingly, clinical trials testing immune checkpoint inhibitors have been initiated to preserve bladder for muscle invasive bladder cancer patients using radiation and immune checkpoint inhibitors with/without chemotherapy. The objective of this review is to summarize the evidence of trimodal therapy for muscle invasive bladder cancer during the past decade and to discuss the future directions of bladder preservation therapy in immuno-oncology era.

scholarly journals Expression of ADAM Proteases in Bladder Cancer Patients with BCG Failure: A Pilot Study

2021 ◽  
Vol 10 (4) ◽  
pp. 764
Author(s):  
Renate Pichler ◽  
Andrea Katharina Lindner ◽  
Georg Schäfer ◽  
Gennadi Tulchiner ◽  
Nina Staudacher ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Checkpoint Inhibitors ◽  
Cell Types ◽  
Current Data ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Advanced Tumor ◽  
Adam10 Expression ◽  
Bcg Failure ◽  
Muscle Invasive

Although Bacillus Calmette Guérin (BCG) remains a mainstay of adjuvant treatment in high-risk, non-muscle-invasive bladder cancer, BCG failure occurs in up to 40% of patients, with radical cystectomy (RC) as the inevitable therapeutic consequence. Current data suggest that PD-L1 immunosuppressive signaling is responsible for BCG failure, supporting the therapeutic rationale of combining checkpoint inhibitors with BCG. To address the immune cascade in 19 RC specimens obtained after BCG failure, we applied a small immunohistochemical (IHC) panel consisting of selected markers (PD-L1, GATA-3, a disintegrin and metalloproteinase (ADAM) proteases, IL-10/IL-10R). A modified quick score was used for IHC semi-quantification of these markers in tumor cells (TC) and immune cells (IC) within two different regions: muscle-invasive bladder cancer (MIBC) and primary/concurrent carcinoma in situ (CIS). Contrary to expectation, PD-L1 was consistently low, irrespective of tumor region and cell type. Intriguingly, expression of ADAM17, which has been reported to release membrane-bound PD-L1, was high in both tumor regions and cell types. Moreover, expression of GATA3, IL-10, and IL-10R was also increased, indicative of a generally immunosuppressive tumor microenvironment in BCG failure. ADAM10 expression was associated with advanced tumor disease at RC. Our findings raise the possibility that ADAM proteases may cleave PD-L1 from the surface of bladder TC and possibly also from IC. Therefore, IHC assessment of PD-L1 expression seems to be insufficient and should be supplemented by ADAM10/17 in patients with BCG failure.

scholarly journals A Web-Based Tool to Facilitate Shared Decision-Making Regarding Neoadjuvant Chemotherapy Use in Muscle-Invasive Bladder Cancer

Iproceedings ◽  
2017 ◽  
Vol 3 (1) ◽  
pp. e43
Author(s):  
Matthew Galsky ◽  
Michael Diefenbach ◽  
Nihal Mohamed ◽  
Charles Baker ◽  
Sumit Pokhriya ◽  
...  
Keyword(s):  
Decision Making ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Shared Decision Making ◽  
Invasive Bladder Cancer ◽  
Shared Decision ◽  
Muscle Invasive Bladder Cancer ◽  
Web Based ◽  
Muscle Invasive

scholarly journals Avelumab as neoadjuvant therapy in patients with urothelial non-metastatic muscle invasive bladder cancer: a multicenter, randomized, non-comparative, phase II study (Oncodistinct 004 - AURA trial)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nieves Martinez Chanza ◽  
Louisa Soukane ◽  
Philippe Barthelemy ◽  
Aurélien Carnot ◽  
Thierry Gil ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Predictive Biomarkers ◽  
Complete Response ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
To Receive

Abstract Introduction Cisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). Unfortunately, many patients are not candidates to receive cisplatin due to renal impairment. Additionally, no predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Studies evaluating immune checkpoint inhibitors in the peri-operative setting are emerging with promising results. Clinical trials are clearly required in the neoadjuvant setting in order to improve therapeutic strategies. Methods and analysis Oncodistinct 004 – AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC. Patients are enrolled in two distinct cohorts according to their eligibility to receive cisplatin-based NAC. In the cisplatin eligible cohort, patients are randomized in a 1:1 fashion to receive avelumab combined with cisplatin-gemcitabine or with dose-dense methotrexate-vinblastine-doxorubicin-cisplatin. In the cisplatin ineligible cohort, patients are randomized at a 1:1 ratio to paclitaxel-gemcitabine associated to avelumab or avelumab alone. Primary endpoint is pCR. Secondary endpoints are pathological response and safety. Ethics and dissemination The study is approved by ethics committee from all participating centers. All participants provide informed consent prior inclusion to the study. Once completed, results will be published in peer-reviewed journals. Trial registration number ClinicalTrials.gov (NCT03674424).

Potential underuse of repeat resection among patients with high-grade non-muscle invasive bladder cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16028-e16028
Author(s):  
Devon Check ◽  
David S. Aaronson ◽  
Valerie S. Lee ◽  
Matthew Nielsen ◽  
Li Tang ◽  
...  
Keyword(s):  
Decision Making ◽  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Social Characteristics ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Repeat Resection ◽  
Adjusted Risk ◽  
Comorbidity Burden ◽  
Muscle Invasive

e16028 Background: For patients diagnosed with non-muscle invasive bladder cancer (NMIBC), guidelines recommend that those with high-grade (HG) T1 disease and potentially those with lower risk HG Ta disease receive a repeat resection within six weeks of initial resection. For these patients, repeat resection has diagnostic, prognostic, and therapeutic value and is critical for informing treatment decision-making, and ultimately optimizing outcomes. Current rates of repeat resection in practice are unknown. Methods: We conducted a retrospective analysis of patients diagnosed with HG T1 and HG Ta NMIBC between 1/1/2015 and 3/1/2016 using cancer registry-linked electronic medical record data. Our analysis included 118 patients with HG T1 disease and 114 patients with HG Ta disease who did not undergo a cystectomy. We used modified Poisson regression with clustered standard errors to assess the associations of patients’ clinical and socio-demographic characteristics and providers’ characteristics with patients’ receipt of repeat resection. We present adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results: 40% of HG patients (55% of T1 patients; 24% of Ta patients) underwent repeat resection, with no differences in receipt by patient age, gender, race, or comorbidity burden. In addition to HG T1 (vs. HG Ta) disease (aRR: 2.20, 95% CI: 1.53-3.22), higher census-tract median household income was associated with increased likelihood of repeat resection (aRR highest vs. lowest income quartile: 1.42, 95% CI: 1.08-2.23). At the treating urologist level, more time in practice was negatively associated with likelihood of repeat resection receipt (aRR highest vs. lowest quartile of number of years in practice: 0.56, 95% CI: 0.41-0.77). Conclusions: Our data suggest that a large proportion of potentially eligible HG patients did not undergo a repeat resection, and that variation in practice is driven by patients’ social characteristics and treating urologist characteristics. Further research is needed to understand whether the variation observed reflects a quality improvement need versus patient-centered decision-making that accounts for preferences and treatment eligibility.

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