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1.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802203

RESUMO

Currently, bladder cancer (BC) represents a challenging problem in the field of Oncology. The high incidence, prevalence, and progression of BC have led to the exploration of new avenues in its management, in particular in advanced metastatic stages. The recent inclusion of immune checkpoint blockade inhibitors as a therapeutic option for BC represents an unprecedented advance in BC management. However, although some patients show durable responses, the fraction of patients showing benefit is still limited. Notwithstanding, cell-based therapies, initially developed for the management of hematological cancers by infusing immune or trained immune cells or after the engineering of chimeric antigen receptor (CAR) expressing cells, are promising tools to control, or even cure, solid tumors. In this review, we summarize recent cell-based immunotherapy studies, with a special focus on BC.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos/uso terapêutico , Neoplasias da Bexiga Urinária/terapia , Humanos , Neoplasias da Bexiga Urinária/patologia
2.
Am J Case Rep ; 22: e930090, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33875632

RESUMO

BACKGROUND The main causes for takotsubo syndrome (TS) in oncological patients are stress related to cancer diagnosis and treatment, pain in the course of the disease, treatment complications, and paraneoplastic syndromes. CASE REPORT An obese 62-year-old female patient, with a 3-day history of chest pain, was admitted to the hospital with a suspected acute coronary event. She had been diagnosed with high-grade bladder cancer 6 months before. After the transurethral electroresection of the tumor 5 months before and subsequent chemotherapy (gemcitabine and cisplatin), the patient was qualified for the next cancer surgery. On admission, the patient remained without chest pain. The ECG record demonstrated inverted T waves in the leads from above the anterior and lateral wall. The coronarography demonstrated minor atherosclerotic changes in the coronary arteries. The left ventriculography presented akinesis of the apex and the apical and mid-segment of the anterior wall, and the ejection fraction (EF) was 38%. Takotsubo syndrome was diagnosed. Laboratory testing revealed elevated concentration of troponin and N-terminal pro-B-type natriuretic peptide. The subsequent ECG records demonstrated deeply inverted T waves and numerous ventricular premature beats and increased QTc (528 ms). A control echocardiography showed improved left ventricular contractive function (EF - 47%). On the 4th day of hospitalization, the patient was discharged and referred for further oncological treatment. CONCLUSIONS The diagnosis of TS in oncology patients is difficult, especially in the presence of atherosclerotic lesions in coronary arteries. Takotsubo syndrome in cancer patients delays the next stages of oncological treatment, which worsens the prognosis of these patients.


Assuntos
Cardiomiopatia de Takotsubo/diagnóstico , Neoplasias da Bexiga Urinária/complicações , Dor no Peito/etiologia , Ecocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/terapia , Troponina/sangue , Neoplasias da Bexiga Urinária/terapia
3.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803085

RESUMO

Exosomes are extracellular vesicles, enriched in biomolecular cargo consisting of nucleic acids, proteins, and lipids, which take part in intercellular communication and play a crucial role in both physiologic functions and oncogenesis. Bladder cancer is the most common urinary malignancy and its incidence is steadily rising in developed countries. Despite the high five-year survival in patients diagnosed at early disease stage, survival substantially drops in patients with muscle-invasive or metastatic disease. Therefore, early detection of primary disease as well as recurrence is of paramount importance. The role that exosomal biomarkers could play in bladder cancer patient diagnosis and surveillance, as well as their potential therapeutic applications, has not been extensively studied in this malignancy. In the present review, we summarize all relevant data obtained so far from cell lines, animal models, and patient biofluids and tissues. Current literature suggests that urine is a rich source of extracellular vesicle-derived biomarkers, compared with blood and bladder tissue samples, with potential applications in bladder cancer management. Further studies improving sample collection procedures and optimizing purification and analytical methods should augment bladder cancer diagnostic, prognostic, and therapeutic input of extracellular vesicles biomarkers in the future.


Assuntos
Biomarcadores Tumorais/metabolismo , Exossomos/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/terapia , Exossomos/patologia , Humanos , Metástase Neoplásica , Neoplasias da Bexiga Urinária/patologia
4.
Medicine (Baltimore) ; 100(14): e25397, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832133

RESUMO

ABSTRACT: Decision-making to stop cancer treatment in patients with advanced cancer is stressful, and it significantly influences subsequent end-of-life palliative treatment. However, little is known about the extent to which the patient's self-decisions influenced the prognostic period. This study focused on the patient's self-decision and investigated the impact of the self-decision to stop cancer treatment on their post-cancer treatment survival period and place of death.We retrospectively analyzed 167 cases of advanced genitourinary cancer patients (kidney cancer: 42; bladder cancer: 68; prostate cancer: 57) treated at the University of Fukui Hospital (UFH), who later died because of cancer. Of these, 100 patients decided to stop cancer treatment by themselves (self-decision group), while the families of the remaining 67 patients (family's decision group) decided to stop treatment on their behalf because the patient's decision-making ability was already impaired. Differences in the post-cancer-treatment survival period and place of death between the 2 groups were examined. The association between place of death and survival period was also analyzed.The median survival period after terminating cancer treatment was approximately 6 times longer in the self-decision group (145.5 days in self-decision group vs 23.0 days in family's decision group, P < .001). Proportions for places of death were as follows: among the self-decision group, 42.0% of patients died at UFH, 45.0% at other medical institutions, and 13.0% at home; among the family's decision group, 62.7% died at UFH, 32.8% at other medical institutions, and 4.5% at home. The proportion of patients who died at UFH was significantly higher among the family's decision group (P = .011). The median survival period was significantly shorter for patients who died at UFH (UFH: 30.0 days; other institutions/home: 161.0 days; P < .001).Significantly longer post-cancer-treatment survival period and higher home death rate were observed among patients whose cancer treatment was terminated based on their self-decision. Our results provide clinical evidence, especially in terms of prognostic period and place of death that support the importance of discussing bad news, such as stopping cancer treatment with patients.


Assuntos
Família/psicologia , Doente Terminal/psicologia , Neoplasias Urogenitais/mortalidade , Neoplasias Urogenitais/terapia , Suspensão de Tratamento/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Atitude Frente a Morte , Estudos de Casos e Controles , Tomada de Decisões/fisiologia , Feminino , Humanos , Japão/epidemiologia , Neoplasias Renais/epidemiologia , Neoplasias Renais/mortalidade , Neoplasias Renais/psicologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/ética , Cuidados Paliativos/psicologia , Prognóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Assistência Terminal/ética , Assistência Terminal/psicologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/psicologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias Urogenitais/patologia , Neoplasias Urogenitais/psicologia
5.
Nat Commun ; 12(1): 2301, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863885

RESUMO

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/genética , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Bexiga Urinária/genética , Idoso , Vacina BCG/administração & dosagem , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/terapia , Instabilidade Cromossômica , Cistectomia/métodos , Dinamarca/epidemiologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Genômica , Humanos , Estimativa de Kaplan-Meier , Masculino , Mutação , Recidiva Local de Neoplasia/genética , Prognóstico , Intervalo Livre de Progressão , RNA-Seq , Bexiga Urinária/imunologia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/terapia
6.
Arch Ital Urol Androl ; 93(1): 71-76, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33754613

RESUMO

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy.


Assuntos
Neoplasias Urológicas/terapia , Administração Intravesical , Adulto , Vacina BCG/uso terapêutico , /terapia , Carcinoma de Células de Transição/patologia , Angiografia por Tomografia Computadorizada , Cistectomia , Fístula/complicações , Fístula/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Paraganglioma/cirurgia , Paraganglioma/terapia , Pneumonia/complicações , Pneumonia/terapia , Complicações Pós-Operatórias/terapia , Púrpura Trombocitopênica Trombótica/etiologia , Púrpura Trombocitopênica Trombótica/terapia , Doenças Ureterais/complicações , Doenças Ureterais/diagnóstico por imagem , Doenças Ureterais/terapia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/terapia , Neoplasias Urológicas/complicações , Neoplasias Urológicas/diagnóstico por imagem
7.
Crit Rev Oncol Hematol ; 159: 103235, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33493633

RESUMO

AIM: To compare trimodality therapy (TMT) versus radical cystectomy (RC) and develop GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) for treatment of muscle-invasive bladder cancer (MIBC). MATERIAL AND METHODS: Prospective and retrospective studies comparing TMT and RC for MIBC patients were included. Qualitative and quantitative evaluation of evidence was made. RESULTS: Ten studies were included in the analysis. Pooled analysis showed salvage cystectomy and pathological complete response rates after TMT of 12 % and 72-77.5 %, respectively. Pooled rates of G3-G4 GU toxicity and serious toxicity rate were 18 vs 3% and 45 vs 29 % for patients undergoing TMT vs RC, respectively. The panel assessed a substantial equivalence in terms of OS and CSS at 5 years between TMT and RC. CONCLUSIONS: TMT could be suggested as an alternative treatment to RC in non-metastatic MIBC patients, deemed fit for surgery.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Itália/epidemiologia , Oncologia , Músculos , Invasividade Neoplásica , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/terapia
8.
Artigo em Inglês | MEDLINE | ID: mdl-33450864

RESUMO

Cancer treatment causes adverse effects that lead to refusal or discontinuation of treatment. The purposes of this study were to identify 1) the factors associated with and 2) the reasons for refusing and discontinuing treatment in patients with bladder cancer (BC). We conducted a retrospective cohort study in patients diagnosed with BC in Taiwan from 1 January 2014 to 30 June 2019 using a linked cancer registry database. Of the 1247 BC patients in the study cohort, 2.1% reported refusing treatment. Patients with less education and those diagnosed at cancer stage II-IV were more likely to refuse treatment. The major reason for refusing treatment was "patient or the family considered patient's poor physical condition (chronic disease or unstable systemic disease), difficulty in enduring any condition likely to cause physical discomfort from disease treatment". A total of 4.3% of BC patients reported discontinuing treatment. Patients not living in the northern region of Taiwan and those diagnosed at cancer stage II-IV were more likely to terminate treatment before completion. The major reason given for discontinuing treatment was inconvenient transportation. Sufficient social resources and supportive care can help BC patients cope with the physical and psychological burden of treatment.


Assuntos
Neoplasias da Bexiga Urinária , Estudos de Coortes , Humanos , Sistema de Registros , Estudos Retrospectivos , Taiwan/epidemiologia , Recusa do Paciente ao Tratamento , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/terapia
9.
Cancer Treat Rev ; 93: 102142, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33453566

RESUMO

Urothelial bladder cancer (UC) is the most common malignancy involving the urinary system and represents a significant health problem. Immunotherapy has been used for decades for UC with intravesical bacillus Calmette-Guérin (BCG) set as the standard of care for non-muscle-invasive bladder cancer (NMIBC). The advent of immune checkpoint inhibitors (ICIs) has completely transformed the treatment landscape of bladder cancer enabling to expand the treatment strategies. Novel ICIs have successfully shown improved outcomes on metastatic disease to such an extent that the standard of care paradigm has changed leading to the development of different trials with the aim of determining whether ICIs may have a role in early disease. The localized muscle-invasive bladder cancer (MIBC) scenario remains challenging since the recurrence rate continues to be high despite all therapeutic efforts. This article will review the current experience of ICIs in the neoadjuvant setting of UC, the clinical trials landscape and finally, an insight of what to expect in the immediate and mid-term future.


Assuntos
Neoplasias da Bexiga Urinária/terapia , Humanos , Imunoterapia/métodos , Terapia Neoadjuvante/métodos , Invasividade Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/terapia
10.
Cancer Sci ; 112(3): 1084-1094, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33368857

RESUMO

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.


Assuntos
Carcinoma de Células de Transição/mortalidade , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ureterais/patologia , Neoplasias da Bexiga Urinária/mortalidade , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/terapia , Quimioterapia Adjuvante , Cistectomia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Músculo Liso/patologia , Músculo Liso/cirurgia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Nefroureterectomia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/terapia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/secundário , Neoplasias da Bexiga Urinária/terapia
12.
J Urol ; 205(1): 100-108, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32783489

RESUMO

PURPOSE: Although neoadjuvant chemotherapy is associated with a survival advantage in pure urothelial, muscle invasive bladder cancer, the role of neoadjuvant chemotherapy is less clear in variant histology or urothelial carcinoma with divergent differentiation. We compared chemotherapy response and survival outcomes of patients with nonpure urothelial carcinoma histology who were managed with neoadjuvant chemotherapy followed by cystectomy vs cystectomy alone. MATERIALS AND METHODS: We analyzed 768 patients with clinical muscle invasive bladder cancer (cT2-4N0M0) who were treated with cystectomy at a tertiary care center from 2007 to 2017. Patients were stratified by histology and treatment strategy. Adjusted logistic and Cox regression models were used to evaluate pathological downstaging, cancer specific survival and overall survival. RESULTS: The cohort consisted of 410 patients (53%) with pure urothelial carcinoma, 185 (24%) with urothelial carcinoma with divergent differentiation and 173 (23%) with variant histology. Overall, 314 patients (41%) received neoadjuvant chemotherapy prior to cystectomy. There were similar rates of complete (18% to 30%) and partial (37% to 46%) pathological downstaging with neoadjuvant chemotherapy across all histological subgroups (p=0.30 and p=0.40, respectively). However, while patients with pure urothelial carcinoma experienced an overall survival benefit (HR 0.71, 95% CI 0.51-0.98, p=0.0013) and those with variant histology experienced a cancer specific survival benefit (HR 0.55, 95% CI 0.30-0.99, p=0.0495) with neoadjuvant chemotherapy, patients with urothelial carcinoma with divergent differentiation did not experience overall or cancer specific survival benefits with the use of neoadjuvant chemotherapy prior to cystectomy. CONCLUSIONS: Among patients with muscle invasive bladder cancer those with nonpure urothelial carcinoma histology with variant histology achieved nearly equivalent response rates and survival benefits with the use of neoadjuvant chemotherapy as those with pure urothelial carcinoma, while patients with urothelial carcinoma with divergent differentiation experienced significantly worse survival outcomes regardless of the use of neoadjuvant chemotherapy prior to cystectomy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/terapia , Cistectomia/estatística & dados numéricos , Terapia Neoadjuvante/métodos , Neoplasias da Bexiga Urinária/terapia , Idoso , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Quimioterapia Adjuvante/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/estatística & dados numéricos , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
13.
J Oncol Pharm Pract ; 27(2): 514-515, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33349147

RESUMO

Immunotherapy is gradually revolutionizing bladder cancer treatment. In this extensive review published by Hanna et al. in your journal, the authors presented recent studies that are trying to challenge the standard platinum-based chemotherapy as first-line treatment of metastatic bladder cancer by chemoimmunotherapy. However, upfront pembrolizumab, atezolizumab and durvalumab association with standard of care chemotherapy did not improve overall survival when compared to chemotherapy alone.We hereby highlight a study that was not included in this review, the INDUCOMAIN trial, by discussing its results and its future implications on immunotherapy for metastatic bladder cancer.


Assuntos
Carcinoma de Células de Transição/terapia , Imunoterapia/tendências , Neoplasias da Bexiga Urinária/terapia , Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Ensaios Clínicos como Assunto , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico
14.
Urologiia ; (5): 133-138, 2020 Nov.
Artigo em Russo | MEDLINE | ID: mdl-33185361

RESUMO

The prevalence of bladder cancer in Russia over the past 10 years has increased from 49.6 to 74.1 patients per 100,000 population. Hematuria is a life-threatening complication and one of the common causes of mortality in advanced stages of bladder cancer. Conservative methods of hemostasis do not always allow to achieve a stable effect. In addition, in the cases of intractable bleeding, the patients may require surgical treatment. Due to the prevalence of patients with a high anesthetic risk group in bladder cancer patients cohort, the minimally invasive hemostasis technologies are more preferable. This review is devoted to one of such methods - superselective embolization of the urinary bladder arteries.


Assuntos
Embolização Terapêutica , Neoplasias da Bexiga Urinária , Artérias , Hematúria/etiologia , Hematúria/terapia , Humanos , Federação Russa , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/terapia
15.
Actas urol. esp ; 44(9): 574-585, nov. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-198084

RESUMO

CONTEXTO: El tratamiento estándar de los tumores de vejiga no músculo-invasivos (TVNMI) de alto riesgo es la resección transuretral de vejiga e instilaciones de bacilo de Calmette-Guérin (BCG). Sin embargo, las respuestas son limitadas. Es necesario buscar nuevas alternativas terapéuticas para estos pacientes. Los resultados en tumores avanzados de los inhibidores de puntos de control han dado lugar al interés en el uso de estas moléculas en TVNMI. MÉTODOS: Hemos realizado una búsqueda en PubMed utilizando los términos «bladder cancer» y «check point inhibitors». Para la búsqueda de ensayos clínicos, hemos utilizado los buscadores clinicaltrials.gov y clinicaltrialsregister.eu RESULTADOS: Actualmente hay 5 ensayos en marcha de pacientes no tratados con BCG. No hay resultados disponibles. En cuanto a los pacientes no respondedores a BCG, existen 15 ensayos en marcha, 2 de ellos con resultados preliminares: el Keynote 057, con resultados prometedores con pembrolizumab y que ha llevado a la FDA a aprobar su uso en enero de 2020 y el SWOG S1605, que ha mostrado resultados similares con atezolizumab. Otros ensayos administran estos fármacos intravesicalmente, una opción atractiva si resulta efectiva para el control oncológico. CONCLUSIONES: Los inhibidores de puntos de control ofrecen una nueva posibilidad para los pacientes no respondedores al BCG. Probablemente en el futuro se podrán usar en pacientes no tratados previamente con BCG. Los datos preliminares de ensayos clínicos muestran resultados prometedores. Es importante un buen conocimiento de estas moléculas por los urólogos y la formación de equipos multidisciplinares para ofrecer las mejores alternativas terapéuticas a estos pacientes


BACKGROUND: The standard treatment for high-risk non-muscle invasive bladder tumors (NMIBT) is transurethral resection of the bladder and BCG instillations. However, responses are limited, and new therapeutic alternatives for these patients are required. The results of checkpoint inhibitors in advanced tumors have led to interest in the use of these molecules in NMIBT. METHODS: We conducted a search on PubMed using the terms «bladder cancer» and «check point inhibitors». We have used the search engines clinicaltrials.gov and clinicaltrialsregister.eu for the search of clinical trials. RESULTS: There are currently 5 trials in progress on BCG untreated patients. There are no results available. As for BCG non-responders, there are 15 ongoing trials, two of them with preliminary results: Keynote 057, with promising results with pembrolizumab, which has led the FDA to approve its use in January 2020, and SWOG S1605, which has shown similar results with atezolizumab. Other trials are using intravesical administration of these drugs, which is an attractive option if it is effective for cancer control. CONCLUSIONS: Checkpoint inhibitors offer a new possibility for patients who do not respond to BCG. These will probably be used in the future for previously BCG untreated patients. Preliminary data from clinical trials show promising results. A good understanding of these molecules by urologists and the creation of multidisciplinary teams are crucial in order to offer the best therapeutic alternatives to these patients


Assuntos
Humanos , Neoplasias da Bexiga Urinária/terapia , Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Fatores de Risco , Vacina BCG/uso terapêutico , Resultado do Tratamento
16.
Actas urol. esp ; 44(9): 586-596, nov. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-198085

RESUMO

OBJETIVO: Conocer las últimas evidencias sobre Urología oncológica de tumores de riñón, vejiga y próstata. MÉTODOS: Se revisan los resúmenes sobre cáncer renal, de vejiga y de próstata (CaP) presentados en los congresos del año 2019 (EAU, AUA, ASCO y ESMO) y las publicaciones de mayor impacto en este periodo con mayor valoración por parte del comité del OncoForum. RESULTADOS: En pacientes con cáncer renal metastásico, los regímenes que incluyen inmunoterapia (nivolumab + ipilimumab, pembrolizumab) han mostrado ser superiores a sunitinib en términos de supervivencia. En pacientes con cáncer de vejiga no músculo-invasivo, pembrolizumab ha demostrado ser una alternativa efectiva en aquellos refractarios al bacilo de Calmette-Guérin, mientras que, en pacientes con cáncer urotelial metastásico, enfortumab vedotin en tercera línea logró una tasa de respuesta considerable (44%). En pacientes con CaP localizado, la radioterapia externa ultrafraccionada no mostró mayor toxicidad aguda que la radioterapia fraccionada o hipofraccionada. Se ha confirmado el beneficio de enzalutamida y apalutamida asociados a la castración en pacientes con CaP M1, independientemente del volumen de la enfermedad. En los pacientes con CaP resistente a la castración (CPRC) M0, el tratamiento con enzalutamida, apalutamida o darolutamida se ha asociado con un retraso de la aparición de metástasis y la prolongación de la supervivencia. Cabazitaxel ha demostrado un beneficio en la supervivencia de pacientes con CPRC metastásico, mientras que olaparib mostró actividad antitumoral tras la quimioterapia en aquellos tumores con mutaciones en genes de reparación del ADN. CONCLUSIONES: Estos datos ponen de manifiesto la incorporación de la inmunoterapia como alternativa novedosa para combatir el cáncer renal y de vejiga. Cabe destacar la llegada de nuevos agentes para líneas avanzadas en el carcinoma urotelial y queda establecida la eficacia de enzalutamida y apalutamida en CaP metastásico de novo. En el CPRC metastásico, cabacitaxel y olaparib (dirigido a mutaciones) son opciones terapéuticas prometedoras


OBJECTIVE: Review the latest evidence on urologic oncology on kidney, bladder and prostate tumors. METHODS: Abstracts on kidney, bladder and prostate cancer presented at the 2019 congresses (EAU, AUA, ASCO and ESMO) and the publications with the greatest impact in this period, with the highest evaluation by the OncoForum committee, are reviewed. RESULTS: In patients with metastatic kidney cancer, regimens including immunotherapy (nivolumab + ipilimumab, pembrolizumab) have been shown to be superior to sunitinib in terms of survival. In patients with non-muscle invasive bladder cancer, pembrolizumab has been shown to be an effective alternative in those refractory to bacillus Calmette-Guérin, while in patients with metastatic urothelial cancer, third-line enfortumab vedotin achieved a significant response rate (44%). In patients with localized prostate cancer (PCa), ultrafractionated external radiotherapy did not show any greater acute toxicity than fractionated or hypofractionated radiotherapy. The benefit of enzalutamide and apalutamide associated with castration has been confirmed in M1 PCa patients, regardless of disease volume. In patients with castration-resistant M0 PCa, treatment with enzalutamide, apalutamide or darolutamide has been associated with a delay in the occurrence of metastasis and prolonged survival. Cabazitaxel has demonstrated a survival benefit in patients with metastatic CRPC, while olaparib showed anti-tumor activity after chemotherapy in those tumors with mutations in DNA repair genes. CONCLUSIONS: These data show the implementation of immunotherapy as a novel alternative against renal and bladder cancer. The arrival of new agents for advanced urothelial carcinoma should be highlighted, and the efficacy of enzalutamide and apalutamide in de novo metastatic prostate cancer is established. In metastatic CRPC, cabazitaxel and olaparib (targeting mutations) are promising therapeutic options


Assuntos
Humanos , Oncologia/tendências , Neoplasias Renais/terapia , Neoplasias da Próstata/terapia , Neoplasias da Bexiga Urinária/terapia , Congressos como Assunto , Imunoterapia/métodos , Antineoplásicos Imunológicos/uso terapêutico , Metástase Neoplásica
17.
Urol Clin North Am ; 47(4): 433-442, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008494

RESUMO

Natural killer (NK) cells are potently cytolytic innate lymphocytes involved in the immune surveillance of tumors and virally infected cells. Although much progress has been made in manipulating the ability of T cells to recognize and eliminate tumors, a comprehensive understanding of NK-cell infiltration into solid tumors, and their amenability to immunomodulation, remains incomplete. This article discusses recent studies showing that urologic tumors are infiltrated by NK cells and that these NK cells are often dysfunctional, but that strategies interfering with inhibitory axes have significant potential to alleviate this dysfunction.


Assuntos
Imunoterapia/métodos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Terapia de Alvo Molecular/métodos , Neoplasias Urogenitais/terapia , Terapia Biológica/métodos , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Masculino , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Medição de Risco , Resultado do Tratamento , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias Urogenitais/imunologia
18.
Rev Med Suisse ; 16(710): 1920-1923, 2020 Oct 14.
Artigo em Francês | MEDLINE | ID: mdl-33058578

RESUMO

Intravesical bacillus Calmette-Guérin immunotherapy is currently the most effective treatment for non-infiltrating bladder tumors. Although rare, « BCGitis ¼, local or disseminated, is a serious complication of this therapy. The diagnosis is difficult and often delayed but the infection may progress to multi-systemic failure and can be fatal. The microbiological samples are often negative, and biopsies sometimes do not help. Treatment consists of antimycobacterial agents in combination with corticosteroids in case of severe presentation.


Assuntos
Vacina BCG/administração & dosagem , Vacina BCG/efeitos adversos , Imunoterapia/efeitos adversos , Inflamação/induzido quimicamente , Administração Intravesical , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Neoplasias da Bexiga Urinária/terapia
19.
Jpn J Clin Oncol ; 50(10): 1097-1107, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32895714

RESUMO

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.


Assuntos
Músculos/patologia , Tratamentos com Preservação do Órgão/tendências , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Humanos , Invasividade Neoplásica , Qualidade de Vida , Resultado do Tratamento
20.
Science ; 369(6510): 1481-1489, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32792462

RESUMO

Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances antitumor immunity are unclear. In this study, we isolated three bacterial species-Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species-that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer. We found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated antitumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required costimulation. Collectively, our study identifies a previously unknown microbial metabolite immune pathway activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.


Assuntos
Bifidobacterium/metabolismo , Microbioma Gastrointestinal , Imunoterapia , Inosina/metabolismo , Neoplasias Intestinais/terapia , Lactobacillus johnsonii/metabolismo , Melanoma/terapia , Neoplasias Cutâneas/terapia , Neoplasias da Bexiga Urinária/terapia , Animais , Anticorpos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/terapia , Receptor A2A de Adenosina/metabolismo , Linfócitos T/imunologia
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