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2.
Arch Esp Urol ; 72(9): 972-974, 2019 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-31697260

RESUMO

OBJECTIVE: To show and report two new cases of urological cutaneous metastasis. METHODS: We describe two skin metastases cases. The first patient corresponds to a renal tumor and the other to a urothelial tumor. RESULTS: 52-year-old female with stage IV renal tumor,which is treated with Sunitinib. 34 months later, she refers ajaw angle skin ulcer, considered metastasis.75-year-old male with stage IV mixed urothelial carcinoma,which is treated with cystoprostatectomy and adjuvantchemotherapy. 9 months later, he showed 5 skin lesionsin his thorax. A core biopsy was diagnostic of urothelialcutaneous metastases. CONCLUSIONS: Genitourinary skin metastasis are rareand have poor prognosis. The largest incidence is in renaltumors, followed by bladder and prostate malignancies.


Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Cutâneas , Neoplasias Urogenitais , Idoso , Carcinoma de Células de Transição/secundário , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/secundário , Neoplasias Urogenitais/patologia
3.
Medicine (Baltimore) ; 98(48): e18000, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770212

RESUMO

RATIONALE: Bladder cancer (BC) is commonly diagnosed in the urinary system and the most common subtype is transitional urothelial carcinoma (TCC). Even with the best treatment, tumor recurrence and metastases always occur. While clinicians commonly observe the metastases to pelvic lymph nodes, liver, lung, and bone, it may infrequently spread to some uncommon locations. PATIENT CONCERNS: The patient was a 67-year-old man with a diagnosis of high-grade TCC with squamous differentiation in the bladder and prostate. Subsequently, radical cystoprostatectomy, adjuvant radiotherapy, and chemotherapy were performed. However, he felt intermittent right scrotal pain about 1 year later. DIAGNOSIS: Ultrasound strongly suggested a testicular neoplasm of right testis, but the left was normal. INTERVENTIONS: The patient underwent a right radical orchiectomy and histopathology confirmed testicular metastatic neoplasm from bladder. Moreover, further examination with positron emission tomography revealed no visible distant spread of the urothelial carcinoma. OUTCOMES: No signs of tumor recurrence or distant metastasis were visible under follow-up 1 year after radical orchiectomy. LESSONS: Testicular mass may be metastatic tumor during follow-up for patients who were diagnosed as BC, especially for TCC with variant histology. The reason of this could be explained of residual micrometastases after surgery and need more examination to discover local micrometastases to apply more aggressive treatment.


Assuntos
Carcinoma de Células de Transição/secundário , Cistectomia/efeitos adversos , Prostatectomia/efeitos adversos , Neoplasias da Próstata/patologia , Neoplasias Testiculares/secundário , Neoplasias da Bexiga Urinária/patologia , Idoso , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Humanos , Masculino , Período Pós-Operatório , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Urotélio/patologia
6.
Urology ; 131: 130-135, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202854

RESUMO

OBJECTIVE: To address the incidence and potential risk factors of port site metastasis (PSM) in patients who underwent laparoscopic radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. MATERIALS AND METHODS: Between January 2013 and December 2018 laparoscopic RNU were performed in 240 patients at our institution, including 145 with renal pelvic tumor and 135 with ureteral tumor (40 patients have both tumor). Laparoscopies were performed through the transperitoneal approach in 28 patients, and retroperitoneal in 212 patients. Clinical data are retrospectively collected. RESULTS: Perioperative and pathologic data are available in all 240 cases. After a mean follow-up of 12.6 months (range 3-45 months), 4 patients (1.7%) developed PSM following retroperitoneal RNU at an average of 4.3 months. Tumor stage is T2N0M0 in one, T3N0M0 in two, and T3N1M0 in one, respectively. Tumor grade are high-grade urothelial carcinoma in all. The incidence of PSM is 2.8% (4/145) and 0.7% (1/135) in renal pelvic and ureteral tumor, respectively. CONCLUSION: We report a 1.7% incidence of PSM in upper tract urothelial carcinoma after laparoscopic RNU. We suggest that air leakage during retroperitoneal approach, high tumor stage (pT3) and grade, and advanced renal pelvic tumor with micrometastases could increase the potential risks of PSM.


Assuntos
Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/secundário , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Pelve Renal , Laparoscopia/efeitos adversos , Inoculação de Neoplasia , Nefroureterectomia/efeitos adversos , Nefroureterectomia/métodos , Neoplasias Ureterais/patologia , Neoplasias Ureterais/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/cirurgia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
7.
Int J Surg ; 66: 12-17, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31018160

RESUMO

OBJECTIVE: We investigated the impact of cisplatin-based adjuvant chemotherapy (AC) on oncologic outcomes including recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) after radical nephroureterectomy (RNU) for patients with pT3NanyM0 upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively reviewed 293 patients who underwent RNU for UTUC between 1995 and 2017. Clinicopathologic characteristics of patients were examined and compared according to the use of AC. Kaplan-Meier survival analysis was used to illustrate RFS, CSS and OS. Cox proportional hazard models were applied to identify factors predicting oncologic outcomes. RESULTS: Among the 293 total patients, 127 (43.3%) patients received AC. During a mean follow-up of 59.7 months, recurrence and/or distant metastasis were identified in 124 (42.3%) patients, and 106 (36.2%) patients died overall, of which 93 (31.7%) died from UTUC. The 5-year RFS, CSS and OS rates of overall patients were 51.3%, 68.0% and 64.7%, respectively. In multivariate analysis, AC was inversely associated with tumor recurrence (HR = 0.74, P = 0.028) but not significantly associated with death from UTUC (P = 0.237) and death from all-cause (P = 0.433). The 5-year RFS of patients who had received AC was 58.0%, while 44.0% for patients who had only been observed after RNU. CONCLUSION: AC improved RFS, but did not have a significant effect on CSS and OS in patients with pT3NanyM0 UTUCs following RNU. Further efforts are needed to identify reliable criteria in the clinic for patients that would benefit from AC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Idoso , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Nefroureterectomia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Urológicas/cirurgia
8.
Dermatol Online J ; 25(2)2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30865407

RESUMO

Enfortumab vedotin is an antibody-drug conjugate targeting nectin-4 and is being studied in the treatment of various epithelial carcinomas including urothelial carcinoma; early data suggests efficacy and tolerability. Rash has been described as an adverse event associated with treatment with enfortumab vedotin, but has not been characterized to date. We report a patient with metastatic urothelial carcinoma treated with enfortumab vedotin who developed erythematous, scaly papules and plaques on his torso and extremities with corresponding histologic features of vacuolar interface dermatitis and maturation disarray of keratinocytes. He was successfully treated with topical corticosteroids. Cutaneous toxicity appears to be a common adverse reaction in this growing class of antibody-drug conjugates.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Erupção por Droga/etiologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Ureterais/tratamento farmacológico , Idoso , Carcinoma de Células de Transição/secundário , Erupção por Droga/patologia , Humanos , Imunoconjugados/efeitos adversos , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Neoplasias Ureterais/secundário
9.
Surg Oncol ; 28: 208-213, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30851902

RESUMO

OBJECTIVE: To investigate the impact of variant urothelial carcinoma of the bladder (UCB) histologies on extra nodal extension (ENE) and survival in lymph node (LN) positive bladder cancer patients undergoing radical cystectomy (RC). MATERIAL AND METHODS: We meticulously reviewed all bladder specimens for presence of variant UCB histologies and LN specimen for presence and extent of ENE in 517 UCB patients treated with RC. Descriptive statistics, the Kaplan Meier method and multivariable Cox regression models evaluated the association between variant UCB histology, ENE and survival metrics including disease recurrence-free, cancer-specific, and overall survival, respectively. RESULTS: Overall, 138 patients had LN metastasis (27%), with a median number of 15 (IQR 9; 18) LNs removed. Among LN positive patients, 43 (31%) had ENE with a median length of 10 mm. Variant histology was present in 96 patients (18.6%) with squamous cell (12.0%) and sarcomatoid (2.5%) differentiation being the most common. In all patients, the presence of variant histology was neither associated with presence of LN metastasis nor ENE (all p-values = n.s.). In Kaplan-Meier analyses the presence of LN metastases and ENE in LN positive patients was significantly associated with disease recurrence and cancer-specific mortality, respectively (all p < 0.001). The presence of variant histology did not influence these outcomes (p = n.s.). In multivariable analyses, adjusted for standard UCB prognosticators, ENE, but not variant histology, independently predicted disease recurrence-free (hazard ratio (HR) 3.88, 95% confidence intervall (CI) 2.24-6.71, p < 0.001), cancer-specific (HR 4.60; 95% CI, 2.57-8.23, p < 0.001), and overall survival (HR 3.51; 95% CI, 2.10-5.86, p < 0.001). CONCLUSION: Variant UCB histologies do not seem to increase the incidence of LN metastasis or ENE. This study confirms ENE being a powerful predictor for outcomes in node positive UCB patients - regardless of variant histological differentiation. Our findings warrant validation in larger cohort setting.


Assuntos
Carcinoma de Células de Transição/mortalidade , Diferenciação Celular , Cistectomia/mortalidade , Excisão de Linfonodo/mortalidade , Linfonodos/patologia , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/cirurgia , Feminino , Seguimentos , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
10.
Eur Urol ; 75(5): 707-711, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30665814

RESUMO

Preclinical data indicate that radiotherapy works synergistically with pembrolizumab, but the effect and toxicity of this combination may depend on radiotherapy timing. We conducted a randomized phase 1 trial combining pembrolizumab with either sequential (A) or concomitant (B) stereotactic body radiotherapy (SBRT) in metastatic urothelial carcinoma (mUC). No dose-limiting toxicity occurred. Treatment-related adverse events (trAEs; Common Terminology Criteria for Adverse Events v4.0) of grade 1-2 occurred in six of nine and all nine patients in arms A and B, respectively. One grade 3 trAE occurred in arm B. No grade 4-5 trAEs occurred. Overall response rates of 0% and 44.4% were noted in arms A and B, respectively, as per Response Evaluation Criteria in Solid Tumors v1.1. The trial was not powered to compare efficacy between arms. Targeted sequencing of tissue DNA and circulating tumor DNA (ctDNA) revealed high genomic concordance. Treatment response was associated with ctDNA fraction decline. We conclude that sequential and concomitant SBRT can be safely combined with pembrolizumab in mUC and that the effect of SBRT timing on efficacy is worth exploring further. PATIENT SUMMARY: This study assessed the safety of pembrolizumab combined with radiotherapy at two different time points in metastatic bladder cancer. We conclude that the combination treatment was well tolerated.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células de Transição/terapia , Radiocirurgia/efeitos adversos , Neoplasias da Bexiga Urinária/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células de Transição/secundário , Terapia Combinada/efeitos adversos , Humanos , Critérios de Avaliação de Resposta em Tumores Sólidos , Fatores de Tempo , Neoplasias da Bexiga Urinária/patologia
11.
World J Urol ; 37(1): 95-105, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30238401

RESUMO

The SIU (Société Internationale d'Urologie)-ICUD (International Consultation on Urologic Diseases) working group on systemic therapy for metastatic bladder cancer has summarized the most recent findings on the aforementioned topic and came to conclusions and recommendations according to the evidence published. In Europe and the United States, treatment for metastatic UC has changed a great deal recently, mainly involving a move from chemotherapy to immune checkpoint blockers. This is particularly true in platinum-refractory disease, where supportive randomized data exist. Five checkpoint blockers have been approved in this setting by the FDA: avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab. Nivolumab, pembrolizumab, and atezolizumab have been approved in Europe.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma de Células de Transição/secundário , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Doxorrubicina/uso terapêutico , Humanos , Neoplasias Hepáticas/secundário , Metotrexato/uso terapêutico , Nivolumabe/uso terapêutico , Paclitaxel/administração & dosagem , Neoplasias da Bexiga Urinária/patologia , Vimblastina/uso terapêutico
13.
Eur Urol Focus ; 5(2): 242-249, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-28753897

RESUMO

BACKGROUND: Limited data is available on the role, and extent of, postchemotherapy lymphadenectomy (PC-LND) in patients with clinical evidence of pelvic (cN1-3) or retroperitoneal (RP) lymph node spread from urothelial bladder carcinoma. OBJECTIVE: To compare the outcomes of operated versus nonoperated patients after first-line chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Data from 34 centers was collected, totaling 522 patients, treated between January 2000 and June 2015. Criteria for patient selection were the following: bladder primary tumor, lymph node metastases (pelvic±RP) only, first-line platinum-based chemotherapy given. INTERVENTION: LND (with cystectomy) versus observation after first-line chemotherapy for metastatic urothelial bladder carcinoma. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Overall survival (OS) was the primary endpoint. Multiple propensity score techniques were adopted, including 1:1 propensity score matching and inverse probability of treatment weighting. Additionally, the inverse probability of treatment weighting analysis was performed with the inclusion of the covariates, that is, with doubly robust estimation. RESULTS AND LIMITATIONS: Overall, 242 (46.4%) patients received PC-LND and 280 (53.6%) observation after chemotherapy. There were 177 (33.9%) and 345 (66.1%) patients with either RP or pelvic LND only, respectively. Doubly robust estimation-adjusted comparison was not significant for improved OS for PC-LND (hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.31, p=0.479), confirmed by matched analysis (HR: 0.91, 95% CI: 0.60-1.36, p=0.628). This was also observed in the RP subgroup (HR: 1.12, 95% CI: 0.68-1.84). The retrospective nature of the data and the heterogeneous patient population were the major limitations. CONCLUSIONS: Although there were substantial differences between the two groups, after accounting for major confounders we report a nonsignificant OS difference with PC-LND compared with observation only. These findings may be hypothesis-generating for future prospective trials. PATIENT SUMMARY: We found no differences in survival by adding postchemotherapy lymphadenectomy in patients with pelvic or retroperitoneal lymph node metastatic bladder cancer. The indication to perform postchemotherapy lymphadenectomy in the most suitable patients requires additional studies.


Assuntos
Carcinoma de Células de Transição/secundário , Quimioterapia Adjuvante/efeitos adversos , Excisão de Linfonodo/efeitos adversos , Linfonodos/cirurgia , Neoplasias da Bexiga Urinária/secundário , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante/métodos , Cistectomia/métodos , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Pelve/patologia , Intervalo Livre de Progressão , Pontuação de Propensão , Espaço Retroperitoneal/patologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
14.
Urologia ; 86(3): 161-164, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30373476

RESUMO

INTRODUCTION: Primary carcinomas of the urethra differ by location and histologic subtype. Primary urethral cancer of the proximal urethra is rare and aggressive tumor with a high propensity for regional and distant metastases. CASE DESCRIPTION: In this case report, we present primary urothelial carcinoma of the prostatic urethra, diagnosed by transrectal ultrasound-guided biopsy of the prostate and having multiple metastases at the time of diagnosis. Metastatic patients were initiated chemotherapy according to the histological type of urethral cancer. CONCLUSION: Urothelial carcinomas of the urethra are rarely seen, and therefore there is no standard treatment regimen for early-stage or metastatic disease. Gemcitabine-, platinum-, and taxane-based treatments are used in the metastatic stage.


Assuntos
Carcinoma de Células de Transição/secundário , Neoplasias Uretrais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Próstata
15.
World J Urol ; 37(9): 1785-1799, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30367205

RESUMO

PURPOSE: Urothelial carcinoma of the bladder (UCB) is clinically and genetically a highly heterogeneous disease. Treatment decisions are usually based on histopathological workup and molecular diagnostics on tissue biopsies of the primary tumor or the metastatic site. Next to completely different molecular genotypes of phenotypically similar tumors, standard biopsies do not unconditionally allow real-time insight during the natural course of disease progression. Indeed, in UCB there is an imperative need of biomarkers for improving clinical staging, detecting minimal residual disease, predicting therapy response and prognosis and finally enabling patient stratification for multimodal, individualized treatment and therapy monitoring.Liquid biopsies of blood-based circulating biomarkers have evolved from bench to bedside in some cancer entities. METHODS: In a narrative review we are summerizing the latest evidence on CTC and ctDNA in muscle-invasive and metastatic UCB. RESULTS: In this review, we summarize the current status, limitations and future needs of circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA) in UCB. Moreover, we discuss the potential clinical application of CTC and ctDNA as prognostic markers at different UCB stages and their value for target therapy guidance. CONCLUSIONS: CTC and ctDNA are promising circulating biomarkers in UCB, but none of both has progressed from bench to bedside yet. These markers may support outcome prognostication, patient counseling follow-up monitoring, and potentially decision-making regarding chemotherapy. Further prospective clinical or randomized studies are urgently warranted.


Assuntos
Carcinoma de Células de Transição/sangue , DNA Tumoral Circulante/sangue , DNA de Neoplasias/sangue , Células Neoplásicas Circulantes , Neoplasias da Bexiga Urinária/sangue , Carcinoma de Células de Transição/secundário , Previsões , Humanos , Neoplasias da Bexiga Urinária/patologia
16.
Ophthalmic Plast Reconstr Surg ; 35(3): 213-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30489454

RESUMO

PURPOSE: To review the clinical features of orbital and choroidal metastases from urothelial carcinomas of the urinary tract among cases reported in the literature, and to describe a case of orbital metastasis from bladder cancer presenting as apparent internuclear ophthalmoplegia. METHODS: Case reports of orbital and choroidal metastases from urothelial carcinomas published in the literature from 1965 to 2018 were reviewed. Data collected included patient demographics, cancer stage and primary site, time to onset of ocular symptoms, length of presenting ocular symptoms, types of primary ocular symptoms, diagnostic imaging, histology, systemic and ocular treatments, and survival time. RESULTS: Twenty-eight cases of urothelial carcinoma with metastasis to the orbit or choroid were reviewed. Men were significantly more likely to suffer from this condition than women (p = 0.011). The average age of presentation with orbital symptoms was 63 years, with an average time of 19 months between primary cancer diagnosis and onset of orbital symptoms. Twenty-two patients had metastasis to the orbit and 6 to the choroid. In 4 cases, ocular deficits secondary to orbital and/or choroidal metastases were the initial presenting symptoms in patients with previously undiagnosed urothelial carcinoma. The most commonly noted primary ocular symptoms and signs consisted of decreased visual acuity, decreased ocular motility, proptosis, and diplopia. Average survival from onset of ocular symptoms was 4.67 months. CONCLUSIONS: Urothelial carcinoma may metastasize to the orbit or choroid; furthermore, its presentation may mimic internuclear ophthalmoplegia. It is recommended that any patient with visual symptoms and known urothelial cancer should undergo expedited workup for metastatic disease.


Assuntos
Carcinoma de Células de Transição/secundário , Estadiamento de Neoplasias , Órbita/diagnóstico por imagem , Neoplasias Orbitárias/secundário , Neoplasias Urológicas/patologia , Biópsia , Carcinoma de Células de Transição/diagnóstico , Humanos , Neoplasias Orbitárias/diagnóstico , Tomografia Computadorizada por Raios X
17.
Urol Oncol ; 37(2): 108-115, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30478012

RESUMO

OBJECTIVES: Serum γ-glutamyltransferase (GGT) is reportedly associated with prognosis in patients with various malignancies. However, the prognostic role of GGT is unknown among patients with advanced urothelial carcinoma (aUC). This study was designed to examine the prognostic role of serum GGT in patients with aUC. MATERIALS AND METHODS: Charts of 125 consecutive aUC patients (inoperable cT4 and/or metastasis to lymph nodes/distant organs) managed at a single cancer center between 2004 and 2016 were retrospectively reviewed. Variables collected included age, sex, body mass index, Karnofsky performance status, primary site, clinical tumor stage, lymph node/visceral metastasis, hepatic comorbidities, the presence of curative treatment before the diagnosis of aUC, white blood cell count, neutrophil-to-lymphocyte ratio, hemoglobin, albumin, lactate dehydrogenase, alkaline phosphatase, GGT, C-reactive protein, and treatments given after the diagnosis of aUC. Associations of variables with overall survival (OS) were analyzed using the Cox proportional hazard model. RESULTS: Serum GGT was elevated (≥60 U/l) at the diagnosis of aUC in 16 patients (13%). During follow-up period (median 12.1 months), 101 patients died (2-year OS rate, 32%). Patients with elevated GGT at the diagnosis of aUC had a significantly poorer prognosis than those with normal GGT with respective 2-year OS rates of 0% and 37% (P < 0.001). On multivariate analysis, elevated GGT was a significant and independent risk factor for shorter OS (hazard ratio, HR = 2.97; P < 0.001) as were poorer Karnofsky performance status (HR = 3.47; P < 0.001), elevated lactate dehydrogenase (HR = 1.86; P = 0.033), advanced age (HR = 1.82; P = 0.013), elevated neutrophil-to-lymphocyte ratio (HR = 1.80; P = 0.015), elevated C-reactive protein (HR = 1.73; P = 0.018), the absence of systemic chemotherapy (HR = 1.71; P = 0.035), and primary site of upper urinary tract (HR = 1.71; P = 0.014) in descending order by HR. The prognostic significance of elevated GGT was also observed in a subset of 101 patients who had been diagnosed with aUC at their first presentation. CONCLUSION: The present study for the first time demonstrated that elevated serum GGT was an independent adverse prognostic factor in aUC patients.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células de Transição/secundário , Neoplasias Urológicas/patologia , gama-Glutamiltransferase/sangue , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/enzimologia , Carcinoma de Células de Transição/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Neoplasias Urológicas/sangue , Neoplasias Urológicas/enzimologia , Neoplasias Urológicas/terapia
18.
Cancer ; 125(4): 533-540, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30570744

RESUMO

BACKGROUND: The authors evaluated mocetinostat (a class I/IV histone deacetylase inhibitor) in patients with urothelial carcinoma harboring inactivating mutations or deletions in CREB binding protein [CREBBP] and/or E1A binding protein p300 [EP300] histone acetyltransferase genes in a single-arm, open-label phase 2 study. METHODS: Eligible patients with platinum-treated, advanced/metastatic disease received oral mocetinostat (at a dose of 70 mg 3 times per week [TIW] escalating to 90 mg TIW) in 28-day cycles in a 3-stage study (ClinicalTrials.gov identifier NCT02236195). The primary endpoint was the objective response rate. RESULTS: Genomic testing was feasible in 155 of 175 patients (89%). Qualifying tumor mutations were CREBBP (15%), EP300 (8%), and both CREBBP and EP300 (1%). A total of 17 patients were enrolled into stage 1 (the intent-to-treat population); no patients were enrolled in subsequent stages. One partial response was observed (11% [1 of 9 patients; the population that was evaluable for efficacy comprised 9 of the 15 planned patients]); activity was deemed insufficient to progress to stage 2 (null hypothesis: objective response rate of ≤15%). All patients experienced ≥1 adverse event, most commonly nausea (13 of 17 patients; 77%) and fatigue (12 of 17 patients; 71%). The median duration of treatment was 46 days; treatment interruptions (14 of 17 patients; 82%) and dose reductions (5 of 17 patients; 29%) were common. Mocetinostat exposure was lower than anticipated (dose-normalized maximum serum concentration [Cmax ] after TIW dosing of 0.2 ng/mL/mg). CONCLUSIONS: To the authors' knowledge, the current study represents the first clinical trial using genomic-based selection to identify patients with urothelial cancer who are likely to benefit from selective histone deacetylase inhibition. Mocetinostat was associated with significant toxicities that impacted drug exposure and may have contributed to modest clinical activity in these pretreated patients. The efficacy observed was considered insufficient to warrant further investigation of mocetinostat as a single agent in this setting.


Assuntos
Benzamidas/uso terapêutico , Proteína de Ligação a CREB/genética , Carcinoma de Células de Transição/tratamento farmacológico , Proteína p300 Associada a E1A/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Mutação , Pirimidinas/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/secundário , Feminino , Seguimentos , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia
19.
Int J Surg Pathol ; 27(2): 120-133, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30509113

RESUMO

The differential diagnosis between high-grade prostate carcinoma and infiltrating urothelial carcinoma (UC) in transurethral resection prostate specimens as well as cystoprostatectomy specimens may often be challenging due to morphologic and clinical overlap of the 2 entities. Such distinction has critical therapeutic and staging consequences, yet it is hampered by both issues in morphology and by the low accuracy rates of single immunohistochemical markers, as reported in literature. This review aims to provide a comprehensive analysis of the available morphological and immunohistochemical parameters, which may allow to discriminate between prostate carcinoma and urothelial carcinoma in the proper clinical context and to discuss their diagnostic applications in daily practice.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/diagnóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Carcinoma de Células de Transição/secundário , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Neoplasias da Próstata/secundário , Neoplasias da Bexiga Urinária/patologia
20.
Curr Urol Rep ; 19(12): 109, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30406502

RESUMO

PURPOSE OF REVIEW: Until recently, effective treatment options for patients with advanced urothelial carcinoma were limited to platinum-based chemotherapy. In the post-platinum setting and for patients ineligible for cisplatin, minimally effective second-line chemotherapy was used and outcomes were poor. The approval of immune checkpoint inhibitors has significantly changed the treatment landscape of urothelial carcinoma. Here, we review current data demonstrating their efficacy in advanced disease and ongoing trials investigating novel combination strategies. RECENT FINDINGS: Since May 2016, five agents targeting the programmed cell death 1 (PD-1) pathways have been approved for use after progression on platinum-based chemotherapy. Further, atezolizumab and pembrolizumab are approved for use in cisplatin-ineligible patients with high programmed death-ligand 1 (PD-L1) expression. Preliminary studies have shown their safety and efficacy as neoadjuvant therapy in muscle-invasive bladder cancer. Several ongoing trials are investigating these agents in combination with radiation therapy, platinum-based chemotherapy, other immune checkpoint inhibitors, and targeted agents. Immune checkpoint inhibitors have demonstrated durable efficacy in patients with advanced urothelial carcinoma as first- and second-line therapy. Ongoing studies will help define the optimal sequence, combination strategies, and predictive biomarkers of response.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células de Transição/terapia , Neoplasias da Bexiga Urinária/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/secundário , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/imunologia , Cisplatino/uso terapêutico , Terapia Combinada , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia
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