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BACKGROUND: About 30% of Prostate cancer (PCa) patients progress to metastatic PCa that remains largely incurable. This evidence underlines the need for the development of innovative therapies. In this direction, the potential research focus might be on long non-coding RNAs (lncRNAs) like H19, which serve critical biological functions and show significant dysregulation in cancer. Previously, we showed a transcriptional down-regulation of H19 under combined pro-tumoral estrogen and hypoxia treatment in PCa cells that, in turn, induced both E-cadherin and ß4 integrin expression. H19, indeed, acts as transcriptional repressor of cell adhesion molecules affecting the PCa metastatic properties. Here, we investigated the role of H19/cell adhesion molecules circuitry on in vivo PCa experimental tumor growth and metastatic dissemination models. METHODS: H19 was silenced in luciferase-positive PC-3 and 22Rv1 cells and in vitro effect was evaluated by gene expression, proliferation and invasion assays before and after treatment with the histone lysine demethylase inhibitor, GSK-J4. In vivo tumor growth and metastasis dissemination, in the presence or absence of GSK-J4, were analyzed in two models of human tumor in immunodeficient mice by in vivo bioluminescent imaging and immunohistochemistry (IHC) on explanted tissues. Organotypic Slice Cultures (OSCs) from fresh PCa-explant were used as ex vivo model to test GSK-J4 effects. RESULTS: H19 silencing in both PC-3 and 22Rv1 cells increased: i) E-cadherin and ß4 integrin expression as well as proliferation and invasion, ii) in vivo tumor growth, and iii) metastasis formation at bone, lung, and liver. Of note, treatment with GSK-J4 reduced lesions. In parallel, GSK-J4 efficiently induced cell death in PCa-derived OSCs. CONCLUSIONS: Our findings underscore the potential of the H19/cell adhesion molecules circuitry as a targeted approach in PCa treatment. Modulating this interaction has proven effective in inhibiting tumor growth and metastasis, presenting a logical foundation for targeted therapy.
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Metastatic urothelial carcinoma (mUC) is a lethal disease for which platinum-based chemotherapy represents the standard of care; however, long-term survival is achieved only in a minority of patients. Recently, along with important advances in the comprehension of the biology of this disease, the treatment paradigm of mUC has undergone a rapid expansion with the approval of several immune-checkpoint inhibitors (ICIs) and targeted agents in both first- and second-line settings. Cisplatin-based chemotherapy remains the backbone of first-therapy for mUC; nevertheless, for those patients who do not progress after the full course of first-line chemotherapy, maintenance treatment with the anti-PD-L1 avelumab showed to prolong overall survival compared observation alone. Moreover, the disappointing results of chemotherapy in pre-treated patients have led to the investigation and the subsequent approval of the anti-PD-1 pembrolizumab, which showed an unprecedented survival benefit when compared to second-line chemotherapy. Recently, target therapy with the antibody-drug conjugate (ADC) enfortumab vedotin, directed against Nectin-4, showed outstanding results in patients treated with both chemotherapy and immunotherapy. The FGFR inhibitor erdafitinib and sacituzumab govitecan, an ADC targeting Trop-2, demonstrated encouraging activity in phase II studies and are currently under investigation in randomized phase III trials. ICIs and targeted therapies also demonstrated promising results as first-line treatment of cisplatin-ineligible patients; randomized trials of ICIs alone or in combination with targeted agents are ongoing and may broaden the therapeutic armamentarium for this category of patients. In this review, we describe the current state of art for the treatment of mUC; in addition, we present the latest evidences from the most recent literature and congress presentations. Finally, we illustrate the key ongoing clinical trials, focusing on ICIs and target therapies.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Cisplatino/uso terapêutico , Imunoterapia/métodosRESUMO
BACKGROUND: Recently, it was reported that the Bladder EpiCheck test is likely to represent a valid tool in the diagnostic process of patients who have suspected bladder carcinoma, with some controversial management decisions because of the technical limitations of cytology. METHODS: Two hundred ninety patients with a diagnosis of nonmuscle-invasive bladder carcinoma who were admitted at the authors' department from March 2019 to December 2019 were treated and followed for 1 year. During follow-up, all patients were evaluated by voided urine cytology, white-light cystoscopy (according to European Association of Urology guidelines), and the Bladder EpiCheck test. RESULTS: The cytologic diagnoses of high-grade urothelial carcinoma (HGUC) and suspicious for HGUC were histologically confirmed in 5 of 20 patients (25%) who had quantitative Bladder EpiCheck scores (EpiScores) from 60 to 69, in 23 of 36 patients (64%) who had EpiScores from 70 to 79, and in 42 of 56 patients (75%) and 57 of 63 patients (90%) who had EpiScores between 80 and 89 and EpiScores >90, respectively. Of 48 patients who had a cytologic diagnosis of HGUC or suspicious for HGUC with EpiScores ≥60 and negative histology, 20 (42%) had a recurrence of HGUC, which was cytologically and histologically confirmed, at 6-12 months during follow-up. CONCLUSIONS: To the best of the authors' knowledge, this is the first study in which patients at high risk for HGUC were stratified using the Bladder EpiCheck EpiScore. The results validate this methylation analysis tool as a useful method for predicting recurrent HGUC during the follow-up of patients with nonmuscle-invasive bladder carcinoma.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Sistema Urinário , Humanos , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/patologia , Bexiga Urinária/patologia , Metilação de DNA , Sistema Urinário/patologia , Citodiagnóstico/métodos , Urina , Urotélio/patologiaRESUMO
BACKGROUND: The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection of a bladder tumor consists of adjuvant intravesical therapy and strict and long surveillance with urine cytology and cystoscopy. The Bladder EpiCheck test (Nucleix Ltd) (BE) is a newly developed urinary markers based on DNA methylation changes in a panel of 15 genomic biomarkers, with a promising performance in term of non-invasive NMIBC detection. METHODS: In this study we prospectively enrolled 151 consecutive patients with high grade NMIBC, treated with intravesical BCG and mitomycin C therapy and evaluated during the follow-up by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. The Bladder EpiCheck test was performed at the same time of urine cytology in voided specimen. In all cases with positive cytology the diagnosis was confirmed by histology and a diagnosis was made according to the 2017 tumor, node, metastasis (TNM) classification and graded using both the 1973 and the 2004 World Health Organization (WHO) classifications. RESULTS: At three months of follow-up, we reported similar overall specificity rates for BE and urine cytology (85,1% vs 86,3%). In the group of patients with carcinoma in situ (CIS), we found the same specificity for BE and urine cytology (81,4%), while in the groups of patients with papillary high grade NMIBC, the specificity of BE was higher compared to cytology (96,3% vs 90,4%). The sensitivity of BE was always higher compared to cytology during all the follow-up both for papillary NMIBC and CIS. CONCLUSION: In the early follow-up of NMIBC the EpiCheck test might replace urinary cytology.
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Carcinoma in Situ , Neoplasias da Bexiga Urinária , Carcinoma in Situ/patologia , Cistoscopia , Feminino , Seguimentos , Humanos , Masculino , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
Numerous studies showed that bladder urothelial carcinoma and upper urothelial tract carcinoma (UTUC) display clinical and genomic similarities. In order to analyze that the same panel of biomarkers used in the diagnosis of bladder urothelial carcinoma could be suitable for early detection of UTUC, we performed a retrospective study in which we analyzed Bladder EpiCheck scores in the urinary samples obtained by selective ureteral catheterization in a high-grade UTUC cohort, correlating the results with urinary cytology and diagnostic urethral biopsies. The present study represents a retrospective analysis of 82 patients with clinically localized high-grade UTUC (60 renal pelvis UTUC, 22 ureter UTUC) who had undergone a radical nephroureterectomy (RNU) at our Urology department from June 2018 to November 2020. Before any surgical procedure, one sample of urine, obtained by selective ureteral catheterization, was collected for each patient for cytological examination, and the remaining material was stored for the Bladder EpiCheck test. Our results showed that the sensitivity of the methylation test for high-grade UTUC was about 97.4%, significantly higher than the sensitivity of urinary cytology either considering the HGUC cytological diagnosis or including in the positive cases the SHGUC cytological diagnosis (97.4% versus 59% or 70.5%). The methylation analysis of urinary samples may represent a valid tool in the diagnostic process of patients with suspected UTUC. In cases with a difficult clinical decision after upper urinary tract biopsy and cytology, the methylation test could assist in the clinical management of UTUC patients.
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Carcinoma de Células de Transição/urina , Citodiagnóstico/métodos , Metilação de DNA , Neoplasias Urológicas/urina , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Urológicas/diagnósticoRESUMO
OBJECTIVE: To identify in which cases after cytological diagnosis, the Bladder EpiCheck test could represent an effective tool in non-muscle invasive bladder carcinoma or an useless expence. MATERIALS AND METHODS: 375 patients diagnosed with non-muscle invasive bladder cancer, 269 with high grade urothelial carcinoma and 106 with carcinoma in situ, were treated and followed for 1 year. The treatment was an intravesical instillation of Bacillus Calmette-Guerin in 305 patients and Mitomycin-C in 70 patients. During the follow-up patients were evaluated by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. Bladder EpiCheck test was performed together with cytology in all cases. RESULTS: Analyzing Bladder Epicheck results for each category defined by the Paris System for Reporting Urinary Cytology, we found that the Episcore >60 correlates with histological diagnosis of high grade urothelial carcinoma (HGUC) in atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma (Pâ¯=â¯0.0002 Odds Ratio 0.05926 95% Confidence Interval from 0.01127 to 0.3116 and Pâ¯=â¯0.0009 Odds Ratio 0.03155 95% Confidence Interval from 0.001683 to 0.5914, Fisher's exact test, respectively), while in Negative for high grade urothelial carcinoma and HGUC patients Episcore is not helpful to identify cases with histological diagnosis of HGUC (Pâ¯=â¯0.101 and Pâ¯=â¯0.58 Fisher's exact test, respectively). Considering an Episcore ≥ 90 in the HGUC cytological group, this seems not to be correlated with a histological diagnosis of HGUC (Pâ¯=â¯0.090 Fisher's exact test). CONCLUSIONS: Cytology and Bladder EpiCheck test in combination may have the potential to reduce cystoscopies in the follow-up of non-muscle invasive bladder cancer only for cytological diagnoses of atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma . Moreover, in patients with a cytological diagnosis of Negative for high grade urothelial carcinoma or HGUC, cytology alone seems to be safe and cost-effective.
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Carcinoma in Situ/patologia , Carcinoma in Situ/urina , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/urina , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/urina , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Vacina BCG/administração & dosagem , Carcinoma in Situ/tratamento farmacológico , Carcinoma de Células de Transição/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Invasividade Neoplásica , Estudos Retrospectivos , Urinálise/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
AIMS: Bladder EpiCheck is one of several urinary tests studied to identify bladder tumours and analyses 15 methylation biomarkers determining bladder cancer presence on the basis of methylation profile. METHODS: 374 patients diagnosed with high-grade non-muscle invasive bladder cancer were treated and followed for 1 year with voided urine cytology and white-light cystoscopy and biopsies according to European Association of Urology Guidelines. 268 cases were diagnosed with high-grade papillary carcinoma, while 106 cases were carcinoma in situ. Bladder EpiCheck test was performed together with cytology in all cases. RESULTS: Comparing cytological categories of negative for high-grade urothelial carcinoma (NHGUC) and atypical urothelial cells (AUCs), we found that an EpiScore <60 correlates with NHGUC (p=0.0003, Fisher's exact test), while comparing AUC and suspicious for high-grade urothelial carcinoma (SHGUC) or SHGUC and high-grade urothelial carcinoma (HGUC) categories, an EpiScore ≥60 correlates with SHGUC and HGUC, respectively (p=0.0031 and p=0.0027, Fisher's exact test). In each TPS category, we found that sensitivity, specificity, Positive Predicitve Value (PPV) and Negative Predictive Value (NPV) of the Bladder EpiCheck test in HGUC category were higher than those observed in SHGUC group (sensitivity=98%, specificity=100%, NPV=85.7%, PPV=100% vs sensitivity=86.6%, specificity=52.3%, NPV=84.6%, PPV=56.5%). CONCLUSIONS: Analysing methylation study results, we demonstrated that different TPS cytological categories also carry a distinct molecular signature. Moreover, our results confirm that cytological categories SHGUC and HGUC are different entities also from a molecular point of view and should continue to represent distinct groups in TPS.
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Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/diagnóstico , Metilação de DNA , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/urina , Citodiagnóstico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/urinaRESUMO
Biopsy proven Gleason score is essential to decide treatment modalities for prostate cancer, either surgical (radical prostatectomy) or non-surgical (active surveillance, watchful waiting, radiation therapy and hormone therapy). Several studies indicated that biopsy proven Gleason score may underestimate Gleason score at radical prostatectomy, hence we aimed to calculate the minimum length of biopsy cores needed to have Gleason score agreement. We evaluated 115 prostate cancer patients who underwent multiparametric magnetic resonance/transperineal ultrasonography fusion biopsy and subsequently, radical prostatectomy. Biopsy proven Gleason score was consistent with Gleason score at subsequent radical prostatectomy in 82.6% of patients, while in 17.4% of patients, Gleason score was higher at radical prostatectomy. Gleason score agreement showed a strong direct association with a ratio > 0.05 between the total volume of biopsies performed in tumor area and the volume of the corresponding tumor at radical prostatectomy. A significant association was also found with a ratio ≥ 0.0034 between the tumor volume in the biopsy and the volume of the corresponding tumor at radical prostatectomy and with a ratio ≥ 0.086 between the tumor volume in the biopsy and the total volume of biopsies performed in the tumor area. These results could be exploited to calculate the minimum length of biopsy cores needed to have a correct Gleason score estimation and therefore be used in fusion targeted biopsies with volume adjustments.
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This correction is being done to update the right surname of first name of authors of this manuscript. This does not change the results or the views presented in this manuscript.
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Carcinoma in situ (CIS) is believed to be a precursor of muscle-invasive carcinomas that may arise from these flat high-grade, superficial urothelial lesions. CIS accounts for approximately 10% of all bladder tumors. Therapeutic options for urothelial CIS are limited, and in order to inhibit disease progression and recurrence, current guidelines recommend transurethral resection (TURBT) followed by intravesical administration of Bacillus of Calmette-Guerin (BCG). Approximately 30-40% of patients fail the BCG therapy with recurrence and progression of disease. In the present study, we examined the expression of PD-L1 both in neoplastic epithelial cells and in stromal inflammatory cells in patients with diagnosis of CIS primary responders and not responders to BCG therapy, in order to verify if the PD-L1 expression could identify patients resistant to BCG treatment. Moreover, we analyzed on the same cases the immunoreactivities of anti-PD-L1 MoAbs such as SP263, C23, and SP142. Our results have showed that PD-L1 expression in tumor cells and in immune cell compartment is higher in BCG-unresponsive group than in BCG responders, but only the PD-L1 22C3 expression in tumor cells seems to be associated with recurrence of disease (p = 0.035; OR 0.1204; CI 95% from 0.0147 to 1.023). Hence, our data suggest that the PD-L1 22C3 expression could help to identify CIS that fail the BCG therapy, supporting the hypothesis that enhanced levels of intratumoral PD-L1 22C3 expressed by the tumor cells may explain the failure of BCG immunotherapy.
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Recidiva Local de Neoplasia/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Bexiga Urinária/metabolismo , Neoplasias Urológicas/metabolismo , Idoso , Anticorpos Monoclonais/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologiaRESUMO
Estrogen and hypoxia promote an aggressive phenotype in prostate cancer (PCa), driving transcription of progression-associated genes. Here, we molecularly dissect the contribution of long non-coding RNA H19 to PCa metastatic potential under combined stimuli, a topic largely uncovered. The effects of estrogen and hypoxia on H19 and cell adhesion molecules' expression were investigated in PCa cells and PCa-derived organotypic slice cultures (OSCs) by qPCR and Western blot. The molecular mechanism was addressed by chromatin immunoprecipitations, overexpression, and silencing assays. PCa cells' metastatic potential was analyzed by in vitro cell-cell adhesion, motility test, and trans-well invasion assay. We found that combined treatment caused a significant H19 down-regulation as compared with hypoxia. In turn, H19 acts as a transcriptional repressor of cell adhesion molecules, as revealed by up-regulation of both ß3 and ß4 integrins and E-cadherin upon H19 silencing or combined treatment. Importantly, H19 down-regulation and ß integrins induction were also observed in treated OSCs. Combined treatment increased both cell motility and invasion of PCa cells. Lastly, reduction of ß integrins and invasion was achieved through epigenetic modulation of H19-dependent transcription. Our study revealed that estrogen and hypoxia transcriptionally regulate, via H19, cell adhesion molecules redirecting metastatic dissemination from EMT to a ß integrin-mediated invasion.
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Regulação Neoplásica da Expressão Gênica , Integrina beta3/genética , Integrina beta4/genética , Neoplasias da Próstata/genética , RNA Longo não Codificante/metabolismo , Animais , Adesão Celular , Linhagem Celular , Linhagem Celular Tumoral , Estrogênios/metabolismo , Estrogênios/farmacologia , Humanos , Hipóxia , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/fisiopatologia , Ratos , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
De-novo metastatic castration sensitive prostate cancer (mCSPC) is a subgroup of prostate cancer associated with poor prognosis. Recently, the treatment of mCSPC has been enriched by new life-prolonging options, including the combination of docetaxel or abiraterone acetate with androgen deprivation therapy (ADT). Of note, the advantage of chemohormonal therapy was more relevant in the subgroup of high-volume disease compared to low-volume, while the survival prolongation of abiraterone was observed only in high-risk patients. Choosing the most appropriate therapy is one of the most debated issues. This review describes the latest news on de-novo mCSPC to better outline patients' management. At the ESMO 2018 Congress two novel studies focused on this setting have been presented, trying to define the role of radiotherapy to the primary tumour and the efficacy of abiraterone acetate in the subset of low-risk patients. We have analysed these results in light of the evidence already available.
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Seleção de Pacientes , Neoplasias de Próstata Resistentes à Castração/classificação , Neoplasias de Próstata Resistentes à Castração/terapia , Terapia Combinada , Gerenciamento Clínico , Humanos , Masculino , Prognóstico , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
ABSTRACT Objectives: To evaluate the neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor for response of high risk non muscle invasive bladder cancer (HRNMIBC) treated with BCG therapy. Materials and Methods: Between March 2010 and February 2014 in a tertiary center 100 consecutive patients with newly diagnosed HRNMIBC were retrospectively analyzed. Patients were divided according to NLR value: 46 patients with NLR value less than 3 (NLR < 3 group), and 54 patients with NLR value more than 3 (NLR ≥ 3 group). At the end of follow-up 52 patients were high grade disease free (BCG-responder group) and 48 patients underwent radical cystectomy for high grade recurrence or progression to muscle invasive disease (BCG non-responder group). The average follow-up was 60 months. Intervention: analysis and correlation of preoperative NLR value with response to BCG in terms of recurrence and progression. Results: The optimal cut-off for NLR was ≥ 3 according to the receiver operating characteristics analysis (AUC 0.760, 95% CI, 0.669-0.850). Mean NLR value was 3.65 ± 1.16 in BCG non-responder group and 2.61 ± 0.77 in BCG responder group (p = 0.01). NLR correlated with recurrence (r = 0.55, p = 0.01) and progression risk scores (r = 0.49, p = 0.01). In multivariate analysis, NLR (p = 0.02) and EORTC recurrence risk groups (p = 0.01) were associated to the primary endpoint. The log-rank test showed statistically significant difference between NLR < 3 and NLR ≥ 3 curves (p < 0.05). Conclusions: NLR value preoperatively evaluated could be a useful tool to predict BCG response of HRNMIBC. These results could lead to the development of prospective studies to assess the real prognostic value of NLR in HRNMIBC.
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Humanos , Masculino , Feminino , Idoso , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vacina BCG/uso terapêutico , Linfócitos/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Neutrófilos/patologia , Prognóstico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/patologia , Biomarcadores Tumorais/sangue , Cistectomia , Estudos Retrospectivos , Contagem de Linfócitos , Progressão da Doença , Gradação de Tumores , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de NeoplasiasRESUMO
OBJECTIVES: To evaluate the neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor for response of high risk non muscle invasive bladder cancer (HRNMIBC) treated with BCG therapy. MATERIALS AND METHODS: Between March 2010 and February 2014 in a tertiary center 100 consecutive patients with newly diagnosed HRNMIBC were retrospectively analyzed. Patients were divided according to NLR value: 46 patients with NLR value less than 3 (NLR < 3 group), and 54 patients with NLR value more than 3 (NLR ≥ 3 group). At the end of follow-up 52 patients were high grade disease free (BCG-responder group) and 48 patients underwent radical cystectomy for high grade recurrence or progression to muscle invasive disease (BCG non-responder group). The average follow-up was 60 months. INTERVENTION: analysis and correlation of preoperative NLR value with response to BCG in terms of recurrence and progression. RESULTS: The optimal cut-off for NLR was ≥ 3 according to the receiver operating characteristics analysis (AUC 0.760, 95% CI, 0.669-0.850). Mean NLR value was 3.65 ± 1.16 in BCG non-responder group and 2.61 ± 0.77 in BCG responder group (p = 0.01). NLR correlated with recurrence (r = 0.55, p = 0.01) and progression risk scores (r = 0.49, p = 0.01). In multivariate analysis, NLR (p = 0.02) and EORTC recurrence risk groups (p = 0.01) were associated to the primary endpoint. The log-rank test showed statistically significant difference between NLR < 3 and NLR ≥ 3 curves (p < 0.05). CONCLUSIONS: NLR value preoperatively evaluated could be a useful tool to predict BCG response of HRNMIBC. These results could lead to the development of prospective studies to assess the real prognostic value of NLR in HRNMIBC.
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Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Linfócitos/patologia , Neutrófilos/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Biomarcadores Tumorais/sangue , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Cistectomia , Progressão da Doença , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND: In case of high grade non-muscle invasive bladder cancer (HG-NMIBC), intravesical BCG represents the first-line treatment; despite the "gold" standard therapy, up to 50% of patients relapse, needing radical cystectomy. Hence, alternative therapeutic strategies have been developed. The aim of the study was to evaluate a first-line salvage treatment with EMDA®-MMC in patients with HGNMIBC unresponsive to BCG. METHODS: We carried out a prospective, single-center, single-arm Phase II study in order to evaluate the efficacy (in terms of recurrence and progression) and the safety of the EMDA®-MMC treatment in 26 (21 male, 5 female) consecutive patients with "BCG refractory" HGNMIBC on a 3 years follow-up. EMDA®-MMC treatment consisted of 40 mg of MMC diluted in 100 ml of sterile water retained in the bladder for 30 min with 20 mA pulsed electric current. EMDA®-MMC regimen consisted of an induction course of 6 weekly instillations followed by a maintenance course of 6 monthly instillations. Follow-up was performed with systematic mapping biopsies of the bladder (with sampling in the prostatic urethra for men), voiding and washing urinary cytology, radiological study of the upper urinary tract. We performed Survival Kaplan-Meier curves and Log-rank test in order to analyze high grade disease-free survival. RESULTS: At the end of follow-up, 16 patients (61.5%) preserved their native bladder; 10 patients (38.4%) underwent radical cystectomy, in 6 patients (23.1%) for recurrent HGNMIBC and in 4 patients (15.4%) for progression to muscle-invasive disease. At the end of follow-up, stratifying patients based on TNM classification (TaG3, T1G3, Cis, TaT1G3 + Cis), disease-free rates were 75, 71.4, 50 and 25%, respectively; survival curves showed statistically significant differences (p value < 0.05). Regarding toxicity, we reported severe adverse systemic event of hypersensitivity to the MMC in 3 patients (11.5%), and local side effects in 6 patients (26.1%). CONCLUSIONS: In the field of alternative strategies to radical cystectomy, the EMDA®-MMC could be considered safe and effective in high-risk NMIBC unresponsive to BCG, as a "bladder sparing" therapy in selected patients. Multicenter studies with a larger number of patients and a longer follow-up might confirm our preliminary results. TRIAL REGISTRATION: EudraCT2017-002585-43. 17 June 2017 (retrospectively registered).
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Antibióticos Antineoplásicos/administração & dosagem , Bombas de Infusão , Mitomicina/administração & dosagem , Mycobacterium bovis , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Feminino , Seguimentos , Humanos , Bombas de Infusão/tendências , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Estudos Prospectivos , Fatores de Risco , Terapia de Salvação/tendências , Fatores de Tempo , Falha de Tratamento , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
BACKGROUND: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. METHODS: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). RESULTS: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. CONCLUSIONS: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.
Assuntos
Terapia Neoadjuvante/psicologia , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Atividades Cotidianas , Fatores Etários , Idoso , Inquéritos Epidemiológicos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Intervenção Coronária Percutânea , Estudos Prospectivos , Neoplasias da Próstata/fisiopatologia , Análise de Regressão , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Chemohyperthermia (C-HT) or electromotive drug administration (EMDA) are alternative therapies to radical cystectomy in patients with non-muscle-invasive bladder cancer who do not respond to intravesical therapy with bacille Calmette-Guérin. METHODS: The authors investigated a group of 87 patients with a diagnosis of high-grade non-muscle-invasive bladder carcinoma or carcinoma in situ. Of these, 45 patients received EMDA of mitomycin (EMDA/MMC) and 42 patients were treated with C-HT and mitomycin therapy (C-HT/MMC). In accordance with the Paris System for Reporting Urinary Cytology, a cytological diagnosis was made and patients with diagnoses of atypical urothelial cells (AUC), suspicious high-grade urothelial carcinoma (SHGUC), or high-grade urothelial carcinoma also underwent histological bladder biopsies. RESULTS: In accordance with the Paris System for Reporting Urinary Cytology, the AUC cases may have cytological features of SHGUC present on atypical degenerated cells. In analyzing the AUC group without the SHGUC cases diagnosed on the basis of degenerated urothelial cells, the authors found a significant association between the AUC category and a negative histological biopsy. The SHGUC group, including cases with a SHGUC diagnosis rendered on degenerated urothelial cells, was associated with high-grade urothelial carcinoma or carcinoma in situ (P = .0269 for patients treated with EMDA/MMC and P = .0049 for patients treated with C-HT/MMC). CONCLUSIONS: In the urine samples from patients treated with EMDA/MMC or C-HT/MMC, a diagnosis of SHGUC could be made even on degenerated urothelial cells when considering cellular degeneration as a "physiological" consequence of the treatment that involves either normal or neoplastic cells. Cancer Cytopathol 2018;126:200-6. © 2018 American Cancer Society.
Assuntos
Antineoplásicos/uso terapêutico , Hipertermia Induzida , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/terapia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Biópsia , Terapia Combinada , Vias de Administração de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/patologiaRESUMO
AIMS: The injection of botulinum neurotoxin A (BTA) into the prostate represents a minimally invasive treatment in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH). We evaluated the effectiveness of BTA in treating patients with BPH unresponsive to combined medical therapy (CMT), using urodynamic investigations. METHODS: This is a randomized, placebo-controlled, double blind trial. Twenty consecutive patients were randomly assigned to receive intraprostatic BTA injection (n = 10) or saline solution (SS) (n = 10). Patients in the intervention group (IG) received 200-300 UI of BTA diluted in 6-8 mL of SS and injected into the transitional zone. Patients in the control group (CG) were treated with SS alone. Primary endpoint was International Prostate Symptom Score (IPSS). Secondary endpoints were: maximum flow rate (Qmax), postvoid residual volume (PVR), maximum cystometric capacity (MCC), bladder outlet obstruction index (BOOI), safety, quality of life (QoL) score, and Patient Reported Outcome (PROs). RESULTS: All patients in the IG reported subjective improvement starting after 1 month. At 3 months of follow-up IPSS, QoL, PVR were reduced by 55,3% (P < 0.01), and 50% (P < 0.01), 80,6%, (P < 0.01), respectively. Qmax was increased by 68% (P < 0.01). MCC increased by 27% (P < 0.01) and BOOI decreased by 54% (P < 0.01). PROs analysis revealed that 90% of patients in the IG reported a subjective symptomatic relief and treatment satisfaction. No local or systemic side effects were observed in any group. CONCLUSIONS: These results indicated that intraprostatic BTA is safe and can improve LUTS and QoL in patients with BPH and unsatisfactory response to CMT.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/complicações , Urodinâmica/efeitos dos fármacos , Agentes Urológicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Toxinas Botulínicas Tipo A/administração & dosagem , Método Duplo-Cego , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento , Agentes Urológicos/administração & dosagemRESUMO
Pros-IT CNR study provides a real-life report on changes in quality of life 6 mo after the diagnosis of prostate cancer.
Assuntos
Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/psicologia , Qualidade de Vida/psicologia , Idoso , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapiaRESUMO
The treatment of non muscle-invasive bladder cancer (NMIBC) encompasses a range of different procedures. Electromotive drug administration (EMDA) and chemo-hyperthermia (C-HT; Synergo) represent a minimally-invasive methods of intravesical instillation of therapeutic agents as mitomycin C (MMC). We selected patients with high grade NMIBC, BCG non responder, treated with EMDA/MMC and C-HT/MMC and we also examined the morphological changes in urine cytology samples. During the period from 2012 to 2014, 110 patients with high grade NMIBC, BCG refractory were selected. All cases examined were classified according to The Paris System Classification as negative for high urothelial carcinoma (NHGUC) or atypical urothelial cells (AUC) with a mean of follow-up of 15 months and the cytological diagnosis were confirmed by histological biopsies. In particular 50 patients were treated with EMDA/MMC and 60 patients underwent to C-HT/MMC. The morphological changes were evaluated in urine samples processed by Thin Prep method. In the 50 patients treated with EMDA/MMC, 35 samples were classified as NHGUC and 15 cases were classified as AUC, while in the 60 patients treated with C-HT/MMC, 43 samples were NHGUC and 17 cases were classified AUC. The increase of cellularity and nuclear size with the alteration of nuclear/cytoplasmatic ratio (N/C) were common in patients treated with EMDA/MMC and C-HT/MMC without clinical and histological evidence of recurrence of neoplasia. The hyperchromasia and irregular nuclear chromatin were rarely observed. The irregular nuclear membrane rarely identified in urine cytology after EMDA/MMC treatment, is a feature present in patients C-HT/MMC treated.