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1.
PLoS One ; 19(5): e0302548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728337

RESUMO

BACKGROUND: This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France. METHODS: A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses. RESULTS: Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER. CONCLUSIONS: This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.


Assuntos
Anticorpos Monoclonais Humanizados , Análise Custo-Benefício , Humanos , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , França , Masculino , Feminino , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/economia , Neoplasias da Bexiga Urinária/patologia , Anos de Vida Ajustados por Qualidade de Vida , Idoso , Pessoa de Meia-Idade , Adulto , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/economia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Metástase Neoplásica , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/economia , Neoplasias Urológicas/patologia , Quimioterapia de Manutenção/economia
2.
Pathol Res Pract ; 220: 153410, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33765474

RESUMO

BACKGROUND: In recent years, HER2 amplification has been evaluated as a potential prognostic biomarker and therapeutic target in urothelial carcinoma (UC). In this retrospective study, we aimed at exploring the prognostic role of HER2 amplification in UC, measured by chromogenic in situ hybridization (CISH). METHODS: We retrospectively evaluated the presence of HER2 amplification by using CISH in 31 UC patients followed at a single institution between 2018 and 2020. The primary objective was to assess the frequency of HER2 amplification and to compare clinical outcomes of HER2-amplified patients with non-amplified UCs. RESULTS: HER2 amplification was identified in 4 out of 31 patients (12.9 %). After a median follow-up of 28.1 months (95 % Confidence Intervals [CI] 11.2-45.1), median overall survival (OS) in the whole population was 10.9 months (95 % CI 3.5-22.1). Despite not reaching statistical significance, median OS was shorter in HER2-amplified patients (6.8 months, 95 % CI 3.9-9.7) compared to HER2-negative UCs (15.4 months, 95 % CI 7.5-23.3) (p = 0.45). CONCLUSIONS: Although limited by the small sample size, the results of our study suggest that HER2 amplifications by CISH could represent a prognostic factor for shorter survival in UC patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Amplificação de Genes , Hibridização In Situ , Receptor ErbB-2/genética , Neoplasias Urológicas/genética , Urotélio/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/terapia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia
3.
J Med Econ ; 23(9): 967-977, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32412387

RESUMO

Aims: Pembrolizumab demonstrated significantly prolonged overall survival (OS) vs. chemotherapy in the Phase III KEYNOTE-045 trial, and is approved in the US for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who progressed after platinum-based chemotherapy. Using longer follow-up and individual patient-data from KEYNOTE-045, this study evaluates the cost-effectiveness of pembrolizumab vs. chemotherapy or atezolizumab from a US payer perspective.Materials and methods: A partitioned-survival model was developed over a 20-year time horizon. Progression-free survival (PFS) and OS for pembrolizumab and chemotherapy were extrapolated using a piecewise modelling approach, where patient-level data from KEYNOTE-045 were used for the initial period followed by parametric distributions. OS of atezolizumab was estimated by indirect treatment comparisons based on KEYNOTE-045 and IMvigor211. Different scenarios were explored in the absence of indirect comparisons on PFS and time-on-treatment (ToT) between pembrolizumab and atezolizumab. Drug acquisition/administration, disease management, adverse events, and terminal care costs were considered.Results: Compared with chemotherapy, pembrolizumab resulted in a mean gain of 1.33 life-years and 1.14 quality-adjusted life-years (QALYs) and an incremental cost of $106,299, yielding an incremental cost-effectiveness ratio of $93,481/QALY gained. Pembrolizumab dominated atezolizumab in extending patients' life by 0.89 years and 0.76 QALYs, while reducing costs by $26,458. Key drivers of cost-effectiveness included survival extrapolation, OS hazard ratio of pembrolizumab vs. atezolizumab, and time horizon. Pembrolizumab had a 66% and 100% probability of being cost-effective vs. chemotherapy and atezolizumab, respectively, at a $100,000 willingness-to-pay threshold.Limitations and conclusions: Uncertainties remain with extrapolated PFS and OS for pembrolizumab, OS indirect comparison, and ToT for atezolizumab. Despite these limitations, the model used robust methods to estimate key clinical endpoints with patient-level data from longer follow-up of KEYNOTE-045. Pembrolizumab dominates atezolizumab and is very likely cost-effective vs. chemotherapy in 2 L mUC at a $100,000 willingness-to-pay threshold.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Neoplasias Urológicas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/economia , Antineoplásicos Imunológicos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Análise Custo-Benefício , Gastos em Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Humanos , Modelos Econométricos , Metástase Neoplásica , Anos de Vida Ajustados por Qualidade de Vida , Análise de Sobrevida , Estados Unidos , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia
4.
Urol Oncol ; 38(7): 638.e7-638.e13, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32088105

RESUMO

PURPOSE: The aim of the study was to assess upper tract urothelial carcinoma (UTUC) health care needs and specific mortality rates in an arsenic-exposed region in Northern Chile and compare them to those of the rest of the country. MATERIAL AND METHODS: Arsenic levels of drinking water were correlated with UTUC hospital discharges and cancer-specific mortality rates. Mortality and hospital admission rate ratios were estimated using a Poisson regression model. RESULTS: There were 257 UTUC-specific deaths in Chile between 1990 and 2016; 81 (34%) of them occurred in Antofagasta, where only 3.5% of the population lives. The peak mortality rate observed in Antofagasta was 2.15/100,000 compared to 0.07/100,000 in the rest of the country. Mortality in the exposed region was significantly higher when compared to the rest of the country (MRR 17.6; 95%CI: 13.5-22.9). The same trend was observed for UTUC hospital discharges (RR 14.8; 95%CI: 11.5-19.1). CONCLUSION: Even stronger than for bladder cancer, exposure to arsenic is related to a significant need for UTUC health care and high mortality rates, even 25 years after having controlled arsenic levels in drinking-water. Awareness of this ecologic factor in these affected regions is therefore mandatory.


Assuntos
Arsênio/efeitos adversos , Neoplasias Urológicas/induzido quimicamente , Feminino , Humanos , Masculino , Análise de Sobrevida , Neoplasias Urológicas/mortalidade
5.
Cancer Chemother Pharmacol ; 84(6): 1257-1267, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542806

RESUMO

PURPOSE: To determine the exposure-response (ER) relationships between atezolizumab exposure and efficacy or safety in patients with advanced non-small cell lung cancer (NSCLC) or urothelial carcinoma (UC) and to identify alternative dosing regimens. METHODS: ER analyses were conducted using pooled NSCLC and UC data from phase 1 and 3 studies (PCD4989g, OAK, IMvigor211; ClinicalTrials.gov IDs, NCT01375842, NCT02008227, and NCT02302807, respectively). Objective response rate, overall survival, and adverse events were evaluated vs pharmacokinetic (PK) metrics. Population PK-simulated exposures for regimens of 840 mg every 2 weeks (q2w) and 1680 mg every 4 weeks (q4w) were compared with the approved regimen of 1200 mg every 3 weeks (q3w) and the maximum assessed dose (MAD; 20 mg/kg q3w). Phase 3 IMpassion130 (NCT02425891) data were used to validate the PK simulations for 840 mg q2w. Observed safety data were evaluated by exposure and body weight subgroups. RESULTS: No significant ER relationships were observed for safety or efficacy. Predicted exposures for 840 mg q2w and 1680 mg q4w were comparable to 1200 mg q3w and the MAD and consistent with observed PK data from IMpassion130. Observed safety was similar between patients with a Cmax above and below the predicted Cmax for 1680 mg q4w and between patients in the lowest and upper 3 body weight quartiles. CONCLUSION: Atezolizumab regimens of 840 mg q2w and 1680 mg q4w are expected to have comparable efficacy and safety as the approved regimen of 1200 mg q3w, supporting their interchangeable use and offering patients greater flexibility.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Modelos Biológicos , Neoplasias Urológicas/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células de Transição/mortalidade , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase III como Assunto , Simulação por Computador , Conjuntos de Dados como Assunto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/mortalidade , Masculino , Método de Monte Carlo , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/mortalidade
6.
Eur Urol Oncol ; 2(5): 565-571, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31412011

RESUMO

BACKGROUND: There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients. OBJECTIVE: To assess the cost-effectiveness of pembrolizumab for first-line treatment of urothelial carcinoma ineligible for cisplatin-based therapy in patients with strongly PD-L1-positive tumours in Sweden. DESIGN, SETTING, AND PARTICIPANTS: Parametric survival curves were fitted to overall survival, progression-free survival, and time on treatment data from KEYNOTE-052 to extrapolate clinical outcomes. A simulated treatment comparison and a network meta-analysis were conducted to estimate the comparative efficacy of pembrolizumab versus carboplatin plus gemcitabine and gemcitabine monotherapy. EQ-5D data from KEYNOTE-052 were used to estimate utility, while resource use and cost inputs were estimated using Swedish regional pricing lists and clinician opinion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model reported costs, life years, and quality-adjusted life years (QALYs), and results were tested using deterministic and probabilistic sensitivity analysis. RESULTS AND LIMITATIONS: We estimated that pembrolizumab would improve survival by 2.11 and 2.16 years and increase QALYs by 1.71 and 1.75 compared to carboplatin plus gemcitabine and gemcitabine monotherapy, respectively. Pembrolizumab was associated with a cost increase of €90520 versus carboplatin plus gemcitabine and €95055 versus gemcitabine, with corresponding incremental cost-effectiveness ratios of €53055/QALY and €54415/QALY. CONCLUSIONS: At a willingness-to-pay threshold of €100000/QALY, pembrolizumab is a cost-effective treatment versus carboplatin plus gemcitabine and versus gemcitabine. PATIENT SUMMARY: This is the first analysis to show that pembrolizumab is a cost-effective option for first-line treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma in Sweden.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Análise Custo-Benefício/estatística & dados numéricos , Neoplasias Urológicas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos Imunológicos/economia , Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Carboplatina/economia , Carboplatina/uso terapêutico , Carcinoma de Células de Transição/economia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Cisplatino/efeitos adversos , Simulação por Computador , Desoxicitidina/análogos & derivados , Desoxicitidina/economia , Desoxicitidina/uso terapêutico , Custos de Medicamentos , Humanos , Modelos Econômicos , Intervalo Livre de Progressão , Anos de Vida Ajustados por Qualidade de Vida , Suécia/epidemiologia , Neoplasias Urológicas/economia , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Gencitabina
7.
J Med Econ ; 22(7): 662-670, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30836812

RESUMO

Aims: Medicare patients with metastatic or surgically unresectable urothelial carcinoma (mUC) often receive platinum-based chemotherapy as first line of therapy (LOT), but invariably progress, requiring additional LOTs and healthcare resource use (HCRU). To better understand the evolving mUC treatment landscape, the economic burden of chemotherapy-based mUC treatments among US Medicare patients was estimated. Methods: Newly diagnosed Medicare patients with mUC were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were followed from diagnosis to death, disenrollment, or end of study to characterize LOTs (first [LOT1], second [LOT2], and third or greater [LOT3+]). Kaplan-Meier methods were used to estimate overall survival (OS) by LOT. HCRU and mean costs were reported over the follow-up period, LOT duration, and maximum LOT received. Results: Among 1,873 eligible patients with mUC (median age = 77 years; median follow-up = 7.5 months), 1,035 (55%) received no chemotherapy. Among chemotherapy-treated patients, 61% had LOT1 only, 25% had LOT1 and LOT2 only, and 14% had LOT3+. Median OS was 8.1 months, range was 4.3 (untreated) to 29.8 (LOT3+) months. HCRU frequency increased with additional LOTs. Mean cumulative per-patient cost was $82,912 for all patients, increasing with additional LOTs (untreated = $57,207; LOT1 = $99,213; LOT2 = $125,190; LOT3+ = $163,884). Mean per patient per month cost was $18,827 for all patients, decreasing with increasing number of LOTs received (untreated = $27,211; LOT1 = $9,601; LOT2 = $7,325; LOT3+ = $6,017). Limitations: Potential for treatment misclassification when using the algorithm defining LOTs and non-generalizability of results to younger patients. Conclusions: Over 50% of Medicare patients with mUC received no chemotherapy. Among chemotherapy-treated patients, most received only one LOT. Additional LOTs led to higher mean costs and HCRU, but as patients were followed longer, monthly costs decreased. As treatments evolve to include immuno-oncology agents, these findings provide a clinically relevant economic benchmark for mUC treatment across different traditional LOTs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/economia , Carcinoma de Células de Transição/mortalidade , Custos de Cuidados de Saúde , Recursos em Saúde/economia , Neoplasias Urológicas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Medicare/economia , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Análise de Sobrevida , Estados Unidos , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia
8.
Eur Urol Focus ; 5(2): 201-204, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-28802642

RESUMO

Point mutations in the TERT gene promoter occur at high frequency in multiple cancers, including urothelial carcinoma (UC). However, the relationship between TERT promoter mutations and UC patient outcomes is unclear due to conflicting reports in the literature. In this study, we examined the association of TERT alterations, tumor mutational burden per megabase (Mb), and copy number alteration (CNA) burden with clinical parameters and their prognostic value in a cohort of 398 urothelial tumors. The majority of TERT mutations were located at two promoter region hotspots (chromosome 5, 1 295 228 C>T and 1 295 250 C>T). TERT alterations were more frequently present in bladder tumors than in upper tract tumors (73% vs 53%; p=0.001). ARID1A, PIK3CA, RB1, ERCC2, ERBB2, TSC1, CDKN1A, CDKN2A, CDKN2B, and PTPRD alterations showed significant co-occurrence with TERT alterations (all p<0.0025). TERT alterations and the mutational burden/Mb were independently associated with overall survival (hazard ratio[HR] 2.31, 95% confidence interval [CI] 1.46-3.65; p<0.001; and HR 0.96, 95% CI 0.93-0.99; p=0.002), disease-specific survival (HR 2.23, 95% CI 1.41-3.53; p<0.001; and HR 0.96, 95% CI 0.93-0.99; p=0.002), and metastasis-free survival (HR 1.63, 95% CI 1.05-2.53; p=0.029; and HR 0.98, 95% CI 0.96-1.00; p=0.063) in multivariate models. PATIENT SUMMARY: The majority of TERT gene mutations that we detected in urothelial carcinoma are located at two promoter hotspots. Urothelial tumors with TERT alterations had worse prognosis compared to tumors without TERT alterations, whereas tumors with a higher mutational burden had more favorable outcome compared to tumors with low mutational burden.


Assuntos
Carcinoma de Células de Transição/genética , Variações do Número de Cópias de DNA/genética , Telomerase/genética , Neoplasias Urológicas/genética , Carcinoma de Células de Transição/patologia , Classe I de Fosfatidilinositol 3-Quinases , Efeitos Psicossociais da Doença , Intervalo Livre de Doença , Humanos , Mutação , Prognóstico , Regiões Promotoras Genéticas/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias Urológicas/mortalidade
9.
BJU Int ; 117(6): 954-60, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26573216

RESUMO

OBJECTIVE: To perform a population-based study to evaluate contemporary utilisation trends, morbidity, and costs associated with nephroureterectomies (NUs), as contemporary data for NUs are largely derived from single academic institution series describing the experience of high-volume surgeons and it is unclear if the same favourable results occur at a national level. PATIENTS AND METHODS: Using the Premier Hospital Database, we captured patients undergoing a NU with diagnoses of renal pelvis or ureteric neoplasms from 2004 to 2013. We fitted regression models, adjusting for clustering by hospitals and survey weighting to evaluate 90-day postoperative complications, operating-room time (OT), prolonged length of stay (pLOS), and direct hospital costs among open (ONU), laparoscopic (LNU) and robotic (RNU) approaches. RESULTS: After applying sampling and propensity weights, we derived a final study cohort of 17 254 ONUs, 13 317 LNUs and 3774 RNUs for upper tract urothelial carcinoma (UTUC) in the USA between 2004 and 2013. During that period, minimally invasive NU (miNU) increased from 36% to 54%, while the total number of NUs decreased by nearly 20%. No differences were noted in perioperative outcomes between the three surgical approaches, including when the analysis was restricted to the highest-volume hospitals and highest-volume surgeons. The OT was longer for LNU and RNU (P < 0.001), while the pLOS rates were decreased (P < 0.001). Adjusted 90-day median direct hospital costs were higher for LNU and RNU (P < 0.001), which disappeared when adjusting for the highest-volume groups, except for RNUs performed by high-volume surgeons. CONCLUSIONS: During this contemporary 10-year study, miNU has been replacing ONU for UTUC with a recent surge in RNU, along with a concurrent reduction in total NUs performed. Despite not being associated with a clinically significant improvement in perioperative outcomes, the costs for miNUs were consistently higher. However, higher hospital volumes suggest a potential cost containment strategy when performing miNUs.


Assuntos
Carcinoma de Células de Transição/patologia , Nefrectomia , Ureter/patologia , Neoplasias Urológicas/patologia , Urotélio/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/economia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nefrectomia/instrumentação , Nefrectomia/métodos , Nefrectomia/mortalidade , Complicações Pós-Operatórias , Pontuação de Propensão , Medição de Risco , Resultado do Tratamento , Neoplasias Urológicas/economia , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/cirurgia , Urotélio/cirurgia
10.
Transplantation ; 99(4): 818-22, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25208323

RESUMO

BACKGROUND: High urologic malignancy incidence has been reported in end-stage renal disease (ESRD) patients, especially of female sex. This study was undertaken to evaluate whether female recipients still carry an aggravated risk of this malignancy after kidney transplantation (KT). METHODS: The claims data from the Bureau of National Health Insurance of Taiwan were used for analysis. All KT recipients who developed urologic malignancy from January 1, 1999, to December 31, 2007 (n = 2,245) were enrolled in this study. By means of propensity score, a database of 1:4 ratio random incident ESRD patients with matched age, sex, comorbidity rates, and dialysis to index date was used as control (non-KT group, n = 8,980). The last observation period ended on December 31, 2008. RESULTS: The cumulative urologic malignancy incidence rate was significantly higher in female recipients after KT than their female ESRD counterparts without KT (P < 0.001). This gap became more prominent approximately 2 years after transplantation. No similar trend was detected in male KT patients (P = 0.13). Incidence rate ratio of urologic malignancy was significantly higher in female recipients (incidence rate ratio, 2.13; 95% confidence interval [95% CI], 1.53-2.97) than in their male counterparts (incidence rate ratio, 1.43; 95% CI, 0.90-2.25). From multivariate Cox proportional hazard regression tests, female (hazards ratio, 2.10; 95% CI, 1.52-2.95) but not male sex (hazards ratio, 1.47; 95% CI, 0.93-2.32) was determined to be an independent factor for the development of urologic malignancy after KT. After acquiring this malignancy, KT recipients did not have any advantage in cumulative survival compared to ESRD patients without KT (P = 0.07). CONCLUSION: Compared to males, female recipients tended to have a significantly higher urologic malignancy risk after KT.


Assuntos
Disparidades nos Níveis de Saúde , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Uremia/cirurgia , Neoplasias Urológicas/epidemiologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pontuação de Propensão , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Taiwan/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Uremia/diagnóstico , Uremia/mortalidade , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/mortalidade
11.
Clin Genitourin Cancer ; 11(3): 346-52, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23673281

RESUMO

BACKGROUND: Although urothelial cancer is more common in men, women with urothelial cancer have inferior survival outcomes. The potential existence of gender-related disparities in patients with metastatic urothelial cancer has not been extensively explored. PATIENTS AND METHODS: Individual patient data were pooled from 8 phase II and phase III trials evaluating first-line cisplatin-based combination chemotherapy in patients with metastatic urothelial carcinoma. Adverse events, treatment delivery, response proportions, and survival outcomes were compared between male and female patients. RESULTS: Of the 543 patients included in the analysis, 100 patients (18%) were women. There was no significant difference in the number of cycles of chemotherapy administered or in the proportions of patients experiencing severe toxicities when comparing male and female patients. There was no difference in the survival distributions between male and female patients (P = .08); the median survival of male patients was 11.7 months (95% confidence interval [CI], 10.5-13.2) compared with 16.2 months for female patients (95% CI, 12.8-20.4). There was no significant difference in survival between men and women when controlling for baseline performance status and/or the presence of visceral metastases. CONCLUSION: Female patients with metastatic urothelial cancer tolerate cisplatin-based chemotherapy similarly to male patients and achieve comparable clinical outcomes. Although gender-associated survival disparities in patients with metastatic urothelial cancer cannot be completely ruled out, if such disparities exist, they are unlikely related to tolerability or efficacy of chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Fatores Sexuais , Sobrevida , Resultado do Tratamento , Urotélio
12.
Appl Immunohistochem Mol Morphol ; 20(4): 363-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22495372

RESUMO

AIM: Upper urinary tract urothelial carcinoma (UUTUC) is an uncommon neoplasm frequently discovered at a high-stage disease. The prognosis of disseminated UUTUCs is poor despite the use of platinum-based chemotherapy. The aim of the study was to evaluate HER2 overexpression and amplification in a series of 83 UUTUCs. MATERIALS AND METHODS: All tumors were formalin fixed. TNM stage, grade, lymphovascular invasion, surgical margins, morphologic variants were reviewed by 2 pathologists. All tumors were immunostained with anti-HER2 antibody. HER2 gene amplification was determined by dual-color in situ hybridization. Gene amplification was defined by an HER2/CEN 17 ratio >2.2. RESULTS: HER2 immunostaining was observed in 33/83 tumors. Twelve cases were 2+ score and 2 cases were 3+ score. HER2 in situ hybridization was evaluable in 75/83 cases. Amplification was observed in 6 (7%) cases. All amplified tumors were of high grade and 4/6 were stage pT3. A strong correlation between HER2 overexpression and amplification was noted (P<0.0001). HER2 overexpression and amplification were correlated with the pN+ stage but not with specific survival or recurrence. CONCLUSIONS: These results suggest that HER2 amplification is a rare event in UUTUC but may be of interest for targeted therapy in selected high-grade and high-stage tumors.


Assuntos
Carcinoma/diagnóstico , Receptor ErbB-2/metabolismo , Neoplasias Urológicas/diagnóstico , Urotélio/metabolismo , Idoso , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Receptor ErbB-2/genética , Receptor ErbB-2/imunologia , Recidiva , Análise de Sobrevida , Regulação para Cima , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Urotélio/patologia
13.
J Endourol ; 21(6): 583-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17638550

RESUMO

PURPOSE: To evaluate the oncologic results of our operative technique, hand-assisted retroperitoneoscopic nephroureterectomy (HRNU), for the treatment of upper-tract urothelial cancer, various perioperative parameters and oncologic outcomes were compared for HRNU and conventional open nephroureterectomy (CONU). PATIENTS AND METHODS: Thirty-six patients with clinical stage T(1,2)N(0)M(0) renal-pelvic and ureteral tumors underwent HRNU. A retroperitoneoscopic nephrectomy was carried out with hand assistance via a lower-abdominal midline incision. The lower ureter was resected by open surgery through the same incision, and the operative specimen was extracted via the same incision. Thirty-seven cases of CONU were reviewed as historical controls. Various perioperative and parameters and oncologic results were compared for the two procedures. RESULTS: The HRNU was completed in all but one case, which was converted to CONU. The mean operating time (395 minutes) was longer than that for CONU (289 minutes), and the mean estimated blood loss with HRNU (497 g) was greater than that with CONU (296 g). The mean time to oral intake (1.4 days) was shorter than that after CONU (2.3 days), and the mean time to walking was shorter (2.1 days v 2.6 days). There were no statistical differences in the cause-specific survival rate, the disease-free survival rate, or the bladder recurrence-free survival rate between HRNU (median follow-up 23 months) and CONU (median follow-up 56 months). CONCLUSION: The HRNU, a combination of endoscopic and conventional open surgery, seems to be a reasonable surgical procedure, because the lower-abdominal incision can be utilized, not only as a route for hand assistance, but also as a window for open surgery when resecting the distal ureter as well as for extraction of surgical specimens. The procedure is a safe alternative to conventional open surgery for upper urinary-tract tumors from an oncologic viewpoint.


Assuntos
Nefrectomia/métodos , Ureter/cirurgia , Neoplasias Urológicas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Assistência Perioperatória , Espaço Retroperitoneal/cirurgia , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/mortalidade
14.
Oncology ; 73(5-6): 290-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18477854

RESUMO

OBJECTIVE: We evaluated safety and efficacy of first-line gemcitabine/carboplatin in unfit-for-cisplatin patients with advanced urothelial carcinoma and the effect on the quality of life and functional status of elderly patients (aged >70). METHODS: Unfit patients had ECOG performance status (PS) > or =2, creatinine clearance <50 ml/min or comorbidities precluding cisplatin administration. Carboplatin at area under the curve of 2.5 and gemcitabine 1,250 mg/m(2) were administered biweekly. Elderly patients were stratified into group 1 (no activities of daily living (ADL) or instrumental ADL dependency and no comorbidities), group 2 (instrumental ADL dependency or 1-2 comorbidities) and group 3 (ADL dependency or > or =2 comorbidities). RESULTS: Thirty-four patients were enrolled: 68% had PS 2-3, 69% a creatinine clearance <50 ml/min and 65% had 1 or more comorbidities. There were 3 cases of grade 3 toxicity (9%). Response rate was 24% [95% confidence interval (CI) 11-41]. Median follow-up was 8 months, median progression-free survival 4.4 months (95% CI 1.03-7.75) and median overall survival 9.8 months (95% CI 4.7-14.9). Patients in geriatric assessment groups 1 and 2 had a significantly longer median progression-free survival compared to group 3 [6.9 months (95% CI 1.3-12.4) vs. 1.9 months (95% CI 0.5-3.2); p = 0.005]. CONCLUSION: First-line gemcitabine/carboplatin combination is active in unfit-for-cisplatin patients with advanced urothelial carcinoma. Pretreatment quality of life and geriatric assessment may be useful in selecting patients likely to benefit from this treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Qualidade de Vida , Neoplasias Urológicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Cisplatino/efeitos adversos , Creatinina/metabolismo , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Gencitabina
15.
Scand J Urol Nephrol ; 39(4): 271-6, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16118102

RESUMO

OBJECTIVE: Widowhood imposes difficult psychological, social and practical challenges. We investigated the prevalence and predictors of access to bereavement interventions during the first 6 months after the loss of a husband/male partner to prostate or urinary bladder cancer. MATERIAL AND METHODS: All women (n = 506) aged < 80 years living in Sweden who lost their husband/partner owing to cancer of the prostate in 1996 or of the urinary bladder in 1995 or 1996 were asked to answer an anonymous postal questionnaire 2-4 years after their loss. RESULTS: Thirty percent of the widows stated that they would not have needed psychological support by caregivers during the first 6 months of bereavement. Two-thirds of the others (162/242) (those who did not state that they had no need of support) did not have any access to psychological support, 10% (25/242) had little access, 11% (27/242) had moderate access and 12% (28/242) had a large amount of access to psychological support. Similar figures were observed for other bereavement interventions, such as information, economic counselling and support groups. Emotional relations during the last months prior to bereavement, intensity of faith, education, prior mental health problems and a diagnosis of prostate cancer were all positively correlated with access to psychological support by caregivers, whereas previously identified risk factors for excess morbidity in widowhood were not. CONCLUSIONS: A large majority of Swedish widows who lost their husband to urologic cancers in 1995 or 1996 indicated a need for psychological support, information and economic counselling. This need was not met by caregivers and help was not aimed at important groups at risk of morbidity.


Assuntos
Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Cuidados Paliativos na Terminalidade da Vida , Neoplasias Urológicas/psicologia , Viuvez/psicologia , Idoso , Feminino , Humanos , Masculino , Avaliação das Necessidades , Apoio Social , Cônjuges , Estresse Psicológico , Suécia , Neoplasias Urológicas/mortalidade
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