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OBJECTIVE: To identify predictors of immune-related adverse events (IRAEs) in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Assess associations between outcomes and the development of IRAEs. METHODS: Retrospective analysis of patients with NSCLC treated with ICIs between 2016 and 2020 in the Pulmonology Department of our hospital. Patients with and without IRAEs were compared. A logistic regression analysis was performed to determine predictors of IRAEs. Progression-free survival (PFS) and overall survival (OS) curves were calculated using the Kaplan-Meier method, and the long-rank test was used to assess survival differences between groups. Univariate and multivariate Cox proportional-hazards regression models were used to identify factors associated with PFS and OS. The value considered statistically significant was p≤0.05. RESULTS: A total of 184 patients (77.7% men, mean age 66.9±9.5 years) treated with ICIs were analyzed. During follow-up, 49 (26.6%) patients developed IRAEs and 149 (81.0%) died. According to the multivariate logistic regression analysis, treatment with statins (OR:3.15; p = 0.007), previous systemic corticosteroid therapy (OR:3.99; p = 0.001), disease controlled as response to ICI (OR:5.93; p < 0.001) and higher hemoglobin values (OR:1.28; p = 0.040) were independent predictors for the development of IRAEs. Patients who developed IRAEs had significantly longer medians of PFS (41.0 vs 9.0 weeks, p < 0.001) and OS (89.0 vs 28.0 weeks; p < 0.001). CONCLUSIONS: Patients treated with statins, pre-ICI systemic corticosteroids, higher baseline hemoglobin value and controlled disease as initial response to ICI had a higher risk of developing IRAEs. The development of IRAEs was associated with better outcomes.
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OBJECTIVE: To provide latest findings of Urologic Oncology on prostate, kidney, and bladder cancer, and analyze its impact on clinical practice as well as future schemes in the medium- and long-term. METHODS: This document reviews the abstracts on Uro-Oncology presented at the 2020 Congresses (EUA, AUA, ASCO, ESMO and ASTRO), the publications with the highest impact and especially the new lines of development and progress in Uro-Oncology evaluated by the OncoForum committee. RESULTS: The use of prostate-specific membrane antigen (PSMA) radioligands in the diagnosis of prostate cancer may have great potential and utility in the coming years due to their improved sensitivity and specificity. The genetic characterization of the tumor is important at both, germline and somatic levels, due to the significant role of BRCA2 mutations regarding risk. The cohort multiple randomised controlled trial is the most suitable study design at the genitourinary cancer level. The application of big data will lead to process improvements, savings in healthcare costs, and an empowerment of real-life studies through ease of data comparison, management, and storage. CONCLUSIONS: The use of new diagnostic techniques with PSMA ligands will provide a more comprehensive diagnostic modality, increase the number of studies about tumor genetic profiling, and enhance their quality. The practical application of artificial intelligence will improve the treatment genitourinary cancer.
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Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Urologia , Inteligência Artificial , Feminino , Humanos , Masculino , Oncologia , Neoplasias da Próstata/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapiaRESUMO
OBJECTIVE: Review the latest evidence on urologic oncology on kidney, bladder and prostate tumors. METHODS: Abstracts on kidney, bladder and prostate cancer presented at the 2019 congresses (EAU, AUA, ASCO and ESMO) and the publications with the greatest impact in this period, with the highest evaluation by the OncoForum committee, are reviewed. RESULTS: In patients with metastatic kidney cancer, regimens including immunotherapy (nivolumab + ipilimumab, pembrolizumab) have been shown to be superior to sunitinib in terms of survival. In patients with non-muscle invasive bladder cancer, pembrolizumab has been shown to be an effective alternative in those refractory to bacillus Calmette-Guérin, while in patients with metastatic urothelial cancer, third-line enfortumab vedotin achieved a significant response rate (44%). In patients with localized prostate cancer (PCa), ultrafractionated external radiotherapy did not show any greater acute toxicity than fractionated or hypofractionated radiotherapy. The benefit of enzalutamide and apalutamide associated with castration has been confirmed in M1 PCa patients, regardless of disease volume. In patients with castration-resistant M0 PCa, treatment with enzalutamide, apalutamide or darolutamide has been associated with a delay in the occurrence of metastasis and prolonged survival. Cabazitaxel has demonstrated a survival benefit in patients with metastatic CRPC, while olaparib showed anti-tumor activity after chemotherapy in those tumors with mutations in DNA repair genes. CONCLUSIONS: These data show the implementation of immunotherapy as a novel alternative against renal and bladder cancer. The arrival of new agents for advanced urothelial carcinoma should be highlighted, and the efficacy of enzalutamide and apalutamide in de novo metastatic prostate cancer is established. In metastatic CRPC, cabazitaxel and olaparib (targeting mutations) are promising therapeutic options.
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Neoplasias Renais/terapia , Neoplasias da Próstata/terapia , Neoplasias da Bexiga Urinária/terapia , Árvores de Decisões , Humanos , Masculino , Oncologia , UrologiaRESUMO
BACKGROUND: The effect of primary androgen deprivation therapy (ADT) in patients with localized prostate cancer (PCa) has not been well documented. The objective of the present study was to analyze the outcome of tumors treated with ADT as primary therapy in the Spanish Prostate Cancer Registry (19.4% of the series). PATIENTS AND METHODS: Patients were classified in three groups: 1) with low/intermediate risk clinically localized tumors; 2) with high risk and locally advanced (T3-4) tumors; 3) with metastatic tumors. Time to castration resistance and overall cancer-specific survival were analyzed. In non-metastatic tumors, survivals in patients treated with ADT were compared with data from patients who underwent local treatments from the Spanish Prostate Cancer Registry. RESULTS: 703 cases were analyzed. There were significant differences in the time to castration resistance, which was lower in the group of metastatic tumors. During follow-up, there were 179 deaths (25.5%) of which 89 (12.6%) were due to PCa. After 3 years of ADT, only 14.6% of patients in group 1 had died (1% due to PCa), 20.5% in group 2 and 46.8% in group 3 (9.2% and 31.3% due to PCa, respectively). Cancer-specific survival was significantly worse in group 1 using ADT than radical prostatectomy or radiotherapy. In high-risk and locally advanced tumors, ADT also had a lower cancer-specific survival than local treatments. CONCLUSION: A longer time until the castration resistance was observed in patients with well- and intermediate-risk localized tumors treated with ADT. Patients with metastatic tumors showed the shortest time to castration resistance.
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Antagonistas de Androgênios/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Idoso , Humanos , Masculino , Orquiectomia , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Espanha , Taxa de Sobrevida , Fatores de TempoRESUMO
INTRODUCTION: Gleason score biopsy undergrading (GSBU) can have an impact on the management and prognosis of patients with prostate cancer. We analyze the possible impact of time and other clinical and analytical factors in the appearance of GSBU in our series. PATIENTS AND METHOD: Ambispective, multicenter study of 1955 patients with localized prostate cancer undergoing radical prostatectomy between 2005 and 2018. Descriptive statistics and hypothesis testing are reported by univariate and multivariate analyses. RESULTS: Mean age 63.69 (44-80) years, median PSA 8.70 ng / ml (1.23-99). GSBU was observed in 34.7% of the entire cohort. In 72.8% of the cases, the GSBU occurred in one consecutive Gleason score, with the progression from 3 + 3 to 3 + 4 being the most frequent (289 patients, 47.6%). Performing radical prostatectomy 90-180 days before or after the biopsy does not have an impact on its undergrading in any of the groups. In the univariate and multivariate analysis, the presence of tumor or pathological rectal examination in both lobes, the tumor load ≥50% of cylinders and a DPSA ≥0.20, showed independent discriminative capacity to select patients who presented GSBU. CONCLUSIONS: The time from biopsy to radical prostatectomy did not show impact on GSBU. The number of affected cylinders, bilateral tumor and DPSA are easily accessible parameters that can help us select patients with greater probability of presenting GSBU.
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Próstata/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Prostatectomia/métodos , Estudos Retrospectivos , Fatores de Tempo , Tempo para o TratamentoRESUMO
BACKGROUND: Fatigue is one of the most prevalent symptoms among cancer patients. Specifically, in metastatic castration-resistant prostate cancer (mCRPC) patients, fatigue is the most common adverse event associated with current treatments. The purpose of this study is to describe the prevalence of fatigue and its impact on quality of life (QoL) in patients with CRPC in routine clinical practice. METHODS: This was a cross-sectional, multicentre study. Male chemo-naïve adults with high-risk non-metastatic (M0) CRPC and metastatic (M1) CRPC (mCRPC) were eligible. Fatigue was measured using the Brief Fatigue Inventory (BFI) and QoL was assessed using the Functional Assessment of Cancer Therapy questionnaire for patients with prostate cancer (FACT-P) and the FACT-General (FACT-G) questionnaire. Data were analysed using Mann-Whitney or Kruskal-Wallis tests (non-parametric distribution), a T-test or an ANOVA (parametric distribution) and the Fisher or chi-squared tests (categorical variables). RESULTS: A total of 235 eligible patients were included in the study (74 [31.5%] with M0; and 161 [68.5%] with M1). Fatigue was present in 74%, with 38.5% of patients reporting moderate-to-severe fatigue. Mean FACT-G and FACT-P overall scores were 77.6 ± 16.3 and 108.7 ± 21.4, respectively, with no differences between the CRPC M0 and CRPC M1 subgroups. Fatigue intensity was associated with decreased FACT-G/P scores, with no differences between groups. Among 151 mCRPC patients with available treatment data, those treated with abiraterone-prednisone ≥3 months showed a significant reduction in fatigue intensity (p = 0.043) and interference (p = 0.04) compared to those on traditional hormone therapy (HT). Patients on abiraterone-prednisone ≥3 months showed significantly better FACT-G/P scores than patients on HT (p = 0.046 and 0.018, respectively). CONCLUSION: Our data show a high prevalence and intensity of fatigue and its impact on QoL in chemo-naïve CRPC patients. There is an association between greater fatigue and less QoL, irrespective of the presence or absence of metastasis. Chemo-naïve mCRPC patients receiving more than 3 months of abiraterone acetate plus prednisone showed an improvement of fatigue and QoL when compared to those on traditional HT. TRIAL REGISTRATION: Not applicable since it is not an interventional study.
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Fadiga/epidemiologia , Fadiga/etiologia , Neoplasias de Próstata Resistentes à Castração/complicações , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formulation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.
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INTRODUCTION: The objective of the study was to determine the factors independently related with the development of castration resistance (CR) in prostate cancer (PC) in the medium term. MATERIAL AND METHODS: 155 patients diagnosed with metastatic PC with a follow-up of up to 39 months. Data taken from the National PC Registry. The evaluated variables were age, PSA, nadir PSA, Gleason, perineural invasion, TNM stages, and ADT type (intermittent/continuous). RESULTS: Mean follow-up 26,2±13,4 months. 47.1% developed early CR, with mean time until onset of 12,2±8,7 months. Univariate analysis the mean PSA was correlated with CR (290±905,1 ng/mL in non CR, 519,1±1437,2 ng/mL in CR, P<.001), mean age (73,3±8,3 years in non CR, 69,1±9,3 in CR P=.01), mean PSA nadir (15,5±57,3ng/mL in non CR, 15,9±23,7 ng/mL in CR, p<0,001), Gleason (in ≥8, HR:2,11. 95% CI: 1.22-3.65, p=0.006), and T stage (in T3-T4, HR: 2.85. 95% CI: 1.57-5.19, P<.001). Multivariate analysis the independent variables associated to CR are age (HR: 0.96. 95% CI: 0.94-0.99, P=.01), PSA nadir (HR: 1.65. 95% CI: 1,43-1,91, P<.001), and T3-T4 stage (HR: 2.11. 95% CI: 1.10-4.04, P=.02). CONCLUSIONS: PSA nadir and T3-T4 tumor stage at diagnosis are associated to an increased risk of developing CR. In addition, age at diagnosis is shown as a variable that decreases risk. Therefore, an older age would be associated with lower risk probability of CR in the medium term.
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Neoplasias de Próstata Resistentes à Castração/etiologia , Fatores Etários , Idoso , Análise de Variância , Antineoplásicos Hormonais/uso terapêutico , Seguimentos , Humanos , Masculino , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Sistema de Registros , Espanha , Fatores de TempoRESUMO
AIMS: To describe the 3-year progression-free survival (PFS), overall survival (OS) and disease-specific mortality in the prospective prostate cancer GESCAP cohort, as well as the progression to castration resistance in patients on hormone therapy. MATERIAL AND METHODS: Prospective, observational, epidemiological, multicentre study. Of the 4087 patients recruited, 3843 were evaluable. The variables analysed were the risk group (localized, locally advanced, lymph involvement, metastatic), age, prostate-specific antigen (PSA) levels, Gleason score and initial treatment. Kaplan Meier survival analysis, the log-rank test and the Cox model were used to evaluate the survival data. RESULTS: Three-year PFS was 81.4% and OS was 92.4%. During the 3 years of follow-up, 303 patients died (7.9%), 110 of them (36.3%) due to disease-related causes. The probability of castration resistance for all patients on hormone therapy (n=715) was 14.2%: 5%, 9.9%, 26.1% and 44.4% in localized, locally advanced, lymph involvement and metastatic cancer, respectively (log-rank P<.0001). Patients with metastases had poorer outcomes with respect to PFS, OS, disease-specific mortality and castration resistance. In the multivariate analysis, the Gleason score, PSA and presence of metastases were associated with shorter OS and PFS. CONCLUSIONS: Our study showed stratification of risk, with a more unfavourable prognosis for patients with metastases. Patients with locally advanced disease differed with respect to those with localized disease due to their higher risk as regards disease-specific mortality. (Controlled-trials.com ISRCTN19893319).
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Adenocarcinoma/epidemiologia , Neoplasias da Próstata/epidemiologia , Adenocarcinoma/terapia , Idoso , Terapia Combinada , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias da Próstata/terapia , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Neoplasias de Próstata Resistentes à Castração/terapia , Risco , Espanha/epidemiologia , Resultado do TratamentoRESUMO
CONTEXT: The elimination of bone metastases, restoration and/or preservation of bone morphology and prevention and/or delay of skeletal events are a fundamental objective in the management of metastatic castration-resistant prostate cancer (mCRPC). Radium-223 is the first targeted alpha therapy with effects on bone that has been shown to increase survival in these patients, besides providing other bone-related benefits. OBJECTIVE: To analyze the impact of bone metastasis on mCRPC, and the benefits and the window of opportunity provided by radium-223 in the treatment of patients with mCRPC in the current treatment era. EVIDENCE ACQUISITION: A bibliographic search of PubMed and Spanish and international congresses on radium-223 and other first-line treatments for mCRPC was performed. Recent guidelines and recommendations by experts were also consulted. SUMMARY OF THE EVIDENCE: Evidence for the mechanism of action of radium-223 widen its effects to the tumor bone environment. Survival of patients treated with radium-223 is higher in those with mild symptoms as opposed to those with moderate-severe symptoms. The presence of visceral metastases even in the early stages of mCRPC supports starting radium-223 therapy before the symptoms become clinically relevant. A 3-year study has confirmed its good safety profile. Changes in tALP and LDH may be useful markers for monitoring the treatment with radium-223, but they are not predictors of overall survival. CONCLUSION: Radium-223 is a valuable therapeutic alternative in the treatment of patients with mCRPC in early stages of the disease, with a good safety profile. Its benefits extend to the bone environment.
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Neoplasias Abdominais/radioterapia , Neoplasias Abdominais/secundário , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias de Próstata Resistentes à Castração/patologia , Rádio (Elemento)/uso terapêutico , Humanos , Masculino , Fatores de Tempo , VíscerasRESUMO
OBJECTIVE: To put forth new findings of urologic oncology with impact on clinical practice presented during 2017 in the main annual meetings. METHODS: This document reviews abstracts on prostate, kidney and bladder cancer presented at the congresses of 2016 (EAU, AUA, ASCO, ESMO and ASTRO) and publications with the highest impact in this period valued with the highest scores by the OncoForum committee. RESULTS: Among patients at high risk of recurrent renal cell carcinoma after nephrectomy, adjuvant sunitinib compared to placebo showed a benefit in patients at higher risk of recurrence. In cisplatin-ineligible advanced urothelial cancer, pembrolizumab elicits clinically meaningful, durable responses. Among patients with localized prostate cancer, treatment for disease progression was less frequent (absolute difference, 26.2 percentage pontis) and adverse events was more frequent with surgery than with observation. Among patients with locally advanced or merastatic prostate cancer, androgen-deprivation therapy plus abiraterone and prednisolone resulted in fewer deaths and fewer treatment-failure events (P<.001). Among patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate, enzalutamide median radiographic progression free survival was 8,1 months and enzalutamide median overall survival was not reached. CONCLUSIONS: Among patients at high risk of recurrent renal cell carcinoma after nephrectomy, adjuvant sunitinib showed a benefit across subgroups including patients at higher risk of recurrence. Among patients with localized prostate cancer, surgery was not associated with significantly lower all-cause or porstate-cancer mortality than observation. Among patients with locally advanced or merastatic prostate cancer, androgen-deprivation therapy plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than androgen-deprivation therapy alone. In patients with metastatic castration-resistant prostate cancer previously treated with abiraterone enzalutamide remained active.
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Neoplasias Renais/terapia , Neoplasias da Próstata/terapia , Neoplasias da Bexiga Urinária/terapia , Congressos como Assunto , Humanos , MasculinoRESUMO
OBJECTIVE: To determine the actual incidence of prostate cancer (PC) in the healthcare areas of Castilla-Leon in 2014. MATERIAL AND METHODS: A multicentre study was conducted with the participation of 7 of the 9 healthcare areas of Castilla-Leon. We collected retrospective data that included 87.8% of the target population (men diagnosed with PC with histopathological confirmation in 2014). We calculated the raw and age-adjusted incidence rates based on the direct method and consulted the community and national epidemiological data in the Spanish National Institute of Statistics. RESULTS: A total of 1198 new cases of PC were diagnosed, with a raw incidence rate in the community of 109.54 cases per 100,000 men. The adjusted rates for the Spanish and European populations were 115.41 and 110.07, respectively. The age group with the highest diagnostic concentration was the 60-70-year group, with 41.97% of the diagnoses. The group with the highest incidence was the 70-80-year group, with 438.87 cases per 100,000 inhabitants. There were differences in the raw and age-adjusted incidence rates and in the age at diagnosis among the various included healthcare areas. CONCLUSIONS: The community raw incidence rate was higher than most existing data. We observed significant differences among the various geographical areas, which could be explained mainly by the age distribution and the opportunistic screening policies for each area.
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Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Programática de Saúde , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Espanha/epidemiologiaRESUMO
The association of Comamonas kerstersii with peritonitis resulting from the presence of perforated appendix has previously been described by our research team. In the present study, we describe the isolation of this microorganism from two forms of unusual presentations of C. kerstersii infection not previously described in the literature: localized intra-abdominal infection (psoas abscess) and pelvic peritonitis.
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OBJECTIVE: To put forth new findings of urologic oncology with impact on clinical practice presented during 2016 in the main annual meetings. ACQUISITION OF EVIDENCE: This document reviews abstracts on prostate, kidney and bladder cancer presented at the congresses of 2016 (EAU, AUA, ASCO, ESMO and ASTRO) and publications with the highest impact in this period valued with the highest scores by the OncoForum committee. SYNTHESIS OF EVIDENCE: In High-Risk Renal-Cell carcinoma after nephrectomy, disease-free survival was significantly greater for sunitinib than placebo group, with adverse events more frequents. In locally advanced and metastatic urotherial carcinoma patients, aletozumab achieved overall response rate in all subgroups of patients, included poor prognostic. In localized prostate cancer, the difference of prostate-cancer-specific mortality among active monitoring, radical prostatectomy and external-beam radiotherapy was not significant (P=0,48). In TERRAIN study, with castration-resistant prostate cancer patients, adverse events was reported in 31% and 23% of patients treated with enzalutamide and bicalutamide, respectively. Moreover, enzalutamide significantly improved median progression-free survival (15.7 months) compared bicalutamide (5.8 months) (P<.0001). In SRTIVE study, Enzalutamide reduced the risk of progression or death by 76% compared with bicalutamide (P<.001). CONCLUSIONS: In high-risk renal-cell carcinoma after nephrectomy, sunitinb has been considered as treatment choice. In localized prostate cancer, prostate-cancer-specific mortality was low irrespective of the treatment assigned (active monitoring, radical prostatectomy and external-beam radiotherapy). In metastatic castration-resistant prostate cancer new results of treatment with enzalutamide and abiraterone has been published, wich have been shown beneficial effects in metastatic and no metastatic patients.
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Neoplasias Renais , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapiaRESUMO
PURPOSE: Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients. METHODS: Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform. Correlation with clinical data, stem cell biomarkers (such as CD133+), AR amplification and PTEN status was identified. RESULTS: The study included 72 PC patients. AR-V7 signal was detected in 21 (29%) patients: 17 (81%) had a Gleason score ≥7, 15 (71%) castration-resistant prostate cancer (CRPC), 18 (86%) metastatic disease and PSA (median) high than AR-V7 negative (p < 0.05). CD133 was expressed in 69 (96%) patients. The median CD133+ expression in circulating tumor cells CTCs was higher among the 21 AR-V7 positive cases versus AR-V7 negative (7 vs. 3). Androgen Receptor and PTEN fluorescence in situ hybridization (FISH) on CD133+ captured cells were performed: 37 cases showed ≥four CD133+ CTCs, of which 81% showed an increased AR copy number. This percentage was similar in both AR-V7-positive and AR-V7-negative patients. A total of 68% of the cases showed deletion of PTEN: 70% were ARV-7 positive vs. 67%, which were AR-V7 negative. CONCLUSIONS: Assessing the presence of AR-V7 in plasma from PC patients is feasible by a novel capillary nano-immunoassay. AR-V7 was observed in 29% of the tumors and is more frequent in aggressive tumors.
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Antígeno AC133/metabolismo , Processamento Alternativo , Biomarcadores Tumorais/sangue , Células Neoplásicas Circulantes/metabolismo , Neoplasias da Próstata/sangue , Receptores Androgênicos/genética , Biomarcadores Tumorais/genética , Seguimentos , Humanos , Imunoensaio , Masculino , Nanomedicina , Células Neoplásicas Circulantes/patologia , Projetos Piloto , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVE: To assess the adherence to European Association of Urology (EAU) guidelines in the management of prostate cancer (PCa) in Spain. PATIENTS AND METHODS: Epidemiological, population-based, study including a national representative sample of 3,918 incident patients with histopathological confirmation during 2010; 95% of the patient's sample was followed up for at least one year. Diagnosis along with treatment related variables (for localized PCa -low, intermediate, high and locally-advanced by D'Amico risk stratification) was recorded. Differences between groups were tested with Chi-squared and Kruskal-Wallis tests. RESULTS: Mean (SD) age of PCa patients was 68.48 (8.18). Regarding diagnostic by biopsy procedures, 64.56% of all patients had 8-12 cores in first biopsy and 46.5% of the patients over 75 years, with PSA<10ng/mL were biopsied. Staging by Computer Tomography (CT) or Bone Scan (BS) was used for determining tumor extension in 60.09% of high-risk cases and was applied differentially depending on patients' age; 3,293 (84.05%) patients received a treatment for localized PCa. Radical prostatectomy was done in 1,277 patients and 206 out of these patients also had a lymphadenectomy, being 4.64% low-risk, 22.81% intermediate-risk and 36.00% high-risk patients; 86.08% of 1,082 patients who had radiotherapy were treated with 3D or IMRT and 35.77% received a dose ≥75Gy; 419 patients were treated with brachytherapy (BT): 54.81% were low-risk patients, 22.84% intermediate-risk and 12.98% high-risk. Hormonotherapy (HT, n=521) was applied as single therapy in 9.46% of low-risk and 17.92% of intermediate-risk patients. Additionally, HT was combined with RT in 14.34% of lower-risk patients and 58.26% of high-risk patients, and 67.19% low-intermediate risk with RT and/or BT received neoadjuvant/concomitant/adjuvant HT. Finally, 83.75% of high-risk patients undergoing RT and/or BT also received HT. CONCLUSIONS: Although EAU guidelines for PCa management are easily available in Europe, the adherence to their recommendations is low, finding the highest discrepancies in the need for a prostate biopsy and the diagnostic methods. Improve information and educational programs could allow a higher adherence to the guidelines and reduce the variability in daily practice. (Controlled-trials.com: ISRCTN19893319).
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Fidelidade a Diretrizes/estatística & dados numéricos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Idoso , Europa (Continente) , Humanos , Masculino , Sociedades Médicas , Espanha , UrologiaRESUMO
The reduction of the particle size of drugs of pharmaceutical interest down to the nano-sized range has dramatically changed their physicochemical properties. The greatest disadvantage of nanocrystals is their inherent instability, due to the risk of crystal growth. Thus, the selection of an appropriate stabilizer is crucial to obtain long-term physicochemically stable nanocrystals. High pressure homogenization has enormous advantages, including the possibility of scaling up, lack of organic solvents and the production of small particles diameter with low polydispersity index. The sequential use of high shear homogenization followed by high pressure homogenization, can modulate nanoparticles' size for different administration routes. The present study focuses on the optimization of the production process of two formulations composed of different surfactants produced by High Shear Homogenization followed by hot High Pressure Homogenization. To build up the surface response charts, a 22 full factorial design experiment, based on 2 independent variables, was used to develop optimized formulations. The effects of the production process on the mean particle size and polydispersity index were evaluated. The best ibuprofen nanocrystal formulations were obtained using 0.20% Tween 80 and 1.20% PVP K30 (F1) and 0.20% Tween 80 and 1.20% Span 80 (F2). The estimation of the long-term stability of the aqueous suspensions of ibuprofen nanocrystals was studied using the LUMISizer. The calculated instability index suggests that F1 was more stable when stored at 4 °C and 22 °C, whereas F2 was shown to be more stable when freshly prepared.
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OBJECTIVE: The aim of this study is to determine which cancer and demographic criteria influence the indication for surgery (radical prostatectomy) or radiation therapy (external or brachytherapy) in the treatment of prostate cancer. MATERIAL AND METHODS: An analysis of the 2714 patients of the 2010 National Prostate Cancer Registry treated with curative intent. The analysed variables were age, prostate-specific antigen (PSA), prostate volume, the number of biopsy cores, the percentage of positive cores, the stage, Gleason score, the type of pathologist, the presence of perineural invasion and the study centre. We analysed the association among these variables and the type of treatment (surgery vs. radiation therapy/brachytherapy), using a univariate analysis (Student's t test and chi-squared) and a binary multiple logistic regression. RESULTS: The 48.12% of the patients (1306/2714) were treated with surgery, and 51.88% (1,408/2,714) underwent radiation therapy/brachytherapy. Differences were observed between the patients treated with prostatectomy and those treated with radiation therapy/brachytherapy (p<.05) in age (63.50±6.5 vs. 69.0±6.7), PSA (8.76±16.97 vs. 13.21±15.88), biopsied cores, percentage of positives cores (30.0±22 vs. 38.7±29), Gleason score (G6: 53.9% vs. 46.1%; G7: 45% vs. 55% G8-10: 26.6%, 73.4%), stage (localised: 50% vs. 50%; locally advanced: 14.6% vs. 85.4%), perineural invasion and hospital centre. In the multivariate analysis, the selected independent variables were age, PSA, percentage of positives cores, stage, Gleason score and hospital centre. CONCLUSION: According to our study, age, tumour aggressiveness and stage and the centre where the patient will be treated affect the selection of curative treatment for prostate cancer.
Assuntos
Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Idoso , Braquiterapia , Demografia , Humanos , Masculino , Prostatectomia , Neoplasias da Próstata/patologia , Sistema de Registros , EspanhaRESUMO
OBJECTIVE: To review the latest evidence on the oncologic urology of prostate, renal and bladder tumours, analysing their impact on daily clinical practice and future medium to long-term regimens. METHODS: We review the abstracts on prostate, renal and bladder cancer presented at the 2015 congresses (EAU, AUA, ASCO, ESMO y ASTRO) that received the best evaluations by the OncoForum committee. RESULTS: Cabozantinib could represent a new second-line (or subsequent) treatment option for patients with advanced renal cancer. In muscle-invasive bladder cancer, the genetic expression profile could predict the clinical benefit of neoadjuvant therapy in treating urothelial tumours. In metastatic castration-resistant prostate cancer, results were presented from various studies that evaluated the addition of chemotherapy to standard treatment with androgen deprivation, showing a reduction in the progression risk and higher PSA response rates. CONCLUSIONS: New options for the second-line treatment of renal cancer were presented. In metastatic castration-resistant prostate cancer, various studies have been published on treatment with enzalutamide, which has been shown to delay the symptomatic disease and benefit overall survival.
Assuntos
Neoplasias Renais , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Biópsia , Humanos , Neoplasias Renais/terapia , Masculino , Oncologia , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Neoplasias da Bexiga Urinária/terapia , UrologiaRESUMO
OBJECTIVES: To describe the established therapies for localised prostate cancer (PC) in Spain and to assess compliance with the 2010 UAE guidelines. PATIENTS AND METHODS: This was an epidemiological, observational, prospective and multicentre study. Of the 3,918 patients diagnosed with PC during 2010, only those patients with localised PC were included. Follow-up was ultimately conducted for a minimum of one year from the diagnosis for 3,713 patients (94.77%). The treatment groups assessed were as follows: radical prostatectomy, radiation therapy, hormone therapy, brachytherapy, active surveillance or observation and experimental local treatment (cryotherapy or other treatment). Compliance with the recommendations of the EAU guidelines was studied, describing the treatment groups according to D'Amico risk stratification criteria (localised [low, intermediate and high risk] and locally advanced), age, PSA and Gleason score. RESULTS: By applying the D'Amico criteria, we included 3,641 (92.93%) patients. Based on the UAE recommendations: 1) 68.87% of the patients at low-intermediate risk aged≤65 years underwent radical prostatectomy; 2) 34.51% of the patients>65 years at high risk with locally advanced disease were administered radiation therapy and hormone therapy; 3) 30.36% of the patients at high risk with locally advanced disease were only treated with hormone therapy; 4) 15.20% of the patients at low risk were only treated with brachytherapy; 5) active surveillance or observation was selected for 2.44% of the patients aged≤65 years and for 10.63% of the patients at low-intermediate risk who were>65 years. Lastly, 86.5% of the patients at low risk underwent a single treatment, and 43.62% of the patients at high risk with locally advanced disease underwent combined treatments. CONCLUSIONS: This is the first national European study to evaluate the therapeutic management of localised PC based on the risk group to which the patient belonged. Most young patients (≤65 years) with low-intermediate risk localised PC were treated with surgery, which adheres to the recommendations of the 2010 UAE guidelines. Various therapeutic combinations have been employed for patients with high-risk, locally advanced localised tumours, revealing the need for a multidisciplinary approach (Controlled-trials.com number: ISRCTN19893319).