RESUMO
BACKGROUND: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. PATIENTS AND METHODS: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. RESULTS: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. CONCLUSIONS: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy.
Assuntos
Neoplasias não Músculo Invasivas da Bexiga , Pirazóis , Quinoxalinas , Neoplasias da Bexiga Urinária , Humanos , Adolescente , Adulto , Vacina BCG/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Invasividade NeoplásicaRESUMO
Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment.
Assuntos
Partículas alfa/uso terapêutico , Antígeno Prostático Específico/antagonistas & inibidores , Neoplasias da Próstata/terapia , Radioimunoterapia/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Actínio , Ensaios Clínicos Fase III como Assunto , Dipeptídeos/farmacologia , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/farmacologia , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Masculino , Medicina de Precisão/métodos , Intervalo Livre de Progressão , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Radioimunoterapia/efeitos adversos , Compostos Radiofarmacêuticos/farmacologia , Planejamento da Radioterapia Assistida por Computador , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/efeitos da radiaçãoRESUMO
Although sexual-related problems are very prevalent, inadequate training for physicians has been reported. The aim was to investigate the educational situation in sexual medicine, including sexual dysfunctions, gender dysphoria and paraphilia, among German physicians in urology and andrology. Additional, barriers when addressing sexual health issues and confidence in taking care of patients with sexual-related problems were evaluated. A questionnaire was sent to 5955 urologists, urology residents and andrologists throughout Germany. The results of this study emphasise the need for continuing education and training in sexual medicine including sexual dysfunctions (83.9%), gender dysphoria (58.2%) and paraphilia (56.6%). Physicians, especially when working in urology, need basic skills in order to feel confident (89.0% in taking care of patients with sexual dysfunctions, 25.8% with gender dysphoria and 22.9% with paraphilia) and be able to reduce several barriers when addressing sexual health issues. The main reported barriers were lack of time (61.0%), inadequate financial compensation (42.5%), lack of necessity (29.9%) and the assumption of patients feeling uncomfortable (20.9%). It is within the competence of urologists and andrologists to correctly assess the situation and to refer patients to multidisciplinary support, such as psychologists, psychosomatics or couple therapists.
Assuntos
Andrologia/educação , Educação Médica Continuada/tendências , Sexologia/educação , Urologia/educação , Competência Clínica , Barreiras de Comunicação , Feminino , Disforia de Gênero/terapia , Alemanha , Humanos , Internato e Residência , Masculino , Transtornos Parafílicos/terapia , Relações Médico-Paciente , Disfunções Sexuais Fisiológicas/terapia , Inquéritos e Questionários , Urologistas/educaçãoRESUMO
BACKGROUND: Intratumoural lymphocytic infiltration is strongly associated with the outcome of many human epithelial cancers. The current paper investigated whether subpopulations of tumour-infiltrating T lymphocytes are associated with certain clinicopathological parameters and the prognosis of patients with invasive bladder cancer (BCa). PATIENTS AND METHODS: The infiltration densities of the adaptive immune markers CD3 (the whole T cell population), FOXP3 (regulatory T cells; Tregs), CD8 (T effector cells) and CD45R0 (T effector memory cells) were analysed by immunohistochemistry and image analysis with tissue microarrays of tumour tissues from 149 patients with invasive BCa treated with radical cystectomy. The findings were correlated with certain clinicopathological parameters. RESULTS: Higher FOXP3/CD3 [OS: p = 0.016, HR 1.29, 95% confidence intervals (95% CIs 1.05-1.59)] and FOXP3/CD8 (OS: p = 0.013, HR 1.32, 95% CIs 1.06-1.65) ratios were significantly associated with briefer overall survival and time to cancer-specific death; the latter ratio represented an independent prognostic factor according to a multivariate analysis adjusted for pathological T and N stages (HR 1.32, 95% CIs 1.05-1.67, p = 0.018). The infiltration densities of individual markers (CD3, CD8, FOXP3 and CD45R0) were not significantly associated with clinicopathological parameters or survival; however, a trend towards a better outcome was observed for higher log-transformed CD8 (p = 0.070, HR 0.80, 95% CIs 0.63-1.02) and CD3 (p = 0.113, HR 0.84, 95% CIs 0.68-1.04) infiltration values. CONCLUSIONS: A high fraction of Tregs amongst CD3- and CD8-positive lymphocytes indicated a poor prognosis, thereby emphasising the important role that Tregs play in the suppression of the anti-tumour immune response. No single lymphocytic marker was significantly correlated with clinical outcomes, but high CD3 and CD8 infiltration showed trends towards better prognosis.
Assuntos
Imunidade Adaptativa , Linfócitos T CD8-Positivos/patologia , Carcinoma de Células de Transição/imunologia , Linfócitos do Interstício Tumoral/patologia , Estadiamento de Neoplasias , Linfócitos T Reguladores/patologia , Neoplasias da Bexiga Urinária/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Linfócitos T Reguladores/imunologia , Fatores de Tempo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Alterations in the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway are frequent in urothelial bladder cancer (BLCA) and thus provide a potential target for novel therapeutic strategies. We investigated the efficacy of the AKT inhibitor MK-2206 in BLCA and the molecular determinants that predict therapy response. METHODS: Biochemical and functional effects of the AKT inhibitor MK-2206 were analysed on a panel of 11 BLCA cell lines possessing different genetic alterations. Cell viability (CellTiter-Blue, cell counts), apoptosis (caspase 3/7 activity) and cell cycle progression (EdU incorporation) were analysed to determine effects on cell growth and proliferation. cDNA or siRNA transfections were used to manipulate the expression of specific proteins such as wild-type or mutant PIK3CA, DUSP1 or CREB. For in vivo analysis, the chicken chorioallantoic membrane model was utilised and tumours were characterised by weight and biochemically for the expression of Ki-67 and AKT phosphorylation. RESULTS: Treatment with MK-2206 suppressed AKT and S6K1 but not 4E-BP1 phosphorylation in all cell lines. Functionally, only cell lines bearing mutations in the hotspot helical domain of PIK3CA were sensitive to the drug, independent of other genetic alterations in the PI3K or MAPK signalling pathway. Following MK-2206 treatment, the presence of mutant PIK3CA resulted in an increase in DUSP1 expression that induced a decrease in ERK 1/2 phosphorylation. Manipulating the expression of mutant or wild-type PIK3CA or DUSP1 confirmed that this mechanism is responsible for the induction of apoptosis and the inhibition of tumour proliferation in vitro and in vivo, to sensitise cells to AKT target therapy.Conclusion or interpretation:PIK3CA mutations confer sensitivity to AKT target therapy in BLCA by regulating DUSP1 expression and subsequent ERK1/2 dephosphorylation and can potentially serve as a stratifying biomarker for treatment.
Assuntos
Fosfatase 1 de Especificidade Dupla/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Mutação , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Galinhas , Membrana Corioalantoide , Classe I de Fosfatidilinositol 3-Quinases , Humanos , Terapia de Alvo Molecular , Fosfatidilinositol 3-Quinases/genética , Fosforilação , Neoplasias da Bexiga Urinária/patologiaRESUMO
Immune checkpoint inhibitors are standard of care in the treatment of metastatic and locally advanced urothelial cancer. Their use in perioperative treatment is currently under investigation as monotherapy as well as in combination with chemotherapy or radiation regimens. This article provides an overview of recent trials, current data as well as an outlook on future developments in the perioperative management of urothelial cancer.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/cirurgia , Carcinoma de Células de Transição/tratamento farmacológico , Imunoterapia , Terapia Combinada , Músculos/patologiaRESUMO
BACKGROUND: The S3-guideline on bladder cancer recommends radical cystectomy and cisplatin-based perioperative chemotherapy (POC) for muscle-invasive bladder cancer (MIBC). Recommendation for metastatic urothelial cancer (mUC) is cisplatin-based or immuno-oncological (IO) treatment in platinum-ineligible patients (pts) or as 2nd-line therapy. OBJECTIVES: Aim of the study was to obtain representative data on clinical routine treatment of MIBC and mUC in Germany. MATERIALS AND METHODS: A nationwide survey was performed to obtain data on stage-related patient volume in hospitals and office-based physicians. Based on these results, a representative sample of treatment data was collected retrospectively from pts with MIBC and mUC. RESULTS: Data from 956 pts (MIBC 576; mUC: 380) were collected. Of the MIBC pts, 49.8% received a systemic therapy (80.4% of them received cisplatin/gemcitabine) and 50.2% were treated with a cystectomy without POC. Significant factors for cystectomy without POC were higher age >â¯75 years (odds ratio [OR] 4.91, 95% confidence interval [CI] 3.01-8.11, pâ¯< 0.001) and platinum-ineligible pts (OR 2.15, 95% CI 1.30-3.59; pâ¯= 0.003). Treatment decision without interdisciplinary tumor board was also correlated with no POC (OR 2.43, 95% CI 1.65-3.61, pâ¯< 0.001). In mUC platinum-pretreated pts generally receive IO therapy (OR 12.07, 95% CI 6.94-21.82, pâ¯< 0.001). Other significant factors are positive PD-L1 status (OR 3.72, 95% CI 1.30-5.71, pâ¯< 0.001), higher age >â¯75 years (OR 2.83, 95% CI 1.43-5.73, pâ¯= 0.003) and platinum-ineligible pts (OR 2.57, 95% CI 1.30-5.71, pâ¯= 0.007). CONCLUSIONS: The "gold standard" cisplatin/gemcitabine is established in Germany if pts are treated with POC. Nonetheless half of the MIBC pts did not receive a POC, especially if the treatment decision is not discussed in a tumor board. In mUC IO therapy is established as 2nd-line therapy after a platinum-based treatment. Although the guideline recommendations are largely implemented, there is potential for optimization, especially in the establishment of interdisciplinary tumor boards.
Assuntos
Carcinoma , Neoplasias da Bexiga Urinária , Humanos , Idoso , Bexiga Urinária , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , MúsculosRESUMO
In 50% of all cases, bladder cancer patients develop tumor progression despite modern surgical methods such as radical cystectomy. A solution to the problem might be the identification and understanding of molecular biomarkers which could result in the development of advanced methods with better preventive, diagnostic, and therapeutic potential. One suitable approach is the identification of a bladder cancer-specific molecular marker in order to enhance patients' outcome. We and others have identified EMMPRIN as a prognostic biomarker in a variety of tumor diseases. EMMPRIN (CD147, extracellular matrix metalloproteinase inducer) is a cell surface protein that is expressed among other cell types, in particular in tumor cells. Since its first description in 1982 it is established that overexpression of EMMPRIN correlates with tumor progression and patient outcome. EMMPRIN expression levels can be used as an independent prognostic factor for survival. Recently, EMMPRIN has been defined as a potential target for tumor therapy in preclinical studies.
Assuntos
Basigina/análise , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Animais , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/mortalidade , Quimioterapia Adjuvante , Terapia Combinada , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Prognóstico , Taxa de Sobrevida , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
BACKGROUND: CD147 (basigin, EMMPRIN) is a multifunctional, highly conserved glycoprotein enriched in pancreatic ductal adenocarcinomas (PDACs) which is associated with poor prognosis in many malignancies. The role of CD147 in pancreatic cancer, however, remains elusive. METHODS AND RESULTS: Silencing of CD147 by RNA interference (RNAi) reduced the proliferation rate of MiaPaCa2 and Panc1 cells. CD147 is required for the function and expression of the monocarboxylate transporters MCT1 and MCT4 that are expressed in human PDAC cells as demonstrated by real-time reverse transcription-PCR (RT-PCR) as well as immunohistology. MCT1 and MCT4 are the natural transporters of lactate, and MiaPaCa2 cells exhibited a high rate of lactate production, which is characteristic for the Warburg effect, an early hallmark of cancer that confers a significant growth advantage. Further induction of lactate production by sodium azide in MiaPaCa2 cells increased MCT1 as well as MCT4 expression. CD147 silencing inhibited the expression and function of MCT1 and MCT4 and resulted in an increased intracellular lactate concentration. Addition of exogenous lactate inhibited cancer cell growth in a dose-dependent fashion. In vivo, knock-down of CD147 in MiaPaCa2 cells by inducible short hairpin RNA (shRNA)-mediated CD147 silencing reduced invasiveness through the chorioallantoic membrane of chick embryos (CAM assay) and inhibited tumourigenicity in a xenograft model in nude mice. CONCLUSION: The function of CD147 as an ancillary protein that is required to sustain the expression and function of MCT1 and MCT4 is involved in the association of CD147 expression with the malignant potential of pancreatic cancer cells exhibiting the Warburg effect.
Assuntos
Basigina/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Ácido Láctico/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Simportadores/metabolismo , Animais , Basigina/genética , Western Blotting , Carcinoma Ductal Pancreático/patologia , Embrião de Galinha , Relação Dose-Resposta a Droga , Inativação Gênica , Glucose/metabolismo , Ácido Láctico/farmacologia , Camundongos , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/patologia , RNA Interferente Pequeno/genética , Regulação para CimaRESUMO
Wilms tumor, or nephroblastoma, is the most common malignant tumor of the urinary tract in children, but is rarely found in adults. Here, we report the first case of a female patient with a Wilms tumor, diagnosed during pregnancy, who underwent radical nephrectomy and adjuvant chemotherapy before and after delivering a healthy child. Generally, treatment should follow the guidelines established for the pediatric setting.
Assuntos
Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/cirurgia , Tumor de Wilms/tratamento farmacológico , Tumor de Wilms/cirurgia , Adulto , Terapia Combinada , Feminino , Humanos , GravidezRESUMO
BACKGROUND AND OBJECTIVE: The internet provides numerous sources of information about prostate cancer (PCa). The present study investigated internet use among long-term PCa survivors, trust in online PCa-related information, and associated factors. MATERIALS AND METHODS: Based on the German national research project Familial Prostate Cancer long-term PCa survivors were asked about their internet use in 2017. Associations with sociodemographic (age at survey, children, intimate relationship, education) and disease-related parameters (time since diagnosis, PCa family history, progress) were analyzed using multivariable logistic regression. RESULTS: In all, 4636 long-term PCa survivors were included in the analysis (mean age 76.9 years; standard deviation 6.6 years). Mean follow-up was 14.0 years. Of long-term PCa survivors, 62.1% were using the internet. Among non-users 23.5% expressed strong concerns, among users only 2.8%. Furthermore, 47.2% of internet users sought information about PCa, 18.0% of them indicated difficulties while searching for information. More than half of the users found the online information inappropriate. Lower age, shorter time since diagnosis, progress, and a more frequent internet use were associated with search for information. Only one-third fully trusted online information. Trust in online information was associated with high age, higher educational level, and frequent search for online information. Many survivors stressed that they were primarily trusting their treating urologist. CONCLUSIONS: Two-thirds of long-term PCa survivors are using the internet. A significant proportion expressed difficulties finding proper and reliable information. Urologists should be familiar with online resources on PCa in order to offer advice to patients and to recommend adequate information on the internet.
Assuntos
Sobreviventes de Câncer/psicologia , Serviços de Informação/estatística & dados numéricos , Internet , Neoplasias da Próstata/psicologia , Qualidade de Vida , Confiança , Idoso , Criança , Humanos , Masculino , Educação de Pacientes como Assunto , Inquéritos e QuestionáriosRESUMO
The absence of curative treatment strategies for metastatic prostate cancer requires further development of novel, more effective treatment regimens. Because of recent advances in immunologic and translational research, therapeutic vaccines are becoming important as promising treatment modalities against prostate cancer. Immunizing patients who have hormone-refractory prostate cancer with an allogenic IL-2 and IFN-gamma secreting tumor cell vaccine is safe and feasible with no dose-limiting toxicity; it has been shown to reduce the progression of prostate-specific antigen in treated subjects and to induce vaccine-specific immune responses. Despite these results, current vaccine strategies have shown only limited success in clinical settings. There is ample evidence that multiple immunosuppressive mechanisms, such as regulatory T cells and myeloid suppressor cells, exist that considerably dampen antitumor responses and weaken the activity of current immunotherapeutic regimens. Recent insights into the characteristics of the regulatory elements of the immune system have provided new opportunities to enhance vaccine-mediated antitumor immunity by reversing tumor-mediated immunosuppression before immunotherapies can be used successfully for cancer patients.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células de Transição/tratamento farmacológico , Imunoterapia Ativa/métodos , Neoplasias Renais/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Formação de Anticorpos/imunologia , Vacina BCG/administração & dosagem , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/administração & dosagem , Carcinoma de Células Renais/imunologia , Carcinoma de Células de Transição/imunologia , Humanos , Tolerância Imunológica/imunologia , Interferon gama/administração & dosagem , Interleucina-2/administração & dosagem , Neoplasias Renais/imunologia , Masculino , Neoplasias da Próstata/imunologia , Linfócitos T Reguladores/imunologia , Neoplasias da Bexiga Urinária/imunologiaRESUMO
Patients suffering from locally advanced prostate carcinoma are often stressed by debilitating local symptoms limiting their quality of life. At the same time life expectancy often exceeds several years, whereas urologists and oncologists tend to underestimate their patients' life expectancy. Cystoprostatectomy for locally advanced prostate carcinoma is a reasonable therapeutic option concerning frequency and kind of imminent complications and possibly alleviates or completely eliminates local symptoms in 80% or more. According to the literature cancer-specific 10-year survival rates are 38% or median cancer-specific survival lies between 24 and 31 months. The role of neoadjuvant or adjuvant hormonal therapy, chemotherapy, or radiotherapy has not yet been defined. Mostly after cystoprostatectomy due to locally advanced prostate carcinoma an ileal conduit is formed for urinary diversion, but also orthotopic neobladders or continent pouches are used. Incontinence rates for orthotopic neobladders may reach 50% and more. In synopsis cystoprostatectomy may be a viable therapeutic option for patients suffering from locally advanced prostate carcinoma. It surely is important that the indication for surgery is based on an individual decision.
Assuntos
Cistectomia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Intervalo Livre de Doença , Humanos , Excisão de Linfonodo , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Cuidados Paliativos , Neoplasias da Próstata/patologia , Qualidade de Vida , Terapia de Salvação , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Coletores de UrinaRESUMO
Detection of metastases in lymph nodes is an important prognostic factor for progression-free survival in bladder cancer patients. Patients undergoing radical cystectomy with pelvic lymphadenectomy are randomized in the LEA study (AUO AB 25/02) into two groups receiving standard (obturator and external nodes) or extended lymphadenectomy (complete pelvic nodes up to the inferior mesenteric artery).The aim of this study is the detection of lymph node metastases that are not identified with classic pathological methods using RT-PCR as a highly sensitive and specific method. For detection of occult disseminated tumor cells we analyze the expression of the tumor markers cytokeratin 20 (CK-20), uroplakin II (UP II), mucin 2 (MUC2), and mucin 7 (MUC7).We examined 315 lymph nodes from 19 cystectomy patients for the expression of CK-20. In 93 lymph nodes CK-20 expression was detected whereas only 18 lymph nodes were histopathologically positive. More than one third of CK-20-positive lymph node metastases were located outside the standard lymphadenectomy field. We did not detect any skip lesions. Follow-up data will validate if there is a correlation between detection of occult disseminated tumor cells and progression-free survival.
Assuntos
Carcinoma de Células de Transição/patologia , Metástase Linfática/patologia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Cistectomia , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
EMMPRIN (CD147) is a cell surface protein that is highly expressed on tumor cells. Elevated EMMPRIN levels have been detected in a variety of malignant tumors and have been associated with tumor progression in experimental and clinical conditions. Recent studies have shown that EMMPRIN is an independent prognostic factor for overall survival in bladder cancer patients. In a multicenter phase II trial, antibodies against EMMPRIN were shown to be successful in hepatocellular cancer therapy. We are characterizing the functional importance of EMMPRIN in bladder cancer in order to evaluate this protein as a new target molecule for therapy.
Assuntos
Basigina/genética , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Bexiga Urinária/genética , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Modelos Animais de Doenças , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Transdução de Sinais/genética , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologiaRESUMO
Because of the frequency of occurrence and the long protracted course, bladder carcinoma is the most expensive solid tumor in terms of costs, from diagnosis to death of the patient. The most important cost factor within the total cost is the treatment of recurrent, non-muscle invasive bladder carcinoma. Photodynamic diagnosis (PDD) improves the early detection rate of non-muscle invasive bladder cancer, especially the detection of carcinoma in situ and severe dysplasia. PDD also reduces the number of residual tumors after TUR-B compared to white-light guided TUR-B and also the early recurrence rate although long-term outcome with hexylaminolaevulinic acid with regards to the general course of bladder cancer is still lacking. PDD has been used mainly for detection of bladder cancer and specifically carcinoma in situ in conjunction with diagnostic and therapeutic transurethral resection of the bladder. In 2006 hexylaminolaevulinic acid (HAL) was approved in the EU (EMEA) as a photosensitizer for the use in photodynamic diagnosis of the bladder. Several guidelines have incorporated PDD as optional form of diagnosis during endoscopy in proven or suspected bladder cancer, but no specific recommendations regarding indication and application of PDD exist. The German group of urologic oncology (AKO) invited urologists and biologists involved in the development of hexylaminolaevulinic acid as well its clinical use to participate in evaluating the data for HAL and its predecessor delta-aminolaevulinic acid (5-ALA). A consensus with regards to the indications, contraindications, technique, pre-clinical data, comparison of HAL and 5-ALA, current results, costs and follow-up was reached and are presented in this paper.
Assuntos
Ácido Aminolevulínico , Oncologia/normas , Microscopia de Fluorescência/métodos , Guias de Prática Clínica como Assunto , Sociedades Médicas , Neoplasias Urológicas/diagnóstico , Urologia/normas , Humanos , Fármacos FotossensibilizantesRESUMO
The chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent side effects in cytostatic therapy and a profound challenge during the therapy of cancer patients. Therefore, standardized guideline-orientated prophylaxis is essential and a fundamental contribution for the success of treatment. This review summarizes the current recommendations for CINV of the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO), the American Society for Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN) and the S3-guideline Supportive Therapie of the Leitlinienprogramm Onkologie and shall facilitate its use in the daily routine.
Assuntos
Antieméticos , Antineoplásicos , Náusea , Neoplasias , Vômito , Antineoplásicos/efeitos adversos , Humanos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controleRESUMO
BACKGROUND: Beside the classical anticancer treatment tumor patients try to find proactive alternative therapies to fight their disease. Lifestyle changes such as introducing a ketogenic diet is one of the most popular among them. The German Association of Urological Oncology (AUO, Arbeitsgemeinschaft Urologische Onkologie) presents a systematic review investigating the evidence of ketogenic diet in cancer patients. MATERIALS AND METHODS: A systematic literature research was conducted in the databases Medline, Livivo, and the Cochrane Library. Only clinical studies of tumor patients receiving chemotherapy while on a ketogenic diet were included. The assessment of the results was performed according to the predefined primary endpoints overall survival and progression-free survival and secondary endpoints quality of life and reduction of adverse effects induced by cytostatics. RESULTS: Nine studies met the inclusion criteria: eight prospective and one retrospective study case series respectively cohort-studies, with a total of 107 patients. Currently there is no evidence of a therapeutic effect of a ketogenic diet in patients with malignant tumors regarding the clinical outcome or quality of life. CONCLUSION: Based on the current data, a ketogenic diet can not be recommended to cancer patients because prospective, randomized trials are missing.
Assuntos
Dieta Cetogênica , Neoplasias Urológicas/dietoterapia , Humanos , Qualidade de Vida , Neoplasias Urológicas/psicologiaRESUMO
BACKGROUND: At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented. OBJECTIVES: The focus is on the clinical impact of these data. MATERIALS AND METHODS: A group of German experts in the field of urogenital-oncologic expertise discussed the clinical impact with respect to the current data. RESULTS: The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC. CONCLUSIONS: Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20 mg/m2 cabazitaxel.
Assuntos
Segunda Neoplasia Primária/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Docetaxel , Humanos , Masculino , Segunda Neoplasia Primária/tratamento farmacológicoRESUMO
In patients with advanced prostate cancer, quality of life and prevention of complications come to the fore. Besides handling local complications such as obstruction, hematuria and lymphedema, treatment of bone metastases and their complications is of great importance. Analgesic measures, bisphosphonates, radiation therapy, radionuclide therapy and neurosurgical procedures are available. Spinal cord compression with acute motor and sensory deficiency requires immediate neurosurgical and/or radiation therapy. Tumor anemia should be treated appropriately.