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1.
Anticancer Res ; 40(1): 335-339, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892584

RESUMO

BACKGROUND/AIM: The novel taxane cabazitaxel has been shown to exert excellent anticancer effects after androgen receptor axis-targeting (ARAT) agents in clinical data, but not in in vitro data. We investigated the clinical outcome of cabazitaxel chemotherapy after docetaxel according to use of ARAT agents. PATIENTS AND METHODS: Prostate specific antigen (PSA) response, progression-free survival, and overall survival were compared between cases with and without prior use of ARAT agents in 74 Japanese patients with metastatic castration-resistant prostate cancer treated with cabazitaxel chemotherapy. RESULTS: Background characteristics were comparable between patients with and without prior use of ARAT agents. PSA response, progression-free survival, and overall survival in cabazitaxel chemotherapy were comparable between patients with and without prior use of ARAT agents. CONCLUSION: No detrimental effects of prior ARAT agents on clinical outcome were observed for cabazitaxel chemotherapy in the post-docetaxel setting, suggesting that cabazitaxel can be expected to remain active even after ARAT agent therapy.


Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Docetaxel/farmacologia , Terapia de Alvo Molecular , Receptores Androgênicos/metabolismo , Taxoides/farmacologia , Idoso , Antagonistas de Receptores de Andrógenos/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Masculino , Prognóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Resultado do Tratamento
2.
Anticancer Drugs ; 31(3): 298-303, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31913197

RESUMO

This multi-institutional study aimed to identify prognostic factors for cabazitaxel treatment of castration-resistant prostate cancer (CRPC). This study included 74 Japanese patients with CRPC who were treated with cabazitaxel between 2014 and 2017. Associations between clinicopathological factors including serum markers and progression-free survival (PFS) and overall survival (OS) were investigated. On multivariate analysis, high Gleason score [≥9 vs. ≤7; hazard ratio (HR), 95% confidence interval (CI): 2.00 (1.01-4.34); P = 0.047], presence of pain [HR, 95% CI: 2.02 (1.14-3.58); P = 0.016], and lactate dehydrogenase (LDH) level [HR, 95% CI: 47.31 (3.79-577.49); P = 0.0019] were significantly associated with PFS. Similarly, number of docetaxel cycles [HR, 95% CI: 0.050 (0.0037-0.45); P = 0.0057], performance status [≥2 vs. 0; HR, 95% CI: 5.07 (1.57-16.24); P < 0.0001], and LDH level [HR, 95% CI: 2946 (50-420994); P = 0.0001] were significantly associated with OS. This study showed that LDH level is robustly prognostic for both PFS and OS in cabazitaxel chemotherapy for CRPC.

3.
J Urol ; 203(1): 83-91, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430244

RESUMO

PURPOSE: The PROPHET (Prostate Cancer: Prostate Health Index Trial) is a prospective study to clarify the diagnostic impact of laboratory based and prostate volume adjusted p2PSA ([-2] proenzyme prostate specific antigen) related indexes on prostate cancer and clinically significant prostate cancer with prostate specific antigen less than 10 ng/ml. MATERIALS AND METHODS: Between April 2015 and March 2017, 421 men 50 to 79 years old in the prostate specific antigen range above age specific cutoffs and below 10 ng/ml were registered in the PROPHET. We investigated the diagnostic impacts of various clinical laboratory based free prostate specific antigen related and p2PSA related indexes on any grade and high Gleason grade group prostate cancer. RESULTS: Of the 363 eligible participants 179, 141 and 80 were diagnosed with any grade, and Gleason Grade Group 2-5 and 3-5 prostate cancer, respectively. The AUC-ROCs distinguishing nonprostate cancer vs prostate cancer, nonprostate cancer plus low Gleason Grade Group and low volume vs remaining prostate cancer with a higher Gleason Grade group or a higher volume on the PHI (Prostate Health Index) were significantly superior to the AUC-ROCs of prostate specific antigen and free-to-total prostate specific antigen. At 90% sensitivity in all investigated p2PSA related indexes the false-positive rate was superior to that of prostate specific antigen and free-to-total prostate specific antigen in any group comparison in terms of the Gleason Grade Group and positive biopsy cores. In 35% to 42% of men without prostate cancer and/or those with less aggressive prostate cancer the PHI would avoid unnecessary biopsy. CONCLUSIONS: Laboratory based p2PSA related indexes were significantly superior for detecting clinically significant prostate cancer compared to free-to-total prostate specific antigen. The indexes those would avoid up to 42% of prostate biopsies in men without aggressive cancer while maintaining 90% sensitivity.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Biópsia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Precursores de Proteínas
4.
Eur Urol ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31866092

RESUMO

BACKGROUND: No standard therapy has been established for localised prostate cancer patients with prostate-specific antigen (PSA) failure after radical prostatectomy (RP). OBJECTIVE: To determine whether radiotherapy ± hormone therapy is superior to hormone therapy alone in such patients. DESIGN, SETTING, AND PARTICIPANTS: This study is a multicentre, randomised, open-label, phase 3 trial. Patients with localised prostate cancer whose PSA concentrations had decreased to <0.1 ng/ml after RP, and then increased to 0.4-1.0 ng/ml, were randomised to the salvage hormone therapy (SHT) group (80 mg bicalutamide [BCL] followed by luteinising hormone-releasing hormone agonist in case of BCL failure) or the salvage radiation therapy (SRT) ± SHT group (64.8 Gy of SRT followed by the same regimen as in the SHT group in case of SRT failure). From May 2004 to May 2011, 210 patients (105 in each arm) were registered, with the median follow-up being 5.5 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was time to treatment failure (TTF) of BCL. RESULTS AND LIMITATIONS: TTF of BCL was significantly longer in the SRT ± SHT group (8.6 yr) than in the SHT group (5.6 yr; hazard ratio 0.56, 90% confidence interval [0.40-0.77]; one-sided p = 0.001). Thirty-two of 102 patients (31%) in the SRT ± SHT group did not have SRT treatment failure. However, clinical relapse-free survival and overall survival did not differ between the arms. The most frequent grade 3-4 adverse event was erectile dysfunction (83 patients [80%] in the SHT group vs. 76 [74%] in the SRT ± SHT group). Limitations include the short follow-up periods and surrogate endpoint setting to allow definitive conclusions. CONCLUSIONS: Initial SRT prolongs TTF of BCL in patients with post-RP PSA failure, indicating that SRT ± SHT is more beneficial than SHT alone. PATIENT SUMMARY: Patients who have prostate-specific antigen failure after radical prostatectomy benefit from salvage radiation therapy prior to salvage hormone therapy.

5.
J Urol ; : 101097JU0000000000000616, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31647388

RESUMO

PURPOSE: We sought to identify the symptoms and noninvasive test parameters associated with detrusor underactivity and develop a prediction model of detrusor underactivity. We analyzed clinical data on male patients with lower urinary tract symptoms who underwent pressure-flow studies. MATERIALS AND METHODS: Included in analysis were 909 men who met study criteria and whose data included the I-PSS (International Prostate Symptom Score), free uroflowmetry, post-void residual urine volume and prostate volume. Using these data we examined the significant symptoms and noninvasive test parameters associated with detrusor underactivity and developed a prediction model of detrusor underactivity. RESULTS: Of the 909 patients 454 (50%) were classified with detrusor underactivity. On logistic regression analysis older patient age, smaller prostate volume, a lower urgency symptom score, a higher weak stream symptom score and a lower maximum flow rate were selected as independent predictors of detrusor underactivity. The prediction model of detrusor underactivity consisting of these 5 factors showed satisfactory performance (C statistic 0.724). CONCLUSIONS: We developed a prediction model of detrusor underactivity in male patients with nonneurogenic lower urinary tract symptoms. The model was based on 5 predictive factors, namely older age, smaller prostate volume, 2 symptoms (less urgency and a weak stream) and a lower maximum flow rate. The model helps estimate the probability of detrusor underactivity in clinical practice without an invasive pressure-flow study.

6.
Anticancer Res ; 39(8): 4325-4328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366524

RESUMO

BACKGROUND/AIM: The significance of second transurethral resection (TUR), and identification of predictive factors for residual cancer remain unrevealed. This study aimed to find residual cancer and up-staging rates, as well as predictive factors for residual cancer, in patients who undergo second TUR for non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients who underwent second TURs for NMIBC between 2015 and 2017, were included in the study and their clinicopathological characteristics were analyzed for predictors of residual cancer. RESULTS: Among 143 Japanese patients whose tumors were initially diagnosed as high-risk NMIBC, residual cancers detected at second TURs were, Tis: n=22 (15.4%), Ta: n=15 (10.5%) and T1: n=29 (20.3%). No patients showed up-staging from NMIBC to MIBC. The presence of carcinoma-in situ at initial TUR was an independent risk factor for any residual cancer (Tis, Ta and T1), non-flat residual cancer (Ta and T1), and flat residual cancer (Tis). CONCLUSION: The presence of carcinoma-in situ is suggested to be an independent predictor of residual cancer. This may help guide decisions to perform second TUR.


Assuntos
Carcinoma in Situ/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Cistectomia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/patologia , Fatores de Risco , Resultado do Tratamento , Uretra/patologia , Uretra/cirurgia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos Urológicos
7.
Anticancer Res ; 39(8): 4411-4414, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366538

RESUMO

BACKGROUND/AIM: Cabazitaxel use has usually been limited to up to 10 cycles in most countries according to the protocol in the TROPIC trial. Therefore, clinical data on cabazitaxel use beyond 10 cycles is limited. The aim of this study was to report the therapeutic outcome of cabazitaxel chemotherapy administered for >10 cycles. PATIENTS AND METHODS: This study included 74 Japanese patients with prostate cancer between 2014 and 2017. Patients background, and treatment outcomes including PSA decline, progression-free survival, treatment-failure-free survival, overall survival, and adverse events were investigated, comparing patients treated with ≤10 and >10 cycles. RESULTS: Patients characteristics were favorable as indicated by the higher number of cycles of prior docetaxel chemotherapy, absence of pain, and absence of bony and visceral metastases among men who received >10 cycles of cabazitaxel. PSA response, progression-free survival, treatment-failure-free survival and overall survival were better among patients treated with >10 cycles of cabazitaxel compared to those treated with ≤10 cycles. The incidence of severe adverse events was similar between the two groups. CONCLUSION: Taken together, this study suggested that continuous chemotherapy with cabazitaxel beyond 10 cycles may be beneficial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel/efeitos adversos , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/efeitos adversos , Resultado do Tratamento
8.
J Urol ; 202(6): 1127-1135, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31251717

RESUMO

PURPOSE: We investigated the impact of previous, simultaneous or subsequent bladder cancer on the clinical outcomes of upper urinary tract urothelial carcinoma. MATERIALS AND METHODS: We retrospectively collected data on 2,668 patients who underwent radical nephroureterectomy of nonmetastatic upper urinary tract urothelial carcinoma in 1995 to 2009. We evaluated the impact of bladder cancer on overall mortality and the factors predictive of subsequent bladder cancer. RESULTS: A total of 631 patients (23.7%) had previous or simultaneous bladder cancer. Patients with previous or simultaneous bladder cancer had significantly shorter overall survival than patients without previous or simultaneous bladder cancer (HR 1.29, 95% CI 1.09-1.53, p=0.0026). Of the 2,037 patients without previous or simultaneous bladder cancer 683 (33.5%) subsequently had bladder cancer after radical nephroureterectomy. Of patients with pT0-2 disease those with subsequent bladder cancer had significantly shorter overall survival than patients without subsequent bladder cancer (HR 1.81, 95% CI 1.23-2.67, p=0.0025). In patients with pT3-4 disease subsequent bladder cancer was not associated with worse overall survival. On multivariable analyses independent predictors of subsequent bladder cancer were gender, preoperative urine cytology and clinical node status in the preoperative setting, and gender, adjuvant chemotherapy and pathological node status in the postoperative setting. CONCLUSIONS: Bladder cancer was significantly associated with worse clinical outcomes after radical nephroureterectomy of upper urinary tract urothelial carcinoma. Preventing subsequent bladder cancer in patients with pT0-2 upper urinary tract urothelial carcinoma may lead to better prognosis in those who undergo radical nephroureterectomy.


Assuntos
Carcinoma de Células de Transição/cirurgia , Nefroureterectomia , Neoplasias Ureterais/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Estudos Retrospectivos , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/patologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
9.
Cancer Chemother Pharmacol ; 84(3): 561-566, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31115605

RESUMO

OBJECTIVE: This study aimed to reveal the efficacy and safety profiles of 4-weekly cabazitaxel in patients with castration-resistant prostate cancer (CRPC). METHODS: The study included 62 Japanese patients who were treated for CRPC with ≥ 2 courses of cabazitaxel between 2014 and 2017. The oncological outcomes and adverse events were compared between 16 (25.8%) and 46 (74.2%) men who were treated with standard 3-weekly and alternative 4-weekly regimens, respectively. RESULTS: The prostate-specific antigen (PSA) response was comparable between the 3-weekly and 4-weekly regimens (median [interquartile range]: - 9.9% [- 64.5 to 13.0%] and - 30.7% [- 52.8 to 10.9%], P = 0.89), respectively. For patients on the 4-weekly regimen, the risks of progression (hazard ratio [HR], 95% confidence interval [CI] 1.27, 0.71-2.43, P = 0.44), treatment failure (HR, 95% CI 0.84, 0.48-1.55, P = 0.57) and any-cause mortality (HR, 95% CI 1.09, 0.58-2.17, P = 0.79) were comparable to those for patients on the 3-weekly regimen. The incidences of severe adverse events were also similar between the 3-weekly and 4-weekly regimens. CONCLUSIONS: 3-weekly and 4-weekly regimens of cabazitaxel showed similar efficacy and safety profiles in a real-world clinical setting. These data suggest that a 4-weekly regimen may be acceptable for selected patients.

10.
Med Oncol ; 36(4): 32, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30815799

RESUMO

This multi-institutional study aimed to investigate the efficacy and safety profiles of cabazitaxel after prior docetaxel chemotherapy in patients with castration-resistant prostate cancer (CRPC). This study included 63 Japanese patients with CRPC who were treated with cabazitaxel from 2014 to 2017. The oncological outcomes and adverse events (AEs) were documented, and prognostic factors for oncological outcomes and predictive factors for AEs were analysed. PSA decline was observed in 68.3% of patients, including 25.4% who achieved a ≥ 50% decline. The median progression-free survival, treatment failure-free survival, and overall survival were 4.3, 4.1, and 9.0 months, respectively. More cycles of prior docetaxel therapy was identified as common favourable prognostic factors for progression-free survival, treatment failure-free survival, and overall survival. Severe neutropenia, febrile neutropenia, and severe non-haematological AEs were observed in 73.0%, 33.3%, and 23.8% of patients, respectively. However, > 10 cycles of docetaxel was not associated with increased incidence of AEs. In conclusion, cabazitaxel chemotherapy was still active in Japanese CRPC patients treated with > 10 cycles of docetaxel chemotherapy, with an acceptable risk of AE burden. Treatment with cabazitaxel after > 10 cycles of docetaxel may be an appropriate option when it can be administered.


Assuntos
Docetaxel/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Esquema de Medicação , Humanos , Masculino , Resultado do Tratamento
11.
Int J Clin Oncol ; 24(5): 557-566, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30875000

RESUMO

BACKGROUND: Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC. METHODS: Patients with symptomatic mCRPC, ≥ 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality. RESULTS: Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5). CONCLUSIONS: In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Rádio (Elemento)/efeitos adversos , Rádio (Elemento)/uso terapêutico , Administração Intravenosa , Idoso , Anemia/induzido quimicamente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Seguimentos , Doenças Hematológicas/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Lesões por Radiação/etiologia , Radioisótopos/administração & dosagem , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Rádio (Elemento)/administração & dosagem
12.
Anticancer Res ; 38(8): 4767-4773, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30061247

RESUMO

AIM: To elucidate the relationship among tumor attenuation of pre-contrast-enhanced (TApre) computed tomography (CT), washout rate and clear cell ratio (CCR) in adrenal adenoma (AA) and propose a new approach for diagnosing AA on dynamic CT. MATERIALS AND METHODS: The training set consisted of 43 AAs and 15 non-AAs, while the validation set comprised 44 AAs and 11 non-AAs. Using the training set, the pairwise correlation between CCR, TApre and washout rate in AA was evaluated by linear regression analysis. A predictive formula for diagnosing AA was established by multiple logistic regression analysis using washout rate and TApre. Using the validation set, the diagnostic performance of this formula was investigated by comparing with the conventional diagnostic criteria: TApre ≤10 HU or washout rate ≥an optimal threshold calculated in the training set. RESULTS: Washout rate increased as CCR decreased, and as TApre increased. The formula predicting the probability of AA was: p(AA)=1/{1+exp(-1.5257+0.4923× TApre-0.3264×washout rate)}. Diagnostic performance of this formula was sensitivity of 93.2% and accuracy of 89.1%, while for the conventional diagnostic criteria, sensitivity was 81.8-86.4% and accuracy 81.8-83.6%. CONCLUSION: The diagnostic potential of dynamic CT for diagnosing AA may be improved by changing the threshold of washout rate based on substituting TApre for CCR.


Assuntos
Adenoma/patologia , Neoplasias das Glândulas Suprarrenais , Glândulas Suprarrenais/patologia , Tomografia Computadorizada por Raios X/métodos , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
13.
Mol Clin Oncol ; 8(6): 785-790, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29732157

RESUMO

The aim of the present study was to evaluate the prognostic impact of size and number of tumors in primary low-grade (LG) Ta bladder urothelial carcinoma (UC), and thus allow accurate risk stratification of low-risk non-muscle invasive bladder cancer (NMIBC). This study was a retrospective analysis of 245 patients with primary LG Ta UC of the urinary bladder who were treated with transurethral resection. Differences in intravesical recurrence-free survival (RFS) according to various cutoff values of tumor size and tumor number were calculated using Cox proportional hazards model. Median maximum size of tumor was 1.4 cm, and 153 patients (62.4%) had solitary tumors. Forty-nine patients experienced intravesical recurrence during a median 34 months of follow-up. Patients with solitary tumors had significantly longer RFS times compared with those with ≥8 tumors (P=0.003). Patients with larger tumors had significantly shorter RFS times for each cutoff value (P=0.01 for 1.0 cm, P<0.0001 for 1.5 and 2.0 cm, P=0.006 for 3.0 cm). On multivariate analysis, each cutoff value of tumor size was found to be a predictor of RFS; among them, the cutoff of 1.5 cm showed the strongest association (hazard ratio, 4.12; 95% confidence interval, 2.11-8.81; P<0.001). If we consider only lower risk NMIBC patients, such as primary LG Ta, the appropriate cutoff value of tumor size to predict intravesical recurrence might be 1.5 cm, but not 3.0 cm generally adopted in various guidelines. These findings suggest the need for rational risk assessment with consideration of the diversity of patients with NMIBC.

14.
J Urol ; 199(3): 734-740, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28941922

RESUMO

PURPOSE: Serum testosterone suppression during androgen deprivation therapy has been reported to affect the efficacy of androgen deprivation therapy. However, the factors impacting hormonal variations during androgen deprivation therapy remain unclear. Therefore, in this study we investigated the significance of missense polymorphisms in the gene encoding GNRH in men treated with primary androgen deprivation therapy for metastatic prostate cancer. MATERIALS AND METHODS: This study included 80 Japanese patients with metastatic prostate cancer with available serum testosterone levels during androgen deprivation therapy. We examined the association of GNRH1 (rs6185, S20W) and GNRH2 (rs6051545, A16V) gene polymorphisms with clinicopathological parameters, including serum testosterone levels during androgen deprivation therapy, as well as prognosis, including progression-free and overall survival. RESULTS: The CT and CT/TT alleles in the GNRH2 gene (rs6051545) were associated with higher serum testosterone during androgen deprivation therapy compared with those of the CC allele. Consequently the CT alleles were associated with a higher risk of progression after adjustment for age and serum testosterone during androgen deprivation therapy (HR 1.73, 95% CI 1.00-3.00, p = 0.049). CONCLUSIONS: Taken together these findings suggest that rs6051545 (GNRH2) genetic variation may result in inadequate suppression of serum testosterone during androgen deprivation therapy. This may lead to detrimental effects of androgen deprivation therapy on prognosis in men with metastatic prostate cancer.


Assuntos
Antagonistas de Androgênios/uso terapêutico , DNA de Neoplasias/genética , Hormônio Liberador de Gonadotropina/análogos & derivados , Polimorfismo Genético , Neoplasias da Próstata/genética , Testosterona/sangue , Idoso , Alelos , Progressão da Doença , Seguimentos , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Masculino , Metástase Neoplásica , Prognóstico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/secundário , Estudos Retrospectivos , Resultado do Tratamento
15.
Int J Urol ; 25(1): 61-67, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28994196

RESUMO

OBJECTIVES: To show the demographics, type of treatment and clinical outcomes of patients with retroperitoneal tumors in Japan. METHODS: We carried out a retrospective analysis of patients with retroperitoneal tumors treated between 2000 and 2012 at 12 university hospitals in Japan. Histology was re-evaluated using the 2013 World Health Organization classification. RESULTS: A total of 167 patients were included in the analysis. The number of diagnosed patients increased over the 12-year study period. Liposarcoma and schwannoma were the most common histological types among intermediate/malignant and benign tumors, respectively. The intermediate/malignant tumors were larger and were more frequently found in older people. Surgical resection was the primary treatment for 151 patients. The median survival duration for patients with malignant tumors was 91 months, and was significantly shorter than that for patients with benign and intermediate tumors (P < 0.01). R2 resection was associated with significantly shorter survival than R0/R1 resection for malignant tumors (P < 0.01), but not for intermediate. Grossly complete resection of the recurrent tumors improved survival. CONCLUSION: The number of patients diagnosed with retroperitoneal tumors increased over time. R2 resection of primary tumors was found to be associated with poor prognosis in malignant tumors, but not in intermediate tumors. Complete surgical resection of recurrent tumors was associated with a better oncological outcome.


Assuntos
Lipossarcoma/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Neurilemoma/epidemiologia , Neoplasias Retroperitoneais/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Hospitais Universitários/estatística & dados numéricos , Humanos , Incidência , Japão/epidemiologia , Lipossarcoma/patologia , Lipossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neurilemoma/patologia , Neurilemoma/cirurgia , Prognóstico , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Int J Clin Oncol ; 23(1): 173-180, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28770408

RESUMO

BACKGROUND: Radium-223 dichloride (radium-223) is the first targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with bone metastases. This study investigated the efficacy and safety of radium-223 in Japanese patients with symptomatic CRPC and bone metastases. METHODS: In this open-label, multicenter, phase II study, patients with progressive, symptomatic CRPC and bone metastases were treated with radium-223 (55 kBq/kg, intravenously) in a 4-week cycle for six cycles. The primary endpoint was the percent change in total alkaline phosphatase (ALP) from baseline at 12 weeks. Secondary endpoints included the percent ALP change from baseline to end of treatment (EOT), ALP response rates, percent change in prostate-specific antigen (PSA) from baseline to 12 weeks and EOT, PSA response rates, overall survival (OS), and time to symptomatic skeletal events (SSEs). Adverse events were monitored throughout the study period. RESULTS: Of the 49 Japanese patients (median age 74 years), 28 completed all infusions. Mean percent change in total ALP and PSA from baseline to 12 weeks was -19.3 and +97.4%, respectively. One-year OS and SSE-free rate at the end of active follow-up were 78 and 89%, respectively. The ALP response rate was 31%, while the PSA response rate was 6%. Grade 3/4 treatment-emergent adverse events observed in ≥10% of patients included decreased lymphocyte count (14%), anemia (14%), anorexia (10%), and bone pain (10%). CONCLUSIONS: Radium-223 is effective and well tolerated in Japanese patients with CRPC and bone metastases. Results were comparable with the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01929655.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Rádio (Elemento)/efeitos adversos , Rádio (Elemento)/uso terapêutico , Idoso , Fosfatase Alcalina/sangue , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/sangue , Neoplasias Ósseas/tratamento farmacológico , Humanos , Contagem de Linfócitos , Masculino , Antígeno Prostático Específico/análise , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Resultado do Tratamento
17.
J Endourol ; 31(10): 1073-1078, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28726499

RESUMO

INTRODUCTION: The features and usefulness of a novel wide-angle lens flexible cystoscope were assessed with a view to its practical application. MATERIALS AND METHODS: A phantom bladder model, on which a total of 12 markers that resemble lesions were arranged, was created for this study. Twenty-six urologists at three institutions observed this phantom bladder model using a conventional flexible cystoscope and a novel wide-angle lens flexible cystoscope, and they compared the observation time, marker detection rate, number of misidentified marker locations, overlooked locations, and misidentified location sites of both devices. Specific observation procedures that make use of the features of a wide-angle lens flexible cystoscope were also investigated. RESULTS: The observation time tended to be shorter with the wide-angle lens cystoscope than with a conventional cystoscope (104.9 seconds vs 113.6 seconds, p = 0.123). The marker detection rate was higher with the wide-angle lens cystoscope (90.2% vs 85.1%, p = 0.005). The number of marker location misidentifications did not differ between the two devices. Using a specifically designed observation procedure with the wide-angle lens cystoscope tended to further improve the marker detection rate (91.4% vs 88.1%, p = 0.157). CONCLUSION: Compared with a conventional cystoscope, a wide-angle lens cystoscope improved the lesion detection rate and has the potential to reduce observation time. The novel wide-angle lens flexible cystoscope is regarded as a useful device that offers advantages not available with a conventional cystoscope.


Assuntos
Cistoscópios/normas , Cistoscopia/instrumentação , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Cistoscopia/métodos , Desenho de Equipamento , Humanos , Lentes , Modelos Biológicos , Imagens de Fantasmas
18.
Cancer Sci ; 108(8): 1673-1680, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28594447

RESUMO

Despite treatment guidelines recommending observation for men with low-risk prostate cancer with life expectancy <10 years, a majority of elderly patients choose active treatment, which may result in overtreatment. Given the growing burden of prostate cancer among men aged ≥80 years (super-elderly men), accumulation of survival data for evaluation of overtreatment among super-elderly patients is imperative. Here, we report results of a population-based cohort study to clarify potential overtreatment of super-elderly men with localized prostate cancer. We used cancer registry data from the Monitoring of Cancer Incidence in Japan project, which covers 47% of the Japanese population. The subjects were men diagnosed with prostate cancer between 2006 and 2008. Follow-up period was 5 years. We calculated 5-year relative survival rates among the active treatment and observation groups after imputation for missing values. Of the 48 782 patients with prostate cancer included in the analysis, 15.1% were super-elderly men. The 5-year relative survival rates of super-elderly men with localized cancer were 105.9% and 104.1% among the active treatment and observation groups, respectively. This excellent relative survival rate in the observation group remained consistent even after stratification by tumor grade. Of the 2963 super-elderly men with localized cancer, 252 (8.5%) with curative treatment and 1476 (49.8%) with hormone therapy were assumed to have been overtreated. The proportion of overtreatment was estimated to reach 80% after imputation. These specific survival data in super-elderly men in the observation group can be useful in shared decision-making for these patients and may lead to a reduction in overtreatment.


Assuntos
Sobremedicalização/estatística & dados numéricos , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/patologia , Sistema de Registros , Análise de Sobrevida
19.
Drug Alcohol Depend ; 173: 85-91, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28212515

RESUMO

BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms are known to strongly influence alcohol drinking behavior. Given evidence of an association between smoking and drinking behaviors, we hypothesized that ALDH2/ADH1B polymorphisms might also be associated with smoking initiation, and conducted a cross-sectional study to examine this hypothesis. METHODS: Study subjects were first-visit outpatients diagnosed not to have cancer at Aichi Cancer Center Hospital between 2001 and 2005, including 4141 never smokers and 2912 ever smokers. Unconditional logistic regression models were applied to estimate odds ratios (OR) and 95% confidence intervals (CI) for smoking initiation by comparing ever smokers with never smokers. RESULTS: Excessive alcohol drinking was associated with a higher likelihood of ever smoking. After adjustment for drinking behaviors, compared to individuals with ALDH2 Glu/Glu, the ORs of ever smoking were 1.71 (95% CI, 1.49-1.95) and 2.28 (1.81-2.87) among those with ALDH2 Glu/Lys and Lys/Lys, respectively. Combination of ALDH2 Lys/Lys and ADH1B His/His (i.e., the most alcohol-intolerant subpopulation) showed the highest OR [2.44 (1.84-3.23)], whereas combination of ALDH2 Glu/Glu and ADH1B Arg/Arg (i.e., the most alcohol-tolerant subpopulation) showed the lowest OR [0.83 (0.57-1.21)] compared with ALDH2 Glu/Glu and ADH1B His/His. CONCLUSION: Besides the amount and frequency of alcohol drinking, the combination of ALDH2 and ADH1B polymorphisms predicts smoking initiation. This study suggests that alcohol tolerance regulated by ALDH2 and ADH1B polymorphisms is associated with smoking initiation, and facilitates the development of targeted interventions to reduce smoking prevalence.


Assuntos
Álcool Desidrogenase/genética , Alcoolismo/genética , Aldeído-Desidrogenase Mitocondrial/genética , Polimorfismo Genético/genética , Fumar/genética , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estatística como Assunto , Adulto Jovem
20.
Jpn J Clin Oncol ; 47(5): 453-457, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28184442

RESUMO

Objective: To analyze the association between smoking and oncological outcome after radical prostatectomy in patients with prostate cancer. Methods: This study included men who underwent radical prostatectomy between 2003 and 2013. The association of clinicopathological factors with smoking status and the prognostic significance of clinicopathological factors and smoking status on biochemical recurrence (BCR) were evaluated. Results: Of the 1165 included patients, 226 (19.4%) were current smokers and 939 (80.6%) were nonsmokers. The median observation period was 39 months (interquartile range, 15-75 months). Current smokers were younger than nonsmokers and had higher PSA levels, higher biopsy and pathological Gleason scores, and more frequent lymph-node involvement than nonsmokers. Pathological Gleason score, extracapsular extension, seminal vesicle invasion, positive surgical margin, lymph-node involvement, and current smoking (hazard ratio [95% confidence interval]; 1.31 [1.00-1.72], P = 0.046) were identified as significant risk factors of BCR on univariate analysis. However, smoking status was not an independent predictive marker on multivariate analysis. Conclusions: Current smokers had adverse clinicopathological characteristics including high PSA level, high Gleason score, and lymph node involvement, suggesting that smoking promoted the progression of prostate cancer.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Fumar/efeitos adversos , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Resultado do Tratamento
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