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OBJECTIVES: To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. METHODS: We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. RESULTS: A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26 months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter ≥ 30 mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status ≥ 1, cT ≥ 3, cN ≥ 2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN ≥ 2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P = 0.0002), Eastern Cooperative Oncology Group performance status ≥ 1 (4.42; 1.79-10.9; P = 0.0012) and cT ≥ 3 (3.34; 1.11-10.1; P = 0.0319) were identified as independent prognostic factors. CONCLUSIONS: The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN ≥ 2, Eastern Cooperative Oncology Group performance status ≥ 1 and cT ≥ 3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.
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Neoplasias del Pene , Masculino , Humanos , Pronóstico , Estudios Retrospectivos , Neoplasias del Pene/cirugía , Neoplasias del Pene/patología , Japón , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
BACKGROUND: Cabozantinib was established as the standard of care for the treatment of patients with renal cell carcinoma (RCC) whose disease had progressed after vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in the global randomized trial METEOR. A phase 2 study was conducted to bridge the findings in METEOR to Japanese patients. Here, we report a biomarker analysis and update the efficacy and safety results of cabozantinib treatment. METHODS: Japanese patients with RCC who received at least one prior VEGFR-TKI were enrolled and received cabozantinib 60 mg orally once daily. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory analyses included the relationship between plasma protein hepatocyte growth factor (HGF) levels and treatment responses. RESULTS: In total, 35 patients were enrolled. The median treatment duration was 58.3 (range 5.1-131.4) weeks. The objective response rate was 25.7% (90% confidence interval [CI] 14.1-40.6). Kaplan-Meier estimate of median progression-free survival was 11.1 months (95% CI 7.4-18.4). The estimated progression-free survival proportion was 73.1% (95% CI 54.6-85.0) at 6 months. Median overall survival was not reached. Adverse events were consistent with those in METEOR and the safety profile was acceptable. Nonresponders to cabozantinib showed relatively higher HGF levels than responders at baseline. CONCLUSIONS: Updated analyses demonstrate the long-term efficacy and safety of cabozantinib in Japanese patients with advanced RCC after at least one VEGFR-TKI therapy. Responders tended to show lower baseline HGF levels ClinicalTrials.gov Identifier: NCT03339219.
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Carcinoma de Células Renales , Neoplasias Renales , Inhibidores de Proteínas Quinasas , Humanos , Biomarcadores , Carcinoma de Células Renales/tratamiento farmacológico , Pueblos del Este de Asia , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
BACKGROUND: Programmed death-ligand 1 (PD-L1) positivity is associated with poor prognosis in renal cell carcinoma (RCC). Because the prognostic impact and effect of confounding factors are less known, we investigated the prognostic significance of PD-L1 expression in Japanese patients with recurrent/metastatic RCC who started systemic therapy in 2010-2015. METHODS: This multicenter, retrospective study recruited patients from 29 Japanese study sites who had prior systemic therapy for RCC (November 2018 to April 2019) and stored formalin-fixed paraffin-embedded primary lesion samples. The primary outcome was overall survival (OS) by PD-L1 expression. Secondary outcomes included OS in subgroups and duration of first- and second-line therapies by PD-L1 expression. OS distributions were estimated using Kaplan-Meier methodology. RESULTS: PD-L1 expression (on immune cells [IC] ≥ 1%) was observed in 315/770 (40.9%) patients. PD-L1 positivity was more prevalent in patients with poor risk per both Memorial Sloan Kettering Cancer Center [MSKCC] and International Metastatic RCC Database Consortium, and high-risk pathological features (higher clinical stage, nuclear grade and sarcomatoid features). Median OS for PD-L1-positive patients was 30.9 months (95% CI 25.5-35.7) versus 37.5 months (95% CI 34.0-42.6) for PD-L1-negative patients (HR 1.04 [90% CI 0.89-1.22, p = 0.65]; stratified by MSKCC risk and liver metastases). Propensity score weight (PSW)-adjusted OS was similar between PD-L1-positive and -negative patients (median 34.4 versus 31.5 months; estimated PSW-adjusted HR 0.986). CONCLUSIONS: This study suggests PD-L1 status was not an independent prognostic factor in recurrent/metastatic RCC during the study period because PD-L1 positivity was associated with poor prognostic factors, especially MSKCC risk status.
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Carcinoma de Células Renales , Neoplasias Renales , Antígeno B7-H1 , Carcinoma de Células Renales/genética , Humanos , Japón , Recurrencia Local de Neoplasia , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC. METHODS: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features. RESULTS: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years. CONCLUSION: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.
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Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Diagnóstico Diferencial , Femenino , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: To evaluate the efficacy and safety of cabozantinib, through a bridging study to METEOR, in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy. METHODS: This phase II, open-label, single-arm study (ClinicalTrials.gov registration number: NCT03339219) included adult Japanese patients with advanced renal cell carcinoma and measurable disease who had received one or more tyrosine kinase inhibitors. Patients received cabozantinib 60 mg orally once daily while there was clinical benefit, or until unacceptable toxicity or disease progression. The primary end-point was objective response rate per Response Evaluation Criteria in Solid Tumors Version 1.1. Secondary end-points included clinical benefit rate (complete or partial response, or ≥8-week stable disease), progression-free survival, overall survival and safety. RESULTS: Of the 35 patients enrolled, 68.6%, 22.9% and 8.6% had previously received one, two and three prior tyrosine kinase inhibitors, respectively. The median duration of cabozantinib exposure was 27.0 weeks (range 5.1-43.0 weeks). The objective response rate was 20.0% (90% confidence interval 9.8-34.3%), and the clinical benefit rate was 85.7% (95% confidence interval 69.7-95.2%). The 6-month estimated progression-free survival was 72.3% (95% confidence interval 53.3-84.6%); the median progression-free survival and overall survival were not reached. All patients reported adverse events, which were manageable by supportive treatment or dose modification; two patients (5.7%) discontinued therapy due to adverse events. CONCLUSIONS: The results showed that findings from METEOR can be extrapolated, and that cabozantinib 60 mg/day is a viable treatment option in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy.
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Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Adulto , Anilidas/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Humanos , Japón , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , PiridinasRESUMEN
BACKGROUND: In a phase III clinical trial, CheckMate 025, treatment of metastatic renal cell carcinoma (mRCC) with nivolumab demonstrated superior efficacy over everolimus. However, as the clinical trial excluded patients with specific complications and poor performance status (PS), the effectiveness and safety of nivolumab in clinical practice, in which patients with various clinical complications are treated, is unclear. This study explored real-world nivolumab treatment in Japanese mRCC patients. METHODS: This is an interim analysis of a multicenter, non-interventional, medical record review study (minimum follow-up: 9 months). All eligible Japanese mRCC patients who first received nivolumab between February and October 2017 were included; data cut-off was April 2019. We analyzed nivolumab treatment patterns, efficacy (including overall survival, progression-free survival, objective response rate, and duration of response) and safety (including immune-related adverse events). RESULTS: Of 208 evaluable patients, 31.7% received nivolumab as fourth- or later line of treatment. At data cut-off, 26.9% of patients were continuing nivolumab treatment. The major reason for discontinuation was disease progression (n = 100, 65.8%). Median overall survival was not reached; the 12-month survival rate was 75.6%. Median progression-free survival was 7.1 months, the objective response rate was 22.6%, and median duration of response was 13.3 months. Patients who were excluded or limited in number in CheckMate 025, such as those with non-clear cell RCC or poor PS, also received benefits from nivolumab treatment. Immune-related adverse events occurred in 27.4% of patients (grade ≥ 3, 10.1%). CONCLUSION: Nivolumab was effective and well-tolerated in real-world Japanese mRCC patients. TRIAL REGISTRATION: UMIN000033312.
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Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Nivolumab/uso terapéutico , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Pueblo Asiatico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Supervivencia sin Progresión , Sistema de Registros , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: To assess whether the clinical outcome of advanced/metastatic renal cell carcinoma (mRCC) treated with sorafenib, in real-world conditions, differs in patients with cardiovascular disease (CVD). METHODS: mRCC patients (n = 2256 before matching) were matched by propensity score into CVD (n = 560) and non-CVD groups (n = 560), followed by safety and effectiveness analyzes. RESULTS: After matching, patients' features used for matching were balanced between the CVD and non-CVD groups, except for age (p = 0.0049). Renal comorbidity occurred more frequently in the CVD group. Exposure to sorafenib and objective response rate (25.4% [CVD], 28.5% [non-CVD]) were comparable in both groups. Median progression-free survival (PFS; 7.1 months, 95% CI: 6.4-8.6 [CVD]; 6.7 months, 6.3-8.3 [non-CVD]), and hazard ratios for PFS (0.954, 0.821-1.108) and overall survival (0.889, 0.683-1.156), were similar in the matched population. The incidences of adverse drug reactions (ADR, ≥10%) were generally similar between groups, although hypertension (42.1% vs 34.5%), diarrhea (26.3% vs 19.6%), decreased appetite (11.3% vs 7.5%), and non-serious and serious renal failure/dysfunction (3.6% vs 1.4% and 1.8% vs 0.4%), occurred more frequently in the CVD group. CONCLUSION: This analyzes suggests that sorafenib has clinical benefit for mRCC patients regardless of baseline CVD. Serious ADRs increased for renal dysfunction. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT01411423.
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Antineoplásicos/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Enfermedades Cardiovasculares/fisiopatología , Neoplasias Renales/tratamiento farmacológico , Sorafenib/administración & dosificación , Anciano , Antineoplásicos/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Sorafenib/efectos adversos , Encuestas y Cuestionarios , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: To evaluate the relationship between body composition and the oncological outcome of androgen deprivation therapy (ADT), we investigated whether body composition features including the psoas muscle may be predictive factors of ADT. METHODS: This study enrolled patients with hormone-naïve metastatic prostate cancer who were treated with primary ADT from April 1996 to November 2013 at Kyushu University Hospital and who underwent a computed tomography scan before primary ADT for calculating body fat percentage, psoas muscle ratio (psoas muscle, cm3/height, cm), and body mass index. RESULTS: Of the 178 patients enrolled, 60 patients died during follow-up. Median follow-up was 32 months, and progression-free survival and overall survival (OS) were 28 and 80 months, respectively. Multivariate analysis revealed that the psoas muscle ratio was correlated with OS (hazard ratio: 0.448; 95% confidence interval = 0.206-0.922; p = 0.028). CONCLUSIONS: This study demonstrated that higher psoas muscle ratio predicts longer OS among patients with nonlocalized prostate cancer treated with primary ADT.
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Bacillus Calmette-Guérin (BCG) instillation is a key therapy to manage non-muscle invasive bladder cancer (NMIBC). However, intravesical BCG therapy fails in approximately half of the patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG therapy for NMIBC. This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole-blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic variation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in another cohort. The genome-wide association study indicated 19 candidate SNPs (rs1607282, rs7825442, rs1319325, rs3738088, rs4250, rs11894207, rs161448, rs2764326, rs2814707, rs3787194, rs58081719, rs3095966, rs73520681, rs16877113, rs16887173, rs10269584, rs11772249, rs118137814, and rs61094339) associated with BCG failure. Following the cumulative analysis of candidate SNPs, 2-gene (rs73520681 and rs61094339) and 4-gene (rs4250, rs11894207, rs73520681, and rs61094339) models successfully predicted treatment failure after intravesical BCG therapy. This study showed that several SNPs were possibly associated with outcome after intravesical BCG therapy in a Japanese population with NMIBC. The cumulative models of these SNPs may have value in clinical applications, although this should be confirmed in future studies.
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Vacuna BCG/administración & dosificación , Biomarcadores de Tumor/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Neoplasias de la Vejiga Urinaria/genética , Administración Intravesical , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Insuficiencia del Tratamiento , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
PURPOSE: We investigated the relationship between the surgical navigation system and postoperative parenchyma preservation volume, and assessed the feasibility of image guided surgery in robot-assisted partial nephrectomy. MATERIALS AND METHODS: We developed surgical navigation with registration between real-time endoscopic images using 3-dimensional virtual reality models for robot-assisted partial nephrectomy. Surgical outcomes of 44 (nonsurgical navigation group) and 102 (surgical navigation group) patients between June 2013 and December 2018 were retrospectively analyzed. To adjust for potential baseline confounders propensity score matching (1:1) was performed. Renal parenchymal preservation rate and extraparenchymal volume with a tumor including functional and oncological outcomes ("trifecta" defined as warm ischemia time of less than 25 minutes, no complications and negative surgical margins; "pentafecta" defined as trifecta plus greater than 90% preservation of estimated glomerular filtration rate at 12 months postoperatively and chronic kidney disease up staging) were evaluated using volumetric analysis and compared. RESULTS: After matching, 42 patients were allocated to each group. No significant differences in baseline characteristics; complications; and intraoperative, trifecta and pentafecta outcomes were observed between the 2 groups. Pathological T stages were significantly different between the groups (T1a/T1b/T2a or more 25/10/7 in the nonsurgical navigation group vs 35/7/0 in the surgical navigation group, p=0.003). Extraparenchymal volumes and parenchyma volume preservation rates were significantly higher in the surgical navigation group (21.4 vs 17.2 ml, p=0.041 and 83.5% vs 90.0%, p=0.042, respectively). Surgical navigation was positively associated with improved parenchyma preservation volume (p=0.003). CONCLUSIONS: Surgical navigation preserves renal parenchyma in robot-assisted partial nephrectomy and may contribute to improvement in postoperative renal function.
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Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Riñón/diagnóstico por imagen , Nefrectomía/métodos , Procedimientos Quirúrgicos Robotizados , Cirugía Asistida por Computador , Anciano , Estudios de Factibilidad , Femenino , Humanos , Imagenología Tridimensional , Riñón/cirugía , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
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.
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Carcinoma in Situ/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasia Residual/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Adulto , Anciano , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Cistectomía , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculos/patología , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/patología , Factores de Riesgo , Resultado del Tratamiento , Uretra/patología , Uretra/cirugía , Vejiga Urinaria/patología , Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Procedimientos Quirúrgicos UrológicosRESUMEN
PURPOSE: Comorbidity with hypertension (HTN) may affect the outcome of castration-resistant prostate cancer (CRPC). In this study, we evaluated the prognostic impact of antihypertensive agents in patients with CRPC treated with androgen receptor axis-targeting (ARAT) agents or docetaxel chemotherapy. PATIENTS AND METHODS: This study included 156 Japanese men with CRPC who were treated with ARAT agents (nâ¯=â¯85) or docetaxel (nâ¯=â¯71) at our hospital between 2008 and 2017. Associations between clinicopathological factors, HTN status, progression-free survival (PFS) and overall survival (OS) were evaluated by univariate and multivariate analysis. RESULTS: When adjusted for age, prostate-specific antigen levels at pretreatment, Gleason score, and clinical M-stage, comorbid HTN was significantly associated with better OS (hazards ratio, 95% confidence interval: 0.41, 0.21-0.77; Pâ¯=â¯0.0051), but not with PFS (hazards ratio, 95% confidence interval: 0.64, 0.38-1.11; Pâ¯=â¯0.11) in patients treated with ARAT agent. However, HTN was not associated with PFS or OS for patients treated with docetaxel. CONCLUSIONS: Use of antihypertensive agents has prognostic significance for patients with CRPC treated with ARAT agent, but not docetaxel.
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Antihipertensivos/uso terapéutico , Antineoplásicos/uso terapéutico , Hipertensión/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/uso terapéutico , Comorbilidad , Docetaxel/uso terapéutico , Humanos , Hipertensión/epidemiología , Japón/epidemiología , Masculino , Pronóstico , Supervivencia sin Progresión , Neoplasias de la Próstata Resistentes a la Castración/epidemiología , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND/AIM: To date, several serum prognostic factors have been reported in metastatic prostate cancer. In this study, we examined the prognostic value of these serum markers in Japanese men. PATIENTS AND METHODS: This study included 104 patients with metastatic prostate cancer who were treated with primary androgen-deprivation therapy from 2001 to 2013. Clinicopathological factors including several serum markers were investigated for association with progression-free (PFS) and overall (OS) survival. RESULTS: During a median follow-up of 48.1 months, median PFS and OS were 24.0 months and 67.4 months, respectively. When adjusted by age, prostate-specific antigen at diagnosis, Gleason score, and clinical stage, serum lactate dehydrogenase value was significantly associated with PFS [hazard ratio (HR)=1.42, 95% confidence interval (CI)=1.15-1.74; p=0.0004] and OS (HR=1.46, 95% CI=1.13-1.82; p=0.0014), in addition to alkaline phosphatase value for OS (HR=1.04; 95% CI=1.00-1.07; p=0.015). CONCLUSION: This study demonstrates the prognostic significance of alkaline phosphatase and lactate dehydrogenase values in Japanese men with de novo metastatic hormone-sensitive prostate cancer.
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Fosfatasa Alcalina/sangre , Antagonistas de Andrógenos/uso terapéutico , Biomarcadores de Tumor/sangre , L-Lactato Deshidrogenasa/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Antagonistas de Andrógenos/efectos adversos , Humanos , Japón , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Valor Predictivo de las Pruebas , Supervivencia sin Progresión , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Several endocrinological and physical activities orchestrate men's sexual activities. To determine whether body composition calculated by computed tomography measurements is useful for estimating sexual function, we evaluated sexual function of localised prostate cancer patients using the Sexual Health Inventory for Men score, an original questionnaire, and computed tomography and magnetic resonance imaging. The imaging was performed to determine body composition, particularly the psoas muscle. Univariate and multivariate analyses were performed to identify factors affecting sexual activity. The multivariate analysis showed that the volume of the psoas muscle was significantly correlated with sexual activity (odds ratio [95% confidence interval]) (2.507 [1.029-6.109], p = 0.043) and erectile dysfunction (0.261 [0.098-0.692], p = 0.006). We concluded that the psoas muscle is an important predictor of sexual activity and erectile function.
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Composición Corporal/fisiología , Disfunción Eréctil/patología , Neoplasias de la Próstata/complicaciones , Músculos Psoas/patología , Conducta Sexual/fisiología , Anciano , Disfunción Eréctil/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Músculos Psoas/diagnóstico por imagen , Estudios Retrospectivos , Conducta Sexual/estadística & datos numéricos , Encuestas y Cuestionarios/estadística & datos numéricos , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Testosterone suppression in serum during androgen deprivation therapy (ADT) can affect the oncologic outcome of ADT. Although genetic variants in sex hormone-binding globulin (SHBG) were reported to be correlated with serum testosterone level, the association with serum testosterone during ADT remains unclear. Therefore, this study investigated the impact of a missense polymorphism in the SHBG gene among men treated with primary ADT for metastatic prostate cancer. PATIENTS AND METHODS: This study included 104 Japanese men with metastatic prostate cancer. The association of SHBG gene polymorphism (rs6259, D356N) with clinicopathologic parameters including serum testosterone levels during ADT, as well as prognosis, including progression-free survival and overall survival, was examined. RESULTS: The serum testosterone levels during ADT were comparable between men carrying the homozygous wild-type (GG) and heterozygous/homozygous variant (GA/AA) in the SHBG gene. When adjusted for age, Gleason score, initial prostate-specific antigen, and clinical T-stage, the heterozygous/homozygous variant (GA/AA) in the SHBG gene was associated with a higher risk of progression (hazard ratio, 2.20; 95% confidence interval, 1.10-4.18; P = .027) and any-cause death (hazard ratio, 3.21; 95% confidence interval, 1.31-7.35; P = .012). CONCLUSIONS: This study suggested genetic variation in SHBG (rs6259) might be an independent prognostic biomarker among men treated with primary ADT for metastatic prostate cancer.
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Antagonistas de Andrógenos/uso terapéutico , Biomarcadores de Tumor/genética , Polimorfismo Genético , Neoplasias de la Próstata/genética , Globulina de Unión a Hormona Sexual/genética , Testosterona/sangre , Anciano , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Japón , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/secundario , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the detailed immunosuppressive role(s) of PD-L2 given that its detailed role(s) remains unclear in PD-1 signal blockade therapy in animal models and humans. EXPERIMENTAL DESIGN: We generated mouse cell lines harboring various status of PD-L1/PD-L2 and evaluated the tumor growth and phenotypes of tumor-infiltrated lymphocytes using several PD-1 signal blockades in animal models. In humans, the correlation between immune-related gene expression and CD274 (encoding PD-L1) or PDCD1LG2 (encoding PD-L2) was investigated using The Cancer Genome Atlas (TCGA) datasets. In addition, PD-L1 or PD-L2 expression in tumor cells and CD8+ T-cell infiltration were assessed by IHC. RESULTS: In animal models, we showed that PD-L2 expression alone or simultaneously expressed with PD-L1 in tumor cells significantly suppressed antitumor immune responses, such as tumor antigen-specific CD8+ T cells, and was involved in the resistance to treatment with anti-PD-L1 mAb alone. This resistance was overcome by anti-PD-1 mAb or combined treatment with anti-PD-L2 mAb. In clinical settings, antitumor immune responses were significantly correlated with PD-L2 expression in the tumor microenvironment in renal cell carcinoma (RCC) and lung squamous cell carcinoma (LUSC). CONCLUSIONS: We propose that PD-L2 as well as PD-L1 play important roles in evading antitumor immunity, suggesting that PD-1/PD-L2 blockade must be considered for optimal immunotherapy in PD-L2-expressing cancers, such as RCC and LUSC.
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Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Terapia de Inmunosupresión , Neoplasias Renales/inmunología , Neoplasias Experimentales/inmunología , Proteína 2 Ligando de Muerte Celular Programada 1/antagonistas & inhibidores , Microambiente Tumoral/inmunología , Animales , Antígeno B7-H1/inmunología , Linfocitos T CD8-positivos/inmunología , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Linfocitos Infiltrantes de Tumor/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Proteína 2 Ligando de Muerte Celular Programada 1/inmunología , Microambiente Tumoral/efectos de los fármacosRESUMEN
PURPOSE: To assess surgical skills in robot-assisted partial nephrectomy (RAPN) with and without surgical navigation (SN). METHODS: We employed an SN system that synchronizes the real-time endoscopic image with a virtual reality three-dimensional (3D) model for RAPN and evaluated the skills of two expert surgeons with regard to the identification and dissection of the renal artery (non-SN group, n = 21 [first surgeon n = 9, second surgeon n = 12]; SN group, n = 32 [first surgeon n = 11, second surgeon n = 21]). We converted all movements of the robotic forceps during RAPN into a dedicated vocabulary. Using RAPN videos, we classified all movements of the robotic forceps into direct action (defined as movements of the robotic forceps that directly affect tissues) and connected motion (defined as movements that link actions). In addition, we analyzed the frequency, duration, and occupancy rate of the connected motion. RESULTS: In the SN group, the R.E.N.A.L nephrometry score was lower (7 vs. 6, P = 0.019) and the time to identify and dissect the renal artery (16 vs. 9 min, P = 0.008) was significantly shorter. The connected motions of inefficient "insert," "pull," and "rotate" motions were significantly improved by SN. SN significantly improved the frequency, duration, and occupancy rate of connected motions of the right hand of the first surgeon and of both hands of the second surgeon. The improvements in connected motions were positively associated with SN for both surgeons. CONCLUSION: This is the first study to investigate SN for nephron-sparing surgery. SN with 3D models might help improve the connected motions of expert surgeons to ensure efficient RAPN.
Asunto(s)
Neoplasias Renales/cirugía , Nefrectomía , Procedimientos Quirúrgicos Robotizados , Cirujanos , Cirugía Asistida por Computador , Anciano , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Competencia Profesional , Estudios Prospectivos , Arteria Renal , Reproducibilidad de los Resultados , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Cigarette smoking is associated with worse outcomes in prostate cancer, whose growth is dependent on androgen receptor (AR) signaling. We aimed to elucidate the biological effect of cigarette smoking on AR signaling and its clinical influence on oncological outcome. METHODS: Gene expression levels after exposure to tobacco smoke condensate (TSC) were evaluated by quantitative real-time polymerase chain reaction and Western blot analysis in prostate cancer cells. Cellular sensitivities to enzalutamide and docetaxel after TSC exposure were evaluated using a prostate cancer cell proliferation assay. Prognosis was compared between current smokers and nonsmokers when treated with AR-axis-targeting (ARAT) agent enzalutamide and docetaxel. RESULTS: Expression of AR variants as well as prostate-specific antigen was augmented after TSC exposure, which occurred after Akt phosphorylation. These inductions were suppressed by Akt inhibitor LY294002 as well as antioxidant N-acetylcysteine. Consistently, TSC exposure augmented cellular resistance to enzalutamide. In clinical data, cigarette smoking was associated with worse progression-free survival and cancer-specific survival when patients with prostate cancer were treated with ARAT agents but not docetaxel. CONCLUSIONS: It was suggested that cigarette smoking leads to detrimental oncological outcome when prostate cancer patients are treated with ARAT agents through induction of aberrant AR signaling. Accordingly, we recommend that patients with advanced prostate cancer should refrain from cigarette smoking.