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BACKGROUND: Enfortumab vedotin (EV) was approved for patients with metastatic urothelial carcinoma (mUC) who progressed after anticancer therapy on September 2021 in Japan. The association between the occurrence of EV-related side effects and clinical outcome remains to be elucidated. METHODS: We identified 97 mUC patients treated with EV therapy at our five institutions from the date of approval to March 2023. The median follow-up period was 7.0 months. We retrospectively analyzed the efficacy and safety of EV. RESULTS: The median age of the patients was 71 years old, 39% had PS of 1 or more, and 56.7% had primary tumor in upper urinary tract. Overall response rate (ORR) to EV therapy, median progression-free survival (PFS), and overall survival (OS) were 43.3%, 7.52 months, and 12.78 months, respectively. Any grade of treatment-related skin disorder, dysgeusia, peripheral neuropathy, gastrointestinal disorder, and hyperglycemia occurred in 61 (62.9%), 36 (37.1%), 34 (35.1%), 29 (29.9%), and 18 (18.6%) patients, respectively. The patients with EV-associated peripheral neuropathy had significantly higher ORR (58.8% vs. 34.9%, P = .032) and longer median PFS (8.05 vs. 6.31 months, P = .017) and OS (not reached vs. 11.57 months, P = .008, respectively) than those without. The occurrence of peripheral neuropathy after EV treatment and the presence of peritoneal dissemination were factors independently associated with PFS (hazard ratio = 0.46, P = .008 and hazard raito = 3.83, P = .004, respectively) and OS (hazard ratio = 0.30, P = .005 and hazard raito = 4.53, P = .002, respectively). CONCLUSIONS: The occurrence of EV-related peripheral neuropathy might be associated with the efficacy of EV therapy in mUC patients.
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OBJECTIVES: The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. METHODS: Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. RESULTS: In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). CONCLUSIONS: Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Células Transicionales , Quimioterapia de Mantención , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Japón , Quimioterapia de Mantención/métodos , Supervivencia sin Progresión , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patologíaRESUMEN
OBJECTIVES: Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated. METHODS: Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low-grade on URS biopsy) versus same grade (high-grade on URS biopsy) for high-grade UTUC tumors on radical nephroureterectomy (RNU) specimens. RESULTS: This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy-based low- and high-grade tumors, respectively. Median follow-up was 27.3 months. Patients with high-grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high-grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10-2.75; p = 0.018), cancer-specific (HR 1.94; 95% CI, 1.07-3.52; p = 0.03), and recurrence-free survival (HR 1.80; 95% CI, 1.13-2.87; p = 0.013). In subgroup analyses of patients with pT2-T4 and/or positive LN, its significant association retained. Furthermore, high-grade biopsy in clinically non-muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low-grade biopsy. CONCLUSIONS: High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low-grade UTUC that becomes upgraded to high-grade might carry a better prognosis than high-grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high-grade on RNU.
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Carcinoma de Células Transicionales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Humanos , Nefroureterectomía , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/cirugía , Pronóstico , Ureteroscopía , Neoplasias Ureterales/cirugía , Neoplasias Ureterales/patología , Biopsia , Estudios RetrospectivosRESUMEN
A total of 100 patients were retrospectively analyzed with magnetic resonance imaging-ultrasonography (MRI-US) fusion biopsy(KOELIS, TRINITY®) at our institution between October 2019 and May 2020. The median patient age was 71 years, median prostate specific antigen (PSA) level was 7.4 ng/ml, and median PSA-density was 0.183 mg/ml. Sixty-one of the patients were positive for cancer ; 14 of them were positive by targeted biopsy only, 9 were positive by systematic biopsy only, and 38 were positive by both. Clinically significant prostate cancer (CPSC ; Gleason Score ≥3ï¼4 and % core ≥50%) was detected by target biopsies in 46 patients and by systematic biopsies in 33 patients. The positive core detection rate for CSPC was 32.5% for targeted biopsies and 7.0% for systematic biopsies(Pï¼0.0001), with a significantly higher rate for targeted biopsies. These results indicate that in MRI-US fusion biopsy, targeted biopsy has a higher detection rate for cancer and a significantly higher detection rate for clinically significant prostate cancer compared with systematic biopsy.
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Próstata , Neoplasias de la Próstata , Anciano , Humanos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Clasificación del Tumor , Próstata/diagnóstico por imagen , Próstata/patología , Antígeno Prostático Específico , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Ultrasonografía Intervencional/métodosRESUMEN
Bacillus Calmette-Guérin induction with or without maintenance is the gold standard therapy for intermediate-/high-risk non-muscle-invasive bladder cancer; however, one-third of patients treated with adequate bacillus Calmette-Guérin therapy do not achieve sufficient responses, and this is referred to as "bacillus Calmette-Guérin failure." The term, bacillus Calmette-Guérin failure, is ambiguous and includes a very heterogeneous population of patients. By strictly focusing on patients who are unlikely to benefit from additional bacillus Calmette-Guérin therapy and who need to be treated with radical cystectomy, the new concept of "bacillus Calmette-Guérin unresponsive" was recently proposed, and might accelerate the development of novel therapeutic options for bacillus Calmette-Guérin-unresponsive disease. A promising therapeutic strategy for bacillus Calmette-Guérin-unresponsive disease is the blockade of the programmed cell death-1/programmed cell death-ligand 1 pathway, which is considered to be activated by bacillus Calmette-Guérin therapy. Several large clinical trials have been carried out to assess the potential of programmed cell death-1/programmed cell death-ligand 1 blockade in bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer and bacillus Calmette-Guérin-unresponsive disease. Furthermore, clinical trials that are targeting bacillus Calmette-Guérin-unresponsive disease with other strategies, such as vaccines, gene therapy, and targeted and cytotoxic therapies, are ongoing. The findings of these trials are awaited in order to establish appropriate bladder-sparing approaches for patients with bacillus Calmette-Guérin-unresponsive disease.
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Vacuna BCG , Neoplasias de la Vejiga Urinaria , Adyuvantes Inmunológicos/uso terapéutico , Administración Intravesical , Vacuna BCG/uso terapéutico , Cistectomía , Humanos , Invasividad Neoplásica , Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugíaAsunto(s)
Cistectomía , Ganglios Linfáticos , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Ganglios Linfáticos/patología , Estudios Retrospectivos , Metástasis Linfática , Estadificación de Neoplasias , Terapia Neoadyuvante/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: The programmed cell death-1 (PD-1) pathway has been suggested to play an important role in tumor immune escape. We evaluated changes in PD-1 expression before and after Bacillus Calmette-Guérin (BCG) therapy and its prognostic significance in non-muscle-invasive bladder cancer (NMIBC) patients. METHODS: We examined 78 paired tissue samples of NMIBC in tumors just before BCG therapy and BCG-relapsing tumors, defined as recurrence after achieving disease-free status by initial BCG instillations for 6 months. We counted PD-1-positive cells, and PD-1 expression was defined as high when the number of PD-1-positive cells was more than 18 under ×200 magnification. RESULTS: The median number of PD-1-positive cells in tumors just before BCG therapy was 3.5, significantly lower than that in BCG-relapsing tumors (17.0, p < 0.001). High PD-1 expression was observed in 20 tumors just before BCG therapy (25.6%) and 36 BCG-relapsing tumors (46.2%). Fifty-two cases (66.6%) showed an increase in the number of PD-1-positive cells in BCG-relapsing tumors. High PD-1 expression in BCG-relapsing tumors was independently associated with subsequent tumor recurrence (p = 0.011) and stage progression (p = 0.033). The 5-year recurrence-free and progression-free survival rates were 40.7 and 74.1% in patients with high PD-1 expression in BCG-relapsing tumors, significantly lower than those in their counterparts (72.9 and 94.1%, respectively). CONCLUSIONS: PD-1 was induced by BCG therapy, and its expression in BCG-relapsing tumors may be an important indicator for predicting worse clinical outcomes in NMIBC patients treated with BCG therapy.
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Vacuna BCG/administración & dosificación , Biomarcadores de Tumor/metabolismo , Recurrencia Local de Neoplasia/patología , Receptor de Muerte Celular Programada 1/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Administración Intravesical , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismoAsunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Riñón , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéuticoAsunto(s)
Neoplasias de la Vejiga Urinaria , Trombosis de la Vena , Cistectomía/efectos adversos , Humanos , Incidencia , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/cirugía , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Trombosis de la Vena/cirugíaRESUMEN
PURPOSE: Aromatic amines, well-known bladder carcinogens, derived from cigarette smoke are activated by acidic urine. We herein determined whether urinary pH levels are associated with bladder recurrence in upper tract urothelial carcinoma patients with a positive smoking history. METHODS: A total of 256 upper tract urothelial carcinoma patients who were surgically treated at our institution between 1990 and 2013 were included. Urinary pH levels were defined as the median of at least two consecutive measurements within 1 month of surgery. RESULTS: Ninety-six patients (37.5 %) had pH <5.5 and 160 (62.5 %) had pH ≥5.5, and urinary pH levels were identified as one of the significant predictors for bladder recurrence in univariate but not multivariate Cox regression analysis in overall. In patients with a positive smoking history among those without a history of bladder tumor (N = 110), the 5-year bladder recurrence-free survival rate was 52.5 % in patients with pH ≥5.5, which was significantly higher than that in those with pH <5.5 (25.9 %, p = 0.032). In the multivariate analysis, urinary pH <5.5 (p = 0.022, HR; 1.86) was independently associated with bladder recurrence. No significant difference for bladder recurrence was observed between these two groups in patients with no smoking history among them. CONCLUSIONS: Urinary pH <5.5 is associated with an increased risk of bladder recurrence in upper tract urothelial carcinoma patients with a positive smoking history among those without a history of bladder tumor. Modifications to pH for urine alkalization may prevent bladder recurrence.
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Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/orina , Fumar Cigarrillos/epidemiología , Neoplasias Renales/cirugía , Neoplasias Primarias Secundarias/orina , Neoplasias Ureterales/cirugía , Neoplasias de la Vejiga Urinaria/orina , Anciano , Carcinoma de Células Transicionales/epidemiología , Supervivencia sin Enfermedad , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Neoplasias Primarias Secundarias/epidemiología , Nefrectomía , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Urinálisis , Neoplasias de la Vejiga Urinaria/epidemiologíaRESUMEN
AIM: We carried out a clinicopathological analysis of cases presenting with interstitial fibrosis and tubular atrophy (IF/TA) after renal transplantation in an attempt to clarify the mechanisms underlying the development and prognostic significance of IF/TA. METHODS: IF/TA was diagnosed in 35 renal allograft biopsy specimens (BS) obtained from 35 renal transplant recipients under follow up at the Department of Transplant Surgery, Kidney Center, Toda Chuo General Hospital, between January 2014 and March 2015. RESULTS: IF/TA was diagnosed at a median of 39.9 months after the transplantation. Among the 35 patients with IF/TA, 19 (54%) had a history of acute rejection. Among the 35 BS showing evidence of IF/TA, the IF/TA was grade I in 25, grade II in 9, and grade III in 1. Arteriosclerosis of the middle-sized arteries was observed in 30 BS (86%). We then classified the 35 BS showing evidence of IF/TA according to their overall histopathological features, as follows; IF/TA alone (6 BS; 17%), IF/TA + medullary ray injury (12 BS; 34%), and IF/TA + rejection (12 BS; 34%). Loss of the renal allograft occurred during the observation period in one of the patients (3%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 15 patients (43%). CONCLUSIONS: The results of our study suggests that rejection contributes to IF/TA in 30-40% of cases, medullary ray injury in 30-40% of cases, and nonspecific injury in 20% of cases. IF/TA contributes significantly to deterioration of renal allograft function.
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Rechazo de Injerto/patología , Enfermedades Renales/patología , Trasplante de Riñón/efectos adversos , Túbulos Renales/patología , Adolescente , Adulto , Anciano , Aloinjertos , Atrofia , Biopsia , Progresión de la Enfermedad , Femenino , Fibrosis , Rechazo de Injerto/etiología , Rechazo de Injerto/fisiopatología , Supervivencia de Injerto , Hospitales Generales , Humanos , Japón , Enfermedades Renales/etiología , Enfermedades Renales/fisiopatología , Pruebas de Función Renal , Túbulos Renales/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Carcinoma de Células Transicionales , Neoplasias Urológicas , Anilidas , Humanos , Platino (Metal) , PiridinasRESUMEN
PURPOSE: The aims of the present study were to investigate the incidence of injection site reactions (ISRs) following administration of 240 mg degarelix and identify the risk factors for ISRs. METHODS: This study was conducted in 50 consecutive men treated with degarelix for the first time. ISRs after an initial degarelix dose of 240 mg (administered subcutaneously as two 3 ml subcutaneous injection) were evaluated using the five categories of the Common Terminology Criteria for Adverse Events Version 4 of the National Cancer Institute. We also assessed the differences in patient background between patients with and without an ISR. RESULTS: The mean age of patients and prostate-specific antigen (PSA) level just before degarelix administration were 75.6 and 198.4 ng/ml, respectively. Hormonal therapy with degarelix was administered for the first time to 33 patients; 11 of the 50 patients were receiving an oral steroid, 6 for prostate cancer, 1 for hematological disease, and 4 for allergic conditions. ISRs were observed in 25 patients, and all of the ISRs were categorized as grade 1 or 2; however, 2 patients discontinued this procedure due to the ISR. Significant differences in the first experience with subcutaneous therapy (p = 0.007) and rate of combination with a steroid (p = 0.017) were observed between patients with and without ISRs. CONCLUSION: The incidences of ISRs in patients receiving subcutaneous therapy for the first time and in patients also receiving an oral steroid were 64 and 18 %, respectively. Patients should be provided with information concerning the possible occurrence of ISR due to degarelix prior to the administration, particularly patients who are not receiving steroids and patients who have no experience with subcutaneous injections.