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1.
Int J Urol ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822533

ABSTRACT

OBJECTIVES: To determine the effects of prophylactic urethrectomy (PU) on oncological and perioperative outcomes in patients with bladder cancer (BC) undergoing radical cystectomy (RC). METHODS: This retrospective study analyzed data on 1976 evaluable patients with BC who underwent RC. Patients were drawn from 36 institutions within the Japanese Urological Oncology Group. Oncological outcomes were compared using restricted mean survival times (RMSTs) based on inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves for non-urinary tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Interaction terms within IPTW-adjusted Cox regression models were examined to assess the heterogeneity of treatment effect based on the risk of urethral recurrence (UR). The association between PU, estimated blood loss (EBL), and the incidence of severe postoperative surgical complications (SPSCs) (Clavien-Dindo grade 3 or higher) was analyzed. RESULTS: Of 1976 patients, 1448 (73.3%) received PU. IPTW adjustment was used to balance baseline characteristics between the treatment groups. Within the 107-month window of patient monitoring, PU showed no survival benefits (NUTRFS difference: 0.2 months [95% confidence interval: -6.8 to 7.3]; CSS, 1.2 [-4.9 to 7.3]; OS, 0 [-6.5 to 6.5]). No significant interactions were observed with factors associated with UR, and PU was associated with unfavorable perioperative outcomes (EBL, 1179 mL vs. 983 mL; SPSC, 14.6% vs. 7.0%). CONCLUSIONS: This study showed that (1) PU was not associated with survival in patients with BC undergoing RC, regardless of UR-associated factors, and (2) PU was associated with unfavorable perioperative outcomes.

2.
Cancer Cell ; 42(5): 732-735, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38579722

ABSTRACT

Saliby et al. show that a machine learning approach can accurately classify clear cell renal cell carcinoma (RCC) into distinct molecular subtypes using transcriptomic data. When applied to tumors biospecimens from the JAVELIN Renal 101 (JR101) trial, a benefit is observed with immune checkpoint inhibitor (ICI)-based therapy across all molecular subtypes.


Subject(s)
Carcinoma, Renal Cell , Immune Checkpoint Inhibitors , Immunotherapy , Kidney Neoplasms , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/therapy , Carcinoma, Renal Cell/drug therapy , Humans , Kidney Neoplasms/immunology , Kidney Neoplasms/genetics , Kidney Neoplasms/therapy , Kidney Neoplasms/drug therapy , Immunotherapy/methods , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Molecular Targeted Therapy/methods , Treatment Outcome , Machine Learning
3.
BJU Int ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38344879

ABSTRACT

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

4.
Am Soc Clin Oncol Educ Book ; 44(2): e430734, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38207251

ABSTRACT

Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers. Current research is exploring host factors through in-depth characterization of the immune system. Additionally, innovative technological approaches are being developed to overcome challenges presented by existing techniques, such as tumor heterogeneity. Promising avenues in biomarker discovery include the study of the microbiome, radiomics, and spatial transcriptomics.


Subject(s)
Biomedical Research , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/diagnosis , Kidney Neoplasms/genetics , Kidney Neoplasms/therapy , Biomarkers , Gene Expression Profiling
5.
Case Rep Oncol ; 16(1): 621-627, 2023.
Article in English | MEDLINE | ID: mdl-37900835

ABSTRACT

A 66-year-old male was diagnosed with cT4N0M1b small-cell neuroendocrine carcinoma of the prostate. Four months after the administration of combined androgen blockade, multiple novel metastatic regions in the lung and liver and progression of bone metastasis were observed. The patient was referred to our hospital because of biochemical and radiographic progression after four cycles of docetaxel as a first-line therapy for castration-resistant prostate cancer. Transurethral resection of the prostate and hepatic biopsy revealed small-cell carcinoma with positive expression of neuroendocrine markers. The FoundationOne CDx next-generation sequencing test revealed several pathogenic variants, including BRCA2 (W1692fs*3), KEAP1 (R320W), and TP53 (C2385) mutation. After four cycles of chemotherapy with carboplatin plus etoposide (CE), the metastatic regions regressed markedly. The prostate-specific antigen (PSA) and neuron-specific enolase (NSE) level decreased by 96.9% and 91.6%, respectively. However, 2 months after the completion of four cycles of CE, elevation of tumor marker levels, and re-growth of the metastatic regions were observed. Although olaparib, a poly (ADP-ribose) polymerase inhibitor (PARPi), achieved a 45.2% decrease in NSE, the patient rejected to continue therapy because of G2 adverse events. After receiving an additional two cycles of CE and one cycle of cabazitaxel, the patient died because of cancer progression 24 months after the initial treatment for prostate cancer. Here, we present a case of BRCA2-altered small-cell neuroendocrine prostate cancer treated with both platinum-containing chemotherapy and PARPi. Both therapies achieved an initial response; however, durable responses were not obtained. Additional discussion regarding the optimal treatment strategy for BRCA-altered small-cell/neuroendocrine prostate cancer is required.

6.
J Cancer Res Clin Oncol ; 149(16): 15091-15094, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37688628

ABSTRACT

BACKGROUND: We report a case of diffuse large B-cell lymphoma that progressed rapidly after androgen deprivation therapy for prostate cancer in a patient with a history of IgG4-related disease. Estrogen has been reported to be a possible cause of acute exacerbations of malignant lymphoma only in mouse models. Therefore, its clinical significance has not been clarified. CASE PRESENTATION: This case report describes a 75-year-old man with prostate cancer who had IgG4-related disease. Hormone therapy was initiated to treat prostate cancer, but he developed dyspnea and back pain. A diagnosis was made of diffuse large B-cell lymphoma. Immunohistochemistry was positive for estrogen receptor ß, which led us to suspect rapid progression of diffuse large B-cell lymphoma due to estrogen suppression by gonadotropin-releasing hormone antagonists. Hormone therapy was discontinued, and the patient received R-CHOP therapy. Subsequently, the lymphoma masses shrunk, and the patient obtained remission. CONCLUSION: This case is the first report of clinical significance regarding the crucial role of estrogen and estrogen receptor ß in malignant lymphoma in a patient with IgG4-related disease. Our report aims to raise awareness of the need to carefully select treatment options for prostate cancer patients with IgG4-related disease or lymphoma.


Subject(s)
Immunoglobulin G4-Related Disease , Lymphoma, Large B-Cell, Diffuse , Prostatic Neoplasms , Male , Animals , Mice , Humans , Aged , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Androgen Antagonists/therapeutic use , Androgens/therapeutic use , Estrogen Receptor beta , Lymphoma, Large B-Cell, Diffuse/drug therapy , Estrogens , Cell Proliferation
7.
Int J Clin Oncol ; 28(11): 1530-1537, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37552353

ABSTRACT

BACKGROUND: Although nivolumab plus ipilimumab is the standard treatment for metastatic renal cell carcinoma (RCC), its efficacy and safety in older patients remain unclear. Therefore, this study aimed to assess the clinical outcomes of nivolumab plus ipilimumab for metastatic RCC in patients aged ≥ 75 years. METHODS: We enrolled 120 patients with metastatic RCC treated with nivolumab plus ipilimumab from August 2015 to January 2023. Objective response rates (ORRs) were compared between patients aged < 75 and ≥ 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events were compared between the groups. Adverse events were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1. RESULTS: Among the patients, 57 and 63 were classified as intermediate and poor risk, respectively, and one could not be classified. The median follow-up duration after the initiation of treatment was 16 months. The patient characteristics between the groups, except for age, were not significantly different. Intergroup differences in ORR (42% vs. 40%; p = 0.818), PFS (HR: 0.820, 95% CI 0.455-1.479; p = 0.510), and median OS (HR: 1.492, 95% CI 0.737-3.020; p = 0.267) were not significant. The incidence of adverse events (50% vs. 67%; p = 0.111) and nivolumab plus ipilimumab discontinuation due to adverse events was not significantly different between the groups (14% vs. 13%; p = 0.877). CONCLUSIONS: The effectiveness of nivolumab plus ipilimumab was comparable between patients with metastatic RCC aged < 75 and those ≥ 75 years with respect to their ORRs, PFS, OS, and adverse event rates.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Aged , Carcinoma, Renal Cell/pathology , Nivolumab/adverse effects , Ipilimumab/adverse effects , Kidney Neoplasms/pathology , Progression-Free Survival , Antineoplastic Combined Chemotherapy Protocols/adverse effects
8.
Cancer Med ; 12(16): 16837-16845, 2023 08.
Article in English | MEDLINE | ID: mdl-37403728

ABSTRACT

BACKGROUND: Nivolumab plus ipilimumab (NIVO+IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). Approximately 40% of patients achieve a durable response; however, 20% develop primary resistant disease (PRD) to NIVO+IPI, about which little is known in patients with mRCC. Therefore, this investigation aimed to evaluate the clinical implication of PRD in patients with mRCC to select better candidates in whom NIVO+IPI can be initiated as first-line therapy. METHODS: This multi-institutional retrospective cohort study used data collected between August 2015 and January 2023. In total, 120 patients with mRCC treated with NIVO+IPI were eligible. Associations between immune-related adverse events and progression-free survival, overall survival (OS), and objective response rate were analyzed. The relationship between other clinical factors and outcomes was also evaluated. RESULTS: The median observation period was 16 months (interquartile range, 5-27). The median age at NIVO+IPI initiation was 68 years in the male-dominant population (n = 86, 71.7%), and most patients had clear cell histology (n = 104, 86.7%). PRD was recorded in 26 (23.4%) of 111 investigated patients during NIVO+IPI therapy. Patients who experienced PRD showed worse OS (hazard ratio: 4.525, 95% confidence interval [CI]: 2.315-8.850, p < 0.001). Multivariable analysis showed that lymph node metastasis (LNM) (odds ratio: 4.274, 95% CI: 1.075-16.949, p = 0.039) was an independent risk factor for PRD. CONCLUSIONS: PRD was strongly correlated with worse survival rates. LNM was independently associated with PRD in patients with mRCC receiving NIVO+IPI as first-line therapy and might indicate that a candidate will not benefit from NIVO+IPI.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Male , Aged , Nivolumab/adverse effects , Ipilimumab/adverse effects , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/etiology , Retrospective Studies , Kidney Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects
9.
Urol Clin North Am ; 50(2): 335-349, 2023 May.
Article in English | MEDLINE | ID: mdl-36948676

ABSTRACT

The management of advanced renal cell carcinoma has advanced tremendously over the past decade, but most patients still do not receive durable clinical benefit from current therapies. Renal cellcarcinoma is an immunogenic tumor, historically with conventional cytokine therapies, such as interleukin-2 and interferon-α, and contemporarily with the introduction of immune checkpoint inhibitors. Now the central therapeutic strategy in renal cell carcinoma is combination therapies including immunecheckpoint inhibitors. In this Review, we look back on the historical changes in systemic therapy for advanced renal cell carcinoma, and focus on the latest developments and prospects in this field.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Immunotherapy , Combined Modality Therapy
10.
Eur J Clin Pharmacol ; 79(1): 89-98, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36378297

ABSTRACT

PURPOSE: We assessed the impact of plasma trough concentrations of abiraterone (ABI) and its metabolite Δ4-abiraterone (D4A) and related polymorphisms on adverse events (AEs) in patients with metastatic prostate cancer who received abiraterone acetate (AA). METHODS: This prospective study enrolled patients with advanced prostate cancer treated with AA between 2016 and 2021. Plasma trough concentrations of ABI and D4A were measured using high-performance liquid chromatography. The impact of HSD3B1 rs1047303, SRD5A2 rs523349, and cytochrome P450 family 3A member 4 rs2242480 polymorphisms on plasma concentrations of ABI and D4A and the incidence of AEs were also assessed. RESULTS: In 68 patients treated with AA, the median ABI and D4A concentrations were 18.1 and 0.94 ng/mL, respectively. The high plasma trough concentration of ABI (≥ 20.6 ng/mL) was significantly associated with the presence of any AE and its independent risk factor based on multivariable analysis (odds ratio, 7.20; 95% confidence interval (CI): 2.20-23.49). Additionally, a high plasma trough concentration of ABI was an independent risk factor of time to withdraw AA (hazard ratio, 4.89; 95% CI: 1.66-14.38). The risk alleles of three polymorphisms were not statistically associated with the ABI and D4A concentrations and the incidence of AEs. CONCLUSIONS: The plasma trough concentration of ABI is associated with the presence of AEs and treatment failure after AA administration. ABI concentration monitoring may be useful in patients with prostate cancer who received AA.


Subject(s)
Abiraterone Acetate , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Abiraterone Acetate/adverse effects , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Prospective Studies , Androstenes , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Membrane Proteins/therapeutic use , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/therapeutic use
11.
Hinyokika Kiyo ; 68(8): 265-269, 2022 Aug.
Article in Japanese | MEDLINE | ID: mdl-36071018

ABSTRACT

A 65-year-old man was found to have a 1.7 cm right renal mass by follow-up abdominal computed tomography for left total nephrectomy after a traffic accident. The renal mass progressed slowly to 2.2 cm in three years and enhanced magnetic resonance imaging revealed marked T2 weighting hyperintensity of the lesion. Although a radiologist (TK) suggested the diagnosis renal anastomosing hemangioma preoperatively, we could not deny the possibility of renal cell carcinoma completely. Therefore, the patient underwent robot-assisted laparoscopic partial nephrectomy. The tumor was successfully removed without any renal arterial clamping or parenchymal excision. Histopathologically, the lesion was composed of capillary-size blood vessels lined by a single layer of endothelial cells, and was diagnosed as a renal anastomosing hemangioma. There were no signs of postoperative recurrence during the 3 month follow-up.


Subject(s)
Carcinoma, Renal Cell , Hemangioma , Kidney Neoplasms , Aged , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/surgery , Endothelial Cells/pathology , Hemangioma/diagnostic imaging , Hemangioma/surgery , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/surgery , Male , Nephrectomy/methods
12.
Cancer Sci ; 113(12): 4059-4069, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35848083

ABSTRACT

Human leukocyte antigen class I (HLA-I) genotypes are suggested to influence the cancer response to checkpoint blockade immunotherapy. This study assessed the impact of germline HLA genotypes on clinical outcomes in patients with chemoresistant advanced urothelial cancer (UC) treated with pembrolizumab. Zygosity, supertypes, evolutionary divergency, and specific alleles of germline HLA-I and -II were evaluated using the Luminex technique in 108 patients with chemoresistant metastatic or locally advanced UC treated with pembrolizumab. Among the 108 patients, 69 died and 83 showed radiographic progression during follow-up. Homozygous for at least one HLA-I locus, absence of the HLA-A03 supertype, and high HLA-I evolutionary divergence were associated with a radiographic response, but were not associated with survival outcomes. Patients with the HLA-DQB1*03:01 allele had significantly lower disease control rates than patients without the allele (17.4% vs. 53.8%, p = 0.002); its presence was also an independent risk factor for progressive disease (hazard ratio 4.35, 95% confidence interval 1.03-18.46). Furthermore, patients with the HLA-DQB1*03:01 allele had significantly worse progression-free survival than patients without the allele (median progression-free survival 3.1 vs. 4.8 months, p = 0.035). There was no significant relationship between any HLA status and the incidence of severe adverse events. Several germline HLA genotypes, especially HLA-DQB1*03:01, may be associated with radiographic progression. However, their impact on treatment response is limited, and germline HLA genotypes was not independently associated with survival outcomes. Further prospective studies are needed to confirm the relationship between germline HLA genotypes and clinical outcomes in patients with chemoresistant advanced UC treated with pembrolizumab.


Subject(s)
Carcinoma, Transitional Cell , Genes, MHC Class II , Genes, MHC Class I , Urinary Bladder Neoplasms , Humans , Alleles , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/pathology , Genotype , Progression-Free Survival , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology
13.
Genes (Basel) ; 13(7)2022 07 05.
Article in English | MEDLINE | ID: mdl-35885987

ABSTRACT

Single nucleotide polymorphisms (SNPs) reportedly influence the effect of nivolumab in metastatic renal cell carcinoma (mRCC). This study aimed to evaluate the relationship between the clinical outcomes of patients with mRCC and SNPs in programmed cell death protein 1 (PD-1) protein-coding gene (PDCD1) and explore any potential correlation with patient prognosis and incidence of immune-related adverse events (irAEs). In total, 106 patients with mRCC, who were treated with nivolumab alone (n = 59) or nivolumab and ipilimumab (n = 47), were enrolled in the study. Three SNPs in the PDCD1 gene, namely PD-1.3, PD-1.5, and PD-1.6, were assessed. Patients harboring the PD-1.6 G allele experienced more severe (odds ratio, 3.390; 95% confidence interval 1.517-7.756; p = 0.003) and multiple (OR, 2.778; 95% CI, 1.020-6.993 p = 0.031) irAEs than those harboring the AA genotype. Thus, the existence of the PDCD1 PD-1.6 polymorphism (G allele) was associated with the occurrence of severe and multiple irAEs in patients with mRCC. Further evaluation of PDCD1 polymorphisms might help identify patients experiencing irAE by nivolumab treatment.


Subject(s)
Antineoplastic Agents, Immunological , Carcinoma, Renal Cell , Immune System Diseases , Kidney Neoplasms , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Nivolumab/adverse effects , Programmed Cell Death 1 Receptor/genetics
14.
Front Immunol ; 13: 934991, 2022.
Article in English | MEDLINE | ID: mdl-35865543

ABSTRACT

Renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) is an extremely rare variant of kidney cancer with poor prognosis. Recently, immune checkpoint inhibitors (ICIs) have been the mainstay of treatment for advanced clear cell renal cell carcinoma (RCC). However, the efficacy of ICI in the treatment of RCCU-MP remains unclear. Here, we report about a 63-year-old Japanese man who was referred to our hospital with a diagnosis of RCC of the left kidney with multiple-lymph node involvement (cT3aN1M1). The patient underwent nephrectomy with lymph node biopsy, which was histopathologically diagnosed as RCCU-MP. Thereafter, he received combined immune checkpoint blockade with nivolumab and ipilimumab. After induction therapy, follow-up computed tomography revealed shrinkage of the metastatic lymph nodes. Moreover, the patient was relieved of his subjective symptoms and his performance status improved. However, after 15 months, maintenance ICI therapy was discontinued because of disease progression, and the patient died 28 months after diagnosis. Longitudinal analysis of peripheral blood mononuclear cells revealed increased stem cell memory and central memory CD8+ T-cell subsets during response to therapy and enhanced expression of exhaustion markers on CD8+ T cells upon treatment resistance. Combined immune checkpoint blockade could be effective in the treatment of metastatic RCCU-MP.


Subject(s)
Carcinoma, Renal Cell , CD8-Positive T-Lymphocytes/pathology , Humans , Immune Checkpoint Inhibitors/therapeutic use , Leukocytes, Mononuclear/pathology , Male , Phenotype
15.
Int J Clin Oncol ; 27(9): 1477-1486, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35748967

ABSTRACT

PURPOSE: We assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies. METHODS: The medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted. RESULTS: A total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34-0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33-1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42-2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups. CONCLUSIONS: Upfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.


Subject(s)
Abiraterone Acetate , Prostatic Neoplasms, Castration-Resistant , Abiraterone Acetate/therapeutic use , Androgen Antagonists/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Castration , Docetaxel/therapeutic use , Humans , Male , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Risk Assessment , Treatment Outcome
16.
Urology ; 167: 158-164, 2022 09.
Article in English | MEDLINE | ID: mdl-35700751

ABSTRACT

OBJECTIVE: To compare the therapeutic effect of Bacille Calmette-Guérin (BCG) intravesical instillation in older and younger patients with high-risk non-muscle-invasive bladder cancer. The comparison was performed with propensity score matching (PSM) without terminating the death of the older patients using relatively large-scale retrospective data from multiple institutes in Japan. MATERIALS AND METHODS: Overall, 3283 patients diagnosed with non-muscle-invasive bladder cancer treated with intravesical BCG instillation during 2000-2018 in 31 institutes were examined; 1437 and 602 patients with high-grade T1 and Tis tumors were divided into those aged ≥75 and <75 years. Multivariate analysis using the Fine-Gray competing risks regression model before PSM and survival analysis using the cumulative incidence method after PSM were performed. RESULTS: In the pre-PSM series of high-grade T1 tumors, age ≥75 years was an independent prognostic factor for both recurrence and progression in multivariate analysis (P = .015 and P = .013). In the pre-PSM series with Tis tumor, no variables to predict recurrence and progression was found. In the post-PSM series of 870 high-grade T1 tumors, cumulative probability of recurrence after BCG intravesical instillation were significantly higher in patients aged ≥75 years than in those aged <75 years (P = .008). The frequency of discontinuation of BCG instillation in patients aged ≥75 years with high-grade T1 and Tis was not significantly different from those in patients aged <75 years (P = .564 and P = .869). CONCLUSION: The cumulative probability of recurrence after intravesical BCG instillation was significantly higher in older than in younger patients with high-grade T1 bladder cancer.


Subject(s)
Urinary Bladder Neoplasms , Adjuvants, Immunologic/therapeutic use , Administration, Intravesical , Aged , BCG Vaccine/therapeutic use , Humans , Japan/epidemiology , Neoplasm Recurrence, Local/drug therapy , Retrospective Studies , Urinary Bladder Neoplasms/pathology
17.
Eur Urol Focus ; 8(6): 1666-1672, 2022 11.
Article in English | MEDLINE | ID: mdl-35717522

ABSTRACT

BACKGROUND: Although bacillus Calmette-Guerin (BCG) is a standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), a high rate of adverse events with a variety of grades remains a difficulty. OBJECTIVE: In this randomized, prospective, multicenter study, we examined whether levofloxacin, given after each intravesical instillation of BCG, could improve its tolerance in patients with intermediate- to high-risk urothelial carcinoma of the bladder without compromising its efficacy. DESIGN, SETTING, AND PARTICIPANTS: Overall, 106 Japanese patients (85 men and 21 women; age: median, 69.5 yr) with primary or recurrent NMIBC were randomized after transurethral resection to induce treatment with intravesical BCG plus levofloxacin (group 1) or BCG alone (group 2). INTERVENTION: Patients who underwent intravesical instillation of BCG were randomized with or without levofloxacin administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events were assessed using the National Cancer Institute-Common Toxicity Criteria version 3.0. Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. RESULTS AND LIMITATIONS: There was no significant difference in baseline characteristics between the groups. The completion rate of group 1 (85.5%) was not significantly lower than that of group 2 (76.5%; p = 0.321). There was no significant difference in the completion rate of patients with pollakisuria, painful micturition, gross hematuria, fever elevation, and others between the groups. The incidence of adverse events in patients with high-grade pollakisuria (7.3% vs 25.4%, p = 0.041) and fever (0% vs 9.1%, p = 0.034) was significantly lower in group 1. The 5-yr progression-free and cancer-specific survival rates were significantly better in group 1. CONCLUSIONS: Prophylactic levofloxacin administration may reduce the severity of adverse events and contribute to better outcomes from BCG intravesical therapy in patients with NMIBC. PATIENT SUMMARY: Levofloxacin administration seems to be a safe and effective therapy for non-muscle-invasive bladder cancer patients treated with bacillus Calmette-Guerin intravesical therapy.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Female , BCG Vaccine/adverse effects , Carcinoma, Transitional Cell/drug therapy , Urinary Bladder Neoplasms/drug therapy , Levofloxacin/therapeutic use , Prospective Studies
18.
World J Surg Oncol ; 20(1): 202, 2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35701769

ABSTRACT

INTRODUCTION: Warm ischemia time (WIT) is a primary concern for robot-assisted laparoscopic partial nephrectomy (RALPN) patients because longer WIT is significantly associated with postoperative deteriorating kidney function. Tumor complexity, determined by the RENAL nephrometry score (RENAL score), can help predict surgical outcomes, but it is unclear what RENAL score and clinical factors affect WIT. This study explored the clinical factors predicting long WIT in experienced surgeon to RALPN. MATERIALS AND METHODS: In our institute, 174 RALPNs were performed between November 2013 and February 2021, of which 114 were performed by a single surgeon and included in this study. Clinical staging and the total RENAL score were determined based on preoperative CT scans. The cases were divided into three groups based on experience: period 1: 1-38, period 2: 39-76, and period 3: 77-114. The clinical factors associated with longer WIT were analyzed per period. RESULTS: The overall median tumor diameter was 32 mm, and one patient had a positive surgical margin, but there were no cancer-related deaths. In total, there were 18 complications (15.8%). Periods 2 and 3 had larger tumor diameters (p < 0.01) and worse preoperative kidney function (p = 0.029) than period 1. A RENAL L-component score of 3 was associated with longer WIT in period 3 (odds ratio: 3.900; 95% confidence interval: 1.004-15.276; p = 0.044), but the tumor diameter and the total RENAL score were not. CONCLUSIONS: A large tumor in the central lesion indicated by the RENAL L-component score was associated with increased WIT in RALPN.


Subject(s)
Kidney Neoplasms , Laparoscopy , Robotic Surgical Procedures , Robotics , Surgeons , Humans , Kidney Neoplasms/pathology , Nephrectomy/adverse effects , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Treatment Outcome , Warm Ischemia
19.
Hinyokika Kiyo ; 68(4): 99-105, 2022 Apr.
Article in Japanese | MEDLINE | ID: mdl-35613897

ABSTRACT

Magnetic resonance imaging (MRI) ultrasound fusion biopsy is becoming popular owing to the better detection rate of clinically significant prostate cancer (csPCa). We retrospectively evaluated the accuracy of MRI-targeted biopsy during the period of introduction at a single academic center by comparing findings of its specimen and whole-mount histopathology. Between June 2018 and January 2021, 106 transperineal MRI-ultrasound fusion biopsies using BioJet software were performed. Among the cases, 15 subsequently underwent robotic-assisted laparoscopic radical prostatectomy and were eligible for analysis. This study included all regions of interest (ROIs) with a Prostate Imaging Reporting and Data System v2 category of 3 or greater on pre-biopsy MRI.For each lesion, grade group of MRI-targeted biopsy specimens and prostatectomy specimens were compared. From a total of 25 ROIs identified among 15 males, csPCa was found in 21 (84%) of the concordant locations of prostatectomy specimens. However, MRI-targeted biopsy could diagnose csPCa in only 12 (48%) of them. In the csPCa undetected group, the ROI volume was significantly smaller (median volume 0.23 ml vs 0.40 ml, p=0.03). We also found that in cases where PCa was not detected through MRI-targeted biopsy, the biopsy sample length was significantly shorter (median length 9 mm vs 17 mm, p=0.01). Our data suggest that failure of detecting PCa in MRI-targeted biopsy could be due to technical errors at the introduction period of the technique. A sufficient sampling length of 10 mm or more is desirable, especially for small lesions.


Subject(s)
Prostate , Prostatic Neoplasms , Humans , Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Male , Prostate/diagnostic imaging , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Retrospective Studies
20.
Case Rep Urol ; 2022: 4586199, 2022.
Article in English | MEDLINE | ID: mdl-35585958

ABSTRACT

Background: Spontaneous bladder rupture (SBR) is very rare and can be associated with advanced bladder cancer. Because of its rarity, the optimal management of bladder cancer with SBR has not been established. Herein, we report a case of SBR due to locally advanced bladder cancer, which rapidly invaded the ileum and caused peritoneal dissemination. Case Presentation. An 86-year-old man presented with sudden-onset lower abdominal pain and distension. The patient was diagnosed with bladder perforation and bladder tumor on contrast-enhanced computed tomography (CECT). Transurethral resection of the bladder tumor revealed an invasive urothelial carcinoma with squamous differentiation. Although radical cystectomy with lymph node dissection was planned, preoperative CECT and magnetic resonance imaging revealed enlargement of the bilateral iliac regional lymph nodes, multiple peritoneal nodules, and invasion of the bladder tumor to the ileocecum. Therefore, cystectomy and resection of ileocecum with palliative intent and bilateral cutaneous ureterostomy were performed. However, the patient's general condition rapidly worsened after surgery, and he died 74 days after the initial diagnosis. Conclusions: We encountered a case of SBR accompanied by bladder cancer with extremely rapid progression, which suggested the importance of short-interval repeat imaging examinations. Emergency surgery should be considered when bladder cancer is suspected in patients with SBR so as not to miss the window period of a possible cure.

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