Real-world evidence of triplet therapy efficacy in patients with metastatic castration-sensitive prostate cancer: a Japanese multicenter study.

BACKGROUND: Two randomized trials demonstrated that the survival benefits afforded by triplet therapy were greater than those of doublet therapy, thus changing the treatment paradigm for metastatic castration-sensitive prostate cancer (mCSPC). This is the first study to assess the real-world use, performance, and safety of triplet therapy in Japanese patients. METHODS: This retrospective multicenter study included 45 consecutive mCSPC patients who received triplet therapy composed of androgen deprivation therapy (ADT), docetaxel, and darolutamide between January 2023 and June 2024. Baseline patient characteristics and their clinical parameters during triplet therapy were collected. Adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events version 5.0, and imaging responses were evaluated following the RECIST criteria. The prostate-specific antigen (PSA) nadir was defined as the lowest PSA value during follow-up, and the PSA decrease was the initial PSA value minus the PSA nadir. RESULTS: The median patient age was 70 years and the median follow-up duration was 10 months. High-volume disease was present in 82.2% of patients. Concurrent administration of docetaxel and darolutamide was scheduled for 22.2% of cases. The incidence of any AE was 86.7%, with 55.5% of patients experiencing grade 3-4 AEs. Neutropenia was common, but prophylactic granulocyte colony-stimulating factor (G-CSF) significantly reduced the incidence of neutropenia of grade 3 or higher. Febrile neutropenia occurred in four patients (8.9%); these patients had not received prophylactic G-CSF. A decline in PSA of 90% was observed in 95.6% of patients, and an imaging response was seen in 97.8%. CONCLUSIONS: Triplet therapy with ADT, darolutamide, and docetaxel was highly efficacious and tolerable in Japanese mCSPC patients, particularly those with high-volume disease. Prophylactic G-CSF prescription is crucial to manage neutropenia effectively. Further studies with longer follow-ups are needed to confirm these findings and explore the long-term outcomes.

Changes in the treatment landscape of metastatic hormone-sensitive prostate cancer following approval of upfront androgen receptor signaling inhibitors: A multicenter study.

BACKGROUND: A multicenter database was utilized to examine the current treatment landscape and clinical outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC) following approval of upfront androgen receptor signaling inhibitors (ARSIs). METHODS: We retrospectively analyzed patients with mHSPC who commenced treatment between February 2018 and June 2023. The Kaplan-Meier method was used to assess oncological outcomes, including time to castration-resistant prostate cancer (CRPC), progression-free survival 2 (PFS2, duration from initial treatment to tumor progression during second-line treatment), cancer-specific survival (CSS), and overall survival (OS). Cox regression analyses were performed to determine the impact of treatment choices on oncological outcomes. In addition, the incidence rate of adverse events was assessed. RESULTS: In total, 829 patients were analyzed; 42.5% received ARSIs with androgen deprivation therapy (ADT), 44.0% received combined androgen blockade (CAB), and 13.5% received ADT alone. Kaplan-Meier curves and multivariate Cox regression analyses indicated higher rates of CRPC and shorter PFS2 in patients treated with CAB versus ARSIs with ADT. By contrast, CSS and OS were not significantly different between the ARSI with ADT group and the CAB group. Grades 3-4 adverse events occurred in 1.9% of patients receiving CAB and 6.0% of those receiving ARSIs with ADT. CONCLUSIONS: Initial treatment with ARSIs in combination with ADT resulted in a longer time to CRPC and longer PFS2 compared to CAB. Although CAB and ADT alone were associated with fewer adverse events, ARSIs with ADT should be considered a first-line treatment option given its superior oncological outcomes.

Preoperative Tyrosine Kinase Inhibitors Before Percutaneous Cryoablation for Clinical T1b Renal Tumors.

Purpose To treat renal cell carcinoma, local ablative therapy is a viable alternative treatment option. Traditionally, cryoablation has been used for the treatment of T1a renal tumors. However, recent technological developments have expanded its application to encompass select T1b renal tumors. Here, we present a retrospective study of the utilization of preoperative tyrosine kinase inhibitors (TKIs) to induce tumor shrinkage and achieve favorable outcomes in percutaneous cryoablation (PCA). Methods We retrospectively evaluated the data from nine patients with clinical T1b renal tumors who underwent PCA. Six patients with TKI pretreatment at our institution between 2016 and 2018 were included in the study. We evaluated the safety and efficacy of preoperative TKIs prior to PCA. Results All patients received axitinib with a median treatment duration of 80.5 days (IQR: 49-85). All patients experienced tumor shrinkage (median: 13.5 mm; IQR: 7-16); five experienced downstaging to T1a following tumor shrinkage. There were no severe adverse events (common terminology criteria for adverse events (CTCAE) grade ≥ 3) in TKIs. After the discontinuation of TKIs for two weeks, all PCA procedures were performed successfully without any severe complications. During a median follow-up of 46 months, no local recurrence was observed in any of these cases. Conclusion In cases with large renal tumors, TKI pretreatment prior to PCA had potential benefits in terms of tumor shrinkage and long-term local control rate. Further well-designed studies in larger populations are needed to validate our findings.

Does age impact clinical outcomes of radical nephroureterectomy in the elderly?-results from a multicenter retrospective study.

Background: Few studies have addressed the efficacy of nephroureterectomy for managing upper tract urothelial carcinoma (UTUC) in very elderly patients (those aged 85 years and older). We aimed to elucidate the association between age and clinical outcomes in patients with UTUC who underwent radical nephroureterectomy. Methods: We retrospectively analyzed data from 847 patients who underwent nephroureterectomy for UTUC. These patients were classified into four age brackets: young (≤64 years, n=177), intermediate (65-74 years, n=300), elderly (75-84 years, n=312), and very elderly (≥85 years, n=58). We applied logistic regression models to ascertain predictors of postoperative complications. Cox's proportional hazards models were used to evaluate key prognostic factors affecting non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Results: In all, 56 patients reported postoperative complications. An Eastern Cooperative Oncology Group performance status ≥2 was identified as a significant predictor for postoperative complications whereas age did not show a noteworthy correlation. Kaplan-Meier survival analyses indicated that very elderly patients had notably poorer OS than younger groups. Nevertheless, the differences in NUTRFS and CSS across the age brackets were not statistically significant. In multivariable analyses, very elderly age was a substantial independent determinant of OS but not NUTRFS or CSS. Conclusions: The therapeutic benefits of surgical procedures are relatively consistent across age groups. This underscores the potential of considering surgical treatment for UTUC in patients aged 85 and above, provided they are deemed fit to withstand the surgical rigors and associated invasiveness.

The prognostic significance of additional localized treatment to primary lesion in patients undergoing hormone therapy for metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis.

BACKGROUND: We aimed to compare the prognostic values of 'localized treatment to the primary lesion (LT) plus hormone therapy (HT)' versus 'HT alone' in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: We conducted a systematic search through the databases of PubMed®, Web of Science®, and Cochrane library® in April 2023 based on the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) statement. A pooled meta-analysis was performed to assess the prognostic differences between LT + HT and HT alone according to randomized and non-randomized controlled studies (RCTs and NRCTs, respectively). RESULTS: The search identified three RCTs and eight NRCTs. In RCTs, LT did not show prognostic benefits regarding biochemical-failure free rate nor overall survival (OS), although in patients with low tumor burdens, the LT + HT group showed better OS (HR: 0.68, 95% CI: 0.54-0.86). In the NRCTs, the LT+HT group showed superior progression-free survival (hazard ratio (HR): 0.42, 95% confidence interval (CI): 0.21-0.87), cancer-specific survival (HR: 0.39, 95% CI: 0.20-0.76), and OS (HR: 0.63, 95% CI: 0.57-0.69) to the HT alone group. In addition, better OS was observed in the LT +HT group regardless of the type of treatment modality for LT; radical prostatectomy (HR: 0.52, 95% CI: 0.39-0.69), radiotherapy (HR: 0.63, 95% CI: 0.56-0.71) in NRCTs. CONCLUSIONS: LT to the primary lesion in metastatic hormone-sensitive prostate cancer may provide prognostic benefits and especially in patients with low tumor burden.

Associations between early changes in the neutrophil-to-lymphocyte ratio after radical nephroureterectomy and treatment outcomes.

OBJECTIVES: This study explored the impacts of peri-operative changes in the neutrophil-to-lymphocyte ratio (NLR) on the survival rate after radical nephroureterectomy. METHODS: This retrospective analysis included a multicentric cohort of patients diagnosed with upper tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy from 2012 to 2021. We assessed the preoperative NLR, postoperative NLR, delta-NLR (difference between postoperative and preoperative NLRs), and NLR change (ratio of postoperative to preoperative NLR). Additionally, patients were categorized according to increases in their preoperative and/or postoperative NLRs. Associations of survival with peri-operative changes in the NLR were investigated using Cox multivariate regression models. RESULTS: A total of 488 patients were included in the study, with a median age of 73 years. Among the patients, 105 (21.5%) exhibited elevated preoperative and postoperative NLRs, 88 (18.0%) exhibited elevated preoperative NLR only, 53 (10.9%) exhibited elevated postoperative NLR only, and 242 (49.6%) exhibited normal NLRs. Multivariate analysis indicated significant negative correlations between both preoperative and postoperative increased NLRs and oncological outcomes, including nonurothelial tract recurrence-free survival and cancer-specific survival (hazard ratio [HR]: 1.65, P = 0.017; HR: 2.12, P = 0.014, respectively). CONCLUSION: This is the first study to evaluate the association between peri-operative changes in the NLR and the outcomes of patients with UTUC who underwent radical nephroureterectomy. Patients with elevated NLRs at both time points experienced considerably worse outcomes. Further research should explore whether increases in the NLR during long-term follow-up could indicate impending disease recurrence.

Perioperative renal function change and oncological outcomes of radical nephroureterectomy in patients with upper tract urothelial carcinoma: A multicenter retrospective study.

BACKGROUND: The effect of radical nephroureterectomy (RNUx) on postoperative renal function in patients diagnosed with upper tract urothelial carcinoma (UTUC) has not been thoroughly explored. METHODS: We conducted a retrospective analysis including 785 patients who underwent RNUx for UTUC. We assessed the preoperative and postoperative estimated glomerular filtration rates (eGFRs) and factors related to the decline in eGFR. Additionally, we examined the effect of comorbidities (diabetes or hypertension) on the postoperative eGFR at 1 year. Cox proportional hazard models were employed to investigate the clinical effect of RNUx on oncological outcomes, including non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median preoperative and postoperative eGFR levels were 54.7 and 40.6 ml/min/1.73 m2 respectively. The proportions of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m2 were 35.9% and 5.1%, respectively. The median decline in the eGFR after surgery was 26.8%. Patients with preoperative eGFR <60 ml/min/1.73 m2 demonstrated significantly lower odds of a postoperative decline in eGFR of 25% or more. The effect of comorbidities on postoperative eGFR at 1 year was significant (P = 0.048). The 3-year NUTRFS, CSS, and OS rates were 72.9%, 85.2%, and 81.5%, respectively. Preoperative chronic kidney disease was an independent factor associated with inferior NUTRFS, CSS, and OS. CONCLUSION: Different degrees of impairment of renal function occur among UTUC patients. Only 5.1% of patients retain a postoperative eGFR ≥60 ml/min/1.73 m2. Preoperative renal impairment was linked to reduced odds of postoperative eGFR decrease and associated with survival. In addition, the presence of comorbidities had a significant effect on the decline in eGFR. These findings emphasize the importance of developing evidence-based perioperative treatment strategies for UTUC patients with impaired renal function.

C-Reactive Protein-Albumin Ratio Predicts Objective Response to Enfortumab Vedotin in Metastatic Urothelial Carcinoma.

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate that targets Nectin-4, is used for patients with metastatic urothelial carcinoma who have experienced progression on platinum-based chemotherapy and checkpoint inhibitors. Despite the widespread use of the drug, evidence remains scarce regarding clinical indicators that can predict the response to EV treatment. OBJECTIVE: We aimed to explore the predictive value of clinical indicators derived from peripheral blood tests for treatment responses to EV. METHODS: We utilized records of 109 patients with metastatic urothelial carcinoma treated by EV from our multi-institutional dataset. Receiver operating characteristic curve analyses for predicting objective responses including several indicators from blood examinations, such as C-reactive protein-albumin ratio (CAR), hemoglobin, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and lactate dehydrogenase, were performed. The optimal cutoff points were determined by the Youden index. Logistic regression analyses for achieving objective responses to EV treatment were performed among these indicators. RESULTS: The median age of the cohort was 74 years, and the median follow-up duration was 10 months for the entire group. Median overall survival and progression-free survival from the initiation of EV were 12 and 6 months, respectively. The objective response rate and disease control rate were 48% and 70%, respectively. The receiver operating characteristic curve analysis aimed at predicting the achievement of an objective response to EV showed that the concordant index for the CAR was 0.774, significantly surpassing other indicators such as hemoglobin level, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and serum lactate dehydrogenase. The Youden index identified an optimal cutoff value of 1 for CAR (mg/L for C-reactive protein and g/dL for serum albumin level) in predicting the objective response to EV treatment. Using the cutoff value for the CAR, the cohort was divided into 32 patients (29%) with lower CAR and 77 patients (71%) with higher CAR. The objective response rate was observed to be 84% in the lower CAR group and 32% in the higher CAR group (p < 0.0001). A logistic regression analysis revealed that an Eastern Cooperative Oncology Group Performance Status ≥1 (p = 0.04) and a CAR ≥1 (p < 0.001) were identified as independent predictors for the objective response to EV. CONCLUSIONS: The evaluation of the CAR from a concise blood examination at the initiation of EV could effectively predict the treatment response to EV in patients with metastatic urothelial carcinoma after the progression of platinum-based chemotherapy and checkpoint inhibitors.

Enfortumab vedotin, an antibody-drug conjugate that targets Nectin-4, is currently used for patients with metastatic urothelial carcinoma who no longer respond to checkpoint inhibitors. In the present report, we investigated which clinical indicators can predict achieving an objective response to enfortumab vedotin at the initiation of treatment. Among the blood-based putative indicators, the C-reactive protein-albumin ratio showed the highest value for predicting the treatment response to enfortumab vedotin. As the C-reactive protein-albumin ratio can be easily assessed from blood tests, physicians can consider evaluating it at the start of the EV treatment.

Effectiveness and safety of enzalutamide and apalutamide in the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC): a multicenter retrospective study.

OBJECTIVE: Phase III clinical trials demonstrated the efficacy of enzalutamide and apalutamide in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and PSA doubling time ≤10 months. Although these drugs have been shown to vary in their adverse event (AE) profiles, the differences in their efficacy profiles remain to be evaluated. Therefore, this retrospective study was conducted to evaluate the efficacy of these drugs in patients with nmCRPC. METHODS: This study evaluated 191 patients with nmCRPC treated with enzalutamide (n = 137) or apalutamide (n = 54) in the first-line setting at Jikei University Hospital or its affiliated hospitals between May 2014 and November 2022. Endpoints were defined as oncological outcomes (i.e., PSA response, PFS, PSA-PFS, MFS, CSS, and OS) and AEs. RESULTS: No significant differences were noted in patient backgrounds between the two groups. Patients exhibiting a maximum PSA response of >50% and >90% accounted for 74.5% and 48.9% of patients in the enzalutamide group, and 75.9% and 42.6% of patients in the apalutamide group, respectively, with no significant difference between the groups. The median PSA-PFS was 10 months in the enzalutamide group but not in the apalutamide group, with no significant difference between the groups (P = 0.48). No significant differences were observed in MFS, CSS, or OS between the groups. Patients reporting AEs of all grades and grade 3 or higher accounted for 56.2% and 4.3% of those in the enzalutamide group and 57.4% and 7.4% of those in the apalutamide group, respectively. The most common AE was fatigue (26.3%) in the enzalutamide group and skin rash (27.8%) in the apalutamide group. CONCLUSION: In this retrospective study of their efficacy and safety, enzalutamide and apalutamide were shown to exhibit comparable oncological outcomes but quite different AE profiles, suggesting that their differential use may be warranted based on these findings.

Site-Specific Differences of Eligibility for Adjuvant Immunotherapy Among Urothelial Carcinoma Patients Treated With Radical Surgery: Results From a Multicenter Cohort Study.

BACKGROUND: The CheckMate274 trial has reported enhanced disease-free survival rates in patients with stage pT3-4/ypT2-4 or pN+ urothelial carcinoma (UC) undergoing adjuvant nivolumab therapy. This study compares prognostic differences between urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 719 patients with UC who underwent radical surgery, stratifying to patients at stage pT3-4 and/or pN+ without neoadjuvant chemotherapy (NAC) or at ypT2-4 and/or ypN+ with NAC (potential candidates for adjuvant immunotherapy), and to those who were not candidates for adjuvant immunotherapy. We used Kaplan-Meier curves to assess oncological outcomes, particularly nonurothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Risk factors were identified by Cox regression analysis. RESULTS: Kaplan-Meier curves showed significantly lower NUTRFS, CSS, and OS for potential adjuvant immunotherapy candidates than for noncandidates in each UCB and UTUC group. NUTRFS, CSS, and OS did not differ significantly between adjuvant immunotherapy candidates with UBC or UTUC. Trends were similar among patients ineligible for adjuvant immunotherapy. Pathological T stage (pT3-4 or ypT2-4), pathological N stage, and lymphovascular invasion (LVI) were independent predictors of oncological outcomes on multivariate analysis. CONCLUSION: The criteria for adjuvant immunotherapy candidates from the CheckMate 274 trial can also effectively stratify UC patients after radical surgery. Substantial clinical significance is attached to LVI status as well as to pathological T and N status, suggesting that LVI status should be considered when selecting suitable candidates for adjuvant immunotherapy.

Effect of a variant histology on the oncological outcomes of Japanese patients with upper tract urothelial carcinomas after radical nephroureterectomy: a multicenter retrospective study.

Background: An earlier systematic review and meta-analysis found that patients with a certain histological variant of upper tract urothelial carcinoma (UTUC) exhibited more advanced disease and poorer survival than those with pure UTUC. A difference in the clinicopathological UTUC characteristics of Caucasian and Japanese patients has been reported, but few studies have investigated the clinical impact of the variant histology in Japanese UTUC patients. Methods: We retrospectively enrolled 824 Japanese patients with pTa-4N0-1M0 UTUCs who underwent radical nephroureterectomy without neoadjuvant chemotherapy. Subsequently, we explored the effects of the variant histology on disease aggressiveness and the oncological outcomes. We used Cox's proportional hazards models to identify significant predictors of oncological outcomes, specifically intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: Of the 824 UTUC patients, 32 (3.9%) exhibited a variant histology that correlated significantly with a higher pathological T stage and lymphovascular invasion (LVI). Univariate analysis revealed that the variant histology was an independent risk factor for suboptimal RFS, CSS, and OS. However, significance was lost on multivariate analyses. Conclusions: The variant histology does not add to the prognostic information imparted by the pathological findings after radical nephroureterectomy, particularly in Japanese UTUC patients.

Durable Response to Enfortumab Vedotin Compared to Re-challenging Chemotherapy in Metastatic Urothelial Carcinoma After Checkpoint Inhibitors.

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has been used for patients with metastatic urothelial carcinoma (mUC) after progressing on checkpoint inhibitors (CPIs). Re-challenging chemotherapy with platinum agents and continuing CPIs beyond progressive disease (PD) have often been chosen following PD on CPIs, and several studies indicate favorable treatment effects of re-challenging chemotherapy. There is little evidence for comparing EV and re-challenging chemotherapy in real-world clinical practice. OBJECTIVE: The aim was to reveal the real-world treatment outcomes of EV, re-challenging chemotherapy, and continuing CPIs beyond PD in mUC patients. PATIENTS AND METHODS: A multi-institutional dataset of 350 mUC patients treated with CPIs was utilized. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) were evaluated to compare the treatment arms. RESULTS: One hundred and nine mUC patients were treated with EV with a median follow-up of 6.4 months. The ORR and disease control rate (DCR) were 48% and 70%, respectively. The OS from PD on pembrolizumab exhibited significant differences among the three groups, with a median OS of 8, 14, and 29 months in continuing pembrolizumab beyond PD, re-challenging chemotherapy, and EV, respectively. When comparing the survival outcomes from the initiation of the treatment, there is neither a difference in OS (p = 0.124), PFS (p = 0.936), nor ORR (p = 0.816) between EV and re-challenging chemotherapy. Notably, the DOR in patients who achieved an objective response was significantly longer in the EV group than the re-challenging chemotherapy group (a median of 11 and 5 months, p = 0.049). For OS, the difference was not statistically significant (27 and 11 months in EV and re-challenging chemotherapy, respectively: p = 0.05). CONCLUSIONS: A superior effect of EV on patient survival compared to re-challenging chemotherapy and continuing pembrolizumab beyond PD was observed in our real-world analysis, which is attributed to the durable DOR in EV treatment despite the similar ORR to re-challenging chemotherapy.

Enfortumab vedotin (EV) is an antibody­drug conjugate targeting Nectin-4 and is now utilized for patients with metastatic urothelial carcinoma following treatment with checkpoint inhibitors (CPIs). Until recently, repeating chemotherapy using platinum drugs or continuing CPIs were often the treatments used for these patients. In the present study, we reported real-world treatment outcomes, mainly focusing on EV and repeating chemotherapy. Although the objective responses to the treatments were comparable, the duration of response for patients responding to the treatment was significantly longer in patients treated with EV than in those repeating chemotherapy, resulting in extended survival time with EV treatment.

Association between comorbidities and survival in patients with metastatic urothelial carcinoma treated with pembrolizumab.

BACKGROUND: This study aims to investigate the relationship between comorbidities and survival in patients with mUC treated with pembrolizumab as a second-line treatment. METHODS: From February 2018 to October 2021, we analyzed the data of 185 consecutive patients with metastatic UC who received pembrolizumab as second-line therapy at The Jikei University Hospital and five affiliated hospitals. We used the Charlson Comorbidity Index (CCI) to assess the comorbidities. The outcomes of interest were progression-free survival (PFS) and overall survival (OS). To compare the survival differences, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and the IPTW-adjusted Cox regression hazards model were used. RESULTS: After IPTW adjustment, patient characteristics were well-balanced between patients with high CCI and those with low CCI. The IPTW-adjusted Kaplan-Meier curves of PFS and OS based on CCI revealed that the patients with high CCI (2 or more) had a shorter PFS (median, 1.6 vs. 2.8 months) and a shorter OS (median, 12.4 vs. 18.8 months) (0-1). Similarly, in the IPTW-adjusted Cox regression hazards model, patients with high CCI had significantly shorter PFS [HR, 1.84 (95% CI 1.26-2.68; p = 0.002)] and OS [HR, 1.98 (95% CI 1.20-3.27; p = 0.008)] than those with lower CCI. CONCLUSIONS: High CCI was associated with a higher risk of disease progression as well as overall mortality in mUC patients treated with second-line pembrolizumab.

Impact of timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis associated with upper urinary tract stones: a propensity score-matched analysis.

OBJECTIVE: We aimed to assess the impact of the timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis (OPN) associated with upper urinary tract (UUT) stones. METHODS: We retrospectively evaluated the multicenter dataset of 240 patients with OPN associated with UUT stones who underwent urinary drainage. We divided the patients into two groups depending on the timing of urinary drainage; emergency drainage, defined as within 12 h from admission, and delayed drainage, defined as between 12 and 48 h from admission. The outcomes were the length of hospital stay, time to leukocyte normalization, and time to body temperature normalization. One-to-two propensity score matching (PSM) was applied to minimize the effect of confounders between the two groups. Subsequently, predictive patient factors for emergency drainage were analyzed using the logistic regression model. RESULTS: Only the time from admission to normal body temperature was significantly shorter in the emergency drainage group when compared with the delayed drainage group (median: 2 vs. 3 days; p = 0.02), while there was no difference in time from drainage to body temperature normalization between the two groups. On multivariable analysis, high pretreatment C-reactive protein (CRP) was associated with implementing emergency drainage within 12 h. CONCLUSIONS: The timing of urinary drainage was only associated with the duration of high fever, but it did not affect the postdrainage course. Emergency urinary drainage is more likely to be performed in severe patients, such as high pretreatment CRP.

Prognostic value of micrometric substaging in pT1 bladder cancer patients treated with en-bloc transurethral resection.

AIMS: We aimed to assess the oncological impact of micrometric extent of invasion in patients with pT1 bladder cancer (BCa) who underwent en-bloc resection for bladder tumour (ERBT). METHODS AND RESULTS: We retrospectively analysed the records and specimens of 106 pT1 high-grade BCa patients who underwent ERBT. The extent of invasion, such as depth from basal membrane, number of invasive foci, maximum width of invasive focus, muscularis mucosae invasion and infiltration pattern (pattern A: solid sheet-like, nodular or nested growth, pattern B: trabecular, small cluster or single-cell pattern) were evaluated by a single genitourinary pathologist. The end-points were recurrence-free (RFS) and progression-free survival (PFS). Within a median follow-up of 23 months, overall, 36 patients experienced recurrence and 13 patients experienced disease progression. The 2-year PFS differed significantly depending on depth from basal membrane (< 1.3 mm: 94.8% versus ≧ 1.3 mm: 65.2%, P = 0.005), maximum width of invasive focus (< 4 mm: 91.7% versus ≧ 4 mm: 62.3%, P < 0.001), muscularis mucosae (MM) invasion (above MM = 96.1% versus into or beyond MM = 64.8%, P = 0.002) and infiltration pattern (pattern A: 100% versus pattern B: 83.3%, P = 0.037). In a multivariable analysis, MM invasion [hazard ratio (HR) = 4.54, 95% confidence interval (CI) = 1.25-16.5] and maximum width of invasive focus ≧ 4 mm (HR = 4.79, 95% CI = 1.25-16.5) were independent prognostic factors of progression. CONCLUSIONS: En-bloc resection facilitates the evaluation of pathologic variables that might be useful in predicting disease recurrence and progression. In particular, not only the MM invasion but also the maximum width of invasion focus, reflecting the invasive volume, appear to be reliable prognosticators for disease progression.

Effectiveness of Magnetic Resonance Imaging/Ultrasound-guided Target Biopsy in Detecting Clinically Significant Prostate Cancer.

BACKGROUND/AIM: To evaluate the effectiveness of magnetic resonance imaging/ultrasound (MRI-US)-guided fusion biopsy in the detection of clinically significant prostate cancer (CSPC) and analyze the clinical features of patients highly suspected of having prostate cancer (PCa) but shown to be negative in target biopsies (TB) among patients with prostate imaging reporting and data system (PI-RADS) 4 or 5 lesions on multiparametric MRI (mpMRI) evaluations. PATIENTS AND METHODS: We retrospectively evaluated all patients who underwent MRI/transrectal ultrasound (TRUS)-guided fusion biopsies at our institution between April 2018 and April 2022. All patients with at least one PI-RADS 3 or higher lesion and prostate-specific antigen (PSA) ≤20 ng/ml were enrolled in our study and subjected to TB in the region of interest (ROI). CSPC was defined as grade group (GG) ≥2 (equivalent to a Gleason score of 3+4). RESULTS: The detection rates of CSPC were higher in patients who underwent systematic biopsy (SB) and TB (54%; 177/328) than in those who underwent SB alone (39%; 128/328). Significant differences were noted in the detection of CSPC depending on age, prostate volume, PI-RADS score, PSA density (PSAD), number of biopsies obtained, lesion location, and ROI. CONCLUSION: MRI/TRUS-guided fusion prostate biopsy increased the detection rate of CSPC. PCa was less likely to be detected in patients with a low PSAD, large prostate volume and no family history among those with PI-RADS 4 or 5 lesions and should be considered in such patients and addressed by performing additional SB for improving CSPC detection rate.

Updated systematic review and network meta-analysis of first-line treatments for metastatic renal cell carcinoma with extended follow-up data.

Immune checkpoint inhibitor (ICI)-based combination therapies are the recommended first-line treatment for metastatic renal cell carcinoma (mRCC). However, no head-to-head phase-3 randomized controlled trials (RCTs) have compared the efficacy of different ICI-based combination therapies. Here, we compared the efficacy of various first-line ICI-based combination therapies in patients with mRCC using updated survival data from phase-3 RCTs. Three databases were searched in June 2023 for RCTs that analyzed oncologic outcomes in mRCC patients treated with ICI-based combination therapies as first-line treatment. A network meta-analysis compared outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate. Subgroup analyses were based on the International mRCC Database Consortium risk classification. The treatment ranking analysis of the entire cohort showed that nivolumab + cabozantinib (81%) had the highest likelihood of improving OS, followed by nivolumab + ipilimumab (75%); pembrolizumab + lenvatinib had the highest likelihood of improving PFS (99%), ORR (97%), and CR (86%). These results remained valid even when the analysis was limited to patients with intermediate/poor risk, except that nivolumab + ipilimumab had the highest likelihood of achieving CR (100%). Further, OS benefits of ICI doublets were not inferior to those of ICI + tyrosine kinase inhibitor combinations. Recommendation of combination therapies with ICIs and/or tyrosine kinase inhibitors based on survival benefits and patient pretreatment risk classification will help advance personalized medicine for mRCC.

Adjuvant immunotherapy in patients with renal cell carcinoma and urothelial carcinoma: A systematic review and network meta-analysis.

Adjuvant immune checkpoint inhibitor therapies have radically altered the treatment landscape for renal cell carcinoma and urothelial carcinoma. However, studies have reported negative data regarding adjuvant immune checkpoint inhibitor therapies. Thus, this study aimed to assess the role of adjuvant immune checkpoint inhibitor therapy for both renal cell carcinoma and urothelial carcinoma. A systematic review and network meta-analysis were conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases were searched for articles published as of February 2023. Studies were deemed eligible if they evaluated disease-free survival in patients with renal cell carcinoma and urothelial carcinoma receiving adjuvant immune checkpoint inhibitor therapy. Five studies met the inclusion criteria. In a network meta-analysis, pembrolizumab was shown to be the most effective regimen for patients with renal cell carcinoma, whereas nivolumab was found to be the most effective regimen for patients with urothelial carcinoma. Additionally, these results were consistently observed in a sub-analysis of the T stage. The present analysis provides findings that support the usefulness of adjuvant nivolumab therapy in urothelial carcinoma and adjuvant pembrolizumab therapy in renal cell carcinoma, in agreement with the currently available guidelines. However, the caveat is that the randomized controlled trials included in this analysis differed in important respects despite being similar in study design. Therefore, with these differences in mind, care needs to be taken when selecting patients for these immune checkpoint inhibitor therapies to maximize their benefits.

Real-world outcomes of adjuvant immunotherapy candidates with upper tract urothelial carcinoma: results of a multicenter cohort study.

BACKGROUND: Recent clinical trials have reported improved disease-free survival rates of patients with stage pT3-4/ypT2-4 or pN + upper tract urothelial carcinoma (UTUC) on adjuvant nivolumab therapy. However, the appropriateness of the patient selection criteria used in clinical practice remains uncertain. METHODS: We retrospectively analyzed 895 patients who underwent nephroureterectomy to treat UTUC. The patients were divided into two groups: grade pT3-4 and/or pN + without neoadjuvant chemotherapy (NAC) or grade ypT2-4 and/or ypN + on NAC (adjuvant immunotherapy candidates) and others (not candidates for adjuvant immunotherapy). Kaplan-Meier curves were drawn to assess the oncological outcomes, including recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Cox proportional hazards models were used to identify significant prognostic factors for oncological outcomes. RESULTS: The Kaplan-Meier curves revealed notably inferior RFS, CSS, and OS of patients who were candidates for adjuvant immunotherapy. Multivariate analysis revealed that pathological T and N grade and lymphovascular invasion (LVI) status were independent risk factors for poor RFS, CSS, and OS. CONCLUSION: In total, 44.8% of patients were candidates for adjuvant immunotherapy. In addition to pathological T and N status, LVI was a significant predictor of survival, and may thus play a pivotal role in the selection of patients eligible for adjuvant immunotherapy.