Six-year outcomes of robot-assisted radical prostatectomy versus volumetric modulated arc therapy for localized prostate cancer: A propensity score-matched analysis.

BACKGROUND: Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes. METHODS: We compared 6­year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, a rotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy. RESULTS: The median follow-up duration was 79 months (> 6 years). PSM generated a matched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6­year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6 and 68.8% of the patients achieved ≤ 1 pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and a very low rate (4.4%) of grade ≥ 2 gastrointestinal complications. CONCLUSION: On the basis of PSM after a 6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles.

Latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the era of immune checkpoint inhibitors: a narrative review.

The management of advanced (locally advanced or metastatic) urothelial carcinoma has been revolutionized since pembrolizumab was introduced in 2017. Several prognostic factors for advanced urothelial carcinoma treated with pembrolizumab have been reported, including conventional parameters such as performance status and visceral (especially liver) metastasis, laboratory markers such as the neutrophil-to-lymphocyte ratio, sarcopenia, histological/genomic markers such as programmed cell death ligand 1 immunohistochemistry and tumor mutational burden, variant histology, immune-related adverse events, concomitant medications in relation to the gut microbiome, primary tumor site (bladder cancer versus upper tract urothelial carcinoma) and history/combination of radiotherapy. The survival time of advanced urothelial carcinoma has been significantly prolonged (or 'doubled' from 1 to 2 years) after the advent of pembrolizumab, which will be further improved with novel agents such as avelumab and enfortumab vedotin. This review summarizes the latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the contemporary era of immune checkpoint inhibitors.

Changes in the trends of initial treatment for newly diagnosed prostate cancer in Japan: a nationwide multi-institutional study.

BACKGROUND: In previous large-scale studies conducted through 2010, androgen deprivation therapy (ADT) was the most common initial treatment for prostate cancer patients in Japan. However, recent advancements in treatment technologies have significantly affected the management of prostate cancer in Japan. This study analyzed the trends in initial treatments for prostate cancer based on two nationwide surveys. METHODS: Two Japan-wide multi-institutional surveys, J-CaP2010 and J-CaP2016, were conducted to enroll patients newly histologically diagnosed with prostate cancer in 2010 and 2016-18, respectively. Both surveys included age at diagnosis, initial PSA level, ISUP Grade Group, TNM classification, and initial treatment for prostate cancer. RESULTS: J-CaP2010 included data from 8192 patients across 140 institutions, whereas J-CaP2016 included data from 21 841 patients across 186 institutions. In J-CaP2016, the proportion of radical prostatectomy (RP) and radiation therapy (RT) in the initial treatment increased (from 32% to 36% and 21% to 26%, respectively), whereas the proportion of ADT decreased (from 40% to 29%) compared with those in J-CaP2010. The increase in RP or RT was noticeable in patients aged 75 years and older (from 20% to 38%) and those with high-risk localized cancer (from 58% to 74%) or locally advanced cancer (from 38% to 56%). The proportion of active surveillance or watchful waiting increased in patients with low-risk localized cancer (from 21% to 41%). The proportion of robot-assisted RP within all RPs and the proportion of intensity-modulated RT within all RTs increased remarkably (from 2.3% to 78% and 20% to 50%, respectively). CONCLUSIONS: In Japan, RP and RT have increased as initial treatments for prostate cancer, whereas ADT has decreased. Consequently, RP has emerged as the most commonly selected initial treatment, replacing ADT.

Efficacy and safety of intravesical dimethyl sulfoxide treatment for patients with refractory Hunner-type interstitial cystitis: Real-world data postofficial approval in Japan.

OBJECTIVES: To examine real-world data regarding intravesical dimethyl sulfoxide (DMSO) therapy after official approval as a treatment for Hunner-type interstitial cystitis (HIC) in Japan. METHODS: This single institution, retrospective observational study was conducted between 2021 and 2022 to evaluate the outcomes of 30 patients with refractory HIC who received intravesical DMSO therapy according to the approved standardized regimen: administration of DMSO every 2 weeks for a total of 12 weeks. Treatment outcomes were evaluated using a 7-graded global response assessment scale, O'Leary and Sant's symptom and problem indices (OSSI/OSPI), the overactive bladder symptom score (OABSS), an 11-point pain intensity numerical rating scale, quality of life (QOL) score, and frequency volume chart variables. Related complications were also documented. RESULTS: The response rates at 2, 4, 6, 8, 10, and 12 weeks were 36.7%, 43.3%, 53.3%, 60.0%, 70.0%, and 70.0%, respectively. Compared with baseline, OSSI/OSPI, pain intensity, urinary frequency, and the QOL score improved significantly from 4 weeks of treatment. The OABSS score and functional bladder capacity also showed a tendency toward moderate improvement, but the difference was not significant. The mean duration of symptom relapse after termination of treatment was 6.4 ± 3.9 months. No patients discontinued treatment due to adverse events, although acute bladder irritation during infusion was noted in 21 patients (70%), which disappeared within 3 days. CONCLUSIONS: This study verifies the safety, moderately durable efficacy, and tolerability of the standard intravesical treatment with DMSO for HIC in Japan.

Subclassification of pT3 upper tract urothelial carcinoma: a multicenter retrospective study.

PURPOSE: The prognosis of patients with pT3 upper tract urothelial carcinoma (UTUC) varies. The current study aimed to further classify patients with pT3 UTUC into different survival outcome groups based on tumor location and site of invasion. METHODS: This retrospective study included 323 patients with pT3 UTUC who underwent nephroureterectomy at 11 hospitals in Japan. Histological and clinical data were obtained via a chart review. Univariate and multivariate Cox proportional hazards analyses showed the effect of different variables on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median age of the patients was 72 years. Patients with pT3 UTUCs were divided into two groups: those with renal parenchymal invasion only (pT3a, n = 95) and those with peripelvic or periureteral fat invasion (pT3b, n = 228). pT3b UTUC was significantly associated with hydronephrosis, low preoperative estimated glomerular filtration rate (eGFR), histological nodal metastasis, nuclear grade 3, lymphovascular invasion (LVI), carcinoma in situ, and positive surgical margin. Based on the univariate analyses, patients with pT3b UTUC had a significantly lower 5-year RFS (42.4% vs. 70.1%, p < 0.0001), 5-year CSS (54.3% vs. 80.0%, p = 0.0002), and 5-year OS (47.8% vs. 76.8%, p < 0.0001) than those with pT3a UTUC. According to the multivariate analyses, nodal metastasis, LVI, adjuvant chemotherapy, preoperative eGFR, nuclear grade (RFS only), surgical margin (RFS only), and Charlson comorbidity index (OS only), but not pT3b stage, were associated with survival. CONCLUSION: Compared with pT3a UTUC, pT3b UTUC was significantly associated with worse histological features, consequently resulting in unsatisfactory survival outcomes.

A multicenter, retrospective observational study investigating baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer treated with primary androgen deprivation therapy.

OBJECTIVE: This multicenter, retrospective, observational study investigated baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer who received primary androgen deprivation therapy, using Japan Study Group of Prostate Cancer registry data. METHODS: Among patients in the Japan Study Group of Prostate Cancer registry, those who initiated primary androgen deprivation therapy and were aged 20 years or older were enrolled in this study. The primary endpoint was time to disease progression, defined as time from primary androgen deprivation therapy initiation to either prostate-specific antigen or clinical progression. Secondary endpoints included prostate-specific antigen progression-free survival, prostate-specific antigen response (90% or greater reduction from baseline) and distribution of second-line treatment. RESULTS: Of the 2494 patients (goserelin, n = 564; leuprorelin, n = 1148; surgical castration, n = 161; degarelix, n = 621), those who received degarelix had higher prostate-specific antigen levels and Gleason scores and were at a more advanced clinical stage than those receiving goserelin or leuprorelin. The median time to disease progression (identical to the prostate-specific antigen progression-free survival result) was not reached for goserelin and leuprorelin, 52.7 months for surgical castration and 54.0 months for degarelix. Although baseline prostate-specific antigen values in the degarelix cohort were higher than those of the leuprorelin or goserelin cohorts, prostate-specific antigen responses were not different among the three cohorts. Regarding second-line treatment, the largest patient group received degarelix followed by leuprorelin (n = 195). CONCLUSIONS: This study clarified patient characteristics and long-term effectiveness of primary androgen deprivation therapy in real-world clinical practice. Japanese urologists appear to select appropriate primary androgen deprivation therapy based on patient background and tumour characteristics, with degarelix largely reserved for higher risk patients.

Does metabolic syndrome influence the efficacy of mirabegron treatment in female patients with overactive bladder?

INTRODUCTION AND HYPOTHESIS: We aimed to determine whether the presence of metabolic syndrome (MS) affects the efficacy of mirabegron in treatment-naïve women with overactive bladder (OAB). METHODS: Women being treated with mirabegron 50 mg were allocated to MS and non-MS groups, and the efficacy of treatment of OAB was compared using the OAB symptom score (OABSS) and a 3-day voiding diary before and 12 weeks after starting treatment. The Wilcoxon signed-rank and Mann-Whitney U tests and multivariate logistic regression were used for statistical analyses, and a p-value < 0.05 was considered to represent statistical significance. RESULTS: Of the 197 patients who completed the trial, 43 (23.9%) had MS. After 12 weeks of mirabegron treatment, both the MS and non-MS groups showed significant improvements in OABSS score, the number of incontinence episodes/24 h, the number of micturition episodes/24 h, and the number of episodes of urgency/24 h. The factors associated with clinically important differences in OABSS were the presence of hyperglycemia (odds ratio 2.43, 95% confidence interval [CI] 1.05-5.60) and OABSS score at baseline (odds ratio 1.23, 95% CI 1.09-1.39). CONCLUSIONS: Mirabegron is effective in patients with and without MS, and comorbid hyperglycemia and severe OAB symptoms before treatment are predictors of the efficacy of mirabegron treatment.

Surgical resection of retinoblastoma-associated bladder leiomyosarcoma during pregnancy: a case report.

BACKGROUND: Management of a bladder tumor during pregnancy is an uncommon clinical situation. Leiomyosarcoma of the urinary bladder is a rare histological type of bladder tumor and a rare secondary cancer in survivors of retinoblastoma (RB). However, there has been no report of RB-associated bladder leiomyosarcoma during pregnancy. CASE PRESENTATION: A 37-year-old pregnant woman with a medical history of RB in infancy presented with gross hematuria at the 17th week of gestation. Cystoscopy revealed a 40-mm papillary tumor on the left lateral wall of the urinary bladder. At the 25th week of gestation, she underwent transurethral resection of the bladder tumor, and the pathological diagnosis was bladder leiomyosarcoma with loss of RB1 expression. At the 31st week of gestation, she gave birth by caesarean section. One month after the delivery (to allow for involution of the uterus), she underwent partial cystectomy, and the specimen contained no residual leiomyosarcoma tissue. CONCLUSIONS: We have reported a case of RB-associated bladder leiomyosarcoma that was successfully treated during and after pregnancy.

Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study.

OBJECTIVE: Enfortumab vedotin (EV) was approved for advanced urothelial carcinoma (UC) in 2021 after the EV-301 trial showed its superiority to non-platinum-based chemotherapy as later-line treatment after platinum-based chemotherapy and immune checkpoint inhibitors including pembrolizumab. However, no study has compared EV with rechallenging platinum-based chemotherapy (i.e., "platinum rechallenge") in that setting. METHODS: In total, 283 patients received pembrolizumab for advanced UC after platinum-based chemotherapy between 2018 and 2023. Of them, 41 and 25 patients received EV and platinum rechallenge, respectively, as later-line treatment after pembrolizumab. After excluding two patients with EV without imaging evaluation, we compared oncological outcomes, including progression-free survival (PFS) and overall survival (OS), between the EV (n = 39) and platinum rechallenge groups (n = 25) using propensity score matching (PSM). RESULTS: Analyses on crude data (n = 64) showed no significant differences between the two groups regarding patients' baseline characteristics. PFS (5 months) and OS (11 months) in the EV group were comparable to those (8 and 12 months, respectively) in the platinum rechallenge group. After PSM (n = 36), the baseline characteristics between the two groups became more balanced, and PFS (not reached) and OS (not reached) in the EV group were comparable to those (8 and 11 months, respectively) in the platinum rechallenge group. CONCLUSIONS: EV and platinum rechallenge showed equivalent oncological outcomes, even after PSM, and both treatments should therefore be effective treatment options for post-platinum, post-pembrolizumab advanced UC.

Clinical validity of non-contrast-enhanced VI-RADS: prospective study using 3-T MRI with high-gradient magnetic field.

OBJECTIVES: To develop a modified Vesical Imaging Reporting and Data System (VI-RADS) without dynamic contrast-enhanced imaging (DCEI), termed "non-contrast-enhanced VI-RADS (NCE-VI-RADS)", and to assess the additive impact of denoising deep learning reconstruction (dDLR) on NCE-VI-RADS. METHODS: From January 2019 through December 2020, 163 participants who underwent high-gradient 3-T MRI of the bladder were prospectively enrolled. In total, 108 participants with pathologically confirmed bladder cancer by transurethral resection were analyzed. Tumors were evaluated based on VI-RADS (scores 1-5) by two readers independently: an experienced radiologist (reader 1) and a senior radiology resident (reader 2). Conventional VI-RADS assessment included all three imaging types (T2-weighted imaging [T2WI], diffusion-weighted imaging [DWI], and dynamic contrast-enhanced imaging [DCEI]). Also evaluated were NCE-VI-RADS comprising only non-contrast-enhanced imaging types (T2WI and DWI), and "NCE-VI-RADS with dDLR" comprising T2WI processed with dDLR and DWI. All systems were assessed using receiver-operating characteristic curve analysis and simple and/or weighted κ statistics. RESULTS: Muscle invasion was identified in 23/108 participants (21%). Area under the curve (AUC) values for diagnosing muscle invasion were as follows: conventional VI-RADS, 0.94 and 0.91; NCE-VI-RADS, 0.93 and 0.91; and "NCE-VI-RADS with dDLR", 0.96 and 0.93, for readers 1 and 2, respectively. Simple κ statistics indicated substantial agreement for NCE-VI-RADS and almost perfect agreement for conventional VI-RADS and "NCE-VI-RADS with dDLR" between the two readers. CONCLUSION: NCE-VI-RADS achieved predictive accuracy for muscle invasion comparable to that of conventional VI-RADS. Additional use of dDLR improved the diagnostic accuracy of NCE-VI-RADS. KEY POINTS: • Non-contrast-enhanced Vesical Imaging Reporting and Data System (NCE-VI-RADS) was developed to avoid risk related to gadolinium-based contrast agent administration. • NCE-VI-RADS had predictive accuracy for muscle invasion comparable to that of conventional VI-RADS. • The additional use of denoising deep learning reconstruction (dDLR) might further improve the diagnostic accuracy of NCE-VI-RADS.

Clinicopathological features and oncological outcomes of urothelial carcinoma involving the ureterovesical junction.

BACKGROUND: The ureterovesical junction is the boundary between the urinary bladder and upper urinary tract. Because treatment strategies for bladder cancer and upper tract urothelial carcinoma are entirely different, urothelial carcinoma involving the ureterovesical junction requires special attention. Nevertheless, studies focusing on the disease are lacking. METHODS: We reviewed consecutive patients with urothelial carcinoma treated via either transurethral resection of bladder tumor (n = 2791) or radical nephroureterectomy (n = 292) between 2000 and 2020 and identified those with bladder cancer involving the ureteral orifice (n = 64) and those with upper tract urothelial carcinoma involving the intramural ureter (≤2 cm) (n = 41). After excluding overlapping cases (n = 24), 80 patients with urothelial carcinoma involving the ureterovesical junction were analyzed. RESULTS: The initial symptoms or reasons for diagnosing urothelial carcinoma involving the ureterovesical junction were hematuria (n = 30), hydronephrosis (n = 21), follow-up examinations for prior urothelial carcinoma (n = 13), screening examinations (n = 7), frequent urination (n = 6) and unknown causes (n = 3). During a median follow-up period of 42 months, 18 patients died of urothelial carcinoma. The definitive surgical treatments for urothelial carcinoma involving the ureterovesical junction were transurethral resection of bladder tumor alone (n = 26), radical nephroureterectomy (n = 41) and radical cystectomy (n = 13), with different treatments having different cancer-specific survivals. Multivariate analyses identified T stage (≥T2) as an independent predictor of shorter cancer-specific survival. CONCLUSIONS: Given the positional property of urothelial carcinoma involving the ureterovesical junction, the profiles of patients with the disease were highly heterogeneous. Further optimization of treatment strategies for urothelial carcinoma involving the ureterovesical junction is urgently warranted for better clinical outcomes.

Association between Plasma Xanthine Oxidoreductase Activity and the Renal Function in a General Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

INTRODUCTION: Xanthine oxidoreductase (XOR) has been identified as a critical source of reactive oxygen species in various pathophysiological conditions, including hypertension, endothelial dysfunction, and atherosclerosis. This study investigated the association between XOR and renal function in a general Japanese population. METHODS: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a community-based cohort study in Iwate prefecture. Chronic kidney disease (CKD) was estimated using the estimated glomerular filtration rate of cystatin C (eGFRcys). Individuals with a history of hyperuricemia or severe renal dysfunction (eGFRcys <15 mL/min/1.73 m2 or undergoing dialysis) were excluded from the study. We performed a multinominal multivariate logistic analysis adjusted for age, blood pressure, uric acid, glycated hemoglobin A1c, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to associate XOR activity and renal function. RESULTS: The present study included 4,248 participants (male/female: 1,373/2,875, age: 62.9 ± 11.7 years). When participants were divided according to XOR quartiles, blood pressure, body mass index, uric acid, low-density lipoprotein cholesterol, and glycated hemoglobin A1c were highest in the highest XOR quartile (all p < 0.001). The XOR activity was significantly higher in the subgroup with CKD stage G3 and G4 (G1 vs. G2 vs. G3-G4: 44.8 ± 40.5 vs. 52.0 ± 42.9 vs. 54.1 ± 43.9 pmol/h/mL, p = 0.02). The higher XOR activity was significantly associated with an increase of CKD stage: the odd ratios (95% confidence intervals) per 1 pmol/h/mL increase in XOR activity with CKD stage G1 as a reference were 1.37 (1.13-1.73) in G2 and 1.51 (1.30-1.84) in G3-G4. CONCLUSION: The present study concluded that high XOR activity was associated with the severity of CKD in a general Japanese population, suggesting that upregulated XOR activity may be involved in advanced renal dysfunction.

Comparison of full-dose gemcitabine/cisplatin, dose-reduced gemcitabine/cisplatin, and gemcitabine/carboplatin in real-world patients with advanced urothelial carcinoma.

BACKGROUND: While gemcitabine/cisplatin (GC) is the gold standard regimen for patients with advanced urothelial carcinoma (aUC), either dose-reduced GC or gemcitabine/carboplatin (GCa) is an alternative option for "cisplatin-unfit" patients. However, few studies have compared outcomes with these commonly used regimens in the real-world setting. METHODS: We retrospectively reviewed patients with aUC who received full-dose GC, dose-reduced GC, or GCa as first-line salvage chemotherapy at two university hospitals between 2016 and 2020. Progression-free survival, cancer-specific survival, and overall survival, as well as best overall response and adverse event profiles, were compared among these three regimens. RESULTS: Of 105 patients, 41, 27, and 37 patients received full-dose GC, dose-reduced GC, and GCa, respectively. Significant differences were noted in the patients' baseline age, primary site, and renal function among the three regimens. Sixty-nine (65.7%) patients died during a median follow-up period of 14 months. There was no significant difference among the three regimens for all survival outcomes and best overall response. However, the complete response rate of dose-reduced GC (2/27, 7.4%) appeared inferior to that of full-dose GC (9/41, 22.0%) or GCa (6/37, 16.2%). Regarding adverse event profiles, no significant difference was observed among the three regimens, except for significantly fewer cases with elevated alanine aminotransferase in the GCa group compared with the other groups. CONCLUSIONS: This study compared the oncological and toxicological outcomes of full-dose GC, dose-reduced GC, and GCa in real-world patients with aUC. Unlike in the clinical trial setting, there were almost no significant differences among the three regimens.

Improved survival in real-world patients with advanced urothelial carcinoma: A multicenter propensity score-matched cohort study comparing a period before the introduction of pembrolizumab (2003-2011) and a more recent period (2016-2020).

OBJECTIVES: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.

Prospective Validation of Vesical Imaging-Reporting and Data System Using a Next-Generation Magnetic Resonance Imaging Scanner-Is Denoising Deep Learning Reconstruction Useful?

PURPOSE: The Vesical Imaging Reporting and Data System (VI-RADS) was launched in 2018 to standardize reporting of magnetic resonance imaging for bladder cancer. This study aimed to prospectively validate VI-RADS using a next-generation magnetic resonance imaging scanner and to investigate the usefulness of denoising deep learning reconstruction. MATERIALS AND METHODS: We prospectively enrolled 98 patients who underwent bladder multiparametric magnetic resonance imaging using a next-generation magnetic resonance imaging scanner before transurethral resection of bladder tumor. Tumors were categorized according to VI-RADS, and we ultimately analyzed 68 patients with pathologically confirmed urothelial bladder cancer. We used receiving operating characteristic curve analyses to assess the predictive accuracy of VI-RADS for muscle invasion. Sensitivity, specificity, positive/negative predictive value, accuracy and area under the curve were calculated for different VI-RADS score cutoffs. RESULTS: Muscle invasion was detected in the transurethral resection of bladder tumor specimens of 18 patients (26%). The optimal cutoff value of the VI-RADS score was determined as ≥4 based on the receiver operating curve analyses. The accuracy of diagnosing muscle invasion using a cutoff of VI-RADS ≥4 was 94% (AUC 0.92). Additionally, we assessed the utility of denoising deep learning reconstruction. Combination with denoising deep learning reconstruction significantly improved the AUC of category by T2-weighted imaging, and of the 4 patients who were misdiagnosed by the final VI-RADS score 3 were correctly diagnosed by T2-weighted imaging+denoising deep learning reconstruction. CONCLUSIONS: In this prospective validation study with a next-generation magnetic resonance imaging scanner, VI-RADS showed high predictive accuracy for muscle invasion in patients with bladder cancer before transurethral resection of bladder tumor. Combining T2-weighted imaging with denoising deep learning reconstruction might further improve the diagnostic accuracy of VI-RADS.

Comparison of major definitions of sarcopenia based on the skeletal muscle index in patients with urothelial carcinoma.

For the past decade, sarcopenia has been actively investigated in various cancers, including urothelial carcinoma (UC). Although skeletal muscle index (SMI) is the main parameter used to evaluate sarcopenia in oncology, the optimal definition of SMI-based sarcopenia is not entirely standardized. We recently highlighted the potential limitations of current definitions of SMI-based sarcopenia in another journal. In this study, we reviewed studies that assessed sarcopenia in UC patients. We then performed a comparative validation of three major SMI-based definitions of sarcopenia, including Prado's, the international and Martin's definitions in metastatic UC patients. We believe that the standardization of the sarcopenia definition is an urgent issue in oncology, and this paper discusses a possible new direction to address this issue.

Smaller decline of renal function after nephroureterectomy predicts poorer prognosis of upper tract urothelial carcinoma: a multicentre retrospective study.

PURPOSE: Renal function is frequently impaired in the patients with upper tract urothelial carcinoma. We aimed to evaluate the impact of renal function and its change after surgery on survival rates in patients with upper tract urothelial carcinoma after nephroureterectomy. METHODS: The study cohort comprised 755 patients with upper tract urothelial carcinoma who underwent nephroureterectomy between 1995 and 2016 at nine hospitals in Japan. Estimated glomerular filtration rate was calculated using the three-variable Japanese equation for glomerular filtration rate estimation from serum creatinine level and age. Outcomes were recurrence-free, cancer-specific and overall survivals. Univariate and multivariate Cox proportional hazards regression analyses were used. RESULTS: Median patients' age was 72 years old. Pre- and post-surgical median estimated glomerular filtration rate were 55.5 and 42.9 ml/min/1.73 m2, respectively. Median estimated glomerular filtration rate decline after surgery, which represents function of the affected side kidney, was 13.1 ml/min/1.73 m2. The 5-year recurrence-free, cancer-specific and overall survivals were 68.3, 79.4 and 74.0%, respectively. Multivariate analysis indicated that lower preoperative estimated glomerular filtration rate and estimated glomerular filtration rate decline were associated with poorer recurrence-free, cancer-specific and overall survivals, but post-operative estimated glomerular filtration rate was not. Estimated glomerular filtration rate decline was more significant poor-prognosticator than preoperative estimated glomerular filtration rate. Proportions of the patients with estimated glomerular filtration rate <60 ml/min/1.73 m2 before surgery were 50.6 and 73.2% in organ-confined disease and locally advanced disease, respectively (P < 0.0001). After surgery, they were 91.6 and 89.8%, respectively (P = 0.3896). CONCLUSIONS: Lower preoperative renal function, especially of the affected side kidney, was significantly associated with poor prognosis after nephroureterectomy for upper tract urothelial carcinoma. Many patients with locally advanced disease have reduced renal function at diagnosis and even more after surgery.

Impact of Initial Computed Tomography Findings on Management of Atypical Urinary Cytology of the Upper Urinary Tract.

INTRODUCTION: Management of patients with atypical urinary cytology (class III) of the upper urinary tract is often complicated because some patients develop upper urinary tract urothelial carcinoma (UTUC). Here, we aimed to help define the optimal management of these patients. METHODS: We investigated 31 patients who underwent retrograde ureteropyelography (RP) and were diagnosed with atypical findings of upper urinary tract cytology. RESULTS: UTUC was revealed in 17 of 31 patients during the follow-up period of 1 year or longer. Tumor-like lesions and wall thickening in the upper urinary tract on initial computed tomography (CT) were significant predictors of UTUC (p = 0.0002 and p = 0.012, respectively). All 11 patients with tumor-like lesions and 3 of 8 patients with wall thickening on initial CT underwent nephroureterectomy, and UTUC was confirmed histologically. Moreover, 3 of 12 patients with hydronephrosis only or with normal findings later went on to develop UTUC. Repeated RP performed within 6 months from the initial RP was able to distinguish patients with UTUC from those without, even in individuals with normal CT findings. DISCUSSION/CONCLUSION: Repeated RP based on initial CT findings is recommended in patients with atypical urinary cytology of the upper urinary tract. Nephroureterectomy without repeated RP may be warranted in patients with tumor-like lesions on initial CT findings.

Prognostic significance of tertiary Gleason pattern in the contemporary era of Gleason grade grouping: A narrative review.

Since the Gleason score was developed in 1966 as a histological classification for prostate cancer, it has been widely used in clinical practice and has evolved over time. The concept of a "tertiary Gleason pattern" (also known as a minor Gleason pattern) was first proposed in 2000, and has been used in clinical practice since the 2005 International Society of Urological Pathology conference. The prognostic significance of a tertiary Gleason pattern has been widely validated in various settings of prostate cancer, whereas its definition has yet to be fully established. Currently, a provisional definition of tertiary Gleason pattern is "<5% Gleason pattern 4 or 5 in radical prostatectomy specimens." In contrast, "Gleason grade grouping" was proposed in 2013 and came into use in clinical practice in 2016 according to the 2014 International Society of Urological Pathology conference. Although the prognostic significance of Gleason grade grouping has already been widely confirmed, it does not incorporate the concept of tertiary Gleason pattern. Recently, the 2019 International Society of Urological Pathology conference discussed how to handle tertiary Gleason pattern in the current Gleason scoring system, but no consensus was reached on the issue. This review summarizes the evidence on the prognostic significance of tertiary Gleason pattern and discusses how to deal with it in the context of the contemporary Gleason grade grouping. It also refers to reporting of the percentage of Gleason patterns 4 and 5, as well as quantitative Gleason score models incorporating tertiary Gleason pattern.

PKD1-Associated Arachnoid Cysts in Autosomal Dominant Polycystic Kidney Disease.

OBJECTIVES: the prevalence of intracranial aneurysms and arachnoid cysts is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. A genotype correlation was reported for intracranial aneurysms, but it is unclear for arachnoid cysts. Therefore, the genotype correlation with intracranial aneurysms and arachnoid cysts was investigated in ADPKD. MATERIALS AND METHODS: intracranial aneurysms and arachnoid cysts were screened by magnetic resonance imaging (MRI), and PKD genotypes were examined using next-generation sequencing for 169 patients with ADPKD. RESULTS: PKD1-, PKD2- and no-mutation were identified in 137, 24 and 8 patients, respectively. Intracranial aneurysms and arachnoid cysts were found in 34 and 25 patients, respectively, with no significant difference in frequency. Genotype, sex, estimated glomerular filtration rate and age at ADPKD diagnosis significantly affected the age at brain MRI. The proportional hazard risk analyzed using the age at brain MRI adjusted by these four variables was 5.0-times higher in the PKD1 group than in the PKD2 group for arachnoid cysts (P = 0.0357), but it was not different for intracranial aneurysms (P = 0.1605). Arachnoid cysts were diagnosed earlier in the PKD1 group than in the PKD2 group (54.8 vs 67.7 years, P = 0.0231), but no difference was found for intracranial aneurysms (P = 0.4738) by Kaplan-Meier analysis. CONCLUSIONS: this study demonstrated the correlation between arachnoid cysts and PKD1 mutation. The reported association of arachnoid cysts with advanced renal disease may be due to the common correlation of these factors with PKD1 mutation.