Trends and safety of robot-assisted partial nephrectomy during the initial 2-year period after government approval in Japan: A nationwide database study from 2016 to 2018.

OBJECTIVES: To evaluate the trends and safety of robot-assisted partial nephrectomy during the initial 2-year period after government approval for this type of procedure in April 2016. METHODS: This nationwide retrospective study included 3722 received robot-assisted partial nephrectomy cases carried out from April 2016 to March 2018 in 124 participating institutions. The institutions were divided into lower- and higher-volume institutions according to the median of 19 robot-assisted partial nephrectomy cases during the study period. Surgical outcomes between 616 cases from lower-volume institutions and 3106 cases from higher-volume institutions were compared using propensity score matching. RESULTS: During the study period, both the number of robot-assisted partial nephrectomy surgeries and the number of institutions in which the surgery was carried out steadily increased. Overall, the median anesthesia time was 217 min, the median postoperative length of stay was 9 days, and the proportion of blood transfusions, complications and readmissions were 0.8%, 5.1% and 1.0%, respectively. There were no significant differences in anesthesia time, incidence of blood transfusions, and complication rates between the lower-volume and higher-volume institutions. However, a slightly, but significantly, longer postoperative length of stay and a lower incidence of readmission were observed in lower-volume institutions both before and after propensity score matching. CONCLUSIONS: Robot-assisted partial nephrectomy has become widespread during the initial 2-year period after government approval with an acceptable safety profile, regardless of the institutional caseloads. This technique has become a standard of care for stage 1 renal cancer patients in Japan.

Computer-aided diagnosis with a convolutional neural network algorithm for automated detection of urinary tract stones on plain X-ray.

BACKGROUND: Recent increased use of medical images induces further burden of their interpretation for physicians. A plain X-ray is a low-cost examination that has low-dose radiation exposure and high availability, although diagnosing urolithiasis using this method is not always easy. Since the advent of a convolutional neural network via deep learning in the 2000s, computer-aided diagnosis (CAD) has had a great impact on automatic image analysis in the urological field. The objective of our study was to develop a CAD system with deep learning architecture to detect urinary tract stones on a plain X-ray and to evaluate the model's accuracy. METHODS: We collected plain X-ray images of 1017 patients with a radio-opaque upper urinary tract stone. X-ray images (n = 827 and 190) were used as the training and test data, respectively. We used a 17-layer Residual Network as a convolutional neural network architecture for patch-wise training. The training data were repeatedly used until the best model accuracy was achieved within 300 runs. The F score, which is a harmonic mean of the sensitivity and positive predictive value (PPV) and represents the balance of the accuracy, was measured to evaluate the model's accuracy. RESULTS: Using deep learning, we developed a CAD model that needed 110 ms to provide an answer for each X-ray image. The best F score was 0.752, and the sensitivity and PPV were 0.872 and 0.662, respectively. When limited to a proximal ureter stone, the sensitivity and PPV were 0.925 and 0.876, respectively, and they were the lowest at mid-ureter. CONCLUSION: CAD of a plain X-ray may be a promising method to detect radio-opaque urinary tract stones with satisfactory sensitivity although the PPV could still be improved. The CAD model detects urinary tract stones quickly and automatically and has the potential to become a helpful screening modality especially for primary care physicians for diagnosing urolithiasis. Further study using a higher volume of data would improve the diagnostic performance of CAD models to detect urinary tract stones on a plain X-ray.

Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab.

BACKGROUND: The dynamic change in C-reactive protein (CRP) levels, CRP kinetics, is a prognostic factor for metastatic renal cell carcinoma (mRCC) in the tyrosine kinase inhibitor era. We investigated the impact of early CRP kinetics on the efficacy of nivolumab in patients with mRCC. METHODS: We performed a retrospective analysis of 42 mRCC patients who were treated with nivolumab as a second-line or later therapy between 2016 and 2019. All patients had received previous TKI therapy. Patients were divided into three groups based on their early CRP kinetics: CRP levels increased to more than double compared with baseline within 1 month after initiation of nivolumab (flare) and then decreased to a lower value than baseline within 3 months (CRP flare-responders); CRP levels decreased by ≥30% within 3 months without "flare" (CRP responders); and the remaining patients (non-CRP responders). The maximum tumor shrinkage, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. The association of the early CRP kinetics and oncological outcomes was assessed. RESULTS: The median follow-up period was 8 months. The median baseline CRP level was 23 mg/L. CRP flare-responders, CRP responders, and non-CRP responders included 11 (26%), 15 (36%), and 16 (38%) patients, respectively. Thirteen patients (31%) died of mRCC. The maximum changes in target lesions from baseline of CRP flare-responder, CRP-responder, and non-CRP responder groups were -38%, -13%, and 16%, on average, respectively (p<0.001). ORRs of these three groups were 73%, 27%, and 6%, respectively (p<0.001). The median PFS values of each group were not reached, 12 months, and 2.4 months (p=0.005), and the median OS values were not reached, not reached, and 12 months (p=0.048). In a multivariate analysis, early CRP kinetics was a significant independent factor for objective response, PFS, and OS (p<0.001, p=0.004, and p=0.006, respectively). CONCLUSIONS: CRP flare-response was associated with significant tumor shrinkage and improved survival outcomes in patients with mRCC who were treated with nivolumab. Early CRP kinetics could be useful for evaluating nivolumab treatment efficacy.

Association Between the Occurrence and Spectrum of Immune-Related Adverse Events and Efficacy of Pembrolizumab in Asian Patients With Advanced Urothelial Cancer: Multicenter Retrospective Analyses and Systematic Literature Review.

An association between the development of overall or specific immune-related adverse events (irAEs) and outcomes of immune checkpoint inhibitors has recently been suggested. To address this emerging association in patients with urothelial cancer receiving pembrolizumab, we conducted a multicenter retrospective analysis, which is the first and largest in an Asian cohort as well as a systematic literature review. We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab as second- or later-line treatment between January 2018 and March 2019. irAEs were categorized by the involved organs and graded using Common Terminology Criteria for Adverse Events version 5.0. Associations between irAEs and pembrolizumab efficacy, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. In our review of the literature, 28 studies, including 9 studies involving patients with urothelial cancer and 19 studies reporting the association between outcomes and spectrum of irAEs, were analyzed. Patients with irAEs had significantly higher ORR (52% vs. 16%, P < .01), longer PFS (11.0 months vs. 3.6 months, P < .01) and OS (median not reached vs. 13.1 months, P = .12) than in patients without irAEs. Endocrine (P = .02), pneumological (P = .06), and other (gastrointestinal, hematological, hepatic) (P = .04) irAEs were associated with increased ORR, whereas skin irAEs were not. Endocrine irAEs (P = .04) was associated with improved OS, whereas pneumological and skin irAEs were not. The association between the occurrence of irAEs and clinical efficacy of immune checkpoint inhibitors was consistently supported by the multiple studies we reviewed. The association between clinical outcomes and the spectrum of organs/systems affected by irAEs seems to be inconsistent and could be dependent on tumor type. irAEs were associated with a higher ORR and better survival of patients with advanced urothelial cancer treated with pembrolizumab.

Significance of Bladder Neck Involvement in Risk Substratification of Intermediate-Risk Non-muscle-invasive Bladder Cancer.

BACKGROUND: Intermediate-risk non-muscle-invasive bladder cancer (NMIBC) involves heterogeneous patients, resulting in uncertainty regarding its prognosis and the indication of adjuvant therapy. Previous studies suggested a correlation between tumor location, especially bladder neck involvement (BNI), and patient prognosis of NMIBC. OBJECTIVE: We investigated the role of BNI in risk substratification of intermediate-risk NMIBC patients. DESIGN, SETTING, AND PARTICIPANTS: This single-institutional study included 436 primary or recurrent intermediate-risk NMIBC patients based on risk stratification in the European Association of Urology guidelines. INTERVENTION: All patients underwent transurethral resection of the bladder tumor. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were progression and recurrence, respectively. The associations of BNI with the endpoints were examined using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS AND LIMITATIONS: Overall, 205 (47%) patients had multiple tumors and 276 (63%) underwent intravesical therapy. BNI was observed in 53 (12%) patients. During the median follow-up of 42 mo, 12 (3%) and 211 (48%) patients experienced progression and recurrence, respectively. Multivariate analysis showed that BNI was an independent predictor for both progression (hazard ratio 10.98, p < 0.001) and recurrence (hazard ratio 2.12, p < 0.001). The progression rate was significantly higher in patients with BNI compared with those without BNI (13% vs 1% at 3 yr and 20% vs 1% at 6 yr; p < 0.001). Analogous findings were observed for recurrence. The progression rate was more remarkably stratified by BNI in 103 recurrent cases (17% vs 3% at 3 yr and 34% vs 3% at 6 yr in patients with vs without BNI; p < 0.001). A limitation of this study was its retrospective nature. CONCLUSIONS: BNI substratified intermediate-risk NMIBC patients well regarding their risks of progression and recurrence, which could help determine follow-up and therapeutic strategies for these patients. PATIENT SUMMARY: The associations of bladder neck involvement with progression and recurrence were evaluated in patients with intermediate-risk non-muscle-invasive bladder cancer. We found that bladder neck involvement was a good factor for substratifying patients based on their risks of progression and recurrence. Bladder neck involvement can be useful in determining follow-up and therapeutic strategies for intermediate-risk non-muscle-invasive bladder cancer.

Value of extra-target prostate biopsy for the detection of magnetic resonance imaging-missed adverse pathology according to the Prostate Imaging Reporting and Data System scores: Spatial analysis using magnetic resonance-ultrasound fusion images.

OBJECTIVES: To clarify who benefits from extra-target sampling of systematic prostate biopsy to detect magnetic resonance imaging-missed significant cancer and upgrading, when concurrently carried out with magnetic resonance imaging-ultrasound fusion targeted biopsy. METHODS: Targeted biopsy and systematic biopsy were carried out in 301 men with Prostate Imaging Reporting and Data System scores ≥3. All score ≥3 regions were designated as targets. According to patients' highest Prostate Imaging Reporting and Data System scores, spatial relations between targets and biopsy-proven cancer were investigated to identify magnetic resonance imaging-missed pathology. RESULTS: Overall, targeted biopsy and systematic biopsy detected significant cancer in 56.5% and 46.5%, respectively (P < 0.001). Significant cancer was detected only by systematic biopsy in 7.0%, and only outside targets in 5.0%. Upgrading by systematic biopsy was observed in 16.3%, and occurred outside targets in 11.0%. On multivariate analysis, the highest Prostate Imaging Reporting and Data System 4 was predictive for significant cancer only outside targets (odds ratio 5.81, P = 0.002) and for upgrading derived from outside targets (odds ratio 2.64, P = 0.012). According to the scores of 3, 4 and 5, significant cancer was identified only outside targets in 1.0%, 11.2% and 2.9%, respectively (P = 0.003 for Prostate Imaging Reporting and Data System 3 vs 4; P = 0.019 for Prostate Imaging Reporting and Data System 4 vs 5), and upgrading occurred in 6.1%, 18.4% and 8.6%, respectively (P = 0.009 and 0.040). CONCLUSIONS: Men with the highest Prostate Imaging Reporting and Data System score 4 receive the largest benefit from extra-target biopsy for magnetic resonance imaging-missed significant cancer detection and upgrading. In men with a score of 3, less adverse pathology is missed without extra-target biopsy. These findings suggest prostate biopsy strategy could be tailored according to Prostate Imaging Reporting and Data System scores.

Renal epithelioid angiomyolipoma: Incidence in a Japanese cohort and diagnostic utility of diffusion-weighted magnetic resonance imaging.

OBJECTIVES: To show the epidemiological characteristics of epithelioid angiomyolipoma in a Japanese population, and to establish the preoperative diagnosis method of epithelioid angiomyolipoma. METHODS: Among the 855 tumors of patients who underwent partial/radical nephrectomy or renal biopsy for presumed renal cell carcinoma between 2007 and 2018, 39 renal tumors were diagnosed as nonclassical angiomyolipoma, including epithelioid angiomyolipoma and fat-poor angiomyolipoma. We retrospectively evaluated the incidence of epithelioid angiomyolipoma. Furthermore, we analyzed computed tomography and magnetic resonance imaging results, including diffusion-weighted magnetic resonance imaging findings of epithelioid angiomyolipoma and fat-poor angiomyolipoma. RESULTS: The incidence of epithelioid angiomyolipoma (n = 7) was 17.9% of surgically resected non-classical angiomyolipoma. The radiological appearance of epithelioid angiomyolipoma was hyperattenuating on unenhanced computed tomography images with iso or low intensity on T2-weighted magnetic resonance imaging. The mean apparent diffusion coefficient value of the solid component in epithelioid angiomyolipoma was significantly lower than that in fat-poor angiomyolipoma (median 0.79 × 10-3 vs 1.07 × 10-3 mm2 /s, P = 0.0019). CONCLUSIONS: The proportion of epithelioid angiomyolipoma in our Japanese cohort was equivalent to that of the reported series in the USA. The apparent diffusion coefficient value is potentially useful to differentiate between epithelioid angiomyolipoma and fat-poor angiomyolipoma. Further research is required to establish the imaging diagnostic criteria for epithelioid angiomyolipoma.

Longitudinal changes in patient-reported outcomes after artificial urinary sphincter implantation.

OBJECTIVE: To evaluate the time course of lower urinary tract symptoms (LUTS) after artificial urinary sphincter (AUS) implantation based on individual longitudinal changes of patient-reported outcomes. METHODS: This retrospective study included 66 male patients with severe urinary incontinence who were treated with primary AUS implantation between 2009 and 2019. International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and International Prostate Symptom Score (IPSS) questionnaires were used to evaluate continence status and LUTS preoperatively, 1, 3, and 12 months after activation, and then annually. The annual changes in scores were calculated with a linear mixed model. RESULTS: Of the 66 patients, 63 (95%) achieved complete or social continence (number of pads used ≤1/d) at 1 month after activation. Mean preoperative ICIQ-SF, IPSS, and IPSS-quality of life (QOL) score were 18.9, 14.9, and 5.4, respectively; the corresponding scores at 1 month after activation were 4.5, 9.0, and 1.7 (all P < .001), respectively. During the mean follow-up period of 36 months, the annual changes in the scores from 1 month after activation were 0.51 (P = .002), -0.30 (P = .184), and 0.19 (P < .001), respectively. As for individual IPSS items, while incomplete emptying, frequency, urgency, and weak stream improved significantly 1 month after activation, no significant changes from 1 month after activation were observed except for longitudinal deterioration of incomplete emptying score (0.08/y, P = .029). CONCLUSION: Continence status and QOL score markedly improved by AUS implantation immediately, but deteriorated over time. Improved LUTS were maintained without a worsening trend, however.

Postoperative renal impairment and longitudinal change in renal function after adrenalectomy in patients with Cushing's syndrome.

OBJECTIVES: To evaluate the renal function after adrenalectomy in patients with Cushing's syndrome in comparison with that in patients with primary aldosteronism. METHODS: This retrospective study included 35 patients with Cushing's syndrome and 51 patients with primary aldosteronism who underwent unilateral adrenalectomy and were followed up for >6 months. The renal function was analyzed before and after adrenalectomy using the estimated glomerular filtration rate. Postoperative renal impairment was defined as a >25% reduction in the estimated glomerular filtration rate from baseline at 1 month after adrenalectomy. Multivariate logistic regression analyses were carried out to examine whether the differences between Cushing's syndrome and primary aldosteronism increased the risk of postoperative renal impairment. Longitudinal changes were calculated starting 1 month after adrenalectomy using the linear mixed model. RESULTS: The mean estimated glomerular filtration rate in both groups significantly decreased at 1 month after adrenalectomy from baseline. Postoperative renal impairment was observed in four (11%) and 12 (24%) patients in the Cushing's syndrome and primary aldosteronism groups, respectively. Multivariate analysis showed that preoperative systolic blood pressure was independently associated with postoperative renal impairment, but not with the type of the disease. There was no significant increase or decrease in postoperative estimated glomerular filtration rate observed after the initial decrease after adrenalectomy in either group. CONCLUSIONS: Patients with Cushing's syndrome show the same persistent renal impairment after adrenalectomy as that reported in patients with primary aldosteronism. Attention should be given to possible masked renal damage in clinical practice for the management of Cushing's syndrome.

Incidence and Risk Factors of Hypertension Following Partial Nephrectomy in Patients With Renal Tumors: A Cross-sectional Study of Postoperative Home Blood Pressure and Antihypertensive Medications.

INTRODUCTION: We aimed to evaluate the incidence and risk factors for nephrectomy-related hypertension (NR-HT) in patients with renal tumors who underwent partial nephrectomy (PN) or radical nephrectomy (RN). PATIENTS AND METHODS: A retrospective cross-sectional follow-up survey of postoperative home blood pressure (BP) and defined daily dose (DDD) of antihypertensive medications was conducted in patients with renal tumors who underwent PN (210 patients) or RN (120 patients), and they were compared. We evaluated the incidence and risk factors for NR-HT, defined as the addition of antihypertensive medications in doses of 1 DDD or more after surgery, or postoperative BP of 140/90 mmHg with an increase of 20 mmHg from preoperative BP with no reduction in dose of antihypertensive medications. RESULTS: Both systolic (mean, 124 vs. 129 mmHg; P < .001) and diastolic BP (mean, 74 vs. 79 mmHg; P < .001) significantly increased after PN compared with RN. Systolic (P < .001) and diastolic (P = .003) BP increased significantly more after PN than after RN, and NR-HT was more frequent after PN than after RN (16% vs. 5%; P = .002). PN (odds ratio [OR], 2.93; P = .022) and higher postoperative peak C-reactive protein (OR, 2.34; P = .017) were independently associated with NR-HT. When limited to only the patients who underwent PN, acute kidney injury (OR, 2.65; P = .036) and higher postoperative peak C-reactive protein (OR, 2.54; P = .016) were independent risk factors for NR-HT. CONCLUSION: PN may cause postoperative progression of hypertension possibly through renal parenchymal damage.

Feasibility and outcomes of selective tetramodal bladder-preservation therapy in elderly patients with muscle-invasive bladder cancer.

OBJECTIVE: To assess the feasibility and functional/oncological outcomes of selective tetramodal bladder-preservation therapy in elderly patients with muscle-invasive bladder cancer. METHODS: This study analyzed 154 patients with non-metastatic muscle-invasive bladder cancer who were enrolled into the protocol. After maximal transurethral resection and induction chemoradiotherapy, patients with clinical complete response were offered consolidative partial cystectomy to achieve bladder preservation; otherwise, radical cystectomy was recommended. Postoperative complications, preserved bladder function, and oncological outcomes were compared between elderly (aged ≥75 years) and younger patients (aged <75 years). Frailty and sarcopenia were further assessed as potential factors that could affect the feasibility and outcomes of the protocol. RESULTS: A total of 44 patients (29%) were elderly, and 31 (20%) were frail (modified frailty index 2-3). Sarcopenia was observed in 68 (54%) of 126 eligible patients. Clinical complete response to induction chemoradiotherapy was achieved in 125 (81%) patients, and the bladder-preservation protocol was completed in 107 (69%) patients with consolidative partial cystectomy. Over a median follow-up period of 48 months, 5-year cancer-specific and muscle-invasive bladder cancer recurrence-free survival rates after protocol completion were 98% and 95%, respectively. There were no significant differences in complication rates related to partial cystectomy, preserved bladder function, and oncological outcomes between the elderly and younger groups. Neither frailty nor sarcopenia negatively affected these outcomes. CONCLUSIONS: Tetramodal bladder-sparing therapy incorporating consolidative partial cystectomy is feasible and yielded favorable functional/oncological outcomes in patients with muscle-invasive bladder cancer, regardless of advanced age, frailty or sarcopenia. This protocol could be a viable treatment option for such high-risk patient populations.

METastasis Reporting and Data System for Prostate Cancer as a Prognostic Imaging Marker in Castration-resistant Prostate Cancer.

BACKGROUND: METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P) has been proposed as a standard of data acquisition and interpretation for whole-body diffusion-weighted magnetic resonance imaging (WB-DWI) performed in men with advanced prostate cancer. The aim of this study is to demonstrate the clinical significance of the scores in castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: We retrospectively evaluated WB-DWI obtained from 72 patients with CRPC between 2014 and 2017, when disease progression was suspected at the time of starting a new line of anticancer therapy. Twenty-five (35%) and 30 (42%) patients had a treatment history that included taxane-based chemotherapy and new hormonal drugs, respectively. RESULTS: Active bone metastases were identified in 60 patients (83%; number of bone metastasis = 0, 1-2, 3-5, 6-10, and > 10: n = 12 [17%], 20 [28%], 11 [15%], 1 [1%], and 28 [39%], respectively). Progressive lymph node and visceral metastases were identified in 10 (14%) and 4 (6%), respectively. During the median follow-up period of 24 months, 36 (50%) died of prostate cancer. Cancer-specific survival (CSS) was significantly stratified according to the MET-RADS-P scores of osseous metastatic burden and the presence of visceral metastasis (P < .0001). Multivariate analysis revealed that high osseous metastatic burden (> 10) and the presence of visceral metastasis were significant indicators of shorter CSS (P = .0036 and P = .0017, respectively). CONCLUSIONS: The extent of bone metastasis and the presence of visceral metastasis on WB-DWI were associated with a shorter CSS in CRPC. MET-RADS-P score can be a prognostic imaging biomarker for CRPC.

Impact of Bladder Neck Involvement on Recurrence in Patients With Non-muscle-invasive Bladder Cancer: An Analysis Based on a Time-dependent Model.

BACKGROUND: Tumor location in bladder neck has reported to be a prognostic factor for non-muscle-invasive bladder cancer (NMIBC). We investigated the impact of bladder neck involvement (BNI) on recurrence in NMIBC using time-dependent covariate analysis. PATIENTS AND METHODS: We enrolled 585 Japanese patients who underwent transurethral resection for bladder tumors at a single center from 2000 to 2016 and were pathologically diagnosed with Ta and T1 NMIBC. Each patient at each recurrence was assigned to a separate time-dependent stratum with its own baseline hazard function according to the Prentice-Williams-Peterson gap time model for analyzing recurrent events. RESULTS: Over a median follow-up period of 41.3 months (interquartile range, 18.0-82.3 months), 253 (43.2%) patients experienced a total of 475 recurrences. Among the 1001 total transurethral resection procedures, BNI was observed in 122 (12.2%) cases. The 3-year cumulative recurrence rates of patients with and without BNI were 62.5% and 46.3%, respectively. Multivariable analysis revealed that number of tumors ≥ 4 (sub-hazard ratio [SHR], 1.48; P = .004), intravesical bacillus Calmette-Guérin therapy (SHR, 0.44; P < .001), and BNI (SHR, 1.59; P = .004) were all independent predictors of recurrence. Assigning 1 point for each of these 3 predictive factors, the resulting scores enabled us to classify patients into 3 prognostic groups that were clearly stratified according to recurrence. CONCLUSIONS: Our time-dependent covariate analysis shows that BNI is a significant risk factor for recurrence in NMIBC. Our prognostic model incorporating BNI is an easy means of estimating recurrence risk and determining optimal management for individual patients.

Clinical Outcomes of Patients With Histologic Variants of Urothelial Carcinoma Treated With Selective Tetramodal Bladder-preservation Therapy Incorporating Consolidative Partial Cystectomy.

BACKGROUND: Tetramodal bladder-preservation therapy includes maximal transurethral resection (TUR), induction chemoradiotherapy (CRT), and consolidative partial cystectomy with pelvic lymph node dissection. Tetramodal bladder-preservation therapy theoretically provides surgical consolidation of chemotherapy- and radioresistant cells. However, its efficacy in providing optimal cancer control for patients with histologic variants of urothelial carcinoma (VUCs) is currently unknown. We compared the oncologic outcomes between patients with muscle-invasive bladder cancer (MIBC) and pure urothelial carcinoma (PUC) and those with MIBC and VUCs after selective tetramodal bladder-preservation therapy. PATIENTS AND METHODS: We prospectively enrolled 154 patients. After maximal TUR and induction CRT, patients with a clinical complete response were offered consolidative partial cystectomy to achieve bladder preservation, with radical cystectomy recommended for the others. The VUCs identified in the maximal TUR samples were categorized according to the 2004 World Health Organization classification. The primary endpoint was cancer-specific survival. The secondary endpoints included the clinical and pathologic response rates to induction CRT and MIBC recurrence-free survival. RESULTS: A VUC was identified in 37 patients (24%). The most frequent variants involved glandular differentiation (n = 13), squamous differentiation (n = 11), and micropapillary (n = 8). No difference was found in the clinical complete response rate to CRT between PUC and VUCs (P = .81). On an intention-to-treat basis, the 5-year cancer-specific survival rates for those with PUC (n = 116) and VUC (n = 37) were 82% and 81% (P = .86), respectively. CONCLUSION: Tetramodal bladder-preservation therapy incorporating partial cystectomy could provide favorable locoregional control and survival for patients with VUC. Thus, patients with MIBC need not be excluded from the bladder-preservation approach because of the presence of a variant histologic type.

Progressive Site-Directed Therapy for Castration-Resistant Prostate Cancer: Localization of the Progressive Site as a Prognostic Factor.

PURPOSE: Locoregional therapy for oligometastatic prostate cancer has generated great interest. However, its benefit for castration-resistant prostate cancer (CRPC) has not been fully demonstrated. Our objective was to evaluate the treatment outcome of progressive site-directed therapy (PSDT) for oligoprogressive CRPC (OP-CRPC). METHODS AND MATERIALS: This study cohort consisted of 101 patients with CRPC who underwent whole-body diffusion-weighted magnetic resonance imaging between 2014 and 2018, when a new line of anticancer therapy was being considered. For OP-CRPC, PSDT with radiation therapy and unchanged continuation of systemic therapy were recommended. RESULTS: Thirty-eight patients received a diagnosis of OP-CRPC, and 23 (61%) underwent PSDT at a median prostate-specific antigen (PSA) level of 7.8 ng/mL. The regional radiation therapy targets were the prostate/pelvic lymph nodes (n = 7), bone (n = 15), or both (n = 1). A decrease in PSA levels of at least 50% in response to PSDT (50% PSA decline) was observed in 16 cases (70%); the median time to PSA progression was 8.7 months. Intrapelvic localization of progressive lesions was a significant predictor of time to PSA progression (hazard ratio, 6.6; P = .007) as well as volumes of abnormal signal intensity on whole-body diffusion-weighted magnetic resonance imaging (hazard ratio, 0.5; P = .045). A 50% PSA decline was achieved in 16 of the 18 patients with intrapelvic OP-CRPC (89%) and in none of the 5 patients with non-intrapelvic OP-CRPC (P < .001). Intrapelvic OP-CRPC had a significantly longer time to PSA progression than non-intrapelvic OP-CRPC (10.1 vs 4.8 months, P = .0014). CONCLUSIONS: PSDT can be an effective treatment option for OP-CRPC. Progressive site localization was an important factor in good PSA response.

Impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma.

OBJECTIVES: To evaluate the impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma. METHODS: The present study assessed 51 metastatic urothelial carcinoma patients undergoing fluorodeoxyglucose positron emission tomography/computed tomography before first-line systemic chemotherapy. Fluorodeoxyglucose uptake in metastases was evaluated using the maximum standardized uptake value, which was measured for all eligible lesions, and the highest value among the maximum standardized uptake value measurements in each case was defined as the highest maximum standardized uptake value. The associations between the highest maximum standardized uptake value and objective response rate to chemotherapy, progression-free survival or cancer-specific survival were analyzed. For cancer-specific survival, the C-index was compared between multivariate models that incorporated predictors in the Bajorin model including the Karnofsky performance status and the presence of visceral metastasis, and the Apolo model additionally including hemoglobin and albumin levels, with/without the highest maximum standardized uptake value. RESULTS: The median age was 69 years. The Karnofsky performance status was ≥80% for all patients. Visceral metastasis was observed in 12 patients (24%). The objective response rate, median progression-free survival and median cancer-specific survival were 61%, 9 and 26 months in the entire cohort, respectively. The higher highest maximum standardized uptake value was significantly associated with a lower objective response rate, shorter progression-free survival and shorter cancer-specific survival (P = 0.01, <0.001 and 0.004, respectively). On multivariate analyses, the highest maximum standardized uptake value was an independent predictor for all end-points. In the multivariate models for cancer-specific survival, the C-index improved from 0.559 to 0.601 and from 0.604 to 0.652 by adding the highest maximum standardized uptake value to the parameter set of the Bajorin model and Apolo model, respectively. CONCLUSIONS: Higher fluorodeoxyglucose uptake in metastases was significantly and independently associated with poor chemosensitivity and worse survival outcomes. Fluorodeoxyglucose positron emission tomography/computed tomography might aid in patient counseling and treatment decisions for metastatic urothelial carcinoma patients.

Usefulness of the inchworm sign on DWI for predicting pT1 bladder cancer progression.

OBJECTIVE: To evaluate the significance of the presence or absence of an "inchworm sign" on DWI for the recurrence and progression of T1 bladder cancer. MATERIALS AND METHODS: We retrospectively analyzed 91 patients with pT1 urothelial carcinoma who underwent DWI prior to transurethral resection between 2007 and 2016. DWI of the dominant tumors was scrutinized for inchworm signs at b = 1000 s/mm2. The association of the presence of the inchworm sign with progression and recurrence was analyzed; progression was defined as recurrence to stage T2 or higher and/or N+, and/or M1. RESULTS: An inchworm sign was seen in 65 cases (71%), while it was absent in 26 cases. Among the 65, 25 (38%) had confirmed tumor recurrence, while in the remaining 26, 14 (54%) had confirmed recurrence (median time post TURB = 7.9 and 10.1 months for each). At the time of recurrence, the tumor had progressed in one (2%) inchworm-sign-positive and seven (27%) inchworm-sign-negative cases. The progression rate of inchworm-sign-negative cases was significantly higher than that of inchworm-sign-positive cases (hazard ratio = 17.2, p = 0.0017), whereas there was no significant difference in the recurrence rate between two groups. The absence of an inchworm sign and histological grade 3 were independent risk factors for progression (p < 0.001 and 0.010, respectively). CONCLUSIONS: The absence of an inchworm sign on DWI was a significant prognostic factor for progression of T1 bladder cancer. Morphological evaluation of DWI signals may therefore be a useful adjunct to preoperative assessment of biological aggressiveness. KEY POINTS: • An inchworm sign is a simple diagnostic criterion that characterizes only the shape of the tumor signal on DWI, and potentially serves as an imaging biomarker to predict clinical aggressiveness. • The absence of an inchworm sign on DWI is a significant indicator of progression of T1 bladder cancer.

Selective tetramodal bladder-preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle-invasive bladder cancer: oncological and functional outcomes of 107 patients.

OBJECTIVES: To evaluate the oncological and functional outcomes associated with selective tetramodal bladder-sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND). MATERIALS AND METHODS: In the present study, 154 patients with non-metastatic muscle-invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder-preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC-recurrence-free survival (RFS); cancer-specific survival (CSS); overall survival (OS), and cross-sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36-item Short-Form Health Survey (SF-36) score. RESULTS: The median follow-up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder-preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5-year MIBC-RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post-void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF-36, patients had favourable scores, equivalent to the age-matched references in all the QoL scales. CONCLUSION: Selective tetramodal bladder-preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol.

Incidence and predictive factors of hypoglycemia after pheochromocytoma resection.

OBJECTIVES: To determine the incidence and preoperative risk factors of post-excisional hypoglycemia in patients undergoing pheochromocytoma resection. METHODS: Patients who underwent surgical resection of pheochromocytoma at a single institution were retrospectively enrolled in the present study. The primary end-point was the development of post-excisional hypoglycemia; that is, a serum glucose level <70 mg/dL. The serum levels of immunoreactive insulin and glucose levels during the preoperative oral glucose-tolerance test and surgery were analyzed to elucidate the mechanism of hypoglycemia. RESULTS: A total of 49 patients underwent surgical resection of pheochromocytoma, of which 21 patients (43%) developed post-excisional hypoglycemia. The incidence of hypoglycemia was not statistically different between patients with adrenal tumors and those with extra-adrenal tumors (18/41 [44%] vs 3/8 [38%], respectively, P = 0.73). There was no difference in the immunoreactive insulin/glucose ratio during the preoperative oral glucose-tolerance test between patients with and those without post-excisional hypoglycemia. The intraoperative immunoreactive insulin/glucose ratio was significantly higher in patients with hypoglycemia than in those without hypoglycemia. A higher 24-h urinary epinephrine level, but not norepinephrine level, was a predictive factor for post-excisional hypoglycemia. CONCLUSIONS: Post-excisional hypoglycemia is a frequent complication of pheochromocytoma resection, irrespective of the tumor location, and might be common in patients with epinephrine-predominant tumors. All patients undergoing resection of adrenal and extra-adrenal pheochromocytoma require intensive monitoring of serum glucose levels during and after surgery.