Supplementary Figure 1 from Loss of ΔNp63α Promotes Invasion of Urothelial Carcinomas via N-Cadherin/Src Homology and Collagen/Extracellular Signal-Regulated Kinase Pathway

Abstract p63 plays a critical role in normal development and maintenance of stratified epithelia, including the urothelium. In the normal urothelium, urothelial cells in the basal layers abundantly express the predominant p63 isoform ΔNp63α. We previously showed that (a) ΔNp63α expression at the similar level to the normal urothelium is retained in most low-grade papillary noninvasive (LPN) tumors, whereas frequently lost in high-grade invasive carcinomas, and that (b) loss of ΔNp63α is associated with poor prognosis of invasive bladder urothelial carcinoma patients. However, a functional role of ΔNp63α in progression of urothelial carcinomas remains to be elucidated. Here, we show that loss of ΔNp63α expression promotes invasion of urothelial carcinoma cells. In 5637 cells substantially expressing only ΔNp63α isoform at the protein level, knockdown of endogenous p63 upregulated N-cadherin, which recruited more Src homology and collagen to N-cadherin and activated extracellular signal-regulated kinase (ERK) signaling, and consequently potentiated cell motility, excretion of matrix metalloproteinase-9, and invasion. In T24 cells originally lacking endogenous ΔNp63α expression, exogenous expression of ΔNp63α attenuated invasion by downregulating N-cadherin expression and ERK activity, confirming an invasion-suppressive role of ΔNp63α in urothelial carcinoma cells. We further documented loss of ΔNp63 expression accompanied by N-cadherin upregulation during muscle-invasive recurrence in patients whose bladder cancer had progressed from LPN tumors to muscle-invasive disease. These results suggest that loss of ΔNp63α and subsequent upregulation of N-cadherin is one of the mechanisms underlying progression of bladder cancer. [Cancer Res 2009;69(24):9263–70]

Supplementary Figure 2 from Loss of ΔNp63α Promotes Invasion of Urothelial Carcinomas via N-Cadherin/Src Homology and Collagen/Extracellular Signal-Regulated Kinase Pathway

OBJECTIVES:To report experience with focal brachytherapy (FB) and compare its clinical outcomes with those of radical prostatectomy (RP) in localized prostate cancer.METHODS:Fifty-one patients with low- to intermediate-risk prostate cancer underwent low-dose-rate FB. Survival rates free from biochemical failure (BF), additional treatment (AT) including re-FB, and whole-gland or systemic salvage therapy (ST) were calculated and oncological risk factors were investigated. Patient-reported outcomes on genitourinary function were also assessed. Using propensity scoring, 51 pair-matched RP patients were selected. Oncological control, urinary continence, and ejaculation status after FB and RP were compared.RESULTS:During a median 5.7-year follow-up, BF, AT, and ST occurred in 12 (24%), 10 (20%), and 4 FB patients (8%), respectively. 6 of 10 AT patients were managed with re-FB alone. In the RP cohort, 3 patients (6%) underwent ST. 5-year BF-free survival rate after FB was 79%. Compared to 5-year ST-free survival rate of 94% after RP, ST-free and AT-free survival rates after FB were 93% (P = 0.813) and 87% (P = 0.049), respectively. Multivariate analyses of FB-treated patients showed that time to PSA nadir was negatively associated with BF and AT (hazard ratio 0.84 and 0.83, respectively, P <0.001 for each). The difference in oncological outcomes between low- and intermediate-risk categories was not significant. At 2 years after FB and RP, pad-free continence rates were 100% and 81%, respectively (P = 0.001). Ejaculation was preserved in 67% and 0% of patients who had been capable of ejaculation at baseline, respectively (P <0.001).CONCLUSION:In low- to intermediate-risk prostate cancer, FB-treated patients achieved superior genitourinary function compared to pair-matched RP patients. The need for ST was not substantially different between the 2 treatment cohorts. Over half of patients requiring AT could be managed by re-focal treatment rather than whole-gland ST. Early PSA nadir may predict poor oncological control after FB.

PURPOSE: To examine medium-term outcomes of hemi-gland low-dose-rate brachytherapy as a primary treatment for intermediate-risk prostate cancer. METHODS: We recruited intermediate-risk unilateral prostate cancer patients for a prospective trial of hemi-gland brachytherapy. Twenty-four patients underwent hemi-gland iodine-125 seed implantation with a prescribed dose of 160 Gy. Serum prostate-specific antigen (PSA) was measured regularly and follow-up biopsy was scheduled after 2-3 years of treatment. When clinically needed afterward, for-cause biopsy was performed to confirm pathology. Treatment failure (TF)free survival, which was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality, was assessed, as was biochemical failure (BF)-free survival. Urinary and sexual functions were also evaluated. RESULTS: Median follow-up duration was 61 months. Twenty-two patients (92%) exhibited a declining trend or decreased value of PSA for 12 months or longer after the treatment. Follow-up biopsy in the initial triennium and for-cause biopsy in the subsequent triennium were performed in 16 and four patients, respectively, and cancer was found from the treated lobe in one patient (4% of the cohort) and significant cancer was found from untreated lobes in four patients (17%) in total. Secondary treatments were performed in six patients successfully. Five-year freedom from BF, TF, and metastasis was 71%, 90%, and 100%, respectively. The International Prostate Symptom Score significantly deteriorated at 3 months and reversed itself afterward. The International Index of Erectile Function 5 had no significant decrease. CONCLUSIONS: Hemi-gland low-dose-rate brachytherapy provides favorable medium-term oncological outcomes with genito-urinary functional preservation for men with intermediate-risk unilateral prostate cancer. (c) 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

OBJECTIVES:To evaluate the incidence of perioperative infections without antimicrobial prophylaxis in patients undergoing clean surgeries for adrenal and renal tumors.METHODS:We prospectively enrolled 1362 consecutive patients who underwent minimally invasive adrenalectomy (n = 303), radical nephrectomy (n = 499), and partial nephrectomy (n = 560) using the gasless laparoendoscopic single-port surgery technique between 2005 and 2019. In 1059 patients, antimicrobial prophylaxis was not administered. The remaining 303 patients were considered at high risk for infection and received single-dose antimicrobial prophylaxis. The endpoint was the incidence of perioperative infections within 1 month from the surgery date. Perioperative infections were classified into surgical site infections, urinary tract infections, and remote infections.RESULTS:Seventy-four patients whose collecting systems were opened during partial nephrectomy were excluded, and the remaining 1013 patients with nonuse of antimicrobial prophylaxis and 275 patients with single-dose antimicrobial prophylaxis were retrospectively analyzed. The incidence of superficial surgical site infections, deep/organ-space surgical site infections, urinary tract infections, and remote infections was 1.6%, 0.7%, 2.8%, and 1.3%, respectively, in patients with nonuse of antimicrobial prophylaxis and 0.4%, 1.8%, 1.5%, and 1.5%, respectively, in patients with single-dose antimicrobial prophylaxis. All patients who developed perioperative infections were successfully treated. No clinical or surgical variables were significantly associated with the incidence of surgical site infections. One limitation of the present study was its nonrandomized and noncontrolled design.CONCLUSIONS:In minimally invasive clean surgeries for adrenal and renal tumors, antimicrobial prophylaxis is not necessary when individual risk of infection is considered low.

ObjectivesTo investigate the outcomes and feasibilities of gasless laparoendoscopic single‐port clampless sutureless partial nephrectomy.MethodsWe reviewed 356 consecutive patients with primary unilateral non‐metastatic renal masses who underwent gasless laparoendoscopic single‐port partial nephrectomy (2011–2018), which was performed retroperitoneally using a three‐dimensional flexible endoscope, without vascular clamping or renorrhaphy in principle.ResultsThe median tumor size was 2.5 cm, and 213 (60%), 105 (29%), and 38 (11%) patients had peripheral, central, and hilar tumors, respectively. Clampless and sutureless partial nephrectomy was accomplished in 337 patients (95%), while eight (2%) and 16 (4%) patients required vascular clamping and renorrhaphy, respectively. The median operative time and blood loss were 220 min and 266 mL, respectively; eight patients (2%) received blood transfusion. Clavien–Dindo grade 3a complications occurred in 27 patients (8%); all these patients had urinary leakage treated with ureteral stent placement, one of whom also developed a postoperative pseudoaneurysm. Among 324 patients diagnosed with renal cell carcinoma, six (2%) had positive surgical margins, and one (0.3%) and seven (2%) developed metastatic and local recurrences, respectively. During a median follow‐up of 54 months, no patient died from kidney cancer. The median percent decrease in estimated glomerular filtration rate at 3 months after surgery was 5.7%. No patient experienced postoperative acute renal failure, while one patient with preexisting renal impairment started dialysis at 70 months after surgery.ConclusionsClampless and sutureless partial nephrectomy can be safely accomplished in most patients undergoing gasless laparoendoscopic single‐port surgery, yielding favorable oncological and functional outcomes.

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.

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).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.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.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.

To evaluate the significance of the presence or absence of an “inchworm sign” on DWI for the recurrence and progression of T1 bladder cancer.

Tetramodal bladder-preservation therapy incorporating partial cystectomy might theoretically provide good cancer control for patients with muscle-invasive bladder cancer (MIBC) and a histologic variant of urothelial carcinoma (VUC) that is chemotherapy- and radioresistant. In prospectively enrolled patients, pure urothelial carcinoma and a VUC showed no difference in the clinical complete response, MIBC recurrence-free survival, or cancer-specific survival rates. Patients with MIBC need not be excluded from bladder-preservation therapy by the presence of VUCs. 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. (C) 2019 Elsevier Inc. All rights reserved.

You have accessJournal of UrologyProstate Cancer: Staging II1 Apr 2018PD47-11 THE ROLE OF MRI-TARGETED BIOPSY IN PREDICTION OF ADVERSE PATHOLOGICAL AND ONCOLOGICAL OUTCOME AFTER RADICAL PROSTATECTOMY Yoh Matsuoka, Hiroshi Tanaka, Tomo Kimura, Yuma Waseda, Sho Uehara, Yosuke Yasuda, Toshiki Kijima, Soichiro Yoshida, Minato Yokoyama, Junichiro Ishioka, Kazutaka Saito, Kazunori Kihara, and Yasuhisa Fujii Yoh MatsuokaYoh Matsuoka More articles by this author , Hiroshi TanakaHiroshi Tanaka More articles by this author , Tomo KimuraTomo Kimura More articles by this author , Yuma WasedaYuma Waseda More articles by this author , Sho UeharaSho Uehara More articles by this author , Yosuke YasudaYosuke Yasuda More articles by this author , Toshiki KijimaToshiki Kijima More articles by this author , Soichiro YoshidaSoichiro Yoshida More articles by this author , Minato YokoyamaMinato Yokoyama More articles by this author , Junichiro IshiokaJunichiro Ishioka More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , Kazunori KiharaKazunori Kihara More articles by this author , and Yasuhisa FujiiYasuhisa Fujii More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2171AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Multiparametric MRI and MRI-targeted biopsy (MTB) facilitate prostate cancer (PC) detection. We have reported that the Prostate Imaging Reporting and Data System (PI-RADS) version 2 promotes overstaging (AJR 2017) and that risk-group migration occurs when MTB data is applied in systematic biopsy (SB)-based risk models (AUA 2016). We aimed to clarify roles of MTB in the prediction of extraprostatic extension (EPE) and biochemical recurrence (BCR) after radical prostatectomy (RP). METHODS Subjects were 174 clinically localized PC patients who had undergone multiparametric MRI, 12-core SB, and RP without prior treatment. MTB was performed for index lesions with PI-RADS scores ≥3. BCR was defined as PSA >0.2 ng/ml. Preoperative factors were examined for associations with EPE and BCR by logistic and Cox regression analyses, respectively. The performance of models was evaluated. RESULTS SB showed no PC in 19 men (11%) and PC of grade groups (GG) 1/2/3/≥4 in 42/65/24/24 men (24/37/14/14%). MTB (median core number, 4) was performed in 153 men (88%) and showed no PC in 11 men (6%) and PC of GG 1/2/3/≥4 in 25/63/28/26 men (14/36/16/15%). EPE was identified in 35 men (20%). After a median follow-up of 43 months, 28 men (16%) had BCR. In multivariate analyses, T-stage ≥3 on MRI (p <0.001) and MTB-GG ≥4 (p = 0.004) were independent predictors of EPE. Among 92 men at T-stage ≥3 on MRI, EPE was found in 67% (10/15) of men with MTB-GG ≥4 and 30% (23/77) of men without MTB-GG ≥4 (p = 0.007). Regarding BCR, PSA ≥10 ng/ml (hazard ratio [HR] 4.1, p = 0.001), SB-GG ≥3 (HR 2.8, p = 0.02), MTB-GG ≥3 (HR 11.6, p <0.001), and maximal cancer length (MCL) ≥6 mm in MTB (HR 6.4, p <0.001) were independent predictors. A scoring model was developed in which the score was calculated as 1 (if PSA ≥10 ng/ml) + 1 (if SB-GG ≥3) + 2 (if MTB-GG ≥3) + 2 (if MCL ≥6 mm in MTB) or 0 (otherwise). Postoperative courses were stratified with three-year BCR-free rates of 100/78/34% for men with scores 0-2/3-4/5-6 (n = 113/35/26) (p <0.001). The concordance index was 0.82 for this model and 0.58 and 0.63 for the NCCN risk model using SB alone and both SB and MTB, respectively. CONCLUSIONS MTB has predictive values for pathological and oncological outcomes after RP. PC grades on MTB may complement MRI staging, and grades and size on MTB could be useful in risk stratification for BCR. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e902 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Yoh Matsuoka More articles by this author Hiroshi Tanaka More articles by this author Tomo Kimura More articles by this author Yuma Waseda More articles by this author Sho Uehara More articles by this author Yosuke Yasuda More articles by this author Toshiki Kijima More articles by this author Soichiro Yoshida More articles by this author Minato Yokoyama More articles by this author Junichiro Ishioka More articles by this author Kazutaka Saito More articles by this author Kazunori Kihara More articles by this author Yasuhisa Fujii More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging II1 Apr 2018MP36-05 CHANGES IN PATTERN OF RECURRENCE OVER TIME AFTER RADICAL NEPHRECTOMY IN PATIENTS WITH LOCALIZED CLEAR CELL RENAL CELL CARCINOMA Kenji Tanabe, Kazutaka Saito, Kazuaki Nakagomi, Chizuru Arisawa, Tetsuro Tsukamoto, Tetsuo Okuno, Katsushi Nagahama, Akira Noro, Shinji Morimoto, Satoshi Kitahara, Kazunori Kihara, and Yasuhisa Fujii Kenji TanabeKenji Tanabe More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , Kazuaki NakagomiKazuaki Nakagomi More articles by this author , Chizuru ArisawaChizuru Arisawa More articles by this author , Tetsuro TsukamotoTetsuro Tsukamoto More articles by this author , Tetsuo OkunoTetsuo Okuno More articles by this author , Katsushi NagahamaKatsushi Nagahama More articles by this author , Akira NoroAkira Noro More articles by this author , Shinji MorimotoShinji Morimoto More articles by this author , Satoshi KitaharaSatoshi Kitahara More articles by this author , Kazunori KiharaKazunori Kihara More articles by this author , and Yasuhisa FujiiYasuhisa Fujii More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1139AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Late recurrence is one of specific features in renal cell carcinoma (RCC). Longer follow-up more than 5-years is needed for the early detection of recurrence to allow surgical removal with curative intent. However, surveillance strategy should be based on its efficacy and medical burden of economic cost and radiation exposure. We aimed to evaluate the pattern of recurrence over time after radical nephrectomy for localized clear cell RCC (ccRCC). METHODS This study conducted from a multicenter database including RCC (n=2162) since 1981 to 2013 at 9 centers. Among them, patients who experienced recurrence after radical nephrectomy for localized ccRCC were subjects. Recurrence patients were divided in 4 time groups according to time to initial recurrence (<2, 2≤ and <5, 5≤ and <10, and ≥10 years). Associations between time groups and initial recurrence sites (lung, bone, lymph node, local, liver, kidney, adrenal gland, pancreas, others) were analyzed. Then we analyzed proportion of lung and pancreas recurrences as representative sited of early and late recurrence using Kaplan-Meier method. RESULTS During the follow-up period (median, 82.0 months), 161 patients (117 men, 44 women, median age 69 years at recurrence) had recurrence. The number of patients who experienced initial recurrence at lung, bone, and lymph node decrease over time with 24.0, 11.0, 4.0 events per year in these three sites after <2, 2≤ and <5, and 5≤ and <10 years, respectively, while the patients with recurrence at kidney, adrenal gland, and pancreas showed tendency to increase with 0.5, 3.3, 2.6 events per year in these three sites after <2, 2≤ and <5, and 5≤ and <10 years, respectively (Fig 1). As shown in Fig 2, a large proportion of lung recurrences developed earlier, whereas pancreas recurrences increased later. CONCLUSIONS The pattern of recurrence after nephrectomy changed over time in patients with localize ccRCC. On the basis of these findings, surveillance policy could be altered with follow-up duration. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e458 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Kenji Tanabe More articles by this author Kazutaka Saito More articles by this author Kazuaki Nakagomi More articles by this author Chizuru Arisawa More articles by this author Tetsuro Tsukamoto More articles by this author Tetsuo Okuno More articles by this author Katsushi Nagahama More articles by this author Akira Noro More articles by this author Shinji Morimoto More articles by this author Satoshi Kitahara More articles by this author Kazunori Kihara More articles by this author Yasuhisa Fujii More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

ObjectiveTo estimate postoperative residual renal function after radical nephroureterectomy for upper tract urothelial carcinoma using the preoperative dynamic computed tomography renal cortex enhancement ratio in comparison with the split kidney glomerular filtration rate measured by 99mTc‐diethylenetriaminopentacetic acid renography.MethodsA total of 47 patients who received radical nephroureterectomy and underwent both preoperative dynamic computed tomography and renography were the model‐development cohort; and 109 patients who underwent dynamic computed tomography alone were the validation cohort. Postoperative renal function of the unremoved kidney was estimated using the following formulas: preoperative estimated glomerular filtration rate × the percentage of total renal cortex radiodensity for the intact kidney in Hounsfield units obtained from corticomedullary phase images in the computed tomography‐based model, or the percentage of the total glomerular filtration rate measured by renography in the nuclear model. The correlation between observed and estimated postoperative renal function was determined. The computed tomography‐based prediction model derived from linear regression analysis was validated externally.ResultsThe correlation of computed tomography‐based split renal function with the observed postoperative estimated glomerular filtration rate (r = 0.80) was equivalent to that of nuclear split renal function (r = 0.78). In the validation cohort, the computed tomography‐based prediction model showed an equivalently strong correlation (r = 0.78).ConclusionsThe present study showed that the percentage of total renal cortex radiodensity for the intact kidney is a useful tool for predicting unremoved kidney function in upper tract urothelial carcinoma patients, thereby allowing appropriate patient selection for perioperative cisplatin‐based combination chemotherapy.

Purpose: A bladder-sparing strategy is a useful option for patients with muscle-invasive bladder cancer (MIBC), in which the response to chemoradiation therapy (CRT) is primarily important in achieving favorable oncologic outcomes. Our objective is to evaluate the impact of immunohistochemistry (IHC)-based subtyping in MIBC on prediction of CRT response. Methods and Materials: Treatment protocol consisted of induction CRT followed by partial or radical cystectomy as consolidative surgery; 118 eligible patients with non-metastatic MIBC were retrospectively analyzed. Of these patients, 92 eventually underwent partial or radical cystectomy after CRT. We applied the IHC-based subtyping model developed by Lund University, which classifies patients into urobasal (Uro), genomically unstable (GU), and squamous cell cancer-like (SCCL) subtypes. GU and SCCL cancers are supposed to be highly aggressive and to have worse prognoses than Uro. Correlations of subtypes with CRT response were analyzed clinically in all patients and pathologically in 92 cystectomized patients. The impact of each subtype on cancer-specific mortality (CSM) was also analyzed. Results: Of all patients, 26 (22%), 61 (52%), and 31 (26%) were classified into Uro, GU, and SCCL subtypes, respectively. Clinical complete response (CR) was achieved in 42% of patients overall after CRT, with a significantly higher proportion in GU patients (52%) and SCCL patients (45%) than in Uro patients (15%; P<.001 and P=.01, respectively). On multivariate analysis, the GU/SCCL subtype was a significant predictor of clinical CR, as was absence of hydronephrosis or concomitant carcinoma in situ. Analyses for pathologic CR in the cystectomized patients revealed analogous findings. Five-year CSM of Uro, GU, and SCCL patients was 16%, 23%, and 28% overall, respectively, and 19%, 22%, and 23% in cystectomized patients, respectively, with no significant difference among the subtypes. CR status after CRT was significantly and independently correlated with low CSM in both clinical and pathologic evaluations. Conclusions: GU and SCCL cancers showed significantly more favorable CRT response than did Uro cancers. IHC-based subtyping may improve clinical decisions about the indication of CRT for MIBC patients. (C) 2018 Elsevier Inc. All rights reserved.

490 Background: Trimodality bladder-sparing therapy has become an accepted treatment for selected patients with muscle-invasive bladder cancer (MIBC). As some of the histologic variants of urothelial carcinoma (VUC) are more resistant to chemotherapy and radiotherapy compared with pure urothelial carcinoma (PUC), it is still controversial whether bladder-sparing therapy provides comparable disease control in VUC. We have developed a tetra-modality bladder-sparing therapy consisting of maximal transurethral resection (TUR), chemoradiotherapy (CRT), and consolidative partial cystectomy, which has theoretical advantage in locoregional control by surgically eliminating chemo- and radio-resistant cells (Koga et al, Urol Oncol 2013, BJU Int 2012). Methods: After maximal TUR and CRT (40Gy + cisplatin), treatment response was evaluated by cytology, imaging and tumor-site rebiopsy. Complete responders were candidate for consolidative partial cystectomy, while radical cystectomy was recommended for others. VUC identified in maximal TUR samples were categorized according to the 2004 World Health Organization Classification. Response rate to CRT, MIBC recurrence-free survival and cancer-specific survival (CSS) were compared between patients with PUC and VUC. Results: Between 1997 and 2016, 153 consecutive patients with cT2-3N0M0 bladder cancer (median age 69, female/male = 33/120, cT2/3 = 99/54) entered tetra-modality bladder-sparing protocol. VUC was identified in 37 (24%) of the patients, including glandular in 12 (8%), squamous in 11 (7%), micropapillary in 8 (5%), sarcomatoid in 2 (1%), microcystic in 2 (1%), and lymphoepithelioma-like in 1 (0.7%). There was no difference in the response rate to CRT between PUC and VUC (71% vs 84%, p = 0.13). Among the patients with PUC (n = 75) and VUC (n = 31) who underwent partial cystectomy, 5-yr MIBC recurrence-free rates were 92% and 100% (p = 0.21), and 5-yr CSS rates were 93% and 94% (p = 0.64), respectively. Conclusions: Tetra-modality bladder-sparing therapy incorporating partial cystectomy could provide favorable locoregional control and survival for patients with VUC.