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573 Background: Neoadjuvant chemotherapy (NAC)-induced acute kidney injury (AKI) is a frequent complication in patients with muscle-invasive bladder cancer (MIBC). Although previous studies have reported that AKI during cancer treatment was associated with poor oncological outcomes in several cancers, the impact of NAC-induced AKI on oncological outcomes in patients with MIBC remains unclear. Methods: This retrospective study included 398 patients who received 2-4 cycles of NAC followed by radical cystectomy (RC). AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed AKI during NAC (AKI group) and patients who did not (non-AKI group). Multivariable Cox-proportional hazards regression analyses were performed to evaluate the impact of NAC-induced AKI on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: The median age and follow-up period were 69 years and 62 months, respectively. Of the 398 patients, 66 (17%) developed AKI during NAC. The rates of

45 Background: We aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (PC). Methods: We longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 > 14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP. Results: The median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients’ background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, p = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening. Conclusions: Frailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.

206 Background: This study aimed to evaluate the geriatric 8 (G8) screening tool for detecting frailty in patients with prostate cancer. Methods: Between January 2017 and June 2019, we prospectively evaluated the G8 in 540 prostate cancer patients, 444 with localized stage M0 and 96 with metastatic stage M1 disease. The primary endpoint was the comparison of G8 scores in patients treated with robot-assisted radical prostatectomy (RARP), radiotherapy, androgen deprivation therapy alone (ADT-alone) for localized disease, and standard care for the M1 disease. Secondary endpoint included the cutoff estimation of G8 score and the influence of G8 on prognosis. Results: The median age was 75 years. G8 scores ≤14 indicating frailty were seen in 36% of RARP (n = 214), 57% of RT (n = 209), 91% of ADT-alone (n = 21), and 70% of M1 disease (n=96). The median G8 score in M0 patients was significantly higher than that in M1 patients (14.5 vs 12.8, respectively). The median G8 score in patients treated with RARP, RT and ADT-alone was 15, 14, and 12, respectively. The patients with RARP had significantly higher G8 score than that of RT or ADT-alone. The optimal G8 cutoff score for patients with M0 and M1 disease was 13.0 (AUC: 0.681). The overall survival was significantly shorter in patients with G8

238 Background: We aimed to evaluate the treatment sequence for patients with metastatic castration-resistant prostate cancer (mCRPC) in real-world practice and compare overall survival in each sequential therapy. Methods: We retrospectively evaluated 146 patients with mCRPC who were initially treated with androgen deprivation therapy as metastatic hormone-naïve prostate cancer in 14 hospitals between January 2010 and March 2019. The agents for the sequential therapy included new androgen receptor-targeted agents (ART: abiraterone acetate or enzalutamide), docetaxel, and/or cabazitaxel. We evaluated the treatment sequence for mCRPC and the effect of sequence patterns on overall survival. Results: The median age was 71 years. A total of 35 patients received ART-ART, 33 received ART-docetaxel, 68 received docetaxel-ART, and 10 received docetaxel-cabazitaxel sequences. The most prescribed treatment sequence was docetaxel-ART (47%), followed by ART-ART (24%). Overall survival calculated from the initial diagnosis reached 83, 57, 79, 37 months in the ART-ART, ART-docetaxel, docetaxel-ART, and docetaxel-cabazitaxel, respectively. Multivariate Cox regression analyses showed no significant difference in overall survival between the first-line ART (n = 68) and first-line docetaxel (n = 78) therapies (hazard ratio: HR 0.84, P = 0.530), between the ART-ART (n = 35) and docetaxel-mixed (n = 111) sequences (HR 0.82, P = 0.650), and between the first-line abiraterone (n = 32) and first-line enzalutamide (n = 36) sequences (HR 1.58, P = 0.384). Conclusions: The most prescribed treatment sequence was docetaxel followed by ART. No significant difference was observed in overall survival among the treatment sequences in real-world practice.

429 Background: Although measuring frailty is important to estimate risks and to aid shared decision making, the impact of frailty on surgical indication in muscle-invasive bladder cancer (MIBC) remain unclear. We aimed to investigate the impact of frailty on treatment modality selection in patients with MIBC. Methods: Between October 2013 and September 2019, we underwent frailty evaluation in 149 patients with localized or locally advanced MIBC (T2-4N0-1M0). Frailty evaluation included modified Frailty index (mFI), Fried phenotype (FP), and frailty discriminant score (FDS). Primary purpose was comparison of frailty between the patients who underwent radical cystectomy (RC group) and trimodal therapy for bladder preservation (TMT group). Optimal cutoff values of frailty between the RC and non-RC groups was defined by receiver operating characteristic curve. Secondary purpose included overall survival (OS) comparison between in patients with frail and non-frail. Overall survival (OS) was compared using Kaplan-Meier method and Cox regression analysis. Results: Of 149, 88 and 61 patients were classified to RC and TMT group, respectively. The median age in the TMT group was significantly older than that in the RC group (80 vs. 68 years). A significantly higher prevalence of frailty was observed in the TMT group than that of the RC group in FP ≥3 (5.7% vs. 61%, P < 0.001), mFI ≥2 (22% vs. 61%, P < 0.001), and FDS ≥2.30 (40% vs. 72%, P < 0.001). Univariate logistic regression analysis showed that frailty was significantly associated with TMT. Frailty was significantly associated with overall survival between the RC and TMT groups in the FP and FDS, whereas it was not the case in mFI. Conclusions: Frailty was significantly associated with indication of RC in patients with MIBC. Measuring frailty is important to estimate risks and to aid shared decision making.

180 Background: A circulating cell-free DNA (cfDNA) has been suggested as a potential biomarker for castration-resistant prostate cancer (CRPC). However, clinical implication of the parameters in cfDNA remains unclear. We aimed to investigate the impact of copy number variation (CNV) of androgen-receptor amplification (AR-amp) in cfDNA on prognosis in patients with CRPC. Methods: We retrospectively evaluated AR-amp in cfDNA in 154 patients with prostate cancer between April 2018 and September 2019. We compared AR-amp between the patients with CRPC and non-CRPC. An optimal cutoff point was defined using receiver operating characteristic (ROC) curve. The effect of AR-amp on prognosis was evaluated between the CRPC patients with AR-amp high and low. Results: The median age and initial PSA was 75 years and 34 ng/mL, respectively. The number of patients with abiraterone acetate, enzalutamide, docetaxel, cabazitaxel was 24, 15, 21, and 2, respectively. No significant association was observed between the AR-amp and serum prostate-specific antigen (PSA) level at AR-amp measurement. Of 154, 73 (47%) patients developed to CRPC. The AR-amp was significantly higher in the patients with CRPC than that in the non-CRPC (1.07 vs. 0.97, respectively, P1.16, n=27) (8.9 vs. 9.6 months, respectively, P < 0.001). The AR-amp was not significantly different between the pre- and post-docetaxel status in patients with CRPC. Conclusions: AR-amp in cfDNA might be a potential biomarker for poor prognosis in patients with CRPC who were treated with life-prolonging therapies.

556 Background: As the clinical implication of the risk group disagreement between the risk models remains unclear, we aimed to investigate the impact of the risk group disagreement between the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models on prognosis. Methods: We retrospectively evaluated 176 patients with metastatic renal cell carcinoma (mRCC) who were treated with tyrosine kinase inhibitors as first-line therapy in five hospitals between October 2008 and August 2018. The risk group classification differences between the MSKCC and the IMDC models were evaluated using criteria of agreement (identical risk group in both the MSKCC and IMDC models) and disagreement (not identical risk group in both the MSKCC and IMDC models). The agreement of risk stratification between the MSKCC and IMDC models was evaluated using Cohen’s k coefficient. Oncological outcomes were compared between the agreement and disagreement groups. Results: The number of patients with agreement, upgrade, and downgrade was 135/176 (77%), 39/176 (22%), and 2/176 (1.1%), respectively. Of 41 patients with disagreement, reclassification from the MSKCC-intermediate to the IMDC-poor-risk group was most frequent (n = 34/176, 19%). The Cohen’s k coefficient for agreement of the two risk models was substantial with k value of 0.613 ( P < 0.001). Significantly poorer prognosis was observed in patients with disagreement than in those with agreement. Conclusions: Disagreement between the MSKCC and IMDC models may have a negative impact on prognosis in patients with mRCC. Further study is necessary to validate our findings.

537 Background: Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy that is frequently overexpressed in several neoplasms. But there were few reports about PD-L1 expression of pheochromocytoma. In the present study, we examined PD-L1 expression in pheochromocytoma. Methods: PD-L1 mRNA expression was compared across 184 pheochromocytoma, 492 prostate cancer cases and 404 bladder cancer cases based on The Cancer Genome Atlas (TCGA). Furthermore, we enrolled 32 pheochromocytoma patients treated with surgery at our hospital between June 2005 and February 2016. We conducted an immunohistochemistry (IHC) of PD-L1 using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0/1/2). Results: Comparison of PD-L1 mRNA expression based on the TCGA revealed that PD-L1 expression was significantly higher in pheochromocytoma than in bladder cancer and in prostate cancer (p < 0.001). In the SP 142 assay of our 32 pheochromocytoma, the prevalence of positive PD-L1 expression (IHC score 1 or 2 (1/2)) in tumor-infiltrating immune cells (TICs) was 8 patients (25%). The prevalence of positive PD-L1 expression in tumor cells (TCs) was 9 patients (28.1%). Tumor diameter of PD-L1 (+) in TICs patients was 3.36±0.35 cm and that of PD-L1 (-) in TCs patients was 5.37±0.50cm, there was statistically significance between two groups. (unpaired t test: p=0.044) In our cohort, there were two malignant pheochromocytoma. But there were not PD-L1 positive cases in malignant pheochromocytoma. Conclusions: PD-L1 expression is relatively high in pheochromocytoma compared to bladder cancer and prostate cancer based on TCGA. In the SP142 assay of our 32 pheochromocytoma cases, tumor diameter of PD-L1 (-) in TICs cases was larger than that of PD-L1 (+) cases. In our cohort, there were not PD-L1 (+) cases in malignant pheochromocytoma. These findings suggest that PD-L1 expression of pheochromocytoma was comparatively common and PD-L1 positive expression of pheochromocytoma may not be associated with tumor aggressiveness.

555 Background: No previous study has compared the efficacy and safety of first-line axitinib and sunitinib. We aimed to compare oncological outcomes and safety of axitinib and sunitinib in patients with treatment-naïve metastatic renal cell carcinoma (mRCC). Methods: We retrospectively evaluated 169 patients with mRCC who were treated with axitinib or sunitinib as the first-line therapy in five hospitals between October 2008 and August 2018.Oncological outcomes and safety were compared between axitinib (n = 68) and sunitinib (n = 101) groups. Inverse probability of treatment weighted (IPTW)-adjusted Cox regression analysis was performed to evaluate effects of first-line therapies on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: Patients in the axitinib group were significantly older (66 vs 72 years) than those in the sunitinib group. Median relative dose intensity was significantly higher in the axitinib group (94 ± 62%) than in the sunitinib group (65 ± 20%; P = 0.001). Objective response rate was significantly higher in the axitinib group (21%) than in the sunitinib group (10%; P = 0.042). IPTW-adjusted Cox regression analysis revealed significant differences in CSS and OS but not in PFS between the two groups. Safety in terms of grade ≥3 adverse events was significantly different between the axitinib (34%) and sunitinib (55%) groups ( P = 0.006). Conclusions: Compared with sunitinib, axitinib significantly prolonged CSS and OS and showed a safer profile as the first-line therapy for treatment-naïve mRCC.

486 Background: Systemic inflammation is a common host reaction to cancer progression. Serum level of buttyrylcholinesterase (BChE) have been reported to reflect the presence of inflammation and other clinical conditions. BChE is an alphaglycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, injury, infection, and malignant disease. We retrospectively evaluated the potential prognostic significance of buttyrylcholinesterase before chemotherapy as an independent predictor of overall survival in patients with advanced upper-tract urothelial cancer. Methods: We treated seventy-four patients (52 men and 22 women) with advanced upper-tract urothelial cancer (UTUC) at our clinic between August 2004 and September 2017. The average age was 69.3 (43–89), and average eGFR was 50.5 (11.6–99.3) ml/minute/1.73m2. Mean observation period was 28.7 (3–111) months. Levels of serum BChE (normal range 168-470 U/L) were measured 1 week before chemotherapy. The average serum level of BChE were 240.6 U/L (53-509). The patients received 2 courses of GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCcarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (D; 70mg/m2) treatment as second-line treatment. Results: GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR, and the average duration of response of 11.4 (2–29) months. GCarboD treatment was administered in 21 cases, and yielded 2 (9.5%) PR and a duration of response was 31.5(7-50) months. The median over-all survival period was 14.3 months. When analyzed by serum BChE level, the ovearall survival were 22.0 months in the BChE > 168 U/L group and 11.0 months in the BChE < 168 group (p = 0.0035). The level of serum BChE showed no association with treatment effect. Conclusions: Serum BChE level before chemotherapy may have the potential to predict overall survival in patients with advanced upper-tract urothelial cancer.

417 Background: High endothelial venules (HEVs) are present in lymph nodes and tertiary lymphoid organs. It has been reported that low HEV density is associated with the poor prognosis of several carcinomas. MECA-79 antibody recognizes L-selectin ligand (6-sulfosialyl Lewis X glycan) expressed in HEV. In the present study, we examined whether MECA-79 positive HEV density was associated with clinical outcomes of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Methods: Eighty-eight patients with UTUC who underwent RNU at the Hirosaki University hospital between January 2008 and December 2016 were enrolled. Tissue microarray for MECA-79 was performed, and HEV densities were calculated. HEV density < 1.5/mm2 was defined as HEV (−); HEV density ≥1.5/mm2 was defined as HEV(+). Results: Of 88 patients, 64 (72.7%) were male and 24 (27.2%) were female. The average age was 68.5 years (range, 36–84 years). Fifty-three patients (60.2%) had previously undergone neoadjuvant chemotherapy. The mean observation period was 39.0 months. Twenty-one (23.8%) patients developed recurrence, whereas 16 (33.3%) patients died during follow-up. Five-year cause-specific survival (CSS) rate was 66.1%, and five-year disease-free survival (DFS) rate was 70.7%. In our cohort, 25 (28.4%) patients were found to be HEV(−), whereas 63 (71.5%) were found to be HEV(+). The mean HEV density was 6.3/mm2(0-41.6). The 5-year DFS rates for HEV (+) and HEV (−) patients were 78.0% and 53.9%, respectively, with a statistically significant difference between the groups. (log-rank, p = 0.042). Moreover, the 5-year CSS rates for HEV (+) and HEV (−) patients were 72.5% and 53.4%, respectively, with a statistically significant difference between the groups. (log-rank, p = 0.0036). Conclusions: Low MECA-79-positive HEV density may be associated with poor prognosis of patients with UTUC treated with RNU. Despite the small sample size and preliminary nature of our study, our study provides valuable insights to guide future research.

416 Background: Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy that is frequently overexpressed in bladder cancer. In the present study, we examined whether PD-L1 expression is associated with clinical outcomes in bladder cancer patients. Methods: We enrolled 102 bladder cancer patients treated with cystectomy at the Aomori Prefectural Hospital between April 2004 and May 2014. We conducted an immunohistochemical examination of PD-L1 expression using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0/1/2). Results: Of the 102 patients, 82 were men (81.0%) and 20 were women (19.0%) (mean age 60 years, range 43-84 years). Sixty-six patients (64.8%) had previously undergone neoadjuvant chemotherapy [neoadjuvant (+) group]. During the mean observation period of 54.5 months, 42 patients had recurring disease (41.1%) and 34 died (33.3%). The 5-year cause-specific survival (CSS) rate was 66.6%; the 5-year disease-free survival (DFS) rate was 59.7%. In the neoadjuvant (+) group, the 5-year DFS rate was 65.0% for PD-L1 (-) patients and 31.7% for PD-L1 (+) patients (log-rank p = 0.006). In the neoadjuvant (+) groups, the 5-year CSS rate was 69.6% for PD-L1 (-) patients and 48.1% for PD-L1 (+) patients. Differences in CSS and DFS rates between PD-L1 (-) and PD-L1 (+) patients in both treatment groups were statistically significant (log-rank p = 0.006 and 0.039, respectively.) Conclusions: Despite the small study size, our data suggest that post-chemotherapy PD-L1 expression is associated with poor prognosis in patients receiving neoadjuvant chemotherapy who had previously undergone cystectomy.

429 Background: The clinical impact of neoadjuvant chemotherapy (NAC) on oncological outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC) remains unclear. We investigated the oncological outcomes of platinum-based NAC for locally advanced UTUC. Methods: A total of 426 patients who underwent radical nephroureterectomy at five medical centers between January 1995 and April 2017 were examined retrospectively. Of the 426 patients, 234 were treated for a high-risk disease (stages cT3–4 or locally advanced [cN+] disease) with or without NAC. NAC regimens were selected based on eligibility of cisplatin. We retrospectively evaluated post-therapy pathological downstaging, lymphovascular invasion, and prognosis stratified by NAC use. Multivariate Cox regression analysis was performed for independent factors for prognosis. Results: Of 234 patients, 101 received NAC (NAC group) and 133 did not (Control [Ctrl] group). The regimens in the NAC group included gemcitabine and carboplatin (75%), and gemcitabine and cisplatin (21%). Pathological downstagings of the primary tumor and lymphovascular invasion were significantly improved in the NAC than in the Ctrl groups. NAC for locally advanced UTUC significantly prolonged recurrence-free and cancer-specific survival. Multivariate Cox regression analysis using an inverse probability of treatment weighted (IPTW) method showed that NAC was selected as an independent predictor for prolonged recurrence-free and cancer-specific survival. However, the influence of NAC on overall survival was not statistically significant. Conclusions: Platinum-based NAC for locally advanced UTUC potentially improves oncological outcomes. Further prospective studies are needed to clarify the clinical benefit of NAC for locally advanced UTUC.

427 Background: Chronic kidney disease (CKD) is common in elderly patients with bladder cancer. In addition, increasing evidence has suggested that preoperative renal insufficiency indicates poor prognosis in bladder cancer. We aimed to evaluate the impact of CKD on oncologic outcomes in muscle-invasive bladder cancer patients who underwent radical cystectomy. Methods: A total of 581 patients who underwent radical cystectomy at four medical centers between January 1995 and February 2017 were examined retrospectively. We investigated oncologic outcomes, including progression-free, cancer-specific, and overall survival (PFS, CSS, and OS, respectively) stratified by preoperative CKD status (CKD vs. non-CKD). We performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and developed the prognostic factor-based risk stratification nomogram. Results: Of the 581 patients, 215 (37%) were diagnosed with CKD before radical cystectomy. Before the background adjustment, PFS, CSS, and OS after radical cystectomy were significantly lower in the CKD group compared to the non-CKD group. Background-adjusted IPTW analysis showed that preoperative CKD was significantly associated with poor PFS, CSS, and OS after radical cystectomy. The nomogram for predicting 5-year PFS and OS probability showed significant correlation with actual PFS and OS ( c-index = 0.73 and 0.77, respectively). Conclusions: Muscle-invasive bladder cancer patients with preoperative CKD had a significantly lower survival probability than those without CKD.

428 Background: The prognostic benefit of oncological follow-up to detect asymptomatic recurrence after radical cystectomy (RC) remains unclear. We aimed to assess whether routine follow-up to detect asymptomatic recurrence after RC improves patient survival. Methods: We retrospectively analyzed 581 RC cases for muscle invasive bladder cancer at four hospitals between May 1996 and February 2017. All patients had regular follow-up examinations with urine cytology, blood biochemical tests, and computed tomography after RC. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of recurrence (asymptomatic group vs. symptomatic group) was estimated using the Kaplan–Meier method with the log–rank test. Cox proportional hazards regression analysis via inverse probability of treatment weighting (IPTW) was used to evaluate the impact of the mode of diagnosing recurrence on survival. Results: Of the 581 patients, 175 experienced relapse. Among those, 12 without adequate data were excluded. Of the remaining 163 patients, 76 (47%) were asymptomatic and 87 (53%) were symptomatic at the time of diagnosis. The most common recurrence site and symptom were lymph nodes (47%) and pain (53%), respectively. Time of overall survival after RC and from recurrence to death were significantly longer in the asymptomatic group than symptomatic group. A multivariate Cox regression analysis using IPTW showed that in the patients with symptomatic recurrence was an independent risk factor for overall survival after RC and survival from recurrence to death. Conclusions: Routine oncological follow-up for detection of asymptomatic recurrence contributes to a better prognosis after RC.

347 Background: Symptomatic toxicities associated with anticancer treatments are at high risk of under-reporting by clinicians. However, insufficient evidence is available for urothelial carcinoma. To compare toxicity reporting by patients and clinicians in urothelial carcinoma patients who received systemic chemotherapy. Methods: Between June 2013 and March 2016, 100 urothelial carcinoma patients who received two courses of chemotherapy of gemcitabine plus cisplatin (GCis) or gemcitabine plus carboplatin (GCb) were included in this study. Outcome Measurements and Statistical Analysis: During chemotherapy, patients answered QLQ-C30 quality of life (QOL) questionnaires, which included questions on four toxicity-related symptoms (appetite loss, nausea, constipation, and diarrhea). Clinicians evaluated adverse events using CTCAE v4.0. Differences in toxicity reporting were retrospectively compared between patients and clinicians. Logistic regression analyses were performed to investigate potential factors for under-reporting by clinicians. Results: Toxicity under-reporting was most frequent in diarrhea (44%), followed by appetite loss (39%), constipation (33%), and nausea (22%). In total, toxicity under-reporting was observed in 72% patients. Background-adjusted logistic regression analyses showed that pretreatment QOL items, such as global and symptomatic scores, were selected as potential predictors for toxicity under-reporting by clinicians. Limitations of our study included its retrospective nature and small sample size. Conclusions: Toxicity under-reporting by clinicians is frequent in urothelial carcinoma patients who received systemic chemotherapy. Pretreatment QOL evaluation is essential to identify potential individuals at risk for toxicity under-reporting. Clinical trial information: UMIN000020784.

e542 Background: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) for high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing hormone-releasing hormone agonist plus low-dose estramustine (LHRH agonist + EMP) prior to radical prostatectomy (RP). In the present study, we evaluated the efficacy of neoadjuvant therapy comprising a gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate (GnRH antagonist + EMP) in patients with high-risk Pca. Methods: Between September 2005 and March 2016, we identified 406 high-risk Pca patients of whom 136 received neoadjuvant GnRH antagonist + EMP and 270 received LHRH agonist + EMP before RP. We retrospectively evaluated the clinical and pathological covariates between the two groups. The primary endpoint was the rate of pathological ≤ T2 status, and the secondary endpoint was BRFS. Results: The rates of pathological ≤ T2 status were 80.2% and 61.5% in the GnRH antagonist + EMP and LHRH agonist + EMP groups, respectively ( P < 0.001). The 3-year BRFS rates were 97.8% and 85.2% in the GnRH antagonist + EMP and LHRH agonist + EMP groups, respectively ( P = 0.021). Multivariate analysis revealed that biopsy Gleason score, GnRH antagonist + EMP, and clinical T stage were independent predictors of pathological ≤ T2 status in surgical specimens. Conclusions: Our findings suggest that neoadjuvant GnRH antagonist + EMP followed by RP may improve the pathological outcomes and reduce the risk of biochemical recurrence in patients with high-risk Pca. Further prospective studies to confirm these findings are warranted.

e562 Background: We estimated the natural history and predictive factors of oncological outcomes in patients with prostate cancer (PCa) after radical prostatectomy (RP). Methods: In this retrospective study, we reviewed the clinical and pathological records of 1083 PCa patients who underwent RP and bilateral pelvic lymphadenectomy with or without neoadjuvant therapy between July 1996 and December 2014 at Hirosaki University. All patients were followed-up by assessing serum prostate-specific antigen (PSA) and testosterone levels every 3 months for 5 years and every 6 months thereafter. The endpoint was the oncological outcomes after surgery. Univariate analyses were performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model. Results: The 5-year and 10-year overall survival rates were 98.5 % and 92.0 %, respectively. At the end of the study, 226 patients (20.8%) showed biochemical recurrence and 28 patients (2.6%) had developed castration-resistant Pca (CRPC). The patients with CRPC were significantly poor prognosis compared with those without CRPC (P < 0.01). On multivariate analysis, although preoperative variables were no significant differences, only CRPC was significantly associated with OS. Conclusions: RP was shown to provide excellent long-term survival with OS at 10 years. In addition, a small proportion of the patients treated with RP had CRPC and died of Pca within 10 years. Development to castration resistant status may have critical impact on OS.

125 Background: Safety of heparin bridging therapy for transrectal ultrasound-guided prostate (TRUS) biopsy in patients requiring temporary discontinuation of antithrombotic therapy is unknown. This study aimed to assess the relationship between heparin bridging therapy and the incidence of complications after TRUS biopsy. Methods: From January 2005 to November 2015, we performed 1307 consecutive TRUS biopsies on 1134 patients in our hospital. The patients were assigned to two groups: those without heparin bridging (the control group) and those with temporary discontinuation of antithrombotic agents with heparin bridging therapy (the bridging group). A 10–12-core TRUS biopsy was performed; the patients were evaluated for bleeding-related complications. Results: Of 1134 patients, 1109 (1281 biopsies) and 25 (26 biopsies) were assigned to the control and bridging group, respectively. Patient background did not significantly differ between the control and bridging groups, except for age, history of diabetes, cardiovascular diseases, and CHADS2 scores. Compared with the control group, the bridging group showed a significantly higher rate of complication for any complication (35% vs. 8.3%, P < 0.001), bleeding-related complications (27% vs. 4.4%), and urinary tract infection (7.7% vs. 1.2%). No thromboembolic event was observed in the present study. Multivariate logistic analysis showed that heparin bridging therapy was a significant risk factor for the incidence of any complication and bleeding-related complications. Conclusions: Heparin bridging therapy with temporal discontinuation of antithrombotic agents may increase the risk of complications after TRUS biopsy. Further, large-scale studies are required to clarify the safety of heparin bridging therapy.

374 Background: Neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC) has better survival benefit than radical cystectomy (RC) alone. However, recurrences still occur in many cases and recurrent disease is the most lethal factor associated with death in MIBC. On the other hand, the rate and pattern of recurrences after neoadjuvant chemotherapy in MIBC patients remains unclear. Methods: Eligible patients had histologically confirmed stage T2-T4a muscle-invasive urothelial carcinoma of the bladder without lymph node or distant metastasis in this study. The cohort of neoadjuvant group consists of 130 patients with MIBC. The cohort of RC alone group includes 135 patients with MIBC treated with RC and bilateral pelvic lymph node dissection between May 1994 and July 2007. Propensity score matching was used to adjust for potential selection biases associated with treatment type. Recurrence site was defined as local, LN (lymph nodes), and distant metastases. Results: Propensity score-matched analysis indicated 130 matched pairs from both groups. The 5-year overall survival rate was 91% for neoadjuvant GCarbo versus 49% for RC alone group (P < 0.0001). The disease-free survival rate was 87% for neoadjuvant GCarbo versus 57% for surgery alone (P < 0.0001). The distant metastases were comparable in both groups. The total number of local recurrences or LN mets was markedly decreased in neoadjuvant GCarbo compared with RC alone cohort. Conclusions: The MIBC patients treated with neoadjuvant GCarbo achieved an improved oncological outcome with a different recurrence pattern compared to RC alone.

404 Background: According to several guidelines, the standard therapy for carcinoma in situ (CIS) of the upper urinary tract is total nephroureterectomy. However, it is difficult to determine a treatment strategy for elderly patients. Bacillus Calmette-Guerin (BCG) therapy has already been established as a treatment for non-muscle invasive bladder cancer. However, although there are several reports indicating the effectiveness of BCG perfusion therapy for the upper urinary tract CIS, it has not been established yet. We conducted a retrospective study to assess the long-term effects of BCG perfusion therapy for the upper urinary tract CIS for elderly patients. Methods: We treated 34 patients with upper urinary tract CIS at our clinic between August 2004 and March 2015. 29 patients (22 men and 7 women) with the age of 65 years or older were enrolled. 11 subjects had the entire urinary tract CIS, 8 had bilateral, 10 had unilateral CIS of the upper urinary tract. The average period of observation was 45.5 months ( 5 to 151 ), and the average subject age was 76.5 years (66 to 90 ). We used a double-J catheter for 22 cases, a transvesical single-J catheter whose curl was positions in an upper calyx for 6 cases, and a straight ureteral catheter inserted for ureterocutaneostomy for 1 case. We used 80 mg of BCG for the first 4 cases, 40 mg for the late 25 cases. The BCG treatment was given once a week for consecutive 6 weeks. Urine cytology was performed to assess the treatment validity. Results: Urine cytology tests became negative in 22 of the 29 subjects (75.9%) who underwent upper urinary tract perfusion therapy. Among these 22 subjects who had negative tests, 6 subjects had a recurrence in their upper urinary tracts. Side effects were observed in 28 subjects (89.7%), and the most common side effect was bladder irritation. Localized renal tuberculosis which was successfully treated with conservative therapy was seen in two cases. Conclusions: BCG perfusion therapy for the upper urinary tract CIS is safe and effective for elderly patients. Results also suggested that this could be one of the effective treatment options. However, we have to be careful for severe side effects.

401 Background: We retrospectively evaluated the feasibility and effectiveness of a caboplatin-based sequential chemotherapy for the patients with advanced bladder cancer whose creatinine clearance (Ccr) was 60 ml/min or below. Methods: We treated 68 patients with advanced bladder cancer at our clinic between August 2004 and December 2014. 48 patients with advanced bladder cancer (33 men and 15 women) whose Ccr were 60 ml/min or below were enrolled. Their average age was 72.5 years old (43–83), average Ccr of 43.3 ml/min (14.5–57.0), and an average follow-up period of 24.5 months (5–92). The therapeutic regimen consisted of 2 lines: gemcitabine/carboplatin (GCarbo) therapy as the first line, with two courses as a set; GCarbo/docetaxel (GCarboD) therapy as the second line if the response in the first line was insufficient. GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to GCarboD, which consisted of 800mg/m2 gemcitabine on days 1 and 8, 70mg/m2 docetaxel on day 1, and carboplatin (AUC 3) on day 2. Results: Of the 48 subjects who had undergone the GCarbo therapy, the response rate was 35.4% (CR+PR) with 3 and 14 subjects exhibiting complete response (CR) and apartial response (PR), respectively; the average response duration was 10.8 months (2–90). The response rates of 9 instances of GCardoD was 33.3%; the overall median survival was 18.0 months throughout the sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 30 of those who had undergone the GCarbo therapy (62.5%). Conclusions: Although the present study is small and preliminary, the present carboplatin-based sequential chemotherapy is safe and active for advanced bladder cancer with impaired renal function. GCarbo regimen achieved acceptable response rate (35.4%) in advanced bladder cancer. The median overall survival of 18.0 months is acceptable when average Ccr of 43.3 ml/min for the subjects is took into consideration.

507 Background: Tubulocystic carcinoma of the kidney (TubCC) is a new entity of tumor not listed in the 2004 WHO classification. The tumor comprised tubules forming duct-like structures exhibiting hobnail change, and resembled collecting duct carcinoma (CDC) by immunostaining; thus, this tumor was named low grade CDC. Since then, similar tumors have been reportedly called tubulocystic carcinoma (TubCC)We explored the possibility whether Aldo-keto-reductase-1B1 (AKR1B1), osmoregulatory protein and abundant in collecting duct, can be used as a marker for the pathologic diagnosis of TubCC. Methods: We prepared anti-AKR1B1 monoclonal antibodies, examined expression of AKR1B1 protein in the human normal kidney. Immunohistochemical expressions of AKR1B1 was examined on normal kidney, 4 cases of TubCC, 10 cases of papillary renal cell carcinoma (pRCC), and 10 cases of invasive urothelial carcinoma (iUC). Results: AKR1B1 expression distributed preferentially in the renal medulla and not in the cortex, reflected by its high concentration in medulla (2.12 ±1.35 μg/mg) compared with cortex (0.13 ± 0.03 μg/mg). Immunohistochemically, AKR1B1 was strongly positive in 3 of 4 TubCC cases. AKR1B1 was negative in cases of either iUC or pRCC. Conclusions: Although the present study was small and preliminary, AKR1B1 may be a more specific and potentially useful marker for TubCC. [Table: see text]

373 Background: Butyrylcholinesterase (BChE) is an alpha-glycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, inflammation, injury, infection, malnutrition, and malignant disease. In this study, we analyzed the potential prognostic significance of preoperative BChE levels in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Methods: We retrospectively evaluated 327 patients with MIBC who underwent RC from 1996 to 2013 at a single institution. Serum BChE was routinely measured before operation in all patients. Covariates included age, gender, preoperative laboratory data (anemia, BChE, lactate dehydrogenase, C-reactive protein), clinical T (cT) and N stage (cN), tumor grade, and RC with/without neoadjuvant chemotherapy. Univariate and multivariate analyses were performed to identify clinical factors associated with overall (OS) and disease-free survival (DFS). Univariate analyses were performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model. Results: The median BChE level was 187 U/L (normal range, 168–470 U/L). The median age of the enrolled patients was 69 years, and the median follow-up period was 51 months. The 5-year OS and DFS rates were 69.6% and 69.3%, respectively. The 5-year OS rates were 90.1% and 51.3% in the BChE ≥ 168 and < 168 U/L groups, respectively (P < 0.001). The 5-year DFS rates were 83.5% and 55.4% in the BChE ≥ 168 and ≤ 167 U/L groups, respectively (P < 0.001). In the univariate analysis, BChE, cT, cN, and RC with/without neoadjuvant chemotherapy were significantly associated with both OS and DFS. Multivariate analysis revealed that BChE was the factor most significantly associated with OS, and BChE, cT, and cN were significantly associated with DFS. Conclusions: This study validated preoperative serum BChE levels as an independent prognostic factor for MIBC after RC.

172 Background: Aldo-keto reductase family 1 member C3 (AKR1C3) is a key steroidogenic enzyme that is implicated in the development of castration-resistant prostate cancer (CRPC). In this study, we examined AKR1C3 expression in surgical specimens of high risk prostate cancer treated with neoadjuvant LHRH + EMP, and we investigate the correlation between the expression level of AKR1C3 and the occurrence of CRPC. Methods: High-risk Pca was defined by the D’Amico stratification system. A total of 103 patients with high-risk Pca were enrolled in this study. The LHRH + EMP therapy included the administration of the LHRH agonist and 280 mg/day of EMP for six months before the radical prostatectomy. BCR was defined as the prostate-specific antigen (PSA) levels greater than 0.2 ng/mL after the prostatectomy. Castration-resistant prostate cancer (CRPC) is defined by PSA or radiographic progression in the castrate levels of testosterone ( < 50 ng/dL). Along with the routine pathological assessment, AKR1C3 expression was evaluated in tissue microarray analysis (TMA) in all patients. A multivariable Cox proportional hazards model was used to evaluate the association between CRPC and clinical data. Results: The average patient age was 67.2 (49 to 78), and the median initial PSA level was 18.8 ng/mL (4.2–95.6). At a median follow-up period of 79.5 months, BCR occurred in 41 patients (39.8%) and CRPC occurred in nine patients (8.7%). In TMA, overexpression of AKR1C3 was seemed in 14 patients (13.6%). 5-year CRPC free survival rate of AKR1C3(+) patients (64.2%) was significantly lower than that of AKR1C3(-) patients (97.6%). (Log-rank test: p < 0.001) On multivariable analysis, AKR1C3 expression is an independent risk factor for occurrence of CRPC in this study. (p = 0.044). Conclusions: Although the present study was small and preliminary, overexpression of AKR1C3 is an independent risk factor for occurrence of CRPC in the high risk prostate cancer treated with neoadjuvant LHRH + EMP and prostatectomy. Further study is warranted to elucidate its clinical significance.

489 Background: Specific tumor marker for seminoma is still lacking. Moreover, 10% to 15% of the patients with non-seminomatous germ cell tumor (NSGCT) can be expected to have normal marker levels. Glycan-based biomarkers for testicular germ cell tumor (TGCT) have not yet been established. We examined whether the serum N-glycan profiling can be applied to detection in patient with TGCT. Methods: We performed a N-glycan structural analysis of sera from 14 patients with GCT and age-matched 28 healthy volunteers using the glycoblotting methods and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The intensity of the N-glycans was compared between the TGCT patients and the volunteers to select TGCT associate N-glycans. Optimal cut-off values were determined by receiver operating characteristic (ROC) curves. Selected N-glycans were divided according to cut-off values, and positive numbers of TGCT associated N-glycan was added up to risk classification. Results: Six (43%) had seminoma, and eight (57%) patients had NSGCT in this study. The numbers of patients in stage I, II, III were 5, 2, and 4, respectively. Three patients had extragonadal tumor. The numbers of patients in IGCCC good, intermediate and poor risk were 10, 1, and 3, respectively. There were 3 patients (21%) with negative in any tumor markers. We identified 70 kinds of N-glycans in sera from healthy volunteers and GCT patients. A total 6 of N-glycans; m/z 2336.85, 2378.86, 2890.05, 3195.16, 3341.22, 3560.30 were selected as significantly high intensity in the patient with TGCT than in the healthy volunteers, with the area under the curve (AUC) of 0.81, 0.83, 0.86, 0.84, 0.81, and 0.78, respectively. Tumor associated N-glycans were classified as positive or negative, and scored from 0 to 6 points. Optimal cut-off score for detection was determined by ROC curve, and score > 3 were selected (AUC 0.90, P < 0.001). Based on this classification, 2 of 3 patients with negative tumor markers were categorized as a carrier for TCGT. Conclusions: Although the present study is small and preliminary, serum N-glycan analysis is a potential approaches to discover new biomarkers for TGCT. Further validation study is warranted.

375 Background: Standard neoadjuvant chemotherapy has not yet been established for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin (CDDP)-based chemotherapy. We conducted a propensity score analysis to evaluate the clinical significance of neoadjuvant gemcitabine and carboplatin (GCarbo) chemotherapy for CDDP-ineligible patients with MIBC. Methods: We enrolled 381 patients with MIBC, and retrospectively compared two cohorts of CDDP-ineligible patients with MIBC. The GCarbo cohort consisted of 63 patients, who received 2 courses of GCarbo consisting of 800 mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin with an area under the curve of 4 on day 2, prior to RC. The RC alone cohort consisted of 56 patients receiving RC without neoadjuvant or adjuvant chemotherapy. The endpoints were overall (OS), cancer-specific (CSS), and disease-free survival (DFS). The oncological outcomes were analyzed using log-rank test and multivariate Cox regression model. Results: Propensity score-matched analysis indicated 56 matched pairs from both groups. The 3-year OS rates were 77.9% for the GCarbo cohort and 50.7% for the RC alone cohort (P = 0.002). The 3-year CSS rates were 92.8% for the GCarbo cohort and 52.6% for RC alone group (P < 0.001). The 3-year DFS rates were 80.6% for the GCarbo cohort and 48.1% for the RC alone cohort (P = 0.005). Multivariate analysis revealed that GCarbo was an extremely strong predictor of improved survival. Conclusions: Although the present study is non-randomized, neoadjuvant GCarbo chemotherapy followed by immediate RC significantly improved OS, CSS, and DFS in CDDP-ineligible MIBC patients.

364 Background: It is unknown whether routine follow up with body computed tomography (CT) to detect asymptomatic visceral recurrence after nephroureterectomy improves patient survival. We accessed the impact of follow up with body CT on patient survival after nephroureterectomy. Methods: A total 212 nephroureterectomy for upper urinary tract urothelial carcinoma were performed at our hospital between Feb 1995 and Oct 2015. All patients had regular follow up with chest x-ray, urine cytology and cystoscopy every 3 to 6 months, blood biochemical test, and CT of the chest and abdomen every 6 to 12 months. Additional examinations were required for symptomatic recurrence. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of diagnosis (asymptomatic vs. symptomatic) was estimated using the Kaplan-Meier methods and compared with the log rank test. Cox proportional hazard regression models were used to evaluate the impact of the mode of diagnosing recurrence on survival. Results: A total 43 patients (20%) experienced recurrence after surgery, of whom 31 (72%) were asymptomatic and 12 (28%) were symptomatic. The most common symptoms at recurrence were pain in 7, hematuria in 2 , appetite loss in 1 , edema in 1 , palpable mass in 1, general malaise in 1 patients. Overall survival was not significantly different between in patients with asymptomatic vs. symptomatic recurrence; however, survival after tumor recurrence were better in patients with asymptomatic recurrence (P = 0.033). Moreover, multivariate analysis showed symptomatic recurrence was selected as a risk factor for overall survival after recurrence. Conclusions: Routine oncological follow up after nephroureterectomy for early detection of asymptomatic visceral recurrence was associated with patient survival. Further study is necessary to establish the optimal follow up regimen balancing the benefit of asymptomatic detection with the increased cost of routine surveillance.

361 Background: It is unknown whether routine follow-up with computed tomography (CT) to detect asymptomatic visceral recurrence after radical cystectomy improves patient survival. We accessed the impact of symptoms at recurrence on patient survival after radical cystectomy and survival after recurrence. Methods: A total 348 radical cystectomy for muscle invasive bladder cancer (MIBC) were performed at our institution between January 1996 and December 2013. All patients had regular followup examinations with urine cytology every 3 months, blood biochemical test, and CT of the chest and abdomen every 6 months. Additional examinations were required for symptomatic recurrence. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of diagnosis (asymptomatic vs. symptomatic) was estimated using the Kaplan-Meier methods and compared with the log rank test. Cox proportional hazard regression models were used to evaluate the impact of the mode of diagnosing recurrence on survival. Results: A total 91 patients (20%) experienced recurrence after surgery. Seven patients (8%) were excluded due to missing data. Finally, 84 patients were enrolled in this retrospective study. Of those, 46 (55%) were asymptomatic and 38 (45%) were symptomatic. Recurrence sites included lymph nodes in 46 patients (55%), local recurrence in 23 (27%), bone in 14 (17%) and visceral organs in 21 (25%). The most common symptoms at recurrence were pain in 20 patients (53%). Overall survival after radical cystectomy and recurrence were significantly shorter in patients with asymptomatic recurrence. The median survival after surgery and after tumor recurrence in patients with asymptomatic vs. symptomatic recurrence were 33 and 14 vs. 13 and 5 months, respectively (P=0.0142 and P=0.0001). Multivariate analysis showed that a symptomatic recurrence was one of the independent factors for overall survival after surgery and recurrence. Conclusions: Routine CT followup after radical cystectomy for early detection of asymptomatic recurrence may contribute better prognosis in patients with MIBC.

342 Background: We retrospectively evaluated the feasibility and effectiveness of carboplatin based chemotherapy for the patients 65 years or older with advanced bladder cancer. Methods: We treated 86 patients with advanced bladder cancer at our clinic between August 2004 and June 2014. 56 patients (40 men and 16 women) with the age of 65 years or older were enrolled. Their average age was 75.8 years old (65–86), average Ccr was 54.4 ml/min (14.5–113.0), and an average follow-up period was 21.7 months (2–81). There were 18 recurrent cases after radical surgery and 38 inoperable cases. The therapeutic regimen consisted of 2 lines: gemcitabine/carboplatin (GCarbo) therapy as the first line, with two courses as a set; GCarbo/docetaxel (GCarboD) therapy as the second line if the response in the first line was insufficient. GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to GCarboD, which consisted of 800mg/m2 gemcitabine on days 1 and 8, 70mg/m2 docetaxel on day 1, and carboplatin(AUC 3) on day 2. Treatment efficacy was checked every 2 course. Results: Of the 56 subjects who had undergone the GCarbo therapy, the response rate was 37.5% (CR+PR) with 4 and 17 subjects exhibiting CR and a PR, respectively; the average response duration was 10.0 months (2–78). The response rates of 12 instances of GCardoD was25.0 %; the overall median survival was 14.0 months throughout the carboplatin-based sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 33 of those who had undergone the GCarbo therapy (58.9%). In GCarboD regimen, there were 11 (91.7 %) of G3/4 AEs. Conclusions: Although the present study is small and preliminary, the present carboplatin-based sequential chemotherapy is safe and active for advanced bladder cancer of the patients 65 years or older. GCarbo regimen achieved acceptable response rate (37.5%) in advanced bladder cancer. The median overall survival of 14.0 months is acceptable when average age of 75.8 year for the subjects is took into consideration. However, GCardoD had limited effectiveness for non-responder of GCarbo.

344 Background: Gemcitabine + cisplatin may be a promising regimen for advanced upper-tract urothelial carcinoma (UTUC) as well as for advanced bladder cancer. However, cisplatin is proved to be too toxic for the patients with impaired renal function and aged patients. Majority of aged patients with UTUC have impaired renal function. There is no standard regimen for such patients. We assessed the effectiveness and adverse events (AEs) of a sequential chemotherapy with Gemcitabine plus carboplatin(GCarbo) followed by GCcarbo plus docetaxel (GCarboD) for advanced UTUC. Methods: We treated 86 patients with advanced UTUC at our clinic between August 2004 and December 2013. 45 patients (31 men and 14 women) with the age of 65 years or older were enrolled. Mean age was 73.0 (65–89), and mean Ccr was 47.9 (11.6–99.2) ml/minute. Mean observation period was 22.9 (3–87.2) months. The therapeutic regimen consisted of 2 lines: GCarbo therapy as the first line, with two courses as a set; GCarboD therapy as the second line if the response in the first line was insufficient. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to GCarboD. Results: GCarbo regimen yielded 1 cases (2.2%) of CR, 20 (44.4%) of PR, and the mean duration of response of 11.0(3–51) months. GCarboD treatment was administered in 12cases, and yielded one (8.3%) PR and a duration of response was 7.0 months. The median survival period was 14.0 months with GCcarbo/GCarboD regimens. As for ARs with GCcarbo regimen, there were 23 (52.2%) of G3/4 blood toxicity. In GCarboD regimen, there were 11 (91.7%) of blood toxicity and 7 (58.3%) of gastrointestinal AEs. Conclusions: Although the present study is small and preliminary, the present sequential chemotherapy is safe and active for advanced UTUC of the patients sixty-five years or older. GCarbo regimen achieved relatively high response rate (46.6%) in advanced UTUC. The median overall survival of 14.0 months is acceptable when average age of 73.0 year for the subjects is took into consideration. However, GCarboD had limited effectiveness for non-responder of GCarbo.

361 Background: Prognosis and tumor responses of carboplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC) are not well documented. To assess the usefulness of carboplatin-based neoadjuvant chemotherapy, we examined the correlation between radiological responses and pathologic down staging on radical cystectomy (RCx) specimens, disease free survival (DFS), and overall survival (OS). Methods: Between March 2005 and June 2013, we performed carboplatin-based neoadjuvant chemotherapy followed by radical cystectomy in 115 patients with T2-4NxM0 MIBC. After diagnostic TUR biopsy, all participants received two courses of Gemcitabine plus Carboplatin therapy. Baseline and post chemotherapy tumor size from contrast enhanced CT were reviewed. The patients were divided in two groups between responders (CR+PR), and non-responders (SD+PD). RCx and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. DFS and OS distributions within radiologic response subgroups were estimated with the Kaplan-Meier method and compared using the log-rank test. To evaluate independent predictor for DFS and OS, age, gender, performance status, pathological T and N stage, down-staging, tumor grade, renal function, and radiological responses were applied by Cox-regression multivariate analysis. Results: No significant differences were observed in patient backgrounds between the groups. Radiologic responses were observed in 75 (65%) patients with 69±24% decrease in responder group, whereas tumor response was 2.8±14% in non-responders. The rate of pathological down staging to

483 Background: Collecting duct carcinoma (CDC) is a rare tumor but its recognition is important for the prediction of prognosis and decision making of the treatment. However, its diagnosis is challenging because of versatility of pathological features. We explored the possibility whether aldose reductase (AR), osmoregulatory protein and abundant in renal medulla, can be used as a marker for the pathologic diagnosis of CDC. Methods: We prepared anti-AR monoclonal antibodies, examined expression of AR protein in the human normal kidney. Immunohistochemical expressions of AR, 34bE12, a-methyl CoA racemase (AMACR) and expressions of lectins (Ulex europaeus agglutinin 1; UEA-1 and peanut agglutinin; PNA) were examined on normal kidney, 12 cases of CDC, 10 cases of papillary renal cell carcinoma (pRCC), and 10 cases of invasive urothelial carcinoma (iUC). Results: AR expression distributed preferentially in the renal medulla and not in the cortex, reflected by its high concentration in medulla (2.12 ±1.35 μg/mg) compared with cortex (0.13 ± 0.03 μg/mg). Immunohistochemically, AR was strongly positive in 9 of 12 CDC cases. AR was negative in cases of either iUC or pRCC. In contrast, although lectins were positive in all cases of CDC, they were also found in all types of malignancy. iUC was positive for 34bE12 in all cases but also so in some cases of CDC and pRCC. AMACR was positive for all the cases of pRCC but also positive for other tumors. Conclusions: Compared with other markers, AR may be a more specific and potentially useful marker for CDC. [Table: see text]

251 Background: Interstitial fibrosis (IF) have been known to occur in radical prostatectomy specimens treated with hormonal therapy. We previously reported that neoadjuvant therapy for high-risk prostate cancer (Pca) with luteinizing hormone-releasing hormone (LHRH) agonist and low-dose estramustine phosphate (EMP) (LHRH + EMP) significantly improved biochemical recurrence (BCR) free survival. In this study, we quantified IF in radical prostatectomy specimens treated with neoadjuvant LHRH + EMP, and we examined whether degree of IF has impact on BCR free survival or subsequent castration-resistant status. Methods: High-risk Pca was defined by the D’Amico stratification system. A total of 103 patients with high-risk Pca were enrolled in this study from July 2005 to August 2010. The LHRH + EMP therapy included the administration of the LHRH agonist and 280 mg/day of EMP for six months before the radical prostatectomy. BCR was defined as the prostate-specific antigen (PSA) levels greater than 0.2 ng/mL after the prostatectomy. Castration-resistant prostate cancer (CRPC) is defined by PSA or radiographic progression in the castrate levels of testosterone (< 50 ng/dL). A quantitative analysis of IF was performed using computer-assisted imaging. Results: The average patient age was 67.2 (49 to 78), and the median initial PSA level was 18.8 ng/mL (4.2–95.6). All patients completed six months of LHRH + EMP neoadjuvant therapy with no delays in the radical prostatectomy. At a median follow-up period of 64.0 months, BCR occurred in 41 patients (39.8%) and CRPC occurred in nine patients (8.7%). The average IF rate was 0.43 (0.33–0.55). The five year BCR-free survival rates for the groups with IF rates less than 0.42 and greater than 0.42 were 74.7% and 50.0%, respectively. The log-rank test was significantly different between the two groups (p = 0.010). We could not identify CRPC in the patients with IF rates less than 0.42. Conclusions: Although the present study was small and preliminary, the IF rate may have a predictive potential for biochemical outcome and the occurrence of CRPC after neoadjuvant therapy for high-risk Pca. Further study is warranted to elucidate its clinical significance.

259 Background: To date, the different treatment modalities for high-risk prostate cancer (Pca) have not been compared in any sufficiently large-scale, prospective, randomized clinical trial. We used propensity-score matching analysis to compare the oncological outcomes of high-risk prostate cancer between patients treated with radical prostatectomy (RP) and those treated with radiation therapy (RT). Methods: We studied 216 patients who received neoadjuvant therapy followed by RP (RP cohort) and 81 patients who received neoadjuvant androgen-deprivation therapy (ADT) followed by RT (RT cohort). The RP cohort received a luteinizing hormone-releasing hormone agonist and estramustine phosphate (280 mg/day) for 6 months prior to RP. The RT cohort received ADT for at least 6 months prior to RT using a 3-dimensional conformal radiotherapy technique. The total radiation dose was 70–76 Gy administered at 2 Gy/fraction. Results: Propensity-score matching identified 78 matched pairs of patients. The 3-year overall survival (OS) rates were 98.3% and 92.1% in the RP and RT groups, respectively (P = 0.156). The 3-year biochemical recurrence-free survival rates were 86.4% and 89.4% in the RP and RT groups, respectively (P = 0.878). Conclusions: Our study findings may suggest almost identical cancer control of RP and RT with appropriate neoadjuvant therapy in high-risk Pca. Therefore, issues of health-related quality of life may have important impact on decision making of treatment in high-risk Pca.

340 Background: Management of muscle-invasive bladder cancer (MIBC) in elderly patients is issue of vital importance. The aim of the present study was to compare the oncological outcome of radical cystectomy to trimodality bladder preservation therapy. Methods: Between 1996 and 2013, we treated consecutive 419 patients with MIBC. Of these, we identified 44 patients with MIBC (cT2-4aN0M0) aged 80-84 years. We retrospectively reviewed the clinical charts of these patients. All patients received maximally safe transurethral resection of the bladder tumor before definitive therapy. The patients were categorized according to the treatment options into 2 cohorts; radical cystectomy cohort (RCx, n = 22), or radiotherapy with chemotherapy cohort (Trimodality, n = 22). All patients in trimodality cohort received at least 2 courses of gemcitabine plus carboplatin chemotherapy. Each patient was evaluated every 3-6 months by blood test, urine cytology, and computed tomography. Overall survival (OS), progression free survival (PFS) was estimated by Kaplan-Meier method. Multivariate analysis was used to identify independent factors to predict OS or PFS. Results: There were no significant differences in patient backgrounds between the groups, except for ECOG performance status (ECOG-PS), Charlson comorbidity index (CCI) and eligibility for cisplatin. The mean ECOG-PS, CCI and the number of cisplatin-unfit patients were significant higher in trimodality cohort (p = 0.001, p = 0.034, and p = 0.003, respectively). There were no significant differences in OS and PFS between the groups. On multivariate analysis, ECOG-PS >1 was the independent prognostic factors for OS and PFS. Conclusions: Trimodality bladder preservation therapy for MIBC in elderly patients is comparable to those who received radical cystectomy. For patients with MIBC who are non-cystectomy candidates, or select patients who are motivated to keep their native bladders, trimodality bladder preservation therapy should recognized as an effective alternative to radical cystectomy, and be considered.

458 Background: Prognostic factors for overall survival (OS) of the patients with clear cell renal cell carcinoma (cRCC) treated with nephrectomy are still not defined well. Butyrylcholinesterase (BChE) is an α-glycoprotein found in the nervous system and liver. Advanced cancer is a condition with mild to moderate inflammation and interacts with various degree of protein-energy malnutrition. In this study, we analyzed the potential preoperative prognostic significance of BChE in patients with cRCC undergoing nephrectomy. Methods: etween 1992 and 2013, we treated 551 patients with renal cell carcinoma. Of these 400 patients with cRCC who underwent radical or partial nephrectomy were enrolled. Serum BChE was routinely measured before operation in all patients. Covariates included age, gender, performance status (PS), preoperative laboratory data, clinical T stage, and distant metastasis status. Univariate analyses were performed using the Kaplan-Meier and log-rank methods. Multivariate analysis was performed using a Cox proportional hazard model. Univariate and multivariate analyses were performed to determine clinical factors that associated with OS. Results: Of these, 302 patients had an organ-confined disease (T1-2N0M0) and 56 patients had a distant metastasis (any T, any N, and M1). The median BChE level was 250U/L (normal range from 168 to 470U/L). The median follow-up period was 34 months. At the time of analysis, 26 patients (6.5%) had alive with recurrent cRCC and 38 patients (9.5%) had died from cRCC. The 3-year OS rate for our entire cohort of 400 patients was 88%. The 3-year OS rates were 89.3% and 77.7% in the BChE ≥100 and

279 Background: We examined biochemical outcome of small volume prostate cancers (

e15565 Background: Standard neoadjuvant chemotherapy has not yet been established for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin based chemotherapy. In the present study, we conducted a propensity score analysis to elucidate the clinical significance of neoadjuvant gemcitabine and carboplatin chemotherapy (GCarbo) for cisplatin-ineligible patients with MIBC. Methods: The cohort of the neoadjuvant group consisted of 51 patients with MIBC, treated between March 2005 and June 2011, who were ineligible for cisplatin. Patients received 2 courses of GCarbo consisting of 800 mg/m2gemcitabine on days 1, 8, and 15, and carboplatin with an AUC of 4 on day 2. After GCarbo, radical cystectomy (RC) and bilateral pelvic lymph node dissection (PLND) were performed at an interval of 1 month. The cohort of RC alone included 59 cisplatin-ineligible MIBC patients treated with RC and bilateral PLND between June 1998 and February 2010. Propensity score matching was used to adjust for potential selection biases associated with treatment type. The endpoints were overall (OS) and disease-free survival (DFS). Results: Of the 51 patients who received GCarbo and RC, 6 (11.8%) RC specimens were found to be cancer free. Grade 3/4 neutropenia occurred in 17 patients (33.3%) and thrombocytopenia in 11 patients (21.6%). There were no patients who experienced grade3/4 nephrotoxicity or nausea. Propensity score-matched analysis indicated 45 matched pairs from both groups. The median follow-up period was 35.3 months. The 3-year OS rate was 86.5% for neoadjuvant GCarbo vs. 50.6% for the RC alone group (P < 0.0001). The DFS rate was 78.8% for neoadjuvant GCarbo vs. 44.8% for RC alone (P= 0.001). Multivariate analysis revealed that the neoadjuvant GCarbo regimen was an extremely strong and independent predictor of the longer OS and DFS. Conclusions: Although the present study is non-randomized, neoadjuvant GCarbo chemotherapy followed by immediate RC achieved significantly longer OS and DFS than cystectomy alone. The clinical usefulness of the present treatment for cisplatin-ineligible patients with MIBC should be verified by further trials.

223 Background: Prostate cancer (Pca) can be detected coincidentally in radical cystoprostatectomy (RCP) specimens for invasive bladder cancer. However, there is no uniformity of opinion on the need for prostate biopsy prior to RCP. We evaluated the necessity of preoperative prostate biopsy in invasive bladder cancer. Methods: From 1998 through 2009, of 300 patients undergoing radical cystectomy for muscle-invasive bladder cancer, 252 were male. Of these, we focused 212 patients, whose prostate-specific antigen (PSA) was measured preoperatively. Results: The median age was 66years and median follow-up period was 46 months. Thirty-five patients with PSA > 4.0 ng/mL or digital rectal examination (DRE) positive were all subjected to transrectal ultrasound (TRUS)-guided prostate biopsy (Pbx), and Pca was detected in 7 cases (20%) (Group I). Pca was also detected in 5 patients (17.9%) in RCP specimens of the 28 whose Pbx results were negative (Group II). Seventy-seven of the 177 patients with PSA ≤ 4.0ng/mL and DRE negative were underwent TRUS-guided Pbx, and Pca was detected in 1 case (1.3%) (Group III). Pca was detected in 10 patients (13.2%) out of the 76 whose Pbx results were negative (Group IV). Of the 177 patients, 100 underwent RCP without prostate biopsy, and Pca was detected in 16 cases (16%) (Group V). The average Gleason score of each Group, I, II, III, IV, and V were 6.6, 6.6, 7, 6.2, and 6.5, respectively. Tumor volumes of each Group, I, II, III, IV, and V were 3.12mL, 1.0mL, 0.65mL, 0.43mL, and 0.19mL, respectively. No patients experienced recurrence of PC, including biochemical recurrence. Conclusions: In cases with PSA ≤4.0 ng/mL and/or DRE negative, Pbx is not considered necessary. In cases with PSA > 4.0 ng/mL or DRE positive, Pca with an average volume of 3.12 mL were detected by Pbx in 20% of the patients. However, most are localized Pca, and postoperative recurrence of the Pca is not seen during follow-up period. The question of whether all patients in this group require Pbx needs to be examined through further stratification.

266 Background: We retrospectively evaluated the feasibility and effectiveness of a sequential chemotherapy wihtout cisplatin for the patients 70 years or older with advanced bladder cancer. Methods: Fourty-seven patients with advanced bladder cancer (33 men and 14 women) with the age of 70 years or older were enrolled. They were treated at our clinic between August 2004 and December 2010. Their average age was 80.0 years old (70–86), average Ccr was 37.0 ml/min (14.5–113.0), and an average follow-up period was 17.4 months (10–55). There were 15 recurrent cases after radical surgery and 32 inoperable cases (T4b or metastatic). As for prior chemotherapy, 6 underwent MVAC therapy. The therapeutic regimen consisted of 2 lines: gemcitabine/carboplatin (GCarbo) therapy as the first line, with two courses as a set; GCarbo/docetaxel (GCarboD) therapy as the second line if the response in the first line was insufficient. If this regimen was effective, another 2 courses of GCarbo was performed. Treatment efficacy was checked every 2 course according to the RECIST version 1.1. Results: Of the 47 subjects who had undergone the GCarbo therapy, the response rate was 38.3% (CR+PR) with 5 and 12 subjects exhibiting a complete response (CR) and a partial response (PR), respectively; the average response duration was 15.7 months (2–42). Of the subjects with MVAC resistance, 1 exhibited a CR and 3 showed a PR. The response rates of 9 instances of GCarboD was 11.1%; the overall median survival was 15.0 months throughout the sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 30 of those who had undergone the GCarbo therapy (63.8%). Conclusions: Although the present study is small and preliminary, the present sequential chemotherapy is safe and active for advanced bladder cancer of the patients seventy years or older. GCarbo regimen achieved acceptable response rate (38.3%) in advanced bladder cancer including M-VAC-resistant case. The median overall survival of 15 months is acceptable when average age of 80 year for the subjects is took into consideration. However, GCarboD had limited effectiveness for non-responder of GCarbo.

265 Background: Bacillus Calmette-Guerin (BCG) therapy has already been established as a treatment for muscle noninvasive bladder cancer. Although there are several reports indicating the effectiveness of BCG perfusion therapy for the upper urinary tract urothelial carcinoma in situ (CIS), it is not well established yet. We conducted a retrospective study to assess the long-term outcome of BCG perfusion therapy for the upper urinary tract CIS. Methods: Twenty-six subjects (20 male, 6 female) who received BCG perfusion therapy for the upper urinary tract CIS from December 1997 to December 2011 were enrolled. Ten subjects had the entire urinary tract CIS, seven had bilateral, nine had unilateral CIS of the urinary tract. The average period of observation was 52.6 months (ranging from 5 to 156 months), and the average subject age was 73.6 years (ranging from 56 to 90 years). We used a double-J catheter for 17 cases, a transvesical single-J catheter whose curl was positions in an upper calyx for eight cases, and a straight ureteral catheter inserted for ureterocutaneostomy for one case. We used 80 mg of BCG for the first five cases, 40 mg for the late twenty-one cases. Urine cytology was performed to assess the treatment validity. Results: Of the 26 cases, the treatment protocol was completed in 21 cases. Urine cytology tests became negative in 22 of the 26 subjects (84.6%) who underwent upper urinary tract perfusion. Among these 22 subjects who had negative tests, five subjects had a recurrence in their upper urinary tracts. Side effects were observed in 25 subjects (96.5%), and the most common side effect was bladder irritation. Localized renal tuberculosis which was successfully treated with conservative therapy was seen in two cases. Conclusions: BCG perfusion therapy for the upper urinary tract CIS is active. However, severe side effects are possible, and careful observation is essential while using this therapy.

319 Background: AKR1B10 is a member of the aldo-keto reductase superfamily of NAD(P)H-dependent oxidoreductases.AKR1B10 is considered to contribute to cell proliferation and chemo-resistance. In the present study, we examined whether AKR1B10 expression correlates with disease free survival in bladder cancer specimens. Methods: The cohort includes consecutive 57 patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy followed by radical cystectomy. All patients received two cycles of neoadjuvant chemotherapy with gemcitabine plus carboplatin. Bladder cancer specimens were obtained at pre- and post-neoadjuvant chemotherapy, which were subjected to quantitative real-time PCR and immunohistochemistry to evaluate AKR1B10 expression. Intensity scoring for immunohistochemistry was categorized using a 4-graded scoring system according to a previously published method, with positive cells for each specific marker expressed as a percentage of the total number of cells as follows: 0%–10% = 0; 11%–30% = 1; 31%–70% = 2; 71%–100% = 3. Results: AKR1B10 mRNA expression was significantly higher in the post-chemotherapy groups than in the pre-chemotherapy groups (p < 0.001). The average immunohistochemical intensity score in the pre-chemotherapy group was 0.83 ± 1.08, compared to a significantly higher average intensity score of 2.03 ± 1.03 in the post-chemotherapy group (p < 0.001) Disease free survival of the post-chemotherapy AKR1B10(+) patients (61.2%) was significantly lower than that of AKR1B10(−) patients (100%) (log-rank test: p = 0.039). Conclusions: Although the present study is small and preliminary, post-chemotherapy AKR1B10 expression may have a predictive potential for response of chemotherapy and disease recurrence after definitive therapy for muscle-invasive bladder cancer. Further study is warranted to elucidate its clinical significance.

e16100 Background: The neoadjuvant M-VAC followed by radical cystectomy for muscle-invasive bladder cancer has improved survival compared to radical cystectomy alone. Nevertheless, M-VAC has been associated with severe toxicity. The objective of this retrospective study was to evaluate the objective response rate, the impact on overall survival, disease-free survival, disease-free survival and toxicity adverse events of gemcitabine and carboplatin (GC) neoadjuvant chemotherapy in patients with locally advanced bladder cancer. Methods: We reviewed the clinical and pathological data of 140 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for T2N0M0 to T4aN0M0 bladder cancer at our institution between January 2001 and August 2008. Seventy patients were treated with neoadjuvant GC followed by cystectomy between March 2005 and August 2008 (GC group), and 70 patients were treated with cystectomy alone between January 2001 and May 2007 (cystectomy alone group). In the GC group, the patients received 2 courses of GC therapy consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. The primary endpoint was the objective response rate, and the secondary endpoints were overall survival, cancer-specific survival, disease free survival, and toxicity. Results: Fifteen patients (23.8%) had a complete response and 26 patients (41.3%) had a partial response in the GC group. At a mean follow-up period of 26.7 months, the overall survival was 85.0% in the GC group and 47.8% in the cystectomy alone group (p = 0.003). The cancer-specific survival was 78.4% in the GC group and 44.6% in the cystectomy alone group (p = 0.0018). The disease-free survival was 82.9% in the GC group and 35.7% in the cystectomy alone group (p = 0.0001). Hematologic toxicities were the main adverse events. Grade 3/4 neutropenia occurred in 26 patients (37.1%) and thrombocytopenia in 15 (21.4%). There was no grade 3/4 gastrointestinal toxicity and no renal function abnormalities. Conclusions: Although this is not a randomized study, the GC neoadjuvant therapy followed by radical cystectomy is feasible and may be associated with improved survival among patients with muscle-invasive bladder cancer. A randomized trial is warranted. No significant financial relationships to disclose.