Masaaki Oikawa

Prognostic benefit of surgical management in renal cell carcinoma patients with thrombus extending to the renal vein and inferior vena cava: 17-year experience at a single center

BackgroundManagement of renal cell carcinoma (RCC) with tumor thrombus extending to the renal vein and inferior vena cava (IVC) is challenging. The aim of this study was to evaluate the benefit of surgical management in such patients.MethodsFrom February 1995 to February 2013, 520 patients were treated for RCC at Hirosaki University Hospital, Hirosaki, Japan. The RCC patients with tumor thrombus extending to the renal vein (n = 42) and IVC (n = 43) were included in this study. The records of these 85 patients were retrospectively reviewed to assess the relevant clinical and pathological variables and survival. Prognostic factors were identified by multivariate analysis. The benefit of surgical management was evaluated using propensity score matching to compare overall survival between patients who received surgical management and those who did not.ResultsRCC was confirmed by pathological examination of surgical or biopsy specimens in 74 of the 85 patients (87%). Sixty-five patients (76%) received surgical management (radical nephrectomy with thrombectomy). Distant metastasis was identified in 45 patients (53%). The proportion of patients with tumor thrombus level 0 (renal vein only), I, II, III, and IV was 49%, 13%, 18%, 14%, and 5%, respectively. The estimated 5-year overall survival rate was 70% in patients with thrombus extending to the renal vein and 23% in patients with thrombus extending to the IVC. Multivariate analysis identified thrombus extending to the IVC, presence of distant metastasis, surgical management, serum albumin concentration, serum choline esterase concentration, neutrophil-lymphocyte ratio, and Carlson comorbidity index as independent prognostic factors. In propensity score-matched patients, overall survival was significantly longer in those who received surgical management than those who did not.ConclusionsSurgical management may improve the prognosis of RCC patients with thrombus extending to the renal vein and IVC.

BK Virus–Associated Urothelial Carcinoma of a Ureter Graft in a Renal Transplant Recipient: A Case Report

BACKGROUND Urothelial carcinomas of ureter grafts in renal transplant patients are rare. Here we report our experience with a case of BK virus-associated urothelial carcinoma in a ureter graft. CASE REPORT A 47-year-old man developed chronic renal failure secondary to diabetes mellitus and started maintenance hemodialysis in September 2007. Two months later, the patient received a renal transplant from his 70-year-old mother. The patient developed BK virus-associated nephropathy 1 year after transplantation and presented with a decline in renal function and hydronephrosis in the transplanted kidney 4 years 6 months after transplantation. Cystoscopy and retrograde pyelography revealed an irregular filling defect in the ureter graft. Cytologic diagnosis of his urine revealed a high-grade urothelial carcinoma. Computerized tomography showed a cT2 ureteral tumor and no involvement of other organs. The patient subsequently underwent a transplant nephroureterectomy with bladder cuff resection. Histopathologic findings revealed a high-grade urothelial carcinoma, pT2, in the ureter graft with SV40-positive staining. The patient was closely observed without adjuvant chemotherapy therapy and remained disease free 1 year after surgery. Renal transplant recipients with BK virus infection are at high risk of developing urologic malignancies. Close attention is necessary to diagnose post-transplantation urologica malignancies as early as possible.

Significance of Serum N-glycan Profiling as a Diagnostic Biomarker in Urothelial Carcinoma

BACKGROUND The clinical diagnosis of urothelial carcinoma (UC) relies on invasive methods in patients with hematuria. Although more sensitive and noninvasive screening methods are required, a specific serum biomarker for UC is lacking. OBJECTIVE To examine whether serum glycan-based biomarkers can be applied to UC detection. DESIGN, SETTING, AND PARTICIPANTS Between April 1994 and June 2016, serum N-glycan concentrations were retrospectively measured in 212 patients with UC before treatment (UC group) and 212 pair-matched controls using glycoblotting and mass spectrometry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS N-glycan levels were compared between the groups using receiver operating characteristic curves to select candidate N-glycans. We created an N-glycan score based on the combination of candidate N-glycans. The specificity and sensitivity of the candidate N-glycan score were evaluated using receiver operating characteristic curves. RESULTS AND LIMITATIONS The N-glycan score was calculated using six N-glycans (m/z 1566, m/z 1687, m/z 1769, m/z 1871, m/z 2011, and m/z 2337) that were significantly associated with UC. The median N-glycan score was significantly higher in the UC group than in the pair-matched control group (5.0 vs 1.0, p<0.001). The N-glycan score correctly classified UC patients with a sensitivity, specificity, and area under the curve of 93%, 81%, and 0.95, respectively. The limitations of our study included its retrospective nature and nonclinical setting. CONCLUSIONS Serum N-glycan content has the potential to be a specific and sensitive novel serum biomarker that may improve the accuracy of the detection for UC and reduce unnecessary invasive screening. Validation of this test in a large-scale prospective study is needed. PATIENT SUMMARY Combination of serum N-glycan (N-glycan score) is a novel serum marker for urothelial carcinoma that is expressed by 93% of patients and thus is far more sensitive than classic urine cytology. Validation in a large patient cohort is needed.

Neoadjuvant chemohormonal therapy followed by robot-assisted and minimum incision endoscopic radical prostatectomy in patients with high-risk prostate cancer: comparison of perioperative and oncological outcomes at single institution

PurposeOptimal management strategies for patients with high-risk prostate cancer (PCa) have not been established. This study aimed to estimate the impact of surgical procedures on perioperative and oncological outcomes in patients with high-risk PCa who received neoadjuvant chemohormonal therapy (CHT) prior to radical prostatectomy (RP).MethodsIn this retrospective study, we focused on patients with high-risk PCa who received neoadjuvant CHT followed by RP. The enrolled patients were divided into the following two groups according to surgical procedure: the robot-assisted RP (RARP) group and minimum incision endoscopic RP (MIE-RP) group. The primary endpoint was biochemical recurrence-free survival (BRFS).ResultsA total of 522 high-risk PCa patients were enrolled in this study. The median operating time was significantly shorter in the MIE-RP group than in the RARP group. The median estimated blood loss was significantly lower in the RARP group than in the MIE-RP group. The rates of positive surgical margins (PSMs) were not statistically significant in either group. During the follow-up period, biochemical recurrence (BCR) without clinical recurrence occurred in 60 (23.9%) patients in the MIE-RP group and 5 (1.8%) in the RARP group. The 5-year BRFS rate was 76.5% in the MIE-RP group and 97.6% in the RARP group (P < 0.001). On multivariate analysis, RARP, PSM, pathological T stage, and initial prostate-specific antigen were significantly associated with BCR.ConclusionsNeoadjuvant CHT with subsequent RARP may decrease the risk of BCR when compared to MIE-RP.

MP16-13 CLINICAL BENEFIT OF PRESURGICAL AXITINIB THERAPY IN RENAL CELL CARCINOMA PATIENTS WITH THROMBUS EXTENDING TO INFERIOR VENA CAVA

of patients had progressive disease (PD). Median PFS was 5.5 months and median OS was 18.0 months. Among all patients analyzed for Tcell response, five showed vaccine-induced (VI) T-cell responses against at least one HLA class I-restricted TUMAP and two patients with responses to multiple TUMAPs (Figure 1). The T-cell response rate in this study was similar to our previous study in Europe and US. Interestingly, two of the immune responders were of HLA-A*0206 phenotype, a HLA suballele rarely occurring in Europe and US but common in Japan. CONCLUSIONS: This study showed safety and tolerability of IMA901 vaccination and immune responses in Japanese RCC patients.

MP71-14 SIGNIFICANCE OF BUTTYRYLCHOLINESTERASE BEFORE CHEMOTHERAPY AS AN INDEPENDENT PREDICTOR OF OVER-ALL SURVIVAL IN PATIENTS WITH ADVANCED UPPER-TRACT UROTHELIAL CANCER

INTRODUCTION AND OBJECTIVES: 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 December 2015. The average age was 69.3 (43e89), and average eGFR was 50.5 (11.6e99.3) ml/minute/1.73m2. Mean observation periodwas 24.0 (3e96) months. Levels of serumBChE (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 (2e29) 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 over-all survival were 22.0 months in the BChE >168 U/L group and 12.0 months in the BChE <168 group (p1⁄40.036). The level of serum BChE showed no association with treatment effect. CONCLUSIONS: Serum BChE level before chemotherapy may have the potential to predict over-all survival in patients with advanced upper-tract urothelial cancer.

MP44-04 SIGNIFICANCE OF SERUM N-GLYCAN PROFILING AS A DIAGNOSTIC BIOMARKER IN UROTHELIAL CARCINOMA

INTRODUCTION AND OBJECTIVES: Low-grade (LG) urothelial carcinoma of the bladder (UCB) are common malignancies that are costly to surveil and infrequently progress to life threatening, high-grade (HG) malignancies. It is not clear whether the progression of LG to HG is a result of second primaries or transformation of LG tumors. We sought to examine tumor genetics in patients who progressed from LG to HG urothelial carcinoma and compared to patients with no progression. METHODS: An institutional cancer database at a tertiary referral center in the United States was queried for living patients who progressed from LG to HG UCB. Histologic re-review was performed by a genitourinary pathologist. Whole exome sequencing with correction for germline mutations by buffy coat subtraction was performed. Mutations were assessed for continuity or novelty between low grade tumors and subsequent same-patient HG tumors and for LG patients who did not progress. Individual genes were assessed for potential predictors of risk for progression. RESULTS: Five patients were identified with progression. Clinicopathologic variables were identified and median time to progression from initial low-grade diagnosis was 19 months. Both true tumor progression and de novo growth of high grade tumors were identified. Gene alterations associated with tumor grade progression in initial low grade tumors were FBN3, CIT and HECTD4. CONCLUSIONS: Both true tumor progression and de novo high-grade tumors were observed in initial low grade urothelial carcinomas that progressed. Validation of the identified tumor genes that appeared associated with progression may provide a clinically valuable tool to providers managing patients with low grade urothelial carcinomas.

MP86-02 PREVALENCE OF FRAILTY AMONG UROLOGICAL CANCER PATIENTS IN COMPARISON WITH COMMUNITY-DWELLING POPULATION

INTRODUCTION AND OBJECTIVES: Frailty, defined as a measure of decreased physiologic reserve, is strongly associated with increased susceptibility to disability and poor outcomes. The purpose of this study was to describe the extent of frailty among patients with various urologic diagnoses and to explore whether or not frailty differed between patients who did and did not undergo urologic surgery. METHODS: This is a prospective study of men and women ages 65 and older presenting to an academic non-oncologic urology practice between December 2015 and May 2016. Frailty was measured in individuals via the Timed Up and Go Test (TUGT) upon intake. Based on the TUGT, individuals were classified as not frail (1⁄410 sec), intermediately frail (11-14 sec) or frail (1⁄415 sec). The TUGT and other clinical data were abstracted from the electronic medical record using EPIC analytical software into an on-going database. TUGT values were reported overall, by urologic diagnosis, and according to whether or not they were associated with a urologic procedure. RESULTS: There were 1089 unique individuals who presented to our practice and had a TUGT during the study period. Among these individuals, the mean age was 73.3 ( 6.3) years, 77.6% were male, 64.7% were white and the mean TUGT was 11.6 ( 6.0) seconds, with 30.0% and 15.2% classified as intermediately frail and frail, respectively. TUGT time (and hence frailty) increased linearly with increasing age (Figure). TUGT values differed by urologic diagnosis ranging from 9.9 ( 3.0) seconds among individuals with general male urology diagnoses to 14.3 ( 11.9) seconds among individuals with urinary tract infections (UTIs). There were no statistically significant differences in TUGT values between individuals who did and did not undergo urologic surgery. CONCLUSIONS: Frailty is common, increases with age, and varies based on urologic diagnosis among individuals presenting to an academic non-oncologic urology practice. Interestingly, frailty did not differ between individuals who did and did not undergo urologic surgery, suggesting that there is a potential opportunity to incorporate frailty into the perioperative decision-making process. Since frailty is prevalent among urologic patients and linked to poor outcomes, consideration of frailty in the surgical decision-making process is warranted and may improve outcomes. Source of Funding: NIDDK K12 DK83021-07

203 IMMUNOHISTOCHEMICAL DETECTION OF CORE2 β-1,6-N -ACETYLGLUCOSAMINYLTRANSFERASE IS AN INDEPENDENT RISK FACTOR FOR PSA RECURRENCE AFTER RADICAL PROSTATECTOMY

INTRODUCTION AND OBJECTIVES: To avoid over treatment of localized prostate cancer (PCa), it is very important to develop a novel biomarker for malignant potential of PCa. Core2 -1,6-N-acetylglucosaminyltransferase (C2GnT) is an glycosyltransferase which forms core2 branching O-glycan on various glycoproteins. Our research group previously reported that C2GnT expressions were associated with malignant potential of cololectal cancer (Cancer res, 1997), lung cancer (Cancer Res, 2001), prostate cancer (Glycobiology, 2005), testicular cancer (Int J Cancer, 2010) and bladder cancer (EMBO J, 2011). We examined whether immunohistochemical detection of C2GnT can predict PSA recurrence after radical prostatectomy. METHODS: To determine the correlation of C2GnT expression with pathological parameters and biochemical outcome after radical prostatectomy, paraffin embedded specimens of 250 patients with PCa were immunohistochemically examined for C2GnT expression using the anti-C2GnT monoclonal antibody. RESULTS: C2GnT-positive PCa had significantly higher Gleason score and tumor volume than that with negative for C2GnT (p 0.017 and p 0.000). C2GnT positive rate in pT2 (60.1%) was significantly lower than that in pT3/pT4 (80.2%/100%) (chi-square-test, p 0.003). C2GnT-negative patients showed significantly longer PSA free survival than C2GnT-positive patients (log-rank test, p 0.000015). Multivariate analysis revealed initial PSA (iPSA), High risk (D’ammico), margin status (RM) and C2GnT expressions were independent risk factors for PSA recurrence. CONCLUSIONS: These results suggest that immunohistochemical detection of C2GnT on radical prostatectomy specimen is an independent and strong indicator of PSA recurrence after radical prostatectomy. Further clinical trial is necessary to determine the implication of C2GnT as a novel biomarker of prostate cancer.