e234 THE JOURNAL OF UROLOGY� Vol. 191, No. 4S, Supplement, Sunday, May 18, 2014

Bladder Cancer: Detection & Screening

Moderated Poster

Sunday, May 18, 2014 8:00 AM-10:00 AM

MP22-01GENDER DISPARITIES IN DIAGNOSIS OF BLADDER CANCERAFTER INITIAL PRESENTATION WITH HEMATURIA:A NATIONWIDE CLAIMS-BASED INVESTIGATION

Joshua Cohn*, Chicago, IL; Michael Large, Indianapolis, IN;Kyle Richards, Benjamin Vekhter, Christopher Lyttle, Gary Steinberg,Chicago, IL

INTRODUCTION AND OBJECTIVES: Women have dispro-portionately higher mortality rates relative to incidence for bladdercancer. Multiple etiologies have been proposed, including delayeddiagnosis and treatment. Guidelines recommend rule-out of malignancyin men and women presenting with hematuria. We aimed to determinethe difference in timing from presentation with hematuria to diagnosis ofbladder cancer in women versus men.

METHODS: This is a retrospective population-based studyexamining the timing from presentation with hematuria to diagnosis ofbladder cancer, based on data from the MarketScan databases, whichinclude enrollees of more than 100 health insurances plans ofapproximately 40 large US employers from 2004 through 2010. Allstudy patients presented with hematuria and were subsequently diag-nosed with bladder cancer. The primary outcome measure was numberof days between initial presentation with hematuria and diagnosis ofbladder cancer by gender.

RESULTS: 5416 men and 2233 women met inclusion criteria.Mean days from initial hematuria claim to bladder cancer claim wassignificantly longer in women (85.4 vs. 73.6 days, p<0.001), and theproportion of women with >6 month delays in bladder cancer diag-nosis significantly higher (17.3% vs. 14.1%, p<0.001). Women weremore likely to be diagnosed with urinary tract infection (33.1% vs.17.6%, OR 2.32 [95% CI 2.07-2.59]) and less likely to undergoabdominal or pelvic imaging (73.1% vs. 77.3%, OR 0.80 [95% CI 0.71-0.89]). Female gender and urinary tract infection claim remained sig-nificant predictors of >3 month, >6 month, and >9 month delay be-tween hematuria claim and bladder cancer diagnosis on multivariableregression analysis adjusted for age, UTI claim, number of hematuriavisits, Charlson Co-morbidity Index, hematuria ICD-9 code, and year ofdiagnosis (Table).

CONCLUSIONS: Both men and women experience significantdelays between presentation with hematuria and diagnosis of bladdercancer, with longer delays for women. This may be partly responsiblefor the gender-based discrepancy in outcomes associated withbladder cancer.

Source of Funding: This project was supported by the NationalCenter for Advancing Translational Sciences of the NationalInstitutes of Health through Grant Number UL1 TR000430.

MP22-02RISK OF BLADDER CANCER ASSOCIATED WITH FAMILYHISTORY OF CANCER: DO LOW-PENETRANCEPOLYMORPHISMS ACCOUNT FOR THE INCREASE IN RISK?

Dario Garcia-Rojo*, Sabadell, Spain; Cristiane Murta-Nascimento,Nuria Malats, Barcelona, Spain; Debra Silverman, Bethesda, MD;Oscar Bielsa, Antoni Gelabert-Mas, Manolis Kogevinas, Barcelona,Spain; Montserrat Garcia-Closas, Bethesda, MD; Angel Prera, Saba-dell, Spain; Lluis Cecchini, Badalona, Spain; Josep Lloreta, Barcelona,Spain; Consol Serra, Sabadell, Spain; Ramon Abascal, Oviedo, Spain;Alfredo Carrato, Elche, Spain; Jose Maria Rodriguez de Vera, SantaCruz de Tenerife, Spain; Jesus Maria Fernandez, Oviedo, Spain;Manuel Rivas, Cabue~nes, Spain; Jose Luis Guate, Aviles, Spain;Josep Maria Malet, Manresa, Spain; Pedro Munta~nola, Mieres, Spain;Manuel Cespedes, Sant Boi de Llobregat, Spain; Julio Gonzalez-Huergo, Coa~na, Spain; Javier Mosquera, Cangas, Spain;Carlos Abad, Juan Prats, Sabadell, Spain; Francisco Xavier Real,Barcelona, Spain

INTRODUCTION AND OBJECTIVES: Family history of bladdercancer and other types of cancer has been associated with anincreased risk of bladder cancer. The relationship between family his-tory of cancer in first-degree relatives and risk of bladder cancerwas examined.

METHODS: Information on family history of cancer was ob-tained for 1158 newly diagnosed bladder cancer cases and 1244 con-trols included in 18 hospitals between 1998 and 2001. Polymorphismsin NAT2 and GSTM1 were investigated using germ-line DNA from bloodand buccal cell samples. ORs and 95% CIs were calculated from thecoefficients in the regression models.

RESULTS: A total of 464 (40.1%) cases and 436 (35.1%)controls reported a family history of cancer in >1 relative OR 1.32;(95% CI, 1.11-1.59); the OR was 1.23 (95% CI, 1.01-1.50) amongthose with only one relative affected and 1.67 (95% CI, 1.23-2.29)among those with >2 affected relatives (Ptrend ¼ 0.0004). A greaterrisk of bladder cancer was observed among those diagnosed at age<45 years (OR, 2.67; 95% CI, 1.10-6.50) compared with thosediagnosed over age 45 years (OR, 1.27; 95% CI, 1.06-1.52). The ORof bladder cancer among subjects reporting a family history of cancerof the bladder was 2.34 (95% CI, 0.95-5.77). Statistically significantassociations emerged between bladder cancer risk and family historyof cancer of the esophagus, lung, prostate, and brain. The OR ofbladder cancer for those reporting family history of bladder cancerwas 4.76 (95% CI, 1.25-18.09) among NAT2-slow acetylators and1.17 (95% CI, 0.17-7.86) among NAT2-rapid/intermediate acetylators

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(Pinteraction ¼ 0.609). Among individuals with GSTM1 nulland present genotypes, the corresponding ORs were 2.91 (95% CI,0.44-19.09) and 4.21 (95% CI, 1.26-14.14), respectively (Pinteraction¼ 0.712).

CONCLUSIONS: Our findings support the hypothesis that ge-netic factors play a role in bladder cancer etiology. Whether thesecorrespond to low-penetrance cancer-predisposing polymorphismsacting together and/or interacting with environmental factors warrantsfurther research.

Source of Funding: Intramural Research Program of theDivision of Cancer Epidemiology and Genetics, NationalCancer Institute(USA), and FIS Spain,

MP22-03DUAL-SPECIFICITY TYROSINE PHOSPHORYLATION-REGULATED KINASE 2 AS A NOVEL MARKER IN BLADDERCANCER PATIENTS RECEIVING NEOADJUVANTCHEMOTHERAPY

Shunichiro Nomura*, Yasutomo Suzuki, Jun Akatsuka, Ryo Takahashi,Mika Terasaki, Ryoji Kimata, Ichiro Matsuzawa, Tsutomu Hamasaki,Go Kimura, Akira Shimizu, Yukihiro Kondo, Tokyo, Japan

INTRODUCTION AND OBJECTIVES: Radical cystectomy hasbeen widely performed to treat muscle-invasive bladder cancer.However, radical cystectomy only provides 5-year survival in about50% of patients. To improve these unsatisfactory results, the use ofperi-operative chemotherapy has been explored. In particular, ben-efits of neoadjuvant chemotherapy have been observed in severaltrials. However, neoadjuvant chemotherapy fails some patients.Patient selection should thus be optimized for neoadjuvant chemo-therapy. According to some reports, dual-specificity tyrosine phos-phorylation-regulated kinase 2 (DYRK2) is associated withsensitivity to platinum-based chemotherapy. We therefore investi-gated associations between DYRK2 expression and efficacy ofneoadjuvant chemotherapy for patients with T1 high-grade or T2bladder cancer.

METHODS: The cohort under investigation comprised 44 pa-tients who underwent neoadjuvant chemotherapy for cT1 high-grade orcT2N0M0 bladder cancer at our institution between October 2002 andFebruary 2011. Immunohistochemical analysis was used to determineexpression of DYRK2 in specimens of bladder cancer obtained bytransurethral resection before chemotherapy. Relationships betweenDYRK2 expression and both response rates and survival in these pa-tients were analyzed.

RESULTS: DYRK2 expression was positive in 21 of the 44patients (47.7%) and negative in 23 (52.3%). Staining intensity of 0 or1+ was considered DYRK2-negative, and 2+ or 3+ staining wasconsidered DYRK2-positive. 20 of 21 DYRK2-positive cases hadcomplete response to neoadjuvant chemotherapy, whereas 11 of 23DYRK2-negative cases did not have complete response. Sensitivityand specificity were 62.5% and 91.7%, respectively (p ¼ 0.0018). Inaddition, disease-specific survival rate was significantly higherfor DYRK2-positive patients than for DYRK2-negative patients(p ¼ 0.017).

CONCLUSIONS: The results indicate that DYRK2 mightrepresent a new molecular marker for predicting the efficacy of neo-adjuvant chemotherapy in T1 high-grade and T2 bladder cancer.

Source of Funding: none

MP22-04EXTERNAL VALIDATION OF A MULTIPLEX URINARY PROTEINPANEL FOR THE DETECTION OF BLADDER CANCER IN AMULTICENTER COHORT

Diego Aguilar Palacios*, Limei Chen, Orlando, FL; Myron Chang,Yunfeng Dai, Gainesville, FL; Lars Dyrskjøt Andersen, Aarhus,Denmark; Marta Sanchez-Carbayo, Madrid, Spain; Tibor Szarvas,Essen, Germany; Ellen C. Zwarthoff, Rotterdam, Netherlands;Carmen Jeronimo, Porto, Portugal; Alexander S. Parker, Jacksonville,FL; Shanti Ross, Karl X. Chai, Steve Goodison, Charles J. Rosser,Orlando, FL

INTRODUCTION AND OBJECTIVES: Through combinedgenomic and proteomic profiling of urinary components, we have pre-viously identified a bladder cancer (BCa) associated protein panel thatperforms well in test cohorts. The aim of this study was to externallyvalidate the protein biomarker panel from multiple sites in the USand Europe.

METHODS: This phase II, multicenter external validation studyincluded a total of 320 subjects. The 10 biomarkers (IL8, MMP9,MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SDC1 and SER-PINE1) were measured using enzyme-linked immunosorbent assays inan external laboratory. Voided urine specimens from healthy volunteers(n ¼ 41), patients with benign urologic conditions (n ¼ 96), non-muscleinvasive bladder cancer (NMIBC, n ¼ 153) and muscle invasive bladdercancer (MIBC, n ¼ 23) were tested. The diagnostic performance of thebiomarker panel was assessed using receiver operator curves (ROC)and descriptive statistical values.

RESULTS: Utilizing the combination of all 10 biomarkers atoptimal cutoff values defined by the Youden index calculation, theAUROC for the diagnostic panel was noted to be 0.848 [95% CI: 0.796 -0.899], outperforming any single biomarker. The multiplex assay ach-ieved an overall sensitivity of 0.79, specificity of 0.79, PPV of 0.73 andNPV of 0.84 for BCa classification. Sensitivity values of the diagnosticpanel for high-grade BCa, low-grade BCa, MIBC and NMIBC were 0.81,0.90, 0.95 and 0.77, respectively.

CONCLUSIONS: Urinary levels of the biomarker panelenabled discrimination of BCa patients and controls, and the levels ofbiomarker subsets were associated with advancing tumor gradeand stage.

Source of Funding: Florida State Department of Health.