838 INCREASING RATES OF METASTATIC SEMINOMA AND NONSEMINOMA TESTICULAR CANCER: A CAUSE FOR CONCERN?

838 INCREASING RATES OF METASTATIC SEMINOMA AND NONSEMINOMA TESTICULAR CANCER: A CAUSE FOR CONCERN?

Vol. 183, No. 4, Supplement, Monday, May 31, 2010 CONCLUSIONS: Testicular lymphoma is a rare neoplasm that presents primarily in older men. The VACCR...

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Vol. 183, No. 4, Supplement, Monday, May 31, 2010

CONCLUSIONS: Testicular lymphoma is a rare neoplasm that presents primarily in older men. The VACCR is a large and contemporary dataset that includes a large number of patients with PTL. Our investigation shows that despite multimodal therapy, disease eradication is difficult, and a propensity to recur at extranodal sites makes this condition a therapeutic challenge. Source of Funding: None

836 DIFFERENTIAL ENTPD6 EXPRESSION BETWEEN SEMINOMA AND NON-SEMINOMA IN TESTICULAR TUMOR POTENTIALLY MODULATED THE SENSITIVITY TO CISPLATIN Yasuhiro Tada*, Akira Yokomizo, Masaki Shiota, Kentaro Kuroiwa, Yoohyun Song, Seiji Naito, Fukuoka, Japan INTRODUCTION AND OBJECTIVES: Cisplatin is generally accepted as a DNA-damaging agent and broadly used for anticancer drugs in many kinds of cancers, including those occurring in the testes, head, neck, esophagus, lung, ovary and bladder.The development of resistance to cisplatin during treatment is common and constitutes a major obstacle in medical treatment for patients. Objective) We investigated the novel molecules for cisplatin resistance in testicular cancer. METHODS: We performed the microarray between testicular cancer cell (NEC8) and its derived cisplatin-resistant cell (NEC8DDP). To select the target gene for cisplatin resistance in testicular cancer, we screened the candidate genes using semi-quantitative RT-PCR. We also performed quantitative real-time PCR in normal testis, 31 clinical samples of testicular cancer, NEC8 and NEC8DDP. We investigated the immunohistochemistry to identify the localization of ENTPD6 expression. We examined whether ENTPD6 directly modulates the cisplatin sensitivity in testicular cancer by AlamarBlue assay. To confirm the ENTPD6 expression associated with cisplatin resistance, we transfected ENTPD6 expression vector in NEC8DDP and knock down ENTPD6 expression in NEC8 using siRNA. RESULTS: We found 15 genes downregulated in NEC8DDP and four genes upregulated in NEC8DDP compared with NEC8 (more than 3-fold) using microarray system. After screening, we selected the ENTPD6 in these 19 genes. ENTPD6 expression in seminoma was almost 5-fold higher than in non-seminoma by real-time PCR. The suppression of ENTPD6 expression using small interfering RNA in NEC8 increased the resistance for cisplatin. Contrarily, overexpression of ENTPD6 in NEC8DDP induced the increased sensitivity to cisplatin. We showed that ENTPD6 had potentially association with cisplatin resistance in testicular cancer. CONCLUSIONS: Decreased ENTPD6 expression in testicular cancer might have important role for carcinogenesis of non seminoma and modulate the sensitivity to cisplatin in testicular cancer.

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using national cancer registries. The SIR to SMR ratio for each country was calculated to estimate the diagnostic and therapeutic effectiveness of each country. RESULTS: SIR and SMR are reported as cases or deaths per 100,000 people. Testicular cancer SIR is highest in Northern and Western European countries with individual national rates ranging from approximately 200 - 800 and the highest rates in Norway (869) and Switzerland (806). North America had similar SIRs with national rates ranging from 300 - 500. South America and Asia had significantly lower SIRs ranging from approximately 50 - 200. Africa had the lowest incidence with most countries reporting fewer than 100. SMR varied greatly between European countries (Iceland: 0 to Bulgaria: 372) with the highest worldwide rate in Cyprus (855). Central America, South America, and Eastern Europe had relatively high SMR averages of 200 - 300. SIR/SMR ratio was highest in Israel (11) and lowest in Africa (0.2 - 0.5) with values less than 1 suggesting post-mortem diagnoses. CONCLUSIONS: Testicular cancer incidence remains greatest in developed nations with primarily Caucasian populations. Countries with a particularly high incidence were more likely to have relatively low mortality rates. Variable SIR/SMR ratios suggest markedly different geographic-specific reporting mechanisms, presentation patterns, access to care, and treatment capabilities.

Source of Funding: None Source of Funding: None

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838

GLOBAL TRENDS IN TESTICULAR CANCER INCIDENCE AND MORTALITY

INCREASING RATES OF METASTATIC SEMINOMA AND NONSEMINOMA TESTICULAR CANCER: A CAUSE FOR CONCERN?

Alexandre Rosen*, Michael Drazer, Scott Eggener, Chicago, IL INTRODUCTION AND OBJECTIVES: Epidemiologic studies on testicular cancer have focused primarily on European countries. Global incidence and mortality have been less thoroughly evaluated. The Globocan international cancer database is used to investigate recent global trends in testicular cancer incidence and mortality. METHODS: Age-standardized rates for testicular cancer incidence (SIR) and mortality (SMR) were obtained for men age 15 - 44 years in 172 countries using the Globocan 2002 database. The database estimates the incidence, prevalence and mortality for 27 cancers

Lars Buda¨us*, Sascha Ahyai, Hendrik Isbarn, Hamburg, Germany; Giovanni Lughezzani, Milano, Italy; Maxine Sun, Montreal, Canada; Friedemann Honecker, Felix Chun, Hamburg, Germany; Paul Perrotte, Shahrokh F. Shariat, Philippe Arjane, Montreal, Canada; Francesco Montorsi, Milano, Italy; Michael Hartmann, Margit Fisch, Markus Graefen, Hamburg, Germany; Pierre I. Karakiewicz, Montreal, Canada INTRODUCTION AND OBJECTIVES: Elevated rate of metastatic stage at presentation may be indicative of delays in diagnosis and

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is usually considered as an adverse predictor of cancer control outcome. We examined the annual rates of diagnosis of metastatic germ cell tumors as well as the associated 5-year survival rates, in a large population-based cohort over a period of 20 years. METHODS: Between 1988 and 2006, 17080 and 12984 patients were identified with respectively seminoma and nonseminoma of the testis within the 17 SEER registries. Rates and proportions as well as 5 year overall survivals were recorded and analyzed. RESULTS: Metastatic seminoma and nonseminoma was found in 2373 patients (7.8%). Of those, 500 (21%) and 1595 (79%) were metastatic at diagnosis. The rate of metastatic seminoma increased from 1.2 to 4.8% (Chi-square trend: p⬍ 0.001) over the study span vs. 12.7 to 18.4% for nonseminoma (Chi-Square trend: p⬍0.001). The median 5-year survival rate was 98% for both seminoma and nonseminoma. No differences were recorded in temporal 5-years survival rates (p⫽0.08). CONCLUSIONS: The rates of metastatic seminoma and nonseminoma at diagnosis increased over the study period. Therefore better detection strategies might require consideration. Nonetheless despite higher rates of metastatic disease at diagnosis the survival has not changed, which indicates excellent cancer control outcome.

Source of Funding: None

839 DECREASED SURVIVAL OF BLACK AMERICANS WITH TESTICULAR CANCER: A CONTEMPORARY POPULATION-BASED ANALYSIS Daniel Liberman*, Lars Badaus, Giovanni Lughezzani, Maxine Sun, Rodolphe Thuret, Wassim Kassouf, Philippe Arjane, Hugues Widmer, Francesco Montorsi, Shahrokh F. Shariat, Paul Perrotte, Pierre I. Karakiewicz, Montreal, Canada INTRODUCTION AND OBJECTIVES: A previous report (Journal Urology; Bridges P, Sharif R, Razzaq A, Guinan P; 1998) indicated that Black Americans have worse survival after the diagnosis of testicular cancer (TC) than their white counterparts. We re-examined the association between race and survival in a large population-based dataset. METHODS: Between 1998 and 2006, 24388 men were diagnosed and treated for all stages of TC (Seminoma, Non-Seminoma and other testicular malignancies). Analyses focused on the association between Black Amercian race and overall mortality and consisted of univariable and multivariable Cox Regression models. Analyses were adjusted for age, year of surgery, socio-economic status (low vs. high), type of surgery, histological subtype, clinical stage and SEER registry. RESULTS: Of 24388 patients with TC, 616 (2.5%) were Black Americans. Of those, 379 (2.2%) had stage I TC, 130 (2.9%) had stage II TC and 107 (4.1%) has stage III TC. In patients with stage I TC, Black American race was associated with a 1.7-fold increase in overall mortality, which did not reach independent predictor status in multivariable analyses (HR:1.4; p-value⫽0.1) compared to White Americans. Conversely, in patients with stage II TC, the increase in overall mortality associated with Black American race was 2.6-fold (p-value ⬍0.001) in univariable analyses and remained at 2.3-fold (p⫽0.007) in multivariable models relative to White Americans. For Black American patients

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with stage III TC the univariable and multivariable increases in overall mortality were respectively; 1.8 (p-value⬍0.001) and 1,6-fold (p-value⫽0.001) relative to White Americans. CONCLUSIONS: Overall mortality rate is 2.3 and 1.7-fold higher in respectively stage II and III, Black American patients with TC. This parity in overall mortality rate relative to White Amercian patients with TC deserves attention. Source of Funding: None

840 INCREASED MORTALITY FROM TESTIS CANCER AMONG HISPANIC WHITE AMERICANS DESPITE ADJUSTMENT FOR SOCIOECONOMIC STATUS: A SEER STUDY Viraj Master*, Timothy Johnson, Wayland Hsiao, Ashesh Jani, Atlanta, GA INTRODUCTION AND OBJECTIVES: Testis cancer incidence, histology, and tesits cancer-specific survival (tCSS) vary by Hispanic ethnicity. However, the impact of geographic region of the United States and socioeconomic status on tCSS remain unclear. METHODS: We queried 17 Surveillance, Epidemiology, and End Results (SEER) database registries for Hispanic (HW) and NonHispanic white (NHW) patients diagnosed only with testis cancer from 1973 through 2006 with known stage. Multivariate Cox regression analyses evaluated the impact of Hispanic ethnicity on tCSS while adjusting for age, year of diagnosis, marital status, geographic region of the United States, histology, stage, and markers of socioeconomic status (education and income levels). RESULTS: HWs constituted 14.8% of the 25,037 patients who met inclusion criteria. Compared to HWs, NHWs tended to be diagnosed at an older age, married, present with more localized disease, and live in counties with higher education and median household incomes. After controlling for patient and disease characteristics and county demographics, Hispanic ethnicity significantly predicted tCSS. Compared to NHWs, HWs experienced a 33% greater cancer-specific mortality (HR: 1.328, 95% CI: 1.089-1.620, p⫽0.005). CONCLUSIONS: After adjusting for geography and socioeconomic markers, as well as other patient and disease characteristics, Hispanic ethnicity remains a significant predictor of testis-cancer specific survival. Further studies are needed to identify unknown external or genetic factors that account for these differences in survival. Source of Funding: None

841 IMPROVED OUTCOME FOR POOR-PROGNOSIS METASTATIC GERM CELL CANCER: A SINGLE CENTER EXPERIENCE IN JAPAN Shigeyuki Yamada*, Hideo Saito, Yasuhiro Kaiho, Akihiro Ito, Shigeto Ishidoya, Yoichi Arai, Sendai, Japan INTRODUCTION AND OBJECTIVES: The International Germ Cell Consensus (IGCC) classification has identified three prognostic groups of patients with metastatic germ cell cancer. ‘Poor prognosis’ is based on primary tumor localization, presence of non-pulmonary visceral metastases, and/or high serum tumor marker levels. The 5-year overall survival rate of these patients is reportedly 48%. However, treatment outcomes have improved among those treated in or after 1990 and 5-year overall survival has increased to 71%. The present study aimed to evaluate treatment outcomes for a single institution in Japan, and to identify prognostic factors for ‘IGCC poor-prognosis’ germ cell cancer. METHODS: We retrospectively analyzed 341 germ cell cancer patients treated at Tohoku University Hospital between May 1979 and December 2007. Of these, 163 patients showed metastatic disease at initial diagnosis. Fifty-four patients were classified as the poor prognosis group by IGCC classifications.