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157 LYMPHOVASCULAR INVASION IS A PATHOLOGIC FEATURE OF BIOLOGICALLY AGGRESSIVE DISEASE IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT: AN INTERNATIONAL EXTERNAL VALIDATION STUDY
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THE JOURNAL OF UROLOGY姞
Vol. 183, No. 4, Supplement, Sunday, May 30, 2010
Urothelial Cancer: Natural History & Pathophysiology/Markers Podium 9 Sunday, May 30, 2010
8:00 AM-10:00 AM
157 LYMPHOVASCULAR INVASION IS A PATHOLOGIC FEATURE OF BIOLOGICALLY AGGRESSIVE DISEASE IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT: AN INTERNATIONAL EXTERNAL VALIDATION STUDY Giacomo Novara*, Padua, Italy; Kazumasa Matsumoto, Sagamihara, Kanagawa, Japan; Wassim Kassouf, Montreal, Canada; Thomas J. Walton, Derby, United Kingdom; Hans-Martin Fritsche, Rosenburg, Germany; Patrick J Bastian, Munich, Germany; Juan I. Martı´nezSalamanca, Madrid, Spain; Christian Seitz, Bolzano, Italy; R. John Lemberger, Nottingham City, United Kingdom; Maximilian Burger, Regensburg, Germany; Assaad El-Hakim, Montreal, Canada; Shiro Baba, Sagamihara, Kanagawa, Japan; Guido Martignoni, Verona, Italy; Amit Gupta, Dallas, TX; Pierre I. Karakiewicz, Montreal, Canada; Vincenzo Ficarra, Padua, Italy; Shahrokh F. Shariat, Dallas, TX INTRODUCTION AND OBJECTIVES: Lymphovascular invasion (LVI) identified following pathological slide review has been shown to be an independent predictor of recurrence-free (RFS) and cancerspecific survival (CSS) in a multicenter series of patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). However, the validity of LVI in everyday practice, where pathological re-review of all slides is uncommon, has not been assessed. The aim of the study was to evaluate the prognostic role of LVI in an international cohort of patients treated with RNU for UTUC without pathological slide review. METHODS: Data from 762 patients treated with RNU for UTUC without neoadjuvant chemotherapy were collected at 9 centres located in Europe, Asia, and Canada. We evaluated patients’ characteristics, RFS, and CSS. RESULTS: LVI was present in 148 patients (19.4%). At a median follow-up of 34 mo, 23.5% of the patients developed disease recurrence and 19.8% died of UTUC. The five-year RFS and CSS rates were 79.3% and 82.1%, respectively, in the absence of LVI compared with 45.1% and 45.8%, respectively, in the presence of LVI (p values ⬍0.0001). On multivariable Cox regression analyses, LVI was an independent predictor of RFS (Hazard ratio (HR): 1.7; p⫽0.005) and CSS (HR: 1.9; p ⬍0.0001). Similarly, among patients with pN0/Nx disease, LVI was an independent predictor of RFS (HR: 1.9; p⫽0.002) and CSS (HR: 2.1; p⬍0.0001). CONCLUSIONS: In a large multicenter series of patients treated with RNU for UTUC and where no pathological slide review was performed, LVI was present in approximately 20% and was an independent predictor of both RFS and CSS. LVI status should always be included in the pathologic report of RNU specimens and patients with LVI should be considered for adjuvant therapy studies. Finally, LVI should be considered for inclusion in the AJCC TNM staging system. Source of Funding: None
158 CLINICAL OUTCOMES OF PRIMARY BLADDER CARCINOMA IN SITU IN A CONTEMPORARY SERIES Daher C. Chade*, Shahrokh F. Shariat, Guilherme Godoy, Caroline J Savage, Angel M. Cronin, Bernard H. Bochner, S. Machele Donat, Harry W. Herr, Guido Dalbagni, New York, NY INTRODUCTION AND OBJECTIVES: The natural history of primary bladder carcinoma in situ (CIS) has not been well described as
a distinct entity. Our objectives were to describe patterns of disease progression and identify clinical-outcome predictors for primary CIS after BCG therapy. METHODS: We performed a retrospective analysis of 155 patients diagnosed with isolated primary high-grade CIS in a tertiary center from 1990 to 2008, after transurethral resection (TUR) and intravesical BCG therapy. Our endpoints were time to progression to invasive disease (ⱖcT1) or to muscle-invasive disease (ⱖcT2), adjusting for radical cystectomy (RC) before progression. Predictors included gender, age, race, smoking history, presenting symptoms, CIS pattern (focal, multiple or diffuse), and response to BCG. RESULTS: In total, 155 patients received BCG therapy within 6 mo. 69 patients experienced disease progression: 47 progressed to cT1 and 27 to cT2 (all but 5 of the patients who progressed to cT2 progressed directly from CIS). Five-yr cumulative incidence of progression to ⱖcT1 was 45% (95% CI, 37%–55%), to ⱖcT2 was 17% (95% CI, 12%–25%), adjusting for the competing risk of RC before progression. Of 130 patients evaluated for response to BCG, 81 (62%) were considered responders. Response to BCG was significantly associated with progression to ⱖcT1/RC (HR: 0.59; 95% CI, 0.36 – 0.95; p⫽0.029) and to ⱖcT2/RC (HR: 0.53; 95% CI, 0.32– 0.88; p⫽0.015). This association was largely driven by the higher rate of early RC among non-responders. Limitations are its retrospective nature and the cohort of a referral center. CONCLUSIONS: Despite BCG therapy and RC, patients with primary CIS had a high rate of disease progression. Response to BCG was significantly associated with a lower rate of disease progression or RC before progression.
Source of Funding: Supported by: The Sidney Kimmel Center for Prostate and Urologic Cancers. Dr. Chade is supported by CAPES (Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nı´vel Superior, Brazil). Dr. Shariat is supported by NIH T32CA82088.
159 ASSOCIATION OF ANGIOGENESIS-RELATED MARKERS WITH BLADDER CANCER OUTCOMES AND OTHER MOLECULAR MARKERS Shahrokh Shariat*, Ramy Youssef, Daher Chade, Dallas, TX; Pierre Karakiewicz, Hendrik Isbarn, Claudio Jeldres, Montreal, Canada; Arthur Sagalowsky, Raheela Ashfaq, Yair Lotan, Dallas, TX INTRODUCTION AND OBJECTIVES: Angiogenesis is important for tumor growth and metastasis. Angiogenesis contributes to the tumor-promoting extracellular milieu by providing oxygen, nutrients, and growth factors to the neoplastic cells. Development of reliable
THE JOURNAL OF UROLOGY姞
Vol. 183, No. 4, Supplement, Sunday, May 30, 2010
Urothelial Cancer: Natural History & Pathophysiology/Markers Podium 9 Sunday, May 30, 2010
8:00 AM-10:00 AM
157 LYMPHOVASCULAR INVASION IS A PATHOLOGIC FEATURE OF BIOLOGICALLY AGGRESSIVE DISEASE IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT: AN INTERNATIONAL EXTERNAL VALIDATION STUDY Giacomo Novara*, Padua, Italy; Kazumasa Matsumoto, Sagamihara, Kanagawa, Japan; Wassim Kassouf, Montreal, Canada; Thomas J. Walton, Derby, United Kingdom; Hans-Martin Fritsche, Rosenburg, Germany; Patrick J Bastian, Munich, Germany; Juan I. Martı´nezSalamanca, Madrid, Spain; Christian Seitz, Bolzano, Italy; R. John Lemberger, Nottingham City, United Kingdom; Maximilian Burger, Regensburg, Germany; Assaad El-Hakim, Montreal, Canada; Shiro Baba, Sagamihara, Kanagawa, Japan; Guido Martignoni, Verona, Italy; Amit Gupta, Dallas, TX; Pierre I. Karakiewicz, Montreal, Canada; Vincenzo Ficarra, Padua, Italy; Shahrokh F. Shariat, Dallas, TX INTRODUCTION AND OBJECTIVES: Lymphovascular invasion (LVI) identified following pathological slide review has been shown to be an independent predictor of recurrence-free (RFS) and cancerspecific survival (CSS) in a multicenter series of patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). However, the validity of LVI in everyday practice, where pathological re-review of all slides is uncommon, has not been assessed. The aim of the study was to evaluate the prognostic role of LVI in an international cohort of patients treated with RNU for UTUC without pathological slide review. METHODS: Data from 762 patients treated with RNU for UTUC without neoadjuvant chemotherapy were collected at 9 centres located in Europe, Asia, and Canada. We evaluated patients’ characteristics, RFS, and CSS. RESULTS: LVI was present in 148 patients (19.4%). At a median follow-up of 34 mo, 23.5% of the patients developed disease recurrence and 19.8% died of UTUC. The five-year RFS and CSS rates were 79.3% and 82.1%, respectively, in the absence of LVI compared with 45.1% and 45.8%, respectively, in the presence of LVI (p values ⬍0.0001). On multivariable Cox regression analyses, LVI was an independent predictor of RFS (Hazard ratio (HR): 1.7; p⫽0.005) and CSS (HR: 1.9; p ⬍0.0001). Similarly, among patients with pN0/Nx disease, LVI was an independent predictor of RFS (HR: 1.9; p⫽0.002) and CSS (HR: 2.1; p⬍0.0001). CONCLUSIONS: In a large multicenter series of patients treated with RNU for UTUC and where no pathological slide review was performed, LVI was present in approximately 20% and was an independent predictor of both RFS and CSS. LVI status should always be included in the pathologic report of RNU specimens and patients with LVI should be considered for adjuvant therapy studies. Finally, LVI should be considered for inclusion in the AJCC TNM staging system. Source of Funding: None
158 CLINICAL OUTCOMES OF PRIMARY BLADDER CARCINOMA IN SITU IN A CONTEMPORARY SERIES Daher C. Chade*, Shahrokh F. Shariat, Guilherme Godoy, Caroline J Savage, Angel M. Cronin, Bernard H. Bochner, S. Machele Donat, Harry W. Herr, Guido Dalbagni, New York, NY INTRODUCTION AND OBJECTIVES: The natural history of primary bladder carcinoma in situ (CIS) has not been well described as
a distinct entity. Our objectives were to describe patterns of disease progression and identify clinical-outcome predictors for primary CIS after BCG therapy. METHODS: We performed a retrospective analysis of 155 patients diagnosed with isolated primary high-grade CIS in a tertiary center from 1990 to 2008, after transurethral resection (TUR) and intravesical BCG therapy. Our endpoints were time to progression to invasive disease (ⱖcT1) or to muscle-invasive disease (ⱖcT2), adjusting for radical cystectomy (RC) before progression. Predictors included gender, age, race, smoking history, presenting symptoms, CIS pattern (focal, multiple or diffuse), and response to BCG. RESULTS: In total, 155 patients received BCG therapy within 6 mo. 69 patients experienced disease progression: 47 progressed to cT1 and 27 to cT2 (all but 5 of the patients who progressed to cT2 progressed directly from CIS). Five-yr cumulative incidence of progression to ⱖcT1 was 45% (95% CI, 37%–55%), to ⱖcT2 was 17% (95% CI, 12%–25%), adjusting for the competing risk of RC before progression. Of 130 patients evaluated for response to BCG, 81 (62%) were considered responders. Response to BCG was significantly associated with progression to ⱖcT1/RC (HR: 0.59; 95% CI, 0.36 – 0.95; p⫽0.029) and to ⱖcT2/RC (HR: 0.53; 95% CI, 0.32– 0.88; p⫽0.015). This association was largely driven by the higher rate of early RC among non-responders. Limitations are its retrospective nature and the cohort of a referral center. CONCLUSIONS: Despite BCG therapy and RC, patients with primary CIS had a high rate of disease progression. Response to BCG was significantly associated with a lower rate of disease progression or RC before progression.
Source of Funding: Supported by: The Sidney Kimmel Center for Prostate and Urologic Cancers. Dr. Chade is supported by CAPES (Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nı´vel Superior, Brazil). Dr. Shariat is supported by NIH T32CA82088.
159 ASSOCIATION OF ANGIOGENESIS-RELATED MARKERS WITH BLADDER CANCER OUTCOMES AND OTHER MOLECULAR MARKERS Shahrokh Shariat*, Ramy Youssef, Daher Chade, Dallas, TX; Pierre Karakiewicz, Hendrik Isbarn, Claudio Jeldres, Montreal, Canada; Arthur Sagalowsky, Raheela Ashfaq, Yair Lotan, Dallas, TX INTRODUCTION AND OBJECTIVES: Angiogenesis is important for tumor growth and metastasis. Angiogenesis contributes to the tumor-promoting extracellular milieu by providing oxygen, nutrients, and growth factors to the neoplastic cells. Development of reliable