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1429 OVEREXPRESSION OF IGF1R PREDICTS OUTCOME IN INVASIVE UROTHELIAL CARCINOMA OF URINARY BLADDER
Vol. 189, No. 4S, Supplement, Tuesday, May 7, 2013
THE JOURNAL OF UROLOGY姞
e585
features, statin use was not associated with these endpoints anymore while BMI was (p-values⬍0.01). Excluding age and BMI from the multivariable analyses did not change the lack of independent prognostic value of statin use. CONCLUSIONS: Statin users were at higher risk of disease recurrence and cancer-specific mortality in univariate but not in multivariable analyses. We confirmed the worst outcomes of obese patients after RC. These data do not support modifications of statin use in patients with high-risk UCB who are planned for RC. Source of Funding: None
1428 PREDICTORS OF INTRAVESICAL TUMOR RECURRENCE FOLLOWING SELECTIVE BLADDER PRESERVATION IN MUSCLE-INVASIVE BLADDER CANCER PATIENTS Fumitaka KOGA*, Yasuhisa FUJII, Junichiro ISHIOKA, Yoh Matsuoka, Noboru NUMAO, Kazutaka SAITO, Hitoshi MASUDA, Satoru KAWAKAMI, Kazunori KIHARA, Tokyo, Japan INTRODUCTION AND OBJECTIVES: One of the major issues of selective bladder preservation for muscle-invasive bladder cancer (MIBC) patients is intravesical bladder tumor (BT) recurrence. We investigated risk factors for the recurrence. METHODS: Between 1997 and 2012, 184 cT2-3N0M0 bladder urothelial carcinoma patients underwent induction chemoradiation (CRT) composed of RT at 40 Gy to the small pelvis and 2 cycles of concurrent cisplatin at 20 mg/d for 5 d. After CRT, 102 patients (55%) achieved complete response clinically and 2 (1%) had progressive disease. Finally, 84 patients underwent radical cystectomy due to post-CRT residual disease or originally extensive disease, 64 underwent consolidative partial cystectomy (PC) of the original MIBC site, and the remaining 36 had no surgery. Of the 100 bladder-preserved patients, 98 who had achieved tumor-free status (64 PC and 34 no PC) were included in this study. RESULTS: For the 98 eligible bladder-preserved patients (median 71 yr, T2/T3 ⫽ 72/26), 5-yr overall and cancer-specific survival (CSS) rates were 84% and 92%, respectively. During followup (median 50 mo), 21 patients developed intravesical recurrence (5-yr BT recurrence-free survival [BTRFS] rate ⫽ 73%). Of the 21 patients, 4 developed MIBC recurrence (5-yr MIBC recurrence-free survival rate was 96%). Among variables including age, gender, prior recurrence rate, number of tumors, tumor site, tumor diameter, T stage, concurrent CIS, and bladder-sparing modality (PC vs no PC), multivariate analysis revealed that bladder neck involvement (HR 5.3, p ⫽ 0.017) and multiple disease at the diagnosis of MIBC (HR 4.2, p ⫽ 0.041) were significant and independent risk factors for BT recurrence. When patients were stratified according to the number of the risk factors, 5-yr BTRFS rates were 82%, 72%, and 22% for patients having 0, 1, and 2 risk factors, respectively. Of the 4 patients who developed MIBC recurrence, none had undergone PC and 3 had prior history of nonMIBC at the initial diagnosis of MIBC. There was no difference in CSS between the 21 patients with and the rest without BT recurrence (5-yr CSS rates, 88% vs 93%; p ⫽ 0.74). CONCLUSIONS: Bladder neck involvement and multiple disease at the diagnosis of MIBC are risk factors for intravesical tumor recurrence following selective bladder preservation.
Source of Funding: None
1429 OVEREXPRESSION OF IGF1R PREDICTS OUTCOME IN INVASIVE UROTHELIAL CARCINOMA OF URINARY BLADDER Nilda Gonzalez-Roibon*, Jenny KIM, Baltimore, MD; Alcides Chaux, Asuncion, Paraguay; Enrico Munari, Sheila Faraj, Carla Ellis, Rajni Sharma, Trinity Bivalacqua, Mark Schoenberg, Michael Carducci, George Netto, Baltimore, MD INTRODUCTION AND OBJECTIVES: Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase receptor involved in cell proliferation and differentiation. IGF1R is overexpressed in several tumors including bladder cancer and is currently under investigation as a target of therapy. We explored IGF1R expression in urothelial carcinoma (UC) and its association with clinicopathologic parameters and prognostic role. METHODS: Five tissue microarrays (TMA) were constructed from 100 cystectomy specimens performed for invasive UC at our institution (1994 to 2007). Formalin-fixed paraffin-embedded paired tumor and benign samples were spotted 3-4 times each. Membranous IGF1R staining was evaluated using immunohistochemistry (G11, Ventana Medical Systems). A scoring method analogous to that of Her2 expression in breast cancer was used and the highest score was assigned to each tumor. IGF1R was considered overexpressed in cases with score 1. Endpoints of the study included overall survival (OS) and cancer-specific survival (DSS). Patients were followed-up for a median of 33.5 months (range: 1-141 months). RESULTS: We found IGF1R overexpression in 62% of UC. No differences were noted between normal urothelium and UC regarding IGF1R overexpression (74% vs. 60%; P⫽0.14). IGF1R overexpression was more frequent in tumors from African-American patients compared to Caucasians (100% vs. 59%, P⫽0.04). Tumors at stage pT4 overexpressed IGF1R less frequently than tumors at stages pT1-pT3 (29% vs. 71%, P⫽0.005). We did not find any association with other analyzed clinicopathologic parameters such as patient’s age or gender, muscularis propria invasion, or lymph node metastasis. OS and DSS rates were 58% and 69%, respectively. Patients with tumors overexpressing IGF1R had a lower OS and DSS compared to those without IGF1R overexpression (Mantel-Cox P⫽0.0007 and P⫽0.006, respectively). Using Cox proportional hazards regression, IGF1R overexpression remained a significant predictor of OS (HR⫽3.49, P⫽0.001) and DSS (HR⫽3.54, P⫽0.007) after adjusting for pathologic stage. CONCLUSIONS: Overexpression of IGF1R was found in 62% of UC. High stage tumors overexpressed IGF1R more frequently than low stage tumors. More importantly, IGF1R overexpression was a significant independent predictor of OS and DSS, suggesting its usefulness as a prognosticator in UC. The findings also point to IGF1R as a potential target of therapy in UC. Source of Funding: None
THE JOURNAL OF UROLOGY姞
e585
features, statin use was not associated with these endpoints anymore while BMI was (p-values⬍0.01). Excluding age and BMI from the multivariable analyses did not change the lack of independent prognostic value of statin use. CONCLUSIONS: Statin users were at higher risk of disease recurrence and cancer-specific mortality in univariate but not in multivariable analyses. We confirmed the worst outcomes of obese patients after RC. These data do not support modifications of statin use in patients with high-risk UCB who are planned for RC. Source of Funding: None
1428 PREDICTORS OF INTRAVESICAL TUMOR RECURRENCE FOLLOWING SELECTIVE BLADDER PRESERVATION IN MUSCLE-INVASIVE BLADDER CANCER PATIENTS Fumitaka KOGA*, Yasuhisa FUJII, Junichiro ISHIOKA, Yoh Matsuoka, Noboru NUMAO, Kazutaka SAITO, Hitoshi MASUDA, Satoru KAWAKAMI, Kazunori KIHARA, Tokyo, Japan INTRODUCTION AND OBJECTIVES: One of the major issues of selective bladder preservation for muscle-invasive bladder cancer (MIBC) patients is intravesical bladder tumor (BT) recurrence. We investigated risk factors for the recurrence. METHODS: Between 1997 and 2012, 184 cT2-3N0M0 bladder urothelial carcinoma patients underwent induction chemoradiation (CRT) composed of RT at 40 Gy to the small pelvis and 2 cycles of concurrent cisplatin at 20 mg/d for 5 d. After CRT, 102 patients (55%) achieved complete response clinically and 2 (1%) had progressive disease. Finally, 84 patients underwent radical cystectomy due to post-CRT residual disease or originally extensive disease, 64 underwent consolidative partial cystectomy (PC) of the original MIBC site, and the remaining 36 had no surgery. Of the 100 bladder-preserved patients, 98 who had achieved tumor-free status (64 PC and 34 no PC) were included in this study. RESULTS: For the 98 eligible bladder-preserved patients (median 71 yr, T2/T3 ⫽ 72/26), 5-yr overall and cancer-specific survival (CSS) rates were 84% and 92%, respectively. During followup (median 50 mo), 21 patients developed intravesical recurrence (5-yr BT recurrence-free survival [BTRFS] rate ⫽ 73%). Of the 21 patients, 4 developed MIBC recurrence (5-yr MIBC recurrence-free survival rate was 96%). Among variables including age, gender, prior recurrence rate, number of tumors, tumor site, tumor diameter, T stage, concurrent CIS, and bladder-sparing modality (PC vs no PC), multivariate analysis revealed that bladder neck involvement (HR 5.3, p ⫽ 0.017) and multiple disease at the diagnosis of MIBC (HR 4.2, p ⫽ 0.041) were significant and independent risk factors for BT recurrence. When patients were stratified according to the number of the risk factors, 5-yr BTRFS rates were 82%, 72%, and 22% for patients having 0, 1, and 2 risk factors, respectively. Of the 4 patients who developed MIBC recurrence, none had undergone PC and 3 had prior history of nonMIBC at the initial diagnosis of MIBC. There was no difference in CSS between the 21 patients with and the rest without BT recurrence (5-yr CSS rates, 88% vs 93%; p ⫽ 0.74). CONCLUSIONS: Bladder neck involvement and multiple disease at the diagnosis of MIBC are risk factors for intravesical tumor recurrence following selective bladder preservation.
Source of Funding: None
1429 OVEREXPRESSION OF IGF1R PREDICTS OUTCOME IN INVASIVE UROTHELIAL CARCINOMA OF URINARY BLADDER Nilda Gonzalez-Roibon*, Jenny KIM, Baltimore, MD; Alcides Chaux, Asuncion, Paraguay; Enrico Munari, Sheila Faraj, Carla Ellis, Rajni Sharma, Trinity Bivalacqua, Mark Schoenberg, Michael Carducci, George Netto, Baltimore, MD INTRODUCTION AND OBJECTIVES: Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase receptor involved in cell proliferation and differentiation. IGF1R is overexpressed in several tumors including bladder cancer and is currently under investigation as a target of therapy. We explored IGF1R expression in urothelial carcinoma (UC) and its association with clinicopathologic parameters and prognostic role. METHODS: Five tissue microarrays (TMA) were constructed from 100 cystectomy specimens performed for invasive UC at our institution (1994 to 2007). Formalin-fixed paraffin-embedded paired tumor and benign samples were spotted 3-4 times each. Membranous IGF1R staining was evaluated using immunohistochemistry (G11, Ventana Medical Systems). A scoring method analogous to that of Her2 expression in breast cancer was used and the highest score was assigned to each tumor. IGF1R was considered overexpressed in cases with score 1. Endpoints of the study included overall survival (OS) and cancer-specific survival (DSS). Patients were followed-up for a median of 33.5 months (range: 1-141 months). RESULTS: We found IGF1R overexpression in 62% of UC. No differences were noted between normal urothelium and UC regarding IGF1R overexpression (74% vs. 60%; P⫽0.14). IGF1R overexpression was more frequent in tumors from African-American patients compared to Caucasians (100% vs. 59%, P⫽0.04). Tumors at stage pT4 overexpressed IGF1R less frequently than tumors at stages pT1-pT3 (29% vs. 71%, P⫽0.005). We did not find any association with other analyzed clinicopathologic parameters such as patient’s age or gender, muscularis propria invasion, or lymph node metastasis. OS and DSS rates were 58% and 69%, respectively. Patients with tumors overexpressing IGF1R had a lower OS and DSS compared to those without IGF1R overexpression (Mantel-Cox P⫽0.0007 and P⫽0.006, respectively). Using Cox proportional hazards regression, IGF1R overexpression remained a significant predictor of OS (HR⫽3.49, P⫽0.001) and DSS (HR⫽3.54, P⫽0.007) after adjusting for pathologic stage. CONCLUSIONS: Overexpression of IGF1R was found in 62% of UC. High stage tumors overexpressed IGF1R more frequently than low stage tumors. More importantly, IGF1R overexpression was a significant independent predictor of OS and DSS, suggesting its usefulness as a prognosticator in UC. The findings also point to IGF1R as a potential target of therapy in UC. Source of Funding: None