- Email: [email protected]
PSA TRIGGERS FOR INTERVENTION DURING ACTIVE SURVEILLANCE: VELOCITY VS DOUBLING TIME VS GENERAL LINEAR MIXED MODELLING
Vol. 179, No. 4, Supplement, Sunday, May 18, 2008
THE JOURNAL OF UROLOGY®
67
CONCLUSIONS: These results suggest that high intake of dairy products including butter also increase the risk of prostate cancer in Japan. +D]DUGUDWLRV +5V IRU3URVWDWH&DQFHU,QFLGHQFH Item Age Family History of Prostate Cancer Butter
Category
Incidence HR
95%Cl
205
1.12
1.10-1.24 <0.001
P
no
199
1
yes Scarcely any 1-2/m to 1-2/w 3-4/w+
2 62 61 17
4.34 1 1.40 1.53
trend P
1.07-17.53 0.040 0.045 0.98-2.00 0.067 0.89-2.63 0.127
Source of Funding:6XEVLG\IRUVFLHQWL¿FUHVHDUFKIURP the Ministry of Education, Culture, Sports, Science and Technology.
189 ANTHROPOMORPHIC DIFFERENCES IN OBESE MEN WITH BIOCHEMICAL FAILURE AFTER RADICAL RETROPUBIC PROSTATECTOMY Phillip Mucksavage*, Christopher R Mitchell, Alexander Kutikov, Alan J Wein, Drew A Torigian, S Bruce Malkowicz. Philadelphia, PA. INTRODUCTION AND OBJECTIVE: The effect of obesity on biochemical failure after radical retropubic prostatectomy (RRP) is controversial. The differences in study outcomes may be a result of using body mass index (BMI) rather then direct anthropomorphic measurements of fat distribution. To investigate these differences, we used endorectal coil MRI (eMRI) data to directly measure fat thicknesses in obese men who underwent RRP. METHODS: We performed a retrospective analysis on an RRP database containing 1987 men with available BMI, clinicopathologic characteristics and biochemical outcomes. Obese men (BMI>30) were compared to lean men (BMI<25) and overweight men (BMI 25-30) for clinical and pathological differences and biochemical failure. The eMRI data for 143 obese men were reviewed and the fat thicknesses in the anterior, posterior and total anteroposterior diameters were measured and averaged in three separate images at and around the midline in the ZLGHVWVHJPHQWRIWKHVDJLWWDO7ZHLJKWHGORFDOL]LQJVFDQV )LJXUH Percent visceral fat thickness was calculated by subtracting the average anterior and posterior thicknesses from the total anteroposterior diameter and dividing by the total anteroposterior diameter. RESULTS: Kaplan Meyer curves with log rank analysis UHYHDOHG D VLJQL¿FDQW GLIIHUHQFH LQ ELRFKHPLFDO IUHH VXUYLYDO LQ OHDQ men and overweight men compared to obese men. (p=0.016, p=0.021). A BMI>30 also predicted time to biochemical failure (HR 1.43, 95% CI 1.09-1.86, p=0.009). The anterior fat thickness on eMRI in obese men ZLWK ELRFKHPLFDO IDLOXUH Q ZDV VLJQL¿FDQWO\ VPDOOHU WKDQ REHVH men without biochemical failure (n=122) (35mm vs. 44mm, p=0.003). &DOFXODWHGSHUFHQWYLVFHUDOIDWWKLFNQHVVZDVDOVRVLJQL¿FDQWO\ODUJHU in obese men with biochemical failure (74% vs.71%, p=0.02). Subset analysis on patients with extracapsular extension and higher pathological Gleason scores revealed similar trends in anterior and percent visceral fat thicknesses (p=0.003, p=0.02). CONCLUSIONS: All obese men are not created equal DQG VLJQL¿FDQW IDW GLVWULEXWLRQ GLIIHUHQFHV FDQ H[LVW EHWZHHQ WKHP These differences may explain why body mass index alone may not DGHTXDWHO\ SUHGLFW WKH LQÀXHQFH RI REHVLW\ RQ RXWFRPHV RI SURVWDWH cancer treatment.
Source of Funding: None
190 PSA TRIGGERS FOR INTERVENTION DURING ACTIVE SURVEILLANCE: VELOCITY VS DOUBLING TIME VS GENERAL LINEAR MIXED MODELLING Laurence H Klotz*, Andrew Loblaw, Liyang Zhang. Toronto, ON, Canada. INTRODUCTION AND OBJECTIVE: Active surveillance (AS) LVEHFRPLQJDQDFFHSWHGPDQDJHPHQWRSWLRQIRUPHQZLWKORFDOL]HG prostate cancer. PSA kinetics are a commonly used trigger for starting treatment. The objective of this study is to compare commonly used PSA triggers in stable patients. METHODS: A prospective phase II study of patients with favorable clinical parameters (stage T1b-T2b N0M0, Gleason score 36$ QJPO RQ DFWLYH VXUYHLOODQFH ZLWK VHOHFWLYH GHOD\HG intervention (AS) was initiated in 1995. Those who had a PSAdt < 3 y, JUDGHSURJUHVVLRQRQUHELRSV\RUGRXEOLQJLQVL]HRIDFOLQLFDOQRGXOH were offered radical intervention. The remaining patients were closely monitored and formed the cohort for this study. The proportion and frequency of patients who would have been offered treatment based on the following PSAdt triggers were calculated: i) PSA threshold (PSAt) of QJPOIRUSDWLHQWVZLWKDQLQLWLDO36$ LL 36$WRI LLL DOLQHDU UHJUHVVLRQRIOQ 36$ YVWLPH \IRUDOO36$YDOXHV /536$GW LY OQ 36$ YVWLPH \XVLQJWKH¿UVWDQGODVW36$RQUHFRUG )/36$GW Y DFWXDO36$YHORFLW\ D36$Y !\RYHUODVW\HDU YL FDOFXODWHG36$ YHORFLW\!\ F36$Y DQGYLL DJHQHUDOOLQHDUPL[HGPRGHO */00 of ln(PSA). 5(68/76 SDWLHQWV KDG PRUH WKDQ PR IROORZXS 134(58%) remain on AS and form the cohort for this study. As of March 2006, the median follow-up was 4.9 y (1.0-9.6 y). No patient has died RISURVWDWHFDQFHURUKDGPHWDVWDWLFGLVHDVH KDYHGLHGRI other causes. The following proportion patients would have received
68
THE JOURNAL OF UROLOGY®
WUHDWPHQWIRUWKHYDULRXVGH¿QLWLRQV 36$W! 36$W! /536$GW \ )/36$GW \ D36$Y!\ cPSAv > 2y. No patient had a PSAdt < 2y using GLMM. CONCLUSIONS: Patients followed on AS may be overtreated if the PSAdt is calculated using PSAt > 10, PSAt > 20, LR-PSAdt, FLPSAdt, aPSAv > 2y or cPSAv > 2y. Source of Funding: None
191 INFLUENCE OF THE PROSTATE CANCER PREVENTION TRIAL ON FINASTERIDE PRESCRIBING IN THE VETERANS HEALTH ADMINISTRATION Robert J Hamilton*, Leila C Kahwati, Tracey L Krupski, Russell Harris, Linda S Kinsinger. Toronto, ON, Canada, Durham, NC. INTRODUCTION AND OBJECTIVE: The Prostate Cancer 3UHYHQWLRQ7ULDO 3&37 ZKLFKVWXGLHG¿QDVWHULGHDVDFKHPRSUHYHQWLYH agent, yielded promising yet controversial results. Little is known about KRZSK\VLFLDQVDVVLPLODWHGWKLVHYLGHQFH:HH[DPLQHGWKHLQÀXHQFH RI WKH 3&37 RQ ¿QDVWHULGH SUHVFULELQJ ZLWKLQ WKH 9HWHUDQV +HDOWK Administration (VHA). 0(7+2'6 0RQWKO\QHZDQGWRWDOSUHVFULSWLRQVIRU¿QDVWHULGH ¿OOHGZLWKLQWKH9+$EHWZHHQ-DQXDU\DQG'HFHPEHUZHUH REWDLQHGDQGDGMXVWHGIRUFKDQJHVLQWKHVL]HDQGDJHGLVWULEXWLRQRI the VHA male population. Time-series analytic methods were used to DVVHVVWUHQGVLQSUHVFULSWLRQVDQGWKHLQÀXHQFHRIWKH3&37)LQDOO\DOO full-time(FT) VHA urologists and a random sample of FT VHA primary care physicians (PCPs) were invited between September 2006 and )HEUXDU\WRFRPSOHWHDVXUYH\DERXWWKHLUXVHRI¿QDVWHULGH 5(68/76 $WRWDORIPHQVWDUWHG¿QDVWHULGHGXULQJ WKHVWXG\SHULRG7KHQXPEHURIPHQ¿UVWVWDUWLQJ¿QDVWHULGHJUHZRYHU WLPH 7KH SXEOLFDWLRQ RI WKH 3&37 ZDV QRW VLJQL¿FDQWO\ DVVRFLDWHG ZLWKDQ\FKDQJHLQWKLVSDWWHUQ S ¿JXUH 6LPLODUWUHQGVZHUH REVHUYHG IRU WRWDO ¿QDVWHULGH SUHVFULSWLRQV S DV ZHOO DV QHZ SUHVFULSWLRQVIRU¿QDVWHULGHLQPHQZKRZHUHQHYHUSUHVFULEHGDQDOSKD blocker during the study period (p=0.76). A total of 464 (43.3%) PCPs and 135 (44.7%) urologists responded to the survey. 57% of urologists DQGRI3&3VHQGRUVHGSUHVFULELQJ¿QDVWHULGHPRUHIUHTXHQWO\QRZ than compared to 5 years ago. However, among those who reported FKDQJLQJSUHVFULELQJSDWWHUQVOHVVWKDQUHSRUWHGEHLQJLQÀXHQFHG by the PCPT. 64% of urologists and 80% of PCPs stated they never SUHVFULEH ¿QDVWHULGH IRU SURVWDWH FDQFHU FKHPRSUHYHQWLRQ DQG ZKHQ asked why, 55% of urologists cited concerns of inducing high grade tumors as the number one reason, while 52% of PCPs did not know it could be used for chemoprevention. &21&/86,216 7KHQXPEHURIQHZPHQVWDUWLQJ¿QDVWHULGH in the VHA increased over time, even when adjusted for changes in the VL]HDQGDJHGLVWULEXWLRQRIWKHPDOH9+$SRSXODWLRQ7KLV¿QGLQJZDV corroborated by our survey. Publication of the PCPT appears to have KDGOLWWOHLQÀXHQFHRQ¿QDVWHULGHSUHVFULELQJSDWWHUQV
Vol. 179, No. 4, Supplement, Sunday, May 18, 2008
192 HIGHER CHOLESTEROL INCREASES THE RISK OF BIOCHEMICAL FAILURE AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE GROUP Lionel L Banez*, Robert J Hamilton, William J Aronson, Martha K Terris, Joseph C Presti, Christopher J Kane, Christopher L Amling, Stephen J Freedland. Durham, NC, Toronto, ON, Canada, Los Angeles, CA, Augusta, GA, Palo Alto, CA, San Diego, CA, and Birmingham, AL. INTRODUCTION AND OBJECTIVE: Recent epidemiological and experimental data have suggested a possible link between cholesterol and the development and progression of prostate cancer. :H VRXJKW WR GHWHUPLQH ZKHWKHU DEQRUPDO VHUXP OLSLG SUR¿OHV PD\ be associated with increased risk of biochemical recurrence in men undergoing radical prostatectomy for prostate cancer. 0(7+2'6 :HLGHQWL¿HGPHQIURPWKH6KDUHG(TXDO Access Regional Cancer Hospital (SEARCH) database who underwent radical prostatectomy from 1998 to 2007 and had available cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels and known statin medication use status prior to surgery. We used Cox SURSRUWLRQDOKD]DUGVDQDO\VLVWRGHWHUPLQHDVVRFLDWLRQVRIFKROHVWHURO LDL and HDL levels with biochemical recurrence independent of age, race, pre-operative serum PSA levels, year of surgery, body mass index, surgical center, statin drug-use, post-operative Gleason sum, surgical margins, extra-capsular extension, seminal vesicle invasion, lymph node invasion, and prostate specimen weight. RESULTS: After controlling for the various demographic and clinico-pathologic features of prostate cancer, as well as intake of cholesterol-lowering drugs, increased serum cholesterol (p=0.001) and increased serum LDL (p=0.007) taken as continuous terms both VLJQL¿FDQWO\LQFUHDVHGWKHULVNIRUELRFKHPLFDOUHFXUUHQFHDIWHUVXUJHU\ HDL was not associated with biochemical relapse (p=0.79). Men in the KLJKHVWTXDUWLOHRIVHUXPFKROHVWHURO PJGO KDGWLPHVKLJKHU risk for biochemical relapse (HR 2.49, 95% CI 1.28 - 4.86, p=0.007) compared to men in the lowest quartile (<167 mg/dl). &21&/86,216 2XU¿QGLQJVVXJJHVWWKDWDPRQJPHQZLWK prostate cancer undergoing radical prostatectomy, lipid dysregulation, exemplified by high serum cholesterol and LDL is independently associated with increased risk for biochemical recurrence. These ¿QGLQJV VXJJHVW WKDW K\SHUFKROHVWHUROHPLD PD\ SURPRWH SURVWDWH cancer progression. Source of Funding: Department of Veterans Affairs, Department of Defense, National Institutes of Health, the Georgia Cancer Coalition, and the AUA Foundation/Astellas Rising Star in Urology Award.
Urothelial Cancer: Pathophysiology & Markers Podium Session 7 Sunday, May 18, 2008
8:00 - 10:00 am
193
Source of Funding: VA National Center for Health Promotion and Disease Prevention.
A URINE-BASED REAL TIME RT-PCR ASSAY FOR HYAL1 HYALURONIDASE AND HA-SYNTHASE TO DETECT BLADDER CANCER Mario Kramer, Roozbeh Golshani, Daniel J Caruso*, Murugesan Manoharon, Mark S Soloway, Vinata Lokeshwar. Miami, FL. INTRODUCTION AND OBJECTIVE: Identification of accurate bladder tumor markers/tests could improve diagnosis and surveillance for bladder cancer patients. We have previously shown that the HA-HAase test, which measures urinary hyaluronic acid (HA) and hyaluronidase (HAase) levels, detects bladder cancer with high VHQVLWLYLW\ a DQGVSHFL¿FLW\ a +$LVV\QWKHVL]HGE\ 3 different HA-synthases (HAS1, HAS2 and HAS3) and the expression of tumor-derived HAase, HYAL1 is elevated in bladder cancer. Both HAS and HYAL1 are molecular determinants of bladder cancer growth and progression. In this study we evaluated HAS1, HAS2, HAS3 and HYAL1 mRNA expression in exfoliated cells within urine specimens by real time RT-PCR and examined the ability of these PCR-based markers to detect bladder cancer.
THE JOURNAL OF UROLOGY®
67
CONCLUSIONS: These results suggest that high intake of dairy products including butter also increase the risk of prostate cancer in Japan. +D]DUGUDWLRV +5V IRU3URVWDWH&DQFHU,QFLGHQFH Item Age Family History of Prostate Cancer Butter
Category
Incidence HR
95%Cl
205
1.12
1.10-1.24 <0.001
P
no
199
1
yes Scarcely any 1-2/m to 1-2/w 3-4/w+
2 62 61 17
4.34 1 1.40 1.53
trend P
1.07-17.53 0.040 0.045 0.98-2.00 0.067 0.89-2.63 0.127
Source of Funding:6XEVLG\IRUVFLHQWL¿FUHVHDUFKIURP the Ministry of Education, Culture, Sports, Science and Technology.
189 ANTHROPOMORPHIC DIFFERENCES IN OBESE MEN WITH BIOCHEMICAL FAILURE AFTER RADICAL RETROPUBIC PROSTATECTOMY Phillip Mucksavage*, Christopher R Mitchell, Alexander Kutikov, Alan J Wein, Drew A Torigian, S Bruce Malkowicz. Philadelphia, PA. INTRODUCTION AND OBJECTIVE: The effect of obesity on biochemical failure after radical retropubic prostatectomy (RRP) is controversial. The differences in study outcomes may be a result of using body mass index (BMI) rather then direct anthropomorphic measurements of fat distribution. To investigate these differences, we used endorectal coil MRI (eMRI) data to directly measure fat thicknesses in obese men who underwent RRP. METHODS: We performed a retrospective analysis on an RRP database containing 1987 men with available BMI, clinicopathologic characteristics and biochemical outcomes. Obese men (BMI>30) were compared to lean men (BMI<25) and overweight men (BMI 25-30) for clinical and pathological differences and biochemical failure. The eMRI data for 143 obese men were reviewed and the fat thicknesses in the anterior, posterior and total anteroposterior diameters were measured and averaged in three separate images at and around the midline in the ZLGHVWVHJPHQWRIWKHVDJLWWDO7ZHLJKWHGORFDOL]LQJVFDQV )LJXUH Percent visceral fat thickness was calculated by subtracting the average anterior and posterior thicknesses from the total anteroposterior diameter and dividing by the total anteroposterior diameter. RESULTS: Kaplan Meyer curves with log rank analysis UHYHDOHG D VLJQL¿FDQW GLIIHUHQFH LQ ELRFKHPLFDO IUHH VXUYLYDO LQ OHDQ men and overweight men compared to obese men. (p=0.016, p=0.021). A BMI>30 also predicted time to biochemical failure (HR 1.43, 95% CI 1.09-1.86, p=0.009). The anterior fat thickness on eMRI in obese men ZLWK ELRFKHPLFDO IDLOXUH Q ZDV VLJQL¿FDQWO\ VPDOOHU WKDQ REHVH men without biochemical failure (n=122) (35mm vs. 44mm, p=0.003). &DOFXODWHGSHUFHQWYLVFHUDOIDWWKLFNQHVVZDVDOVRVLJQL¿FDQWO\ODUJHU in obese men with biochemical failure (74% vs.71%, p=0.02). Subset analysis on patients with extracapsular extension and higher pathological Gleason scores revealed similar trends in anterior and percent visceral fat thicknesses (p=0.003, p=0.02). CONCLUSIONS: All obese men are not created equal DQG VLJQL¿FDQW IDW GLVWULEXWLRQ GLIIHUHQFHV FDQ H[LVW EHWZHHQ WKHP These differences may explain why body mass index alone may not DGHTXDWHO\ SUHGLFW WKH LQÀXHQFH RI REHVLW\ RQ RXWFRPHV RI SURVWDWH cancer treatment.
Source of Funding: None
190 PSA TRIGGERS FOR INTERVENTION DURING ACTIVE SURVEILLANCE: VELOCITY VS DOUBLING TIME VS GENERAL LINEAR MIXED MODELLING Laurence H Klotz*, Andrew Loblaw, Liyang Zhang. Toronto, ON, Canada. INTRODUCTION AND OBJECTIVE: Active surveillance (AS) LVEHFRPLQJDQDFFHSWHGPDQDJHPHQWRSWLRQIRUPHQZLWKORFDOL]HG prostate cancer. PSA kinetics are a commonly used trigger for starting treatment. The objective of this study is to compare commonly used PSA triggers in stable patients. METHODS: A prospective phase II study of patients with favorable clinical parameters (stage T1b-T2b N0M0, Gleason score 36$ QJPO RQ DFWLYH VXUYHLOODQFH ZLWK VHOHFWLYH GHOD\HG intervention (AS) was initiated in 1995. Those who had a PSAdt < 3 y, JUDGHSURJUHVVLRQRQUHELRSV\RUGRXEOLQJLQVL]HRIDFOLQLFDOQRGXOH were offered radical intervention. The remaining patients were closely monitored and formed the cohort for this study. The proportion and frequency of patients who would have been offered treatment based on the following PSAdt triggers were calculated: i) PSA threshold (PSAt) of QJPOIRUSDWLHQWVZLWKDQLQLWLDO36$ LL 36$WRI LLL DOLQHDU UHJUHVVLRQRIOQ 36$ YVWLPH \IRUDOO36$YDOXHV /536$GW LY OQ 36$ YVWLPH \XVLQJWKH¿UVWDQGODVW36$RQUHFRUG )/36$GW Y DFWXDO36$YHORFLW\ D36$Y !\RYHUODVW\HDU YL FDOFXODWHG36$ YHORFLW\!\ F36$Y DQGYLL DJHQHUDOOLQHDUPL[HGPRGHO */00 of ln(PSA). 5(68/76 SDWLHQWV KDG PRUH WKDQ PR IROORZXS 134(58%) remain on AS and form the cohort for this study. As of March 2006, the median follow-up was 4.9 y (1.0-9.6 y). No patient has died RISURVWDWHFDQFHURUKDGPHWDVWDWLFGLVHDVH KDYHGLHGRI other causes. The following proportion patients would have received
68
THE JOURNAL OF UROLOGY®
WUHDWPHQWIRUWKHYDULRXVGH¿QLWLRQV 36$W! 36$W! /536$GW \ )/36$GW \ D36$Y!\ cPSAv > 2y. No patient had a PSAdt < 2y using GLMM. CONCLUSIONS: Patients followed on AS may be overtreated if the PSAdt is calculated using PSAt > 10, PSAt > 20, LR-PSAdt, FLPSAdt, aPSAv > 2y or cPSAv > 2y. Source of Funding: None
191 INFLUENCE OF THE PROSTATE CANCER PREVENTION TRIAL ON FINASTERIDE PRESCRIBING IN THE VETERANS HEALTH ADMINISTRATION Robert J Hamilton*, Leila C Kahwati, Tracey L Krupski, Russell Harris, Linda S Kinsinger. Toronto, ON, Canada, Durham, NC. INTRODUCTION AND OBJECTIVE: The Prostate Cancer 3UHYHQWLRQ7ULDO 3&37 ZKLFKVWXGLHG¿QDVWHULGHDVDFKHPRSUHYHQWLYH agent, yielded promising yet controversial results. Little is known about KRZSK\VLFLDQVDVVLPLODWHGWKLVHYLGHQFH:HH[DPLQHGWKHLQÀXHQFH RI WKH 3&37 RQ ¿QDVWHULGH SUHVFULELQJ ZLWKLQ WKH 9HWHUDQV +HDOWK Administration (VHA). 0(7+2'6 0RQWKO\QHZDQGWRWDOSUHVFULSWLRQVIRU¿QDVWHULGH ¿OOHGZLWKLQWKH9+$EHWZHHQ-DQXDU\DQG'HFHPEHUZHUH REWDLQHGDQGDGMXVWHGIRUFKDQJHVLQWKHVL]HDQGDJHGLVWULEXWLRQRI the VHA male population. Time-series analytic methods were used to DVVHVVWUHQGVLQSUHVFULSWLRQVDQGWKHLQÀXHQFHRIWKH3&37)LQDOO\DOO full-time(FT) VHA urologists and a random sample of FT VHA primary care physicians (PCPs) were invited between September 2006 and )HEUXDU\WRFRPSOHWHDVXUYH\DERXWWKHLUXVHRI¿QDVWHULGH 5(68/76 $WRWDORIPHQVWDUWHG¿QDVWHULGHGXULQJ WKHVWXG\SHULRG7KHQXPEHURIPHQ¿UVWVWDUWLQJ¿QDVWHULGHJUHZRYHU WLPH 7KH SXEOLFDWLRQ RI WKH 3&37 ZDV QRW VLJQL¿FDQWO\ DVVRFLDWHG ZLWKDQ\FKDQJHLQWKLVSDWWHUQ S ¿JXUH 6LPLODUWUHQGVZHUH REVHUYHG IRU WRWDO ¿QDVWHULGH SUHVFULSWLRQV S DV ZHOO DV QHZ SUHVFULSWLRQVIRU¿QDVWHULGHLQPHQZKRZHUHQHYHUSUHVFULEHGDQDOSKD blocker during the study period (p=0.76). A total of 464 (43.3%) PCPs and 135 (44.7%) urologists responded to the survey. 57% of urologists DQGRI3&3VHQGRUVHGSUHVFULELQJ¿QDVWHULGHPRUHIUHTXHQWO\QRZ than compared to 5 years ago. However, among those who reported FKDQJLQJSUHVFULELQJSDWWHUQVOHVVWKDQUHSRUWHGEHLQJLQÀXHQFHG by the PCPT. 64% of urologists and 80% of PCPs stated they never SUHVFULEH ¿QDVWHULGH IRU SURVWDWH FDQFHU FKHPRSUHYHQWLRQ DQG ZKHQ asked why, 55% of urologists cited concerns of inducing high grade tumors as the number one reason, while 52% of PCPs did not know it could be used for chemoprevention. &21&/86,216 7KHQXPEHURIQHZPHQVWDUWLQJ¿QDVWHULGH in the VHA increased over time, even when adjusted for changes in the VL]HDQGDJHGLVWULEXWLRQRIWKHPDOH9+$SRSXODWLRQ7KLV¿QGLQJZDV corroborated by our survey. Publication of the PCPT appears to have KDGOLWWOHLQÀXHQFHRQ¿QDVWHULGHSUHVFULELQJSDWWHUQV
Vol. 179, No. 4, Supplement, Sunday, May 18, 2008
192 HIGHER CHOLESTEROL INCREASES THE RISK OF BIOCHEMICAL FAILURE AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE GROUP Lionel L Banez*, Robert J Hamilton, William J Aronson, Martha K Terris, Joseph C Presti, Christopher J Kane, Christopher L Amling, Stephen J Freedland. Durham, NC, Toronto, ON, Canada, Los Angeles, CA, Augusta, GA, Palo Alto, CA, San Diego, CA, and Birmingham, AL. INTRODUCTION AND OBJECTIVE: Recent epidemiological and experimental data have suggested a possible link between cholesterol and the development and progression of prostate cancer. :H VRXJKW WR GHWHUPLQH ZKHWKHU DEQRUPDO VHUXP OLSLG SUR¿OHV PD\ be associated with increased risk of biochemical recurrence in men undergoing radical prostatectomy for prostate cancer. 0(7+2'6 :HLGHQWL¿HGPHQIURPWKH6KDUHG(TXDO Access Regional Cancer Hospital (SEARCH) database who underwent radical prostatectomy from 1998 to 2007 and had available cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels and known statin medication use status prior to surgery. We used Cox SURSRUWLRQDOKD]DUGVDQDO\VLVWRGHWHUPLQHDVVRFLDWLRQVRIFKROHVWHURO LDL and HDL levels with biochemical recurrence independent of age, race, pre-operative serum PSA levels, year of surgery, body mass index, surgical center, statin drug-use, post-operative Gleason sum, surgical margins, extra-capsular extension, seminal vesicle invasion, lymph node invasion, and prostate specimen weight. RESULTS: After controlling for the various demographic and clinico-pathologic features of prostate cancer, as well as intake of cholesterol-lowering drugs, increased serum cholesterol (p=0.001) and increased serum LDL (p=0.007) taken as continuous terms both VLJQL¿FDQWO\LQFUHDVHGWKHULVNIRUELRFKHPLFDOUHFXUUHQFHDIWHUVXUJHU\ HDL was not associated with biochemical relapse (p=0.79). Men in the KLJKHVWTXDUWLOHRIVHUXPFKROHVWHURO PJGO KDGWLPHVKLJKHU risk for biochemical relapse (HR 2.49, 95% CI 1.28 - 4.86, p=0.007) compared to men in the lowest quartile (<167 mg/dl). &21&/86,216 2XU¿QGLQJVVXJJHVWWKDWDPRQJPHQZLWK prostate cancer undergoing radical prostatectomy, lipid dysregulation, exemplified by high serum cholesterol and LDL is independently associated with increased risk for biochemical recurrence. These ¿QGLQJV VXJJHVW WKDW K\SHUFKROHVWHUROHPLD PD\ SURPRWH SURVWDWH cancer progression. Source of Funding: Department of Veterans Affairs, Department of Defense, National Institutes of Health, the Georgia Cancer Coalition, and the AUA Foundation/Astellas Rising Star in Urology Award.
Urothelial Cancer: Pathophysiology & Markers Podium Session 7 Sunday, May 18, 2008
8:00 - 10:00 am
193
Source of Funding: VA National Center for Health Promotion and Disease Prevention.
A URINE-BASED REAL TIME RT-PCR ASSAY FOR HYAL1 HYALURONIDASE AND HA-SYNTHASE TO DETECT BLADDER CANCER Mario Kramer, Roozbeh Golshani, Daniel J Caruso*, Murugesan Manoharon, Mark S Soloway, Vinata Lokeshwar. Miami, FL. INTRODUCTION AND OBJECTIVE: Identification of accurate bladder tumor markers/tests could improve diagnosis and surveillance for bladder cancer patients. We have previously shown that the HA-HAase test, which measures urinary hyaluronic acid (HA) and hyaluronidase (HAase) levels, detects bladder cancer with high VHQVLWLYLW\ a DQGVSHFL¿FLW\ a +$LVV\QWKHVL]HGE\ 3 different HA-synthases (HAS1, HAS2 and HAS3) and the expression of tumor-derived HAase, HYAL1 is elevated in bladder cancer. Both HAS and HYAL1 are molecular determinants of bladder cancer growth and progression. In this study we evaluated HAS1, HAS2, HAS3 and HYAL1 mRNA expression in exfoliated cells within urine specimens by real time RT-PCR and examined the ability of these PCR-based markers to detect bladder cancer.