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DO THE 3 SIGNIFICANT 8q24 PROSTATE CANCER SUSCEPTIBILITY REGIONS PREDICT AGGRESSIVE DISEASE?
Vol. 179, No. 4, Supplement, Sunday, May 18, 2008
LQVLJQL¿FDQWGLIIHUHQFHVEHWZHHQVHOIDQGSK\VLFLDQDGPLQLVWHUHG,366 scores (t=0.926, p=0.364). &21&/86,216 'HSUHVVLRQVLJQL¿FDQWO\UDLVHVDSDWLHQW¶V IPSS score, suggesting that depressed patients either have more severe disease states or they misrepresent similar symptoms, the latter predisposing depressed patients to inappropriate care. Source of Funding: None
Prostate Cancer: Staging (II) Podium Session 9 Sunday, May 18, 2008
10:30 am - 12:30 pm
THE JOURNAL OF UROLOGY®
Table 1. Comparison of the Pathological Tumor Features between Carriers and Non-Carriers Prostate rs1447295 rs1447295 rs16901979 rs16901979 rs6983267 rs6983267 Cancer (A) (A) (A) (A) (G) (G) Multiple Multiple Risk Allele Region 1 Region 1 Region 2 Region 2 Region 3 Region 3 NonNonNonNonNo.(%) Carriers Carriers Carriers Carriers Carriers Carriers Carriers Carriers RRP Gleason 77(59.2) 209(49.9) 39(61.9) 247(50.9) 303(52.1) 69(48.6) 89(58.2) 190(49.2) VFRUH Positive 36 Surgical 36 (22.8) 69 (17.0) 15 (22.4) 93 (18.4) 119 (19.9) 25 (16.8) 69 (17.0) (22.8) Margins Extracap35 sular 35 (22.9) 80 (20.6) 13(20.6) 102 (20.9) 123 (21.1) 23 (16.1) 80 (20.6) (22.9) Extension Seminal Vesicle 8 (5.0) 22 (5.4) 3 (4.5 ) 27 (5.3) 31 (5.2 ) 7 (4.7) 8 (5.0) 22 (5.4) Invasion Lymph Node 6 (3.8 ) 2 (0.5) 4 (6.0 ) 4 (0.8) 10 (1.7 ) 0 (0) 6 (3.8 ) 2 (0.5) Metastases
317 DO THE 3 SIGNIFICANT 8q24 PROSTATE CANCER SUSCEPTIBILITY REGIONS PREDICT AGGRESSIVE DISEASE? Brian T Helfand*, Stacy Loeb, Joshua J Meeks, Donghui Kan, Norm D Smith, William J Catalona. Chicago, IL, and Baltimore, MD. INTRODUCTION AND OBJECTIVE: Three regions (regions KDYH EHHQ LGHQWL¿HG ZLWKLQ D NE VHJPHQW RI FKURPRVRPH 8q24 that contribute to CaP susceptibility. Our research group has previously reported an association between alleles in regions 1 and 2 and pathological outcomes following radical prostatectomy in 551 patients. The purpose of the present study was to further examine the contribution of alleles from regions 1 and 2, with the addition of region 3, in a larger surgical cohort. METHODS: From May 2002 to June 2005, 795 Caucasian men underwent radical prostatectomy by a single surgeon and consented to enroll in genetics studies. 8q24 carrier status including single nucleotide polymorphisms rs1447295 (region 1), rs16901979 (region 2) and rs6983267 (region 3) was determined, and statistical analyses were used to compare tumor characteristics between carriers and non-carriers. RESULTS: Approximately 83% of our population were carriers RIDWOHDVWRQHTDOOHOH6SHFL¿FDOO\ZHUHFDUULHUVRIWKH$ allele of rs1447295, 11.7% for the A allele of rs16901979, and 80.1% for WKH*DOOHOHRIUV &DUULHUVRIWKHULVNDOOHOHVZHUHVLJQL¿FDQWO\ PRUHOLNHO\WRUHSRUWDWOHDVWRQH¿UVWGHJUHHUHODWLYHZLWKDKLVWRU\RI CaP. Table 1 shows the pathological outcomes for carriers of each risk allele. In general, carriers of any 8q24 risk alleles were more likely to have a Gleason score >7, positive surgical margins (+SM), seminal vesicle invasion (SVI), and lymph node metastases (LNM). Carriers of DOOHOHVZHUHVLJQL¿FDQWO\PRUHOLNHO\WRKDYHKLJKJUDGHGLVHDVHDQG other aggressive tumor features. CONCLUSIONS: At least one 8q24 CaP susceptibility allele was present in >80% of our cohort, and men with a family history of &D3ZHUHVLJQL¿FDQWO\PRUHOLNHO\WREHFDUULHUV)XUWKHUWKHLUHIIHFWV appear to be additive with regard to the prediction of adverse pathology. 2YHUDOOFDUULHUVRIWKHTVXVFHSWLELOLW\DOOHOHVZHUHVLJQL¿FDQWO\PRUH likely to have high-grade disease, +SM, and LNM. These results suggest that 8q24 alleles are associated with both CaP risk and aggressiveness. Future studies are warranted to examine the relationship between these alleles and long-term survival outcomes.We acknowledge Julius Gudmundsson and deCODE Genetics, Inc.
113
Source of Funding: Urologic Research Foundation.
318 EXTERNAL-BEAM RADIATION THERAPY INCREASES THE RATE OF SECONDARY MALIGNANCIES RELATIVE TO RADICAL PROSTATECTOMY IN MEN WITH PROSTATE CANCER Naeem Bhojani*, Claudio Jeldres, Luigi F Da Pozzo, Monica Morgan, Shahrokh F Shariat, Paul Perrotte, Nazareno Suardi, Fred Saad, Francesco Montorsi, Pierre I Karakiewicz. Montreal, QC, Canada, Milan, Italy, and Dallas, TX. INTRODUCTION AND OBJECTIVE: Several previous reports addressed the effect of external-beam radiation therapy (EBRT) on WKHUDWHRIVHFRQGDU\PDOLJQDQFLHVLQSDWLHQWVZLWKORFDOL]HGSURVWDWH FDQFHU&RQÀLFWLQJUHVXOWVZHUHUHSRUWHG:HDGGUHVVHGWKHDVVRFLDWLRQ between EBRT exposure and secondary malignancies rate in a large administrative database. METHODS: The study population consisted of 10,333 men treated with radical prostatectomy (RP) (n=6196) or EBRT (n= 4137) between 1983 and 2004 without neo- or adjuvant hormonal therapy. The diagnosis of bladder, lung and colo-rectal cancer were established ZLWKWKH,&' DQGVXUJHU\FRGHVWKDWGH¿QHGH[WLUSDWLYHLQWHUYHQWLRQV aimed at eradicating these three malignancies (cystectomy, lobectomy or pneumectomy and colectomy with or without rectal resection). Univariable and multivariable Cox regression analyses addressed the rate of secondary malignancies (bladder, lung and rectal cancer). RESULTS: Overall, 92 (0.9%) cystectomies, 82 (0.8%) lung cancer surgeries and 228 (2.2%) surgeries for colo-rectal cancers were performed. In univariable analyses, the rate of cystectomies (log-rank p=0.002), of treatments for lung cancer (log-rank p<0.001) and for colo-rectal cancers (log-rank p<0.001) were higher in patients treated with EBRT relative to patients treated with RP. At multivariable analyses, after adjusting for age, baseline comorbidities and year of treatment (coded in quartiles), EBRT predisposed to a 3.0-fold higher rate of cystectomy for bladder cancer (p=0.04), to a 1.8-fold higher rate of lung cancer resections (p=0.02) and to a 1.7-fold higher rate of rectal cancer (p=0.02). CONCLUSIONS: The increased rate of secondary PDOLJQDQFLHV DIWHU (%57 VKRXOG EH FRQVLGHUHG LQ ORFDOL]HG SURVWDWH cancer treatment decision-making. Source of Funding:3LHUUH,.DUDNLHZLF]LVSDUWLDOO\ supported by the University of Montreal Health Center Urology Associates, Fonds de la Recherche en Sante du Quebec, the University of Montreal Department of Surgery and the University of Montreal Health Center(CHUM).
319 STAGE IV PROSTATE CANCER: THE EFFECT OF TNM STAGING AND AGE OF DIAGNOSIS ON SURVIVAL Wayland Hsiao*, Guohui Zhou, Michael Goodman, Viraj A Master. Atlanta, GA. INTRODUCTION AND OBJECTIVE: Stage IV prostate cancer can be achieved a number of ways, including distant metastasis, regional metastasis, and local invasion. There is little consensus regarding the optimal treatment for this diverse group of patients. We used the SEER
LQVLJQL¿FDQWGLIIHUHQFHVEHWZHHQVHOIDQGSK\VLFLDQDGPLQLVWHUHG,366 scores (t=0.926, p=0.364). &21&/86,216 'HSUHVVLRQVLJQL¿FDQWO\UDLVHVDSDWLHQW¶V IPSS score, suggesting that depressed patients either have more severe disease states or they misrepresent similar symptoms, the latter predisposing depressed patients to inappropriate care. Source of Funding: None
Prostate Cancer: Staging (II) Podium Session 9 Sunday, May 18, 2008
10:30 am - 12:30 pm
THE JOURNAL OF UROLOGY®
Table 1. Comparison of the Pathological Tumor Features between Carriers and Non-Carriers Prostate rs1447295 rs1447295 rs16901979 rs16901979 rs6983267 rs6983267 Cancer (A) (A) (A) (A) (G) (G) Multiple Multiple Risk Allele Region 1 Region 1 Region 2 Region 2 Region 3 Region 3 NonNonNonNonNo.(%) Carriers Carriers Carriers Carriers Carriers Carriers Carriers Carriers RRP Gleason 77(59.2) 209(49.9) 39(61.9) 247(50.9) 303(52.1) 69(48.6) 89(58.2) 190(49.2) VFRUH Positive 36 Surgical 36 (22.8) 69 (17.0) 15 (22.4) 93 (18.4) 119 (19.9) 25 (16.8) 69 (17.0) (22.8) Margins Extracap35 sular 35 (22.9) 80 (20.6) 13(20.6) 102 (20.9) 123 (21.1) 23 (16.1) 80 (20.6) (22.9) Extension Seminal Vesicle 8 (5.0) 22 (5.4) 3 (4.5 ) 27 (5.3) 31 (5.2 ) 7 (4.7) 8 (5.0) 22 (5.4) Invasion Lymph Node 6 (3.8 ) 2 (0.5) 4 (6.0 ) 4 (0.8) 10 (1.7 ) 0 (0) 6 (3.8 ) 2 (0.5) Metastases
317 DO THE 3 SIGNIFICANT 8q24 PROSTATE CANCER SUSCEPTIBILITY REGIONS PREDICT AGGRESSIVE DISEASE? Brian T Helfand*, Stacy Loeb, Joshua J Meeks, Donghui Kan, Norm D Smith, William J Catalona. Chicago, IL, and Baltimore, MD. INTRODUCTION AND OBJECTIVE: Three regions (regions KDYH EHHQ LGHQWL¿HG ZLWKLQ D NE VHJPHQW RI FKURPRVRPH 8q24 that contribute to CaP susceptibility. Our research group has previously reported an association between alleles in regions 1 and 2 and pathological outcomes following radical prostatectomy in 551 patients. The purpose of the present study was to further examine the contribution of alleles from regions 1 and 2, with the addition of region 3, in a larger surgical cohort. METHODS: From May 2002 to June 2005, 795 Caucasian men underwent radical prostatectomy by a single surgeon and consented to enroll in genetics studies. 8q24 carrier status including single nucleotide polymorphisms rs1447295 (region 1), rs16901979 (region 2) and rs6983267 (region 3) was determined, and statistical analyses were used to compare tumor characteristics between carriers and non-carriers. RESULTS: Approximately 83% of our population were carriers RIDWOHDVWRQHTDOOHOH6SHFL¿FDOO\ZHUHFDUULHUVRIWKH$ allele of rs1447295, 11.7% for the A allele of rs16901979, and 80.1% for WKH*DOOHOHRIUV &DUULHUVRIWKHULVNDOOHOHVZHUHVLJQL¿FDQWO\ PRUHOLNHO\WRUHSRUWDWOHDVWRQH¿UVWGHJUHHUHODWLYHZLWKDKLVWRU\RI CaP. Table 1 shows the pathological outcomes for carriers of each risk allele. In general, carriers of any 8q24 risk alleles were more likely to have a Gleason score >7, positive surgical margins (+SM), seminal vesicle invasion (SVI), and lymph node metastases (LNM). Carriers of DOOHOHVZHUHVLJQL¿FDQWO\PRUHOLNHO\WRKDYHKLJKJUDGHGLVHDVHDQG other aggressive tumor features. CONCLUSIONS: At least one 8q24 CaP susceptibility allele was present in >80% of our cohort, and men with a family history of &D3ZHUHVLJQL¿FDQWO\PRUHOLNHO\WREHFDUULHUV)XUWKHUWKHLUHIIHFWV appear to be additive with regard to the prediction of adverse pathology. 2YHUDOOFDUULHUVRIWKHTVXVFHSWLELOLW\DOOHOHVZHUHVLJQL¿FDQWO\PRUH likely to have high-grade disease, +SM, and LNM. These results suggest that 8q24 alleles are associated with both CaP risk and aggressiveness. Future studies are warranted to examine the relationship between these alleles and long-term survival outcomes.We acknowledge Julius Gudmundsson and deCODE Genetics, Inc.
113
Source of Funding: Urologic Research Foundation.
318 EXTERNAL-BEAM RADIATION THERAPY INCREASES THE RATE OF SECONDARY MALIGNANCIES RELATIVE TO RADICAL PROSTATECTOMY IN MEN WITH PROSTATE CANCER Naeem Bhojani*, Claudio Jeldres, Luigi F Da Pozzo, Monica Morgan, Shahrokh F Shariat, Paul Perrotte, Nazareno Suardi, Fred Saad, Francesco Montorsi, Pierre I Karakiewicz. Montreal, QC, Canada, Milan, Italy, and Dallas, TX. INTRODUCTION AND OBJECTIVE: Several previous reports addressed the effect of external-beam radiation therapy (EBRT) on WKHUDWHRIVHFRQGDU\PDOLJQDQFLHVLQSDWLHQWVZLWKORFDOL]HGSURVWDWH FDQFHU&RQÀLFWLQJUHVXOWVZHUHUHSRUWHG:HDGGUHVVHGWKHDVVRFLDWLRQ between EBRT exposure and secondary malignancies rate in a large administrative database. METHODS: The study population consisted of 10,333 men treated with radical prostatectomy (RP) (n=6196) or EBRT (n= 4137) between 1983 and 2004 without neo- or adjuvant hormonal therapy. The diagnosis of bladder, lung and colo-rectal cancer were established ZLWKWKH,&' DQGVXUJHU\FRGHVWKDWGH¿QHGH[WLUSDWLYHLQWHUYHQWLRQV aimed at eradicating these three malignancies (cystectomy, lobectomy or pneumectomy and colectomy with or without rectal resection). Univariable and multivariable Cox regression analyses addressed the rate of secondary malignancies (bladder, lung and rectal cancer). RESULTS: Overall, 92 (0.9%) cystectomies, 82 (0.8%) lung cancer surgeries and 228 (2.2%) surgeries for colo-rectal cancers were performed. In univariable analyses, the rate of cystectomies (log-rank p=0.002), of treatments for lung cancer (log-rank p<0.001) and for colo-rectal cancers (log-rank p<0.001) were higher in patients treated with EBRT relative to patients treated with RP. At multivariable analyses, after adjusting for age, baseline comorbidities and year of treatment (coded in quartiles), EBRT predisposed to a 3.0-fold higher rate of cystectomy for bladder cancer (p=0.04), to a 1.8-fold higher rate of lung cancer resections (p=0.02) and to a 1.7-fold higher rate of rectal cancer (p=0.02). CONCLUSIONS: The increased rate of secondary PDOLJQDQFLHV DIWHU (%57 VKRXOG EH FRQVLGHUHG LQ ORFDOL]HG SURVWDWH cancer treatment decision-making. Source of Funding:3LHUUH,.DUDNLHZLF]LVSDUWLDOO\ supported by the University of Montreal Health Center Urology Associates, Fonds de la Recherche en Sante du Quebec, the University of Montreal Department of Surgery and the University of Montreal Health Center(CHUM).
319 STAGE IV PROSTATE CANCER: THE EFFECT OF TNM STAGING AND AGE OF DIAGNOSIS ON SURVIVAL Wayland Hsiao*, Guohui Zhou, Michael Goodman, Viraj A Master. Atlanta, GA. INTRODUCTION AND OBJECTIVE: Stage IV prostate cancer can be achieved a number of ways, including distant metastasis, regional metastasis, and local invasion. There is little consensus regarding the optimal treatment for this diverse group of patients. We used the SEER