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VALIDATING THE PARTIN TABLES USING THE NCI SEER DATABASE
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THE JOURNAL OF UROLOGY®
473 VALIDATING THE PARTIN TABLES USING THE NCI SEER DATABASE James B Yu, Danil V Makarov*, Richa Sharma, Richard E. Peschel, New Haven, CT; Alan W. Partin, Baltimore, MD; Cary P. Gross, New Haven, CT INTRODUCTION AND OBJECTIVE: The Partin Tables are a widely used nomogram predicting the pathologic stage of prostate cancer (CaP) given common preoperative clinical characteristics. The model is based on patients undergoing radical prostatectomy (RP) at the Johns Hopkins Medical Institutions, a tertiary care center. We sought to validate the Partin tables using a large national cohort to see whether the model could be applied to all patients undergoing RP for CaP in the United States. METHODS:The published 2007 Partin Tables were used to estimate the risk of positive lymph nodes (LN+), seminal vesicle invasion (SV+), and extraprostatic extension (EPE+) in men with prostate cancer from the NCI-SEER Database using clinical stage, preoperative PSA, and Gleason score. The discriminative and predictive ability of the tables were explored by constructing receiver operating characteristic (ROC) and calibration curves. An overall Brier score was calculated for each endpoint. The utility of the nomogram was determined based on clinically relevant endpoints. RESULTS: We identified 11,185 men who underwent RP for CaP in the years 2004-2005. The Partin tables discriminated between patient groups at risk for lymph node involvement and seminal vesicle involvement well, with an AUC of 0.77 and 0.74, and Brier score 0.026 and 0.042, respectively. Extraprostatic extension discrimination and prediction was more limited (AUC 0.62, Brier score 0.171). CONCLUSIONS: The Partin tables showed excellent discrimination for seminal vesicle and lymph node involvement. Prediction of lymph node involvement was reasonable even within lower risk groups. Prediction of extraprostatic extension and seminal vesicle involvement was somewhat more limited. Source of Funding: The Robert Wood Johnson Foundation
474 BONE MINERAL CONTENT AND PROSTATE CANCER: THE SEED AND SOIL HYPOTHESIS Stacy Loeb*, H. Ballentine Carter, Edward M. Schaeffer, Shari Ling, Anna Kettermann, Luigi Ferrucci, E. Jeffrey Metter, Baltimore, MD INTRODUCTION AND OBJECTIVE: Host factors likely play an important role in cancer development and progression. Since bone is a common site of prostate cancer metastases and bone mineral density is directly associated with the risk of advanced breast cancer, we hypothesized that bone mineral content may represent one host factor related to the development of life-threatening prostate cancer. METHODS: From 1973 to 1984, bone mineral content (BMC, gm/ cm) was assessed among participants in the Baltimore Longitudinal Study of Aging (BLSA) using single photon absorptiometry. We examined the association between serial BMC measurements with the development of overall and high-risk prostate cancer over the next 1 to 2 decades. For all prostate cancer cases, BMC was censored at the time of diagnosis. RESULTS: A total of 778 BMC observations were available in 519 men, including 76 men diagnosed with prostate cancer (18 highrisk and 58 non high-risk), and 443 men without prostate cancer during follow-up. In the overall study population, the mean initial age was 56.3 +/- 17.1 years and median follow-up was 15.5 years (range 0-34.5). Figure 1 shows BMC by age in three groups (no cancer, non high-risk and high-risk cancer). Overall, the distribution of BMC across age was significantly different among men with prostate cancer than healthy controls (p=0.018, likelihood ratio test). The difference in BMC between high-risk and non high-risk prostate cancer did not reach statistical significance; however, the sample sizes were small. CONCLUSIONS: The distribution of BMC was significantly different between men who did and did not develop prostate cancer with extended follow-up. Specifically, BMC appeared to decline at a faster
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
rate with age among healthy controls than men with prostate cancer, especially high-risk disease. The biology underlying this association remains unclear but suggests that host factors in the bony milieu may relate to prostate carcinogenesis, particularly advanced disease.
Source of Funding: NIH
475 INCIDENCE AND ASSOCIATION OF SKELETAL FRACTURES WITH DURATION OF ANDROGEN DEPRIVATION THERAPY AMONG VETERANS Van Anh T Ginger*, Steven B. Zeliadt, Daniel W. Lin, Seattle, WA INTRODUCTION AND OBJECTIVE: The use of androgen deprivation therapy (ADT) for prostate cancer results in known decreased bone mineral density and increased risk of bone fractures. Published rates of skeletal fractures among those exposed to ADT range from 6% to 35% with small patient populations and varying exposures of ADT. We explore the association of ADT with skeletal fracture rates in a Veterans population. METHODS: Data was extracted from the Veterans Integrated Service Network (VISN) 20 Data Warehouse, a central repository of data extracted from the clinical information systems of each of the 8 VA medical facilities in VISN 20 of the Veterans Health Administration. We queried for male patients over 50 years old who had documented leuprolide or goserelin injection. We further stratified exposure of ADT to <1 yr, 1-3 yrs, and >3 yrs. We identified bone fracture events based on ICD-9 codes for fracture and for postoperative fracture care to ensure that we captured events initially treated at non-VA facilities. We assessed cumulative fracture risk following initial ADT use accounting for censoring due to death. RESULTS: We identified 14,096 male veterans >50 yrs old with exposure to ADT between 1995 and 2008 in VISN20 network. We excluded 1,441 subjects with a history of bone fracture prior to ADT for final n=12,655. Stratification of ADT exposure resulted in exposure groups of <1 yr (n=8371), 1-3 yrs (n=2546), >3 yrs (n=1738). There were 1548 (12.2%) bone fractures that occurred after ADT with a cumulative risk at 10 years of 24.3%. Risk was higher among those exposed to ADT for >3 years with 10 yr risk = 29.9% vs 22.4% for those with less than 1 yr ADT use (p<0.001) and 23.4% for those with 1-3 yrs of ADT use (p=0.013). CONCLUSIONS: In one of the largest study evaluating fractures among ADT exposed patients with prolonged follow-up, we found that >3 yrs ADT exposure results in 33% increase risk of fracture seen at 10 yrs from point of ADT initiation compared to patients with less than 1 yr exposure. These findings support efforts focused on fracture prevention treatments in men undergoing ADT.
THE JOURNAL OF UROLOGY®
473 VALIDATING THE PARTIN TABLES USING THE NCI SEER DATABASE James B Yu, Danil V Makarov*, Richa Sharma, Richard E. Peschel, New Haven, CT; Alan W. Partin, Baltimore, MD; Cary P. Gross, New Haven, CT INTRODUCTION AND OBJECTIVE: The Partin Tables are a widely used nomogram predicting the pathologic stage of prostate cancer (CaP) given common preoperative clinical characteristics. The model is based on patients undergoing radical prostatectomy (RP) at the Johns Hopkins Medical Institutions, a tertiary care center. We sought to validate the Partin tables using a large national cohort to see whether the model could be applied to all patients undergoing RP for CaP in the United States. METHODS:The published 2007 Partin Tables were used to estimate the risk of positive lymph nodes (LN+), seminal vesicle invasion (SV+), and extraprostatic extension (EPE+) in men with prostate cancer from the NCI-SEER Database using clinical stage, preoperative PSA, and Gleason score. The discriminative and predictive ability of the tables were explored by constructing receiver operating characteristic (ROC) and calibration curves. An overall Brier score was calculated for each endpoint. The utility of the nomogram was determined based on clinically relevant endpoints. RESULTS: We identified 11,185 men who underwent RP for CaP in the years 2004-2005. The Partin tables discriminated between patient groups at risk for lymph node involvement and seminal vesicle involvement well, with an AUC of 0.77 and 0.74, and Brier score 0.026 and 0.042, respectively. Extraprostatic extension discrimination and prediction was more limited (AUC 0.62, Brier score 0.171). CONCLUSIONS: The Partin tables showed excellent discrimination for seminal vesicle and lymph node involvement. Prediction of lymph node involvement was reasonable even within lower risk groups. Prediction of extraprostatic extension and seminal vesicle involvement was somewhat more limited. Source of Funding: The Robert Wood Johnson Foundation
474 BONE MINERAL CONTENT AND PROSTATE CANCER: THE SEED AND SOIL HYPOTHESIS Stacy Loeb*, H. Ballentine Carter, Edward M. Schaeffer, Shari Ling, Anna Kettermann, Luigi Ferrucci, E. Jeffrey Metter, Baltimore, MD INTRODUCTION AND OBJECTIVE: Host factors likely play an important role in cancer development and progression. Since bone is a common site of prostate cancer metastases and bone mineral density is directly associated with the risk of advanced breast cancer, we hypothesized that bone mineral content may represent one host factor related to the development of life-threatening prostate cancer. METHODS: From 1973 to 1984, bone mineral content (BMC, gm/ cm) was assessed among participants in the Baltimore Longitudinal Study of Aging (BLSA) using single photon absorptiometry. We examined the association between serial BMC measurements with the development of overall and high-risk prostate cancer over the next 1 to 2 decades. For all prostate cancer cases, BMC was censored at the time of diagnosis. RESULTS: A total of 778 BMC observations were available in 519 men, including 76 men diagnosed with prostate cancer (18 highrisk and 58 non high-risk), and 443 men without prostate cancer during follow-up. In the overall study population, the mean initial age was 56.3 +/- 17.1 years and median follow-up was 15.5 years (range 0-34.5). Figure 1 shows BMC by age in three groups (no cancer, non high-risk and high-risk cancer). Overall, the distribution of BMC across age was significantly different among men with prostate cancer than healthy controls (p=0.018, likelihood ratio test). The difference in BMC between high-risk and non high-risk prostate cancer did not reach statistical significance; however, the sample sizes were small. CONCLUSIONS: The distribution of BMC was significantly different between men who did and did not develop prostate cancer with extended follow-up. Specifically, BMC appeared to decline at a faster
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
rate with age among healthy controls than men with prostate cancer, especially high-risk disease. The biology underlying this association remains unclear but suggests that host factors in the bony milieu may relate to prostate carcinogenesis, particularly advanced disease.
Source of Funding: NIH
475 INCIDENCE AND ASSOCIATION OF SKELETAL FRACTURES WITH DURATION OF ANDROGEN DEPRIVATION THERAPY AMONG VETERANS Van Anh T Ginger*, Steven B. Zeliadt, Daniel W. Lin, Seattle, WA INTRODUCTION AND OBJECTIVE: The use of androgen deprivation therapy (ADT) for prostate cancer results in known decreased bone mineral density and increased risk of bone fractures. Published rates of skeletal fractures among those exposed to ADT range from 6% to 35% with small patient populations and varying exposures of ADT. We explore the association of ADT with skeletal fracture rates in a Veterans population. METHODS: Data was extracted from the Veterans Integrated Service Network (VISN) 20 Data Warehouse, a central repository of data extracted from the clinical information systems of each of the 8 VA medical facilities in VISN 20 of the Veterans Health Administration. We queried for male patients over 50 years old who had documented leuprolide or goserelin injection. We further stratified exposure of ADT to <1 yr, 1-3 yrs, and >3 yrs. We identified bone fracture events based on ICD-9 codes for fracture and for postoperative fracture care to ensure that we captured events initially treated at non-VA facilities. We assessed cumulative fracture risk following initial ADT use accounting for censoring due to death. RESULTS: We identified 14,096 male veterans >50 yrs old with exposure to ADT between 1995 and 2008 in VISN20 network. We excluded 1,441 subjects with a history of bone fracture prior to ADT for final n=12,655. Stratification of ADT exposure resulted in exposure groups of <1 yr (n=8371), 1-3 yrs (n=2546), >3 yrs (n=1738). There were 1548 (12.2%) bone fractures that occurred after ADT with a cumulative risk at 10 years of 24.3%. Risk was higher among those exposed to ADT for >3 years with 10 yr risk = 29.9% vs 22.4% for those with less than 1 yr ADT use (p<0.001) and 23.4% for those with 1-3 yrs of ADT use (p=0.013). CONCLUSIONS: In one of the largest study evaluating fractures among ADT exposed patients with prolonged follow-up, we found that >3 yrs ADT exposure results in 33% increase risk of fracture seen at 10 yrs from point of ADT initiation compared to patients with less than 1 yr exposure. These findings support efforts focused on fracture prevention treatments in men undergoing ADT.