- Email: [email protected]
MP39-14 IMPACT OF THE 2012 UNITED STATES PREVENTIVE SERVICES TASK FORCE RECOMMENDATION AGAINST PROSTATE SPECIFIC ANTIGEN SCREENING ON PROSTATE CANCER RISK GROUP STRATIFICATION
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Vol. 195, No. 4S, Supplement, Sunday, May 8, 2016
pathology. Therefore, MRGB adds additional value when assessing especially this subset of patients for AS. Source of Funding: None.
MP39-13 BASELINE PROSTATE-SPECIFIC ANTIGEN (PSA) LEVELS IN MIDLIFE PREDICT TOTAL AND AGGRESSIVE PROSTATE CANCER IN AFRICAN-AMERICAN MEN Mark Preston*, Kathryn Wilson, Travis Gerke, Boston, MA; Sigrid Carlsson, Daniel Sjoberg, New York, NY; Adam Kibel, Quoc-Dien Trinh, Boston, MA; Lisa Signorello, Bethesda, MD; Mark Steinwandel, Rockville, MD; Andrew Vickers, Hans Lilja, New York, NY; Lorelei Mucci, Boston, MA
Source of Funding: none
MP39-12 GLEASON MISCLASSIFICATION IN DIFFERENT ACTIVE SURVEILLANCE PROTOCOLS: CORRELATION BETWEEN FUSION BIOPSIES MRI-ULTRASOUND FUSION GUIDED BIOPSY AND FINAL RADICAL PROSTATECTOMY SPECIMEN Sami-Ramzi Leyh-Bannurah*, Montreal, Canada; Paolo Dell’Oglio, Milano, Italy; Dirk Beyersdorff, Georg Salomon, Markus Graefen, €us, Hamburg, Germany; Wolfgang Picker, Oslo, Norway; Lars Buda Hamburg, Germany INTRODUCTION AND OBJECTIVES: Biopsy Gleason is the main tool to stratify prostate cancer patients (PCa) into risk groups and advise treatment options such as active surveillance (AS) in low-risk patients. Most AS protocols cover low risk patients and only a limited number of protocols include patients harbouring Gleason 4 pattern. Our aim was to assess upgrading risks in different patient risk groups by using final radical prostatectomy (RP) specimen. METHODS: 152 consecutive patients received systematic random biopsy (SB) and MRI-Ultrasound fusion guided biopsy (MRGB) in the same session before surgery. Gleason proportions (%) were calculated for biopsy and final RP specimens and compared with final RP as gold standard. RESULTS: Correlation rates assessed the detection of highest correct Gleason pattern compared to final pathology were 76 (49.3%) for SB, 99 (65.1%) for MRGB and 121 (79.6%) for combined biopsies. Similarly, upgrading in RRP occurred in 53 (34.9%), 30 (19.7%) and 31(20.4%) patients, respectively. Conversely, missed detection rates were identical in random and targeted with 23 (15.1%) patients each and none in combined approach. Correlation with final pathology showed 13(56.5%) and 12(52.2%) high-risk PCa missed within random and targeted biopsies, respectively. Subanalyses revealed that upgrading occurred mostly in biopsies that yielded Gleason score 6 PCa. However, Gleason score 6 biopsies decreased from 37(24.3%) patients in SB to 21(13.8%) in MRGB. Nonetheless, within those 21 patients, 16(76.2%). upgraded to Gleason 4/5. Accordingly, presence of Gleason pattern 4/5 was correctly identified in SB in 92(60.5%), 108(71.1%) in MRGB and 129(84.9%) patients combined. CONCLUSIONS: When compared to final pathology, MRGB and SB combined best reduced the risk of upgrading in all biopsy risk groups. However, the proportion of misclassification in Gleason 3+3 patients remains problematic (76.2%). Conversely, the detection of Gleason 4 pattern by MRGB is highly accurate compared with final
INTRODUCTION AND OBJECTIVES: Prostate specific antigen (PSA) level in midlife predicts prostate cancer (PCa) mortality in Caucasian populations. It is poorly studied whether PSA measured during midlife predicts aggressive PCa among African-American men, a group for which PCa disparities exist. METHODS: We performed a nested case-control study among African-American men age 40-65 years who gave blood at enrollment in the Southern Community Cohort Study between 2002-2009 and followed for median of 9 years. Baseline kallikrein levels (total PSA, free PSA, intact PSA, and human kallikrein 2 [hK2]) were measured in 197 PCa cases and 569 age-matched controls. 55 participants had aggressive disease defined as Gleason ¼4+3¼7, AJCC Stage III or IV, or cancer-specific death. Exact conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PSA and risk of total and aggressive PCa. Area under the curve (AUC) for prediction of total and aggressive disease by total PSA and a previously reported four-kallikrein risk score was calculated using logistic regression. RESULTS: Median total PSA among the controls was 0.72, 0.80, 0.94, and 1.03 ng/mL for men age 40-49, 50-54 and 55-59, and 60-64 years, respectively. Risk of total PCa was strongly associated with baseline total PSA levels in midlife. Total PSA was also highly predictive of risk of aggressive disease. All 22 aggressive cases in men aged <55 years occurred among those with PSA above the age-specific median; among men 40-49 years, all 9 cases of aggressive disease were among those with PSA >90th percentile. Across age groups, the odds ratio of aggressive disease for PSA greater than the 90th percentile vs. less than the median was 38.8 (95% CI: 10.0-237), using age-specific cut-points. PSA-levels in midlife predicted total (AUC 0.88, 95% CI 0.85-0.91) and aggressive (AUC 0.87, 95% CI 0.81-0.92) prostate cancer with high discrimination. Among men with total PSA > 2 ng/ml, the four-kallikrein risk score improved prediction of aggressive disease compared to total PSA alone. CONCLUSIONS: PSA level in midlife strongly predicted total and aggressive PCa in a cohort of African American men subject to opportunistic screening. These data provide further evidence for the utility of risk-stratified screening based on mid-life PSA. Source of Funding: David A. Mazzone Prostate Cancer Disparities Award.
MP39-14 IMPACT OF THE 2012 UNITED STATES PREVENTIVE SERVICES TASK FORCE RECOMMENDATION AGAINST PROSTATE SPECIFIC ANTIGEN SCREENING ON PROSTATE CANCER RISK GROUP STRATIFICATION Deepansh Dalela*, Detroit, MI; Bjorn Loeppenberg, Boston, MA; Akshay Sood, Jesse Sammon, Patrick Karabon, Detroit, MI; Maxine Sun, Quoc-Dien Trinh, Boston, MA; Wooju Jeong, James Peabody, Mani Menon, Detroit, MI; Firas Abdollah, Royal Oak, MI INTRODUCTION AND OBJECTIVES: The United States Preventive Services Task Force (USPSTF) in 2012 recommended against
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prostate specific antigen (PSA) screening in all men, regardless of age or ethnicity. We examined the changes in prostate cancer (PCa) stage at diagnosis before and after the USPSTF recommendation. METHODS: 198708 new cases of PCa within the National Cancer Database (NCDB) 2011 and 2013 were extracted and riskstratified according to the National Comprehensive Cancer Network guidelines (low: T1c-T2a, biopsy Gleason <¼6 and PSA<10 ng/ml; intermediate: T2b-T2c, biopsy Gleason¼7 or PSA 10-20 ng/ml; high: T3a and above, biopsy Gleason 8-10 or PSA >20 ng/ml). Logistic regression models were fitted to test the association between year of diagnosis and likelihood of low, intermediate and high-risk disease, adjusting for all available socio-demographic covariates (age, ethnicity, marital status, Charlson comorbidity index, hospital region, urban/rural residence, insurance, median income and education of the ZIP code, and hospital type) RESULTS: Overall, the proportion of low risk cases decreased (31.9% vs. 25.9%), while intermediate (43.5% vs. 45.1%) and high risk (24.5% vs. 29.0%) cases increased from NCDB 2011 to 2013 (all p<0.001). Patients diagnosed in 2013 had higher PSA (>20 ng/ml: 13.9% vs. 11.5%), biopsy Gleason (8-10: 21.2% vs. 17.0%) and stage (>¼cT3a: 4.8% vs. 4.0%) compared to 2011 (all p<0.01). On regression analyses, men diagnosed in 2013 vs. 2011 were less likely to be low risk (odds ratio [OR] 0.74), and more likely to be intermediate (OR 1.05) and high risk (OR 1.22; all p<0.01). CONCLUSIONS: The USPSTF statement against PSA screening seems to have resulted in increased proportion of intermediate and high risk PCa at diagnosis. Future analyses may help ascertain the presence and degree of this ‘reverse’ stage migration for PCa. Source of Funding: None
MP39-15 SCREENING FOR PROSTATE CANCER: RESULTS FROM THE SWISS SECTION OF THE ERSPC (AARAU) Maciej Kwiatkowski*, Lukas Prause, Stephen F Wyler, Tilmann Moeltgen, Andreas Huber, Rainer Grobholz, Aarau, Switzerland; Lukas Manka, Braunschweig, Germany; Franz Recker, Aarau, Switzerland INTRODUCTION AND OBJECTIVES: In year 1998 Switzerland (Aarau) started participation in the European Randomized Study of Screening for Prostate Cancer (ERSPC) study. The important reason to join this multicenter trial was the epidemiological data showing Switzerland as having one of the highest rates of morbidity and mortality of prostate cancer (PCa) worldwide. This study aims to investigate the influence of the PSA based screening on the PCa specific mortality. The study setting is the prospective randomized population based screening trial with the primary hypothesis that screening can significantly reduce PCa specific mortality by at least 25%. We present the results of the Aarau section of the ERSPC. METHODS: From 1998 to 2003, 10311 men, participants of the Swiss section (Aarau) of the ERSPC, were randomised into the active screening (Gr.1, eligible n¼5130) and control (Gr.2, n¼5121) groups. In the intervention group PSA-screening was undertaken every 4 years with a value of 3.0 ng/ml as indication for prostate biopsy (3 screening rounds). The data for this study are complete until December 2012. Primary endpoint was PCa death or death from any causes. Causes of death were monitored by the Swiss Office of Statistics and reviewed by an independent reviewer panel. The PCa specific mortality was analysed and the group differences tested for their statistical significance using Poisson regression and NelsonAalen cumulative hazard rate. RESULTS: Overall median follow up was 12.2 years (IQR 10.613.3) years. Mean age at study entrance was 60.5 (Gr.1) and 60.7 (Gr.2), respectively. 4932 men in Gr.1 were screened in the first round of screening (compliance 96.1%). PCa incidence was 630 (12.3%) in Gr. 1 vs. 365 (7.1%). 13% of all men randomized died until December 2012. PCa mortality in 00 intention to screen00 was 18 (0.3 rate per 1000 person-years) in the Gr. 1 vs. 25 (0.42 rate per 1000 person-years)
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resulting in the RR of 0.72 (CI 95%; 0.39 - 1.31; p¼0.28) thus the statistically not significant risk reduction of 28%. The resulting PCa mortality rate was 2.7% in the intervention and 3.8% in the control group respectively. CONCLUSIONS: The swiss data support the significant mortality reduction of the ERSPC. Due to the smaller number of participants a statistical significance cannot result as expected. Mortality reduction after 12 years is in line with the natural course of disease but the followup might still be too short. Only the analysis of all data of the ERSPC could confirm the study hypothesis with adequate power. Source of Funding: none
MP39-16 DETECTING HIGH GRADE CANCER AND REDUCING PROSTATE BIOPSY AMONG PLCO PARTICIPANTS USING A PRE-SPECIFIED STATISTICAL MODEL BASED ON LEVELS OF FOUR KALLIKREIN MARKERS AND MICROSEMINOPROTEIN-BETA IN BLOOD Gerald L. Andriole*, St. Louis, MO; Daniel Sjoberg, Andrew Vickers, New York, NY; David Crawford, Aurora, CO; Hans Lilja, NEW YORK, NY INTRODUCTION AND OBJECTIVES: While serum PSA alone lacks specificity for high grade CaP (Gleason score > 7, HGCaP), use of a panel of 4 kallikrein markers (PSA, free PSA, intact PSA, hK2) has been shown to improve specificity for HGCaP detection in European studies with predominately Caucasian participants. The properties of the panel in a multiethnic US population are less clear. There is also some preliminary evidence that microseminoprotein-beta (MSP) is predictive of biopsy outcome. In this study we assess use of this panel of markers (4K) and MSP among men of African American (AA) and European ancestry in PLCO. METHODS: Levels of 4K and MSP were measured in cryopreserved serum from men in the intervention arm of PLCO who were aged less than 75, with PSA above 4.0 ng/ml and who underwent an initial biopsy within one year. 1864 eligible men were identified; all AA men (N¼113) were included. 887 additional non-AA men were then randomly selected. The final cohort consisted of 946 men (52 were excluded due to missing data). Marker levels were incorporated into a pre-specified statistical model to predict CaP and HGCaP. RESULTS: 230 (24%) men had Gleason score 6 CaP, 72 (7.6%) had Gleason 7 CaP and 22 (2.3%) had Gleason > 8 CaP. The detection of high-grade cancer at prostate biopsy was enhanced by the 4K panel with an AUC of 0.79 (95% C.I. 0.75, 0.82) compared to an AUC of 0.69 (95% C.I. 0.64, 0.74) for PSA and age alone. Discrimination was non-significantly higher in African Americans (table). The panel had good decision analytic properties: at one illustrative cut-point, use of the 4K panel in 1000 men would eliminate biopsy in 420 and detect 83 out of 93 HGCaP. Adding MSP to the model increased AUC from 0.79 to 0.81. Results for all analyses were similar for the endpoint of CaP of any grade. CONCLUSIONS: These data among PLCO participants demonstrate the 4K panel can improve detection of HGCaP over PSA and DRE, that there is similar improvement among AA men, and that addition of a fifth marker, MSP, may further improve the ability to identify HGCaP.
Source of Funding: R01CA160816 from NCI to Drs Lilja and Vickers, P30 CA008748 Cancer Center Support Grant from NCI to Memorial Sloan Kettering Cancer Center, P50CA92629 SPORE grant from NCI to Dr. H Scher, and contracts from the NCI to PLCO investigators
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pathology. Therefore, MRGB adds additional value when assessing especially this subset of patients for AS. Source of Funding: None.
MP39-13 BASELINE PROSTATE-SPECIFIC ANTIGEN (PSA) LEVELS IN MIDLIFE PREDICT TOTAL AND AGGRESSIVE PROSTATE CANCER IN AFRICAN-AMERICAN MEN Mark Preston*, Kathryn Wilson, Travis Gerke, Boston, MA; Sigrid Carlsson, Daniel Sjoberg, New York, NY; Adam Kibel, Quoc-Dien Trinh, Boston, MA; Lisa Signorello, Bethesda, MD; Mark Steinwandel, Rockville, MD; Andrew Vickers, Hans Lilja, New York, NY; Lorelei Mucci, Boston, MA
Source of Funding: none
MP39-12 GLEASON MISCLASSIFICATION IN DIFFERENT ACTIVE SURVEILLANCE PROTOCOLS: CORRELATION BETWEEN FUSION BIOPSIES MRI-ULTRASOUND FUSION GUIDED BIOPSY AND FINAL RADICAL PROSTATECTOMY SPECIMEN Sami-Ramzi Leyh-Bannurah*, Montreal, Canada; Paolo Dell’Oglio, Milano, Italy; Dirk Beyersdorff, Georg Salomon, Markus Graefen, €us, Hamburg, Germany; Wolfgang Picker, Oslo, Norway; Lars Buda Hamburg, Germany INTRODUCTION AND OBJECTIVES: Biopsy Gleason is the main tool to stratify prostate cancer patients (PCa) into risk groups and advise treatment options such as active surveillance (AS) in low-risk patients. Most AS protocols cover low risk patients and only a limited number of protocols include patients harbouring Gleason 4 pattern. Our aim was to assess upgrading risks in different patient risk groups by using final radical prostatectomy (RP) specimen. METHODS: 152 consecutive patients received systematic random biopsy (SB) and MRI-Ultrasound fusion guided biopsy (MRGB) in the same session before surgery. Gleason proportions (%) were calculated for biopsy and final RP specimens and compared with final RP as gold standard. RESULTS: Correlation rates assessed the detection of highest correct Gleason pattern compared to final pathology were 76 (49.3%) for SB, 99 (65.1%) for MRGB and 121 (79.6%) for combined biopsies. Similarly, upgrading in RRP occurred in 53 (34.9%), 30 (19.7%) and 31(20.4%) patients, respectively. Conversely, missed detection rates were identical in random and targeted with 23 (15.1%) patients each and none in combined approach. Correlation with final pathology showed 13(56.5%) and 12(52.2%) high-risk PCa missed within random and targeted biopsies, respectively. Subanalyses revealed that upgrading occurred mostly in biopsies that yielded Gleason score 6 PCa. However, Gleason score 6 biopsies decreased from 37(24.3%) patients in SB to 21(13.8%) in MRGB. Nonetheless, within those 21 patients, 16(76.2%). upgraded to Gleason 4/5. Accordingly, presence of Gleason pattern 4/5 was correctly identified in SB in 92(60.5%), 108(71.1%) in MRGB and 129(84.9%) patients combined. CONCLUSIONS: When compared to final pathology, MRGB and SB combined best reduced the risk of upgrading in all biopsy risk groups. However, the proportion of misclassification in Gleason 3+3 patients remains problematic (76.2%). Conversely, the detection of Gleason 4 pattern by MRGB is highly accurate compared with final
INTRODUCTION AND OBJECTIVES: Prostate specific antigen (PSA) level in midlife predicts prostate cancer (PCa) mortality in Caucasian populations. It is poorly studied whether PSA measured during midlife predicts aggressive PCa among African-American men, a group for which PCa disparities exist. METHODS: We performed a nested case-control study among African-American men age 40-65 years who gave blood at enrollment in the Southern Community Cohort Study between 2002-2009 and followed for median of 9 years. Baseline kallikrein levels (total PSA, free PSA, intact PSA, and human kallikrein 2 [hK2]) were measured in 197 PCa cases and 569 age-matched controls. 55 participants had aggressive disease defined as Gleason ¼4+3¼7, AJCC Stage III or IV, or cancer-specific death. Exact conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PSA and risk of total and aggressive PCa. Area under the curve (AUC) for prediction of total and aggressive disease by total PSA and a previously reported four-kallikrein risk score was calculated using logistic regression. RESULTS: Median total PSA among the controls was 0.72, 0.80, 0.94, and 1.03 ng/mL for men age 40-49, 50-54 and 55-59, and 60-64 years, respectively. Risk of total PCa was strongly associated with baseline total PSA levels in midlife. Total PSA was also highly predictive of risk of aggressive disease. All 22 aggressive cases in men aged <55 years occurred among those with PSA above the age-specific median; among men 40-49 years, all 9 cases of aggressive disease were among those with PSA >90th percentile. Across age groups, the odds ratio of aggressive disease for PSA greater than the 90th percentile vs. less than the median was 38.8 (95% CI: 10.0-237), using age-specific cut-points. PSA-levels in midlife predicted total (AUC 0.88, 95% CI 0.85-0.91) and aggressive (AUC 0.87, 95% CI 0.81-0.92) prostate cancer with high discrimination. Among men with total PSA > 2 ng/ml, the four-kallikrein risk score improved prediction of aggressive disease compared to total PSA alone. CONCLUSIONS: PSA level in midlife strongly predicted total and aggressive PCa in a cohort of African American men subject to opportunistic screening. These data provide further evidence for the utility of risk-stratified screening based on mid-life PSA. Source of Funding: David A. Mazzone Prostate Cancer Disparities Award.
MP39-14 IMPACT OF THE 2012 UNITED STATES PREVENTIVE SERVICES TASK FORCE RECOMMENDATION AGAINST PROSTATE SPECIFIC ANTIGEN SCREENING ON PROSTATE CANCER RISK GROUP STRATIFICATION Deepansh Dalela*, Detroit, MI; Bjorn Loeppenberg, Boston, MA; Akshay Sood, Jesse Sammon, Patrick Karabon, Detroit, MI; Maxine Sun, Quoc-Dien Trinh, Boston, MA; Wooju Jeong, James Peabody, Mani Menon, Detroit, MI; Firas Abdollah, Royal Oak, MI INTRODUCTION AND OBJECTIVES: The United States Preventive Services Task Force (USPSTF) in 2012 recommended against
THE JOURNAL OF UROLOGYâ
Vol. 195, No. 4S, Supplement, Sunday, May 8, 2016
prostate specific antigen (PSA) screening in all men, regardless of age or ethnicity. We examined the changes in prostate cancer (PCa) stage at diagnosis before and after the USPSTF recommendation. METHODS: 198708 new cases of PCa within the National Cancer Database (NCDB) 2011 and 2013 were extracted and riskstratified according to the National Comprehensive Cancer Network guidelines (low: T1c-T2a, biopsy Gleason <¼6 and PSA<10 ng/ml; intermediate: T2b-T2c, biopsy Gleason¼7 or PSA 10-20 ng/ml; high: T3a and above, biopsy Gleason 8-10 or PSA >20 ng/ml). Logistic regression models were fitted to test the association between year of diagnosis and likelihood of low, intermediate and high-risk disease, adjusting for all available socio-demographic covariates (age, ethnicity, marital status, Charlson comorbidity index, hospital region, urban/rural residence, insurance, median income and education of the ZIP code, and hospital type) RESULTS: Overall, the proportion of low risk cases decreased (31.9% vs. 25.9%), while intermediate (43.5% vs. 45.1%) and high risk (24.5% vs. 29.0%) cases increased from NCDB 2011 to 2013 (all p<0.001). Patients diagnosed in 2013 had higher PSA (>20 ng/ml: 13.9% vs. 11.5%), biopsy Gleason (8-10: 21.2% vs. 17.0%) and stage (>¼cT3a: 4.8% vs. 4.0%) compared to 2011 (all p<0.01). On regression analyses, men diagnosed in 2013 vs. 2011 were less likely to be low risk (odds ratio [OR] 0.74), and more likely to be intermediate (OR 1.05) and high risk (OR 1.22; all p<0.01). CONCLUSIONS: The USPSTF statement against PSA screening seems to have resulted in increased proportion of intermediate and high risk PCa at diagnosis. Future analyses may help ascertain the presence and degree of this ‘reverse’ stage migration for PCa. Source of Funding: None
MP39-15 SCREENING FOR PROSTATE CANCER: RESULTS FROM THE SWISS SECTION OF THE ERSPC (AARAU) Maciej Kwiatkowski*, Lukas Prause, Stephen F Wyler, Tilmann Moeltgen, Andreas Huber, Rainer Grobholz, Aarau, Switzerland; Lukas Manka, Braunschweig, Germany; Franz Recker, Aarau, Switzerland INTRODUCTION AND OBJECTIVES: In year 1998 Switzerland (Aarau) started participation in the European Randomized Study of Screening for Prostate Cancer (ERSPC) study. The important reason to join this multicenter trial was the epidemiological data showing Switzerland as having one of the highest rates of morbidity and mortality of prostate cancer (PCa) worldwide. This study aims to investigate the influence of the PSA based screening on the PCa specific mortality. The study setting is the prospective randomized population based screening trial with the primary hypothesis that screening can significantly reduce PCa specific mortality by at least 25%. We present the results of the Aarau section of the ERSPC. METHODS: From 1998 to 2003, 10311 men, participants of the Swiss section (Aarau) of the ERSPC, were randomised into the active screening (Gr.1, eligible n¼5130) and control (Gr.2, n¼5121) groups. In the intervention group PSA-screening was undertaken every 4 years with a value of 3.0 ng/ml as indication for prostate biopsy (3 screening rounds). The data for this study are complete until December 2012. Primary endpoint was PCa death or death from any causes. Causes of death were monitored by the Swiss Office of Statistics and reviewed by an independent reviewer panel. The PCa specific mortality was analysed and the group differences tested for their statistical significance using Poisson regression and NelsonAalen cumulative hazard rate. RESULTS: Overall median follow up was 12.2 years (IQR 10.613.3) years. Mean age at study entrance was 60.5 (Gr.1) and 60.7 (Gr.2), respectively. 4932 men in Gr.1 were screened in the first round of screening (compliance 96.1%). PCa incidence was 630 (12.3%) in Gr. 1 vs. 365 (7.1%). 13% of all men randomized died until December 2012. PCa mortality in 00 intention to screen00 was 18 (0.3 rate per 1000 person-years) in the Gr. 1 vs. 25 (0.42 rate per 1000 person-years)
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resulting in the RR of 0.72 (CI 95%; 0.39 - 1.31; p¼0.28) thus the statistically not significant risk reduction of 28%. The resulting PCa mortality rate was 2.7% in the intervention and 3.8% in the control group respectively. CONCLUSIONS: The swiss data support the significant mortality reduction of the ERSPC. Due to the smaller number of participants a statistical significance cannot result as expected. Mortality reduction after 12 years is in line with the natural course of disease but the followup might still be too short. Only the analysis of all data of the ERSPC could confirm the study hypothesis with adequate power. Source of Funding: none
MP39-16 DETECTING HIGH GRADE CANCER AND REDUCING PROSTATE BIOPSY AMONG PLCO PARTICIPANTS USING A PRE-SPECIFIED STATISTICAL MODEL BASED ON LEVELS OF FOUR KALLIKREIN MARKERS AND MICROSEMINOPROTEIN-BETA IN BLOOD Gerald L. Andriole*, St. Louis, MO; Daniel Sjoberg, Andrew Vickers, New York, NY; David Crawford, Aurora, CO; Hans Lilja, NEW YORK, NY INTRODUCTION AND OBJECTIVES: While serum PSA alone lacks specificity for high grade CaP (Gleason score > 7, HGCaP), use of a panel of 4 kallikrein markers (PSA, free PSA, intact PSA, hK2) has been shown to improve specificity for HGCaP detection in European studies with predominately Caucasian participants. The properties of the panel in a multiethnic US population are less clear. There is also some preliminary evidence that microseminoprotein-beta (MSP) is predictive of biopsy outcome. In this study we assess use of this panel of markers (4K) and MSP among men of African American (AA) and European ancestry in PLCO. METHODS: Levels of 4K and MSP were measured in cryopreserved serum from men in the intervention arm of PLCO who were aged less than 75, with PSA above 4.0 ng/ml and who underwent an initial biopsy within one year. 1864 eligible men were identified; all AA men (N¼113) were included. 887 additional non-AA men were then randomly selected. The final cohort consisted of 946 men (52 were excluded due to missing data). Marker levels were incorporated into a pre-specified statistical model to predict CaP and HGCaP. RESULTS: 230 (24%) men had Gleason score 6 CaP, 72 (7.6%) had Gleason 7 CaP and 22 (2.3%) had Gleason > 8 CaP. The detection of high-grade cancer at prostate biopsy was enhanced by the 4K panel with an AUC of 0.79 (95% C.I. 0.75, 0.82) compared to an AUC of 0.69 (95% C.I. 0.64, 0.74) for PSA and age alone. Discrimination was non-significantly higher in African Americans (table). The panel had good decision analytic properties: at one illustrative cut-point, use of the 4K panel in 1000 men would eliminate biopsy in 420 and detect 83 out of 93 HGCaP. Adding MSP to the model increased AUC from 0.79 to 0.81. Results for all analyses were similar for the endpoint of CaP of any grade. CONCLUSIONS: These data among PLCO participants demonstrate the 4K panel can improve detection of HGCaP over PSA and DRE, that there is similar improvement among AA men, and that addition of a fifth marker, MSP, may further improve the ability to identify HGCaP.
Source of Funding: R01CA160816 from NCI to Drs Lilja and Vickers, P30 CA008748 Cancer Center Support Grant from NCI to Memorial Sloan Kettering Cancer Center, P50CA92629 SPORE grant from NCI to Dr. H Scher, and contracts from the NCI to PLCO investigators