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MP39-08 CLINICAL UTILITY OF AN EPIGENETIC ASSAY TO REDUCE UNNECESSARY REPEAT PROSTATE BIOPSIES
THE JOURNAL OF UROLOGYâ
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a need for more specific tests to avoid unnecessary prostate biopsies and overtreatment of clinically insignificant cancer. The 4Kscore is a new commercially available molecular diagnostic test which predicts risk for clinically significant prostate cancer on prostate biopsy. Our objective was to examine potential correlation between the 4Kscore and other parameters in a screening population and ability to reduce the number of prostate biopsies indicated compared to PSA alone. METHODS: During the annual Prostate Cancer Awareness Week event sponsored by the Prostate Conditions Education Council, 162 men participated in screening for prostate cancer which include PSA, DRE, and 4Kscore. We investigated whether 4Kscore correlates with age, race, testosterone level, prior biopsy history, and presence of nodule on DRE. We also compared patient 4Kscore using a cutoff of 7.5% at different PSA thresholds (4.0, 3.0, 2.5, and 1.5 ng/mL) to determine theoretical reduction in number of biopsies. RESULTS: The mean ( std deviation) age, PSA, and 4Kscore of the study population were 66.5 9.4 years, 2.37 2.3 ng/mL, and 8.3 11.1%, respectively. The mean 4Kscore was significantly lower in patients with prior history of prostate biopsy (2.5% vs 9.1%, p ¼ 0.002) and negative DRE (6.9% vs 15.8%, p < 0.001). There was positive correlation between 4Kscore and age (Pearson correlation coefficient r ¼ 0.34, p < 0.001) but not with testosterone level. Also there was no difference in the 4Kscores between Caucasian and African American patients. Biopsies could be avoided in 38.5% to 56.4% of patients compared to PSA and DRE alone, depending on PSA threshold chosen (Table 1). CONCLUSIONS: The 4Kscore is useful for identifying men in a screening population who can avoid prostate biopsies compared to PSA alone. Further, 4Kscore was lower among men who had a previous biopsy and negative DRE results. These results demonstrate that 4Kscore is a useful biomarker for prostate cancer screening.
Vol. 195, No. 4S, Supplement, Sunday, May 8, 2016
relation to the epigenetic test and how this changed the management of patients. METHODS: A cohort of 150 men with a previous negative biopsy were sequentially enrolled based on eligibility requirements. The Case group consisted of 50 patients with an epigenetic assay-positive result (Pos) and 50 patients with an assay-negative result (Neg) that were prospectively followed for a minimum of 12 months from the date of epigenetic profiling. The Control group consisted of 50 patients managed under SOC. These patients were matched for follow-up time with the Case groups and identified by retrospective medical chart review. All eligible men had at least one initial histologically negative (also excluding atypical small acinar proliferation) transrectal ultrasoundguided biopsy. RESULTS: The average patient was 62 years with a PSA level of 5.7 ng/ml at time of the index biopsy, with no significant differences across the three groups. In the Control group, 17 (34%) men had at least one subsequent biopsy recorded following the index biopsy, compared to 9 (18%) in the Pos and 3 (6%) in the Neg group (p¼0.002). Comparing the Control to the Neg group, there was a significant 82% reduction in the rate of biopsy (p¼0.001). While overall with the use of the epigenetic assay there was a significant 65% reduction in the rate of repeat biopsy (p¼0.003), the difference was, as expected, not significantly different for the Pos group compared to the Control group (p¼0.111). Five out of 9 (56%) biopsies were positive for PCa in the Pos group, of which 2 men (40%) were diagnosed with high-grade disease. In the Control group, 2 out of the 17 repeat biopsies (12%) identified GS6 disease. In the Neg group one GS6 cancer was found at time of repeat biopsy. CONCLUSIONS: The use of the epigenetic assay to help decide which men are at lower risk of harboring occult PCa despite persistent risk factors, resulted in a 65% reduction in the rate of unnecessary repeat biopsies. Men with high-grade PCa are most likely identified through a positive epigenetic assay. Source of Funding: MDxHealth
MP39-09 PROPERTIES OF THE FOUR KALLIKREIN PANEL FOR PREDICTION OF PROSTATE BIOPSY OUTCOME IN MEN WITH HIGH PSA (10-25 NG /ML) Andrew Vickers*, Daniel Sjoberg, Emily Vertosick, New York, NY; Monique Roobol, Rottderdam, Netherlands; Freddie Hamdy, Oxford, United Kingdom; Anders Bjartell, Lund, Sweden; David Neal, Oxford, United Kingdom; Jenny Donovan, Bristol, United Kingdom; Hans Lilja, New York, NY Source of Funding: The Prostate Conditions Education Council sponsored the screening event and OPKO Health provided 4Kscore testing
MP39-08 CLINICAL UTILITY OF AN EPIGENETIC ASSAY TO REDUCE UNNECESSARY REPEAT PROSTATE BIOPSIES Jason Hafron*, Thanh Huynh, Ayad S. Khourdaji, Royal Oak, MI; Richard D. Sarle, St. Clair Shores, MI; Wim Van Criekinge, Ghent, Belgium; Leander Van Neste, Maastricht, Netherlands INTRODUCTION AND OBJECTIVES: Management of men at risk of harboring prostate cancer (PCa), but with a cancer-negative index biopsy remains difficult. An epigenetic assay assessing PCaassociated DNA-methylation of GSTP1, RASSF1 and APC in histologically negative biopsies has shown to improve the negative predictive value (NPV) relative to standard of care (SOC) yielding a NPV of 90% for all PCa and 96% for high-grade (Gleason score (GS) 7) PCa. The primary goal was to ascertain the rate of repeat biopsy in
INTRODUCTION AND OBJECTIVES: A statistical model based on a panel of four kallikrein markers (PSA, free PSA, intact PSA and hK2) has been shown to predict high-grade cancer on prostate biopsy in close to 15,000 patients in 11 different European cohorts. The panel was recently validated in a prospective US trial, and is available clinically as the 4Kscore. Unlike several other reflex tests, the kallikrein panel is not restricted to patients in the diagnostic “grey zone” (such as PSA 4-10 ng / mL, negative DRE). However, properties of the panel for men with higher PSA have not been reported. METHODS: We reanalyzed data from the ProtecT, Rotterdam ERSPC, Rotterdam ERSPC Repeat Biopsy, UPCA, and US validation studies, focusing on men with a PSA > 10 ng / mL (a typical cut point for high PSA) but PSA < 25 ng / mL (the cut-point above which the panel gives uniformly high risks). We calculated the area-under-the-curve (AUC) for the panel and for the base models used as comparators in each study (e.g. a model using PSA, age and DRE). With the exception of ProtecT, where estimates were corrected for optimism using 10-fold cross-validation, all kallikrein models were prespecified and created on an independent data set. Estimates from each study were combined into a fixed effects meta-analysis.
e544
a need for more specific tests to avoid unnecessary prostate biopsies and overtreatment of clinically insignificant cancer. The 4Kscore is a new commercially available molecular diagnostic test which predicts risk for clinically significant prostate cancer on prostate biopsy. Our objective was to examine potential correlation between the 4Kscore and other parameters in a screening population and ability to reduce the number of prostate biopsies indicated compared to PSA alone. METHODS: During the annual Prostate Cancer Awareness Week event sponsored by the Prostate Conditions Education Council, 162 men participated in screening for prostate cancer which include PSA, DRE, and 4Kscore. We investigated whether 4Kscore correlates with age, race, testosterone level, prior biopsy history, and presence of nodule on DRE. We also compared patient 4Kscore using a cutoff of 7.5% at different PSA thresholds (4.0, 3.0, 2.5, and 1.5 ng/mL) to determine theoretical reduction in number of biopsies. RESULTS: The mean ( std deviation) age, PSA, and 4Kscore of the study population were 66.5 9.4 years, 2.37 2.3 ng/mL, and 8.3 11.1%, respectively. The mean 4Kscore was significantly lower in patients with prior history of prostate biopsy (2.5% vs 9.1%, p ¼ 0.002) and negative DRE (6.9% vs 15.8%, p < 0.001). There was positive correlation between 4Kscore and age (Pearson correlation coefficient r ¼ 0.34, p < 0.001) but not with testosterone level. Also there was no difference in the 4Kscores between Caucasian and African American patients. Biopsies could be avoided in 38.5% to 56.4% of patients compared to PSA and DRE alone, depending on PSA threshold chosen (Table 1). CONCLUSIONS: The 4Kscore is useful for identifying men in a screening population who can avoid prostate biopsies compared to PSA alone. Further, 4Kscore was lower among men who had a previous biopsy and negative DRE results. These results demonstrate that 4Kscore is a useful biomarker for prostate cancer screening.
Vol. 195, No. 4S, Supplement, Sunday, May 8, 2016
relation to the epigenetic test and how this changed the management of patients. METHODS: A cohort of 150 men with a previous negative biopsy were sequentially enrolled based on eligibility requirements. The Case group consisted of 50 patients with an epigenetic assay-positive result (Pos) and 50 patients with an assay-negative result (Neg) that were prospectively followed for a minimum of 12 months from the date of epigenetic profiling. The Control group consisted of 50 patients managed under SOC. These patients were matched for follow-up time with the Case groups and identified by retrospective medical chart review. All eligible men had at least one initial histologically negative (also excluding atypical small acinar proliferation) transrectal ultrasoundguided biopsy. RESULTS: The average patient was 62 years with a PSA level of 5.7 ng/ml at time of the index biopsy, with no significant differences across the three groups. In the Control group, 17 (34%) men had at least one subsequent biopsy recorded following the index biopsy, compared to 9 (18%) in the Pos and 3 (6%) in the Neg group (p¼0.002). Comparing the Control to the Neg group, there was a significant 82% reduction in the rate of biopsy (p¼0.001). While overall with the use of the epigenetic assay there was a significant 65% reduction in the rate of repeat biopsy (p¼0.003), the difference was, as expected, not significantly different for the Pos group compared to the Control group (p¼0.111). Five out of 9 (56%) biopsies were positive for PCa in the Pos group, of which 2 men (40%) were diagnosed with high-grade disease. In the Control group, 2 out of the 17 repeat biopsies (12%) identified GS6 disease. In the Neg group one GS6 cancer was found at time of repeat biopsy. CONCLUSIONS: The use of the epigenetic assay to help decide which men are at lower risk of harboring occult PCa despite persistent risk factors, resulted in a 65% reduction in the rate of unnecessary repeat biopsies. Men with high-grade PCa are most likely identified through a positive epigenetic assay. Source of Funding: MDxHealth
MP39-09 PROPERTIES OF THE FOUR KALLIKREIN PANEL FOR PREDICTION OF PROSTATE BIOPSY OUTCOME IN MEN WITH HIGH PSA (10-25 NG /ML) Andrew Vickers*, Daniel Sjoberg, Emily Vertosick, New York, NY; Monique Roobol, Rottderdam, Netherlands; Freddie Hamdy, Oxford, United Kingdom; Anders Bjartell, Lund, Sweden; David Neal, Oxford, United Kingdom; Jenny Donovan, Bristol, United Kingdom; Hans Lilja, New York, NY Source of Funding: The Prostate Conditions Education Council sponsored the screening event and OPKO Health provided 4Kscore testing
MP39-08 CLINICAL UTILITY OF AN EPIGENETIC ASSAY TO REDUCE UNNECESSARY REPEAT PROSTATE BIOPSIES Jason Hafron*, Thanh Huynh, Ayad S. Khourdaji, Royal Oak, MI; Richard D. Sarle, St. Clair Shores, MI; Wim Van Criekinge, Ghent, Belgium; Leander Van Neste, Maastricht, Netherlands INTRODUCTION AND OBJECTIVES: Management of men at risk of harboring prostate cancer (PCa), but with a cancer-negative index biopsy remains difficult. An epigenetic assay assessing PCaassociated DNA-methylation of GSTP1, RASSF1 and APC in histologically negative biopsies has shown to improve the negative predictive value (NPV) relative to standard of care (SOC) yielding a NPV of 90% for all PCa and 96% for high-grade (Gleason score (GS) 7) PCa. The primary goal was to ascertain the rate of repeat biopsy in
INTRODUCTION AND OBJECTIVES: A statistical model based on a panel of four kallikrein markers (PSA, free PSA, intact PSA and hK2) has been shown to predict high-grade cancer on prostate biopsy in close to 15,000 patients in 11 different European cohorts. The panel was recently validated in a prospective US trial, and is available clinically as the 4Kscore. Unlike several other reflex tests, the kallikrein panel is not restricted to patients in the diagnostic “grey zone” (such as PSA 4-10 ng / mL, negative DRE). However, properties of the panel for men with higher PSA have not been reported. METHODS: We reanalyzed data from the ProtecT, Rotterdam ERSPC, Rotterdam ERSPC Repeat Biopsy, UPCA, and US validation studies, focusing on men with a PSA > 10 ng / mL (a typical cut point for high PSA) but PSA < 25 ng / mL (the cut-point above which the panel gives uniformly high risks). We calculated the area-under-the-curve (AUC) for the panel and for the base models used as comparators in each study (e.g. a model using PSA, age and DRE). With the exception of ProtecT, where estimates were corrected for optimism using 10-fold cross-validation, all kallikrein models were prespecified and created on an independent data set. Estimates from each study were combined into a fixed effects meta-analysis.