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EAU Guide to the Scientific Abstracts Regarding the Prostate Health Index (phi)*

Poster Sessions Presented at the 27th Annual EAU Congress Paris, France

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Poster Presentation Schedule and Abstract Index

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Saturday, 25 February, 16:00 – 17:30; Location: Level 2 – Room 251Poster Session 22: Prostate Biopsies 2(259) Serum isoform [-2]proPSA (p2PSA) and its derivates, %p2PSA and phi (Prostate Health Index), are more accurate than the reference standard test (PSA) in men scheduled for repeat biopsy

Saturday, 25 February, 16:00 - 17:30; Location: Level 2 - Room 251Poster Session 22: Prostate Biopsies 2(260) The cost-effectiveness of prostate cancer detection using Beckman Coulter Prostate Health Index

Saturday, 25 February, 16:00 – 17:30; Location: Level 2 – Room 252 A/BPoster Session 23: Chronic Pelvic Pain Syndrome(278) Correlation of chronic histologic prostatic inflammation (CHPI) in biopsy specimens with serum isoform [-2]proPSA (p2PSA), %p2PSA and phi (Prostate Health Index) in men undergoing prostate biopsy for suspected PCa

Monday, 27 February, 12:15 – 13:45; Location: Level 2 – Room 252 A/BPoster Session 76: Prostate Cancer: Biomarkers(909) Clinical cut-offs of isoform [-2]proPSA (p2PSA) derivatives, namely %p2PSA and phi (Prostate Health Index) for guiding biopsy decision in Caucasian population

Monday, 27 February, 12:15 – 13:45; Location: Level 2 – Room 252 A/BPoster Session 76: Prostate Cancer: Biomarkers(910) Isoform [-2]proPSA (p2PSA) and its derivates, %p2PSA and phi values differ between BPH, ASAP, HG-PIN and PCa in a set of contemporary men undergoing prostate biopsy

Monday, 27 February, 12:15 – 13:45; Location: Level 2 – Room 252 A/BPoster Session 76: Prostate Cancer: Biomarkers(912) Comparison of phi (Prostate Health Index) and PCA3 assay in the prediction of prostate biopsy (PBx) outcome in patients who have undergone initial and repeated prostatic biopsies

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The cost-effectiveness of prostate cancer detection using Beckman Coulter Prostate Health Index

AUTHORS: Heijnsdijk EAM1, Huang JT2, Denham D2, de Koning HJ1

CENTERS: 1 Erasmus MC, Department of Public Health, Rotterdam, Netherlands 2 Beckman Coulter, Inc., Brea, California, United States

Introduction & Objectives:Clinical trial results suggested that PSA screening may reduce prostate cancer mortality in the EU healthcare setting. However, the specificity of the PSA of the PSA test for prostate cancer is low, leading to many negative prostate biopsies. The Beckman Coulter Prostate Health Index (phi) demonstrates improved specificity compared to PSA alone, therefore, may reduce negative biopsies. In the present study, the cost-effectiveness of phi testing is compared with PSA screening.

Material & Methods:Based on the results of the European Randomized Study of Screening for Prostate Cancer, the ERSPC trial, a micro-simulation model was used to evaluate the effects of PSA screening and phi testing for a European population. The model simulates individual life histories from birth to death, while taking into account that some individuals will develop prostate cancer, clinically or preclinically. When screening tests are applied to a person in a preclinical disease state, they may result in cancer detection and alteration of the life history of this individual. Utility values were obtained from literature. We predicted the numbers of prostate cancers, negative biopsies, deaths, quality-adjusted life-years (QALYs) gained and the cost-effectiveness of using PSA (cut-off ≥3 ng/ml) and phi (cut-off ≥25) testing methods to recommend prostate biopsies. In the phi testing situation, phi was added to the model for men with a PSA between 3 and 10 ng/ml. The model assumed screening of men from age 50 to 75 years old every four years.

Results:When phi was included as part of PSA screening, the model predicted a 29% reduction in negative biopsies, and a 2% reduction in cancers detected, compared to PSA test alone. This resulted in a 30% increase in testing costs, a 21% reduction in costs for diagnostics, due to the reduction of negative biopsies, and a 2% reduction in total costs for prostate cancer care. Also, 6% more QALYs were gained and the cost-effectiveness increased by 12%, yet 2% less life years were gained with phi versus PSA alone, due to the slightly lower clinical sensitivity of phi when preceded by the PSA test.

Conclusions:The use of phi after a positive PSA test may reduce the number of negative biopsies and potentially improve the cost-effectiveness of prostate cancer screening. Further research is needed to evaluate the performance of phi, especially for various PSA cut-offs, or the use of phi in differentiating indolent and aggressive cancers.

Abstract 260; Saturday, 25 February 2012

Serum isoform [-2]proPSA (p2PSA) and its derivates, %p2PSA and phi (Prostate Health Index), are more accurate than the reference standard test (PSA) in men scheduled for repeat biopsy

AUTHORS: Lazzeri M1, Lughezzani G1, Larcher A1, Gadda G1, Scattoni V1, Sangalli M1, Nava L2, Bini V3, Maga T1, Bellinzoni P1, Cestari A1, Rigatti P1, Guazzoni G1

CENTER: 1 University Vita-Salute, Department of Urology, Milan, Italy 2 Fondazione “Opera S. Camillo”, Department of Urology, Milan, Italy 3 University of Perugia, Department of Internal Medicine, Perugia, Italy

Introduction & Objectives:This study tests the hypothesis that [-2]proPSA (p2PSA) and its derivates, namely %p2PSA and phi (Prostate Health Index), are more accurate than reference standard tests (tPSA, fPSA and %fPSA) in detecting PCa in men scheduled for repeat biopsy.

Material & Methods:This study was an observational prospective evaluation of a cohort of men with one or two previous negative prostate biopsies, with persistent suspicion of PCa (suspected DRE, elevated tPSA and or low %fPSA) who were scheduled for repeat biopsy. Men receiving medical therapy known to affect serum PSA (dutasteride and finasteride), suffering from prostatitis and having had invasive treatment for benign prostatic hyperplasia (BPH), such as TURP or HoLEP, were excluded. Serum p2PSA, and it derivates, namely %p2PSA {([-2]proPSA/10)/fPSA)} and Beckman Coulter phi (Prostate Health Index) {[[-2]proPSA/fPSA] x squart PSA} were considered the index tests and compared with the reference standard tests (tPSA, fPSA and %fPSA). All the patients underwent ambulatory repeated TRUS-guided prostate biopsies (18-22 cores). The primary outcome was to evaluate the accuracy of p2PSA and its derivates in detecting PCa.

Results:From June 2010 and June 2011, 222 men underwent repeated biopsy at our single high-volume centre. PCa cancer was found in 71/222 (31.9%) subjects. p2PSA, %p2PSA and phi values were significantly higher (p<0.0001), and %fPSA values significantly lower (p<0.0001) in patients with PCa. At univariate accuracy analysis, %p2PSA (AUC: 72.5%) and phi (AUC: 67.2%) were the most accurate predictors and significantly outperformed tPSA (AUC: 51.8%). %p2PSA significantly outperformed %fPSA (AUC: 60.2%) in the prediction of PCa (p≤0.001), but not phi (p=0.136). For %p2PSA a cut-off of 1.68 showed the best balance between sensitivity and specificity (respectively 67.6 and 66.9%; 95%C.I 58.8-74.3). For phi a cut-off of 40 showed the best balance between sensitivity and specificity (respectively 62 and 59.6%; 95%C.I 51.3-67.5). At 90% of sensitivity, the cut-off of %p2PSA and phi were respectively of 1.23 and 28.8 with a specificity of 40.4 and 25.2%. At a %p2PSA cut-off of 1.23 a total of 153 (68.9%) biopsies could have been avoided; an overall of 6 PCa patients would have been missed but only 1 (5%) patient with a Gleason score of 7 or greater would have been missed. At a phi cut-off of 28.8 a total of 116 (52.25%) biopsies could have been avoided; an overall of 6 PCa patients would have been missed but no patients with a Gleason score of 7 or greater would have been missed.

Conclusions:%p2PSA and phi are more accurate than the reference standard tests (tPSA, fPSA and %fPSA) in predicting repeat prostate biopsy outcome and may be indicative of cancer aggressiveness.

Abstract 259; Saturday, 25 February 2012

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Clinical cut-offs of isoform [-2]proPSA (p2PSA) derivatives, namely %p2PSA and phi (Prostate Health Index) for guiding biopsy decision in Caucasian population

AUTHORS: Lughezzani G1, Lazzeri M1, Scattoni V1, Larcher A1, Gadda G1, Nava L2, Lista G1, Bini V3, Freschi M4, Rigatti L1, Rigatti P1, Guazzoni G1

CENTERS: 1 University Vita-Salute San Raffaele, Department of Urology, Milan, Italy 2 Fondazione “Opera S. Camillo”, Department of Urology, Milan, Italy 3 University, Department of Internal Medicine, Perugia, Italy 4 University Vita-Salute San Raffaele, Department of Pathology, Milan, Italy

Introduction & Objectives:Preliminary results showed that the isoform [-2]proPSA (p2PSA) and its derivatives, namely %p2PSA and phi (Prostate Health Index), are more accurate of tPSA and %fPSA in predicting prostate cancer (PCa) at initial biopsy. The aim of this study is to translate statistical findings into clinical practice cut-offs and the percentage of biopsies that could be avoided without missing aggressive PCa.

Material & Methods:The study is an observational prospective analysis of sensibility, specificity and accuracy of serum p2PSA, %p2PSA {([-2]proPSA/10)/fPSA)} and Beckman Coulter phi (Prostate Health Index) {[[-2]proPSA/fPSA] x squart PSA}, in Caucasian men referred for prostatic biopsy for suspected PCa. Patients with bacterial prostatitis, previous TURP or HoLEP, or treated with drugs that may alter serum PSA levels, namely Finasteride and Dutasteride, were excluded. All the patients underwent ambulatory TRUS-guided prostate biopsies, performed according to a standardized institutional saturation scheme consisting of at least 18-22 biopsy cores taken from prostate gland in order to obtain the highest detection rate. The primary outcome was to evaluate the clinical practice cut-off of %p2PSA and phi at the best balance and at 90% of sensitivity and specificity. A secondary outcome investigated the potential reduction of unnecessary biopsies and the characteristics of missing PCa.

Results:In over 664 patients, PCa cancer was found in 266 (40%) subjects. p2PSA, %p2PSA and phi values were significantly higher (p<0.0001), and %fPSA values significantly lower (p<0.0001) in patients with PCa. At univariate accuracy analysis, %p2PSA (AUC: 73.4%) and phi (AUC: 72.1%) were the most accurate predictors and significantly outperformed tPSA (AUC: 51%) and %fPSA (AUC: 62.9%) in the prediction of PCa at biopsy (p≤0.001). For %p2PSA a cut-off of 1.78 showed the best balance between sensitivity and specificity (respectively 66.2 and 67.1%; 95%C.I 62.2-71.7). A cut-off of 42 for phi showed the best balance between sensitivity and specificity (respectively 66.5 and 66.6%; 95%C.I 61.7-71.7). At 90% of sensitivity, the cut-off of %p2PSA and phi were respectively 1.26 and 30 with a specificity of 35.4 and 29.1%. At a %p2PSA cut-off of 1.26 a total of 123 (18.5%) biopsies could have been avoided, but 7 (5.4%) cancers with a Gleason score of 7 or greater would have been missed. At a phi cut-off of 30 a total of 125 (18.9%) biopsies could have been avoided and 5 (3.8%) cancers with a Gleason score of 7 or greater would have been missed.

Abstract 909; Monday, 27 February 2012

Correlation of chronic histologic prostatic inflammation (CHPI) in biopsy specimens with serum isoform [-2]proPSA (p2PSA), %p2PSA and phi (Prostate Health Index) in men undergoing prostate biopsy for suspected PCa

AUTHORS: Gadda G1, Lazzeri M1, Freschi M2, Sangalli M1, Larcher A2, Scattoni V2, Lughezzani G1, Nava L3, Buffi N1, Rigatti P1, Guazzoni G1

CENTERS: 1 University Vita-Salute San Raffaele, Department of Urology, Milan, Italy 2 University Vita-Salute San Raffaele, Department of Pathology, Milan, Italy 3 Fondazione “Opera S. Camillo”, Department of Urology, Milan, Italy

Introduction & Objectives:Preliminary data showed that [-2]proPSA (p2PSA) and its derivates, namely %p2PSA and phi (Prostate Health Index), could discriminate between patients with or without PCa in a range of tPSA between 2.5 and 10 ng/mL. We investigated the correlation between the serum p2PSA, %p2PSA and phi and chronic histologic prostatic inflammation in men undergoing prostate biopsy for suspected PCa.

Material & Methods:The analysis consisted of a nested case-control study from an observational prospective trial for the definition of sensibility, specificity and accuracy of p2PSA, %p2PSA {(p2PSA/10)/fPSA)} and Beckman Coulter phi ([[-2]proPSA/fPSA] x squart PSA) in men who underwent prostatic biopsy for suspected PCa. Exclusion criteria included patients with bacterial prostatitis, previous TURP or HoLEP, patients treated with drugs that may alter serum PSA levels, namely Finasteride and Dutasteride. Patients underwent ambulatory TRUS-guided prostate biopsies, performed according to a standardized institutional saturation scheme consisting in least 18-22 biopsy cores taken from prostate gland in order to obtain the highest detection rate. All cases in the cohort study that developed the outcome of interest (chronic histologic prostatic inflammation – CHPI - defined as moderate to large infiltration of lymphomononuclear cells with interstitial and/or glandular disruption in absence of PCa) were considered the cases. p2PSA, %p2PSA and phi were considered the index tests and compared with the established biomarker reference standard tests: tPSA, fPSA, %fPSA.

Results:In over 664 patients, CHPI was found in 177 (26.7%) patients, benign prostatic hyperplasia (BPH) without CHPI in 221 (33.3%) and PCa in 266 (40%). Median p2PSA (17.9 pg/ml), %p2PSA (2.07) and phi (51) values were significantly higher (p0.05). Median %fPSA was statistically lower in patients with PCa than CHPI or BPH: 14.4% vs. 17.7% and 16.6% respectively (p<0.0001).

Conclusions:Our findings showed p2PSA, %p2PSA and phi values might discriminate patients with PCa and CHPI or BPH, but not CHPI than BPH. As tPSA failed to distinguish PCa, BPH and CHPI, isoform p2PSA and its derivates could be useful in biopsy clinical decision making in order to prevent unnecessary biopsies in patients with CHPI and elevated tPSA value.

Abstract 278; Saturday, 25 February 2012

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Isoform [-2]proPSA (p2PSA) and its derivates, %p2PSA and phi values differ between BPH, ASAP, HG-PIN and PCa in a set of contemporary men undergoing prostate biopsy

AUTHORS: Lista G1, Lughezzani G1, Lazzeri M1, Scattoni V1, Nava L2, Centemero A1, Losa A1, Fabbri F1, Bini V3, Rigatti P1, Guazzoni G1

CENTERS: 1 University Vita-Salute San Raffaele, Department of Urology, Milan, Italy 2 Fondazione “Opera S. Camillo”, Department of Urology, Milan, Italy 3 University of Perugia, Department of Internal Medicine, Perugia, Italy

Introduction & Objectives:Preliminary data showed that p2PSA and its derivates, %p2PSA and phi (Prostate Health Index), could discriminate between patients with or without PCa in a range of tPSA between 2.0 and 10 ng/mL. To date there have been no published studies which characterized p2PSA, %p2PSA and phi in patients with benign prostatic hyperplasia (BPH), high-grade prostate intraepithelial neoplasia (HGPIN), atypical small acinar proliferation (ASAP) and prostate cancer. We tested the hypothesis that p2PSA and its derivates may accurately discriminate between BPH, HG-PIN, ASAP and PCa in a set of contemporary men undergoing prostate biopsy.

Material & Methods:The study design consisted of an observational prospective cohort study for the definition of sensibility, specificity and accuracy of serum p2PSA, %p2PSA {([p2PSA/fPSA x 1000]x100)} and Beckman Coulter phi (Prostate Health Index) {[[-2]proPSA/fPSA] x squart PSA}, in men referred for prostatic biopsy. Exclusion criteria included patients with bacterial prostatitis, previous TURP or HoLEP, patients treated with drugs that may alter serum PSA levels, namely finasteride and dutasteride. Patients underwent ambulatory TRUS-guided prostate biopsies, performed according to a standardized institutional saturation scheme consisting of at least 18-22 biopsy cores taken from prostate gland in order to obtain the highest detection rate. The primary endpoint of the study was to determine the diagnostic accuracy of p2PSA, %p2PSA and phi (index tests) compared with the accuracy of established PCa predictors (tPSA, fPSA, %fPSA and PSAD) (reference standard tests).

Results:In over 664 patients, a prostate biopsy detected cancer in 266 (40%) patients, BPH in 339 (51%), HGPIN in 43 (6.5%%) and ASAP in 16 (2.5%) of subjects. p2PSA (17.96 pg/ml), %p2PSA (2.07) and phi (51) values were significantly higher (p<0.0001), and %fPSA (0.14) values significantly lower (p<0.0001) in patients with PCa vs. no cancer patients. Patients with PCa were statistically older (66.7 yrs.) than BPH ones (62.8 yrs) (p<0.0001), but not in HG-PIN (66.7 yrs.) (p=0.975) or ASAP (65.6 yrs.) (p=0.948). No significant difference was observed for the median value of %p2PSA and phi between patients with BPH, HG-PIN and ASAP (1.44; 1.53 and 1.78; 36.8; 39 and 40.5 respectively), and between PCa and ASAP patients (p=0.493; p=0.219).

Conclusions:%p2PSA and phi values may discriminate patients with PCa from patients with BPH and HG-PIN, but fail to distinguish them from ASAP subjects. Further multicentric international studies are mandatory to confirm our findings.

Abstract 910; Monday, 27 February 2012

Comparison of phi (Prostate Health Index) and PCA3 assay in the prediction of prostate biopsy (PBx) outcome in patients who have undergone initial and repeated prostatic biopsies

AUTHORS: Scattoni V1, Lazzeri M1, De Luca S2, Bollito E2, Randone D2, Lughezzani G1, Larcher A1, Lista G1, Gadda G1, Maccagnano C1, Rigatti P1, Guazzoni G1

CENTERS: 1 University Vita-Salute, Department of Urology, Milan, Italy 2 Ospedale Gradenigo, Department of Urology, Turin, Italy

Introduction & Objectives:To compare the diagnostic performance of Beckman Coulter phi and PCA3-Score in men undergoing first and repeat extended PBx.

Material & Methods:The diagnostic performance of phi [(p2PSA/fPSA) x √tPSA)] and PCA3 across different PSA ranges was evaluated in a combined dataset of 194 men (median age 67 yrs, median PSA: 6.4 ng/ml±6.9) undergoing first (n=155 cases) or (multiple) repeat PBx (n=39 cases) (12-22 cores) in two centers. Both tests were performed prior to DRE and PBx. The blood samples were processed using UniCel DxI 800 Immunoassay System analyzer (Beckman Coulter, Brea, CA, USA). The PCA3 score was determined by the PROGENSA PCA3 assay. phi and PCA3 were compared to age, total PSA, prostate volume, DRE, PSA density (PSAD), and %fPSA. Statistical analysis encompassed descriptive statistics, nonparametric analysis of differences in PBx+ vs. PBx- men, ROC-Analysis and calculation of specificity at a sensitivity of 80% and sensitivity at a specificity of 50%.

Results:Cancer was detected in 63/194 patients (32.4 %) in the whole group (33.1% and 28.9% in the initial and repeat group, respectively). Only phi (43.8 vs 65.13; p= 0.01) and prostate volume (86.1 vs 60.1; p=0.04) were significantly different between Bx- and Bx+ men in the whole group. In the initial setting, age (65.8 vs 68.7; p=0.02), PCA3 score (48.2 vs 63.9; p= 0.04), phi (45.2 vs 67.7; p=0.04) and prostate volume (86.6 vs 56.6; p=0.04) were significantly different between PBx- and PBx+ men. On the contrary, no significant differences were found in the parameters in the repeat setting. The ROC-Analysis showed phi had the highest AUC value in the whole group (0.678) and significantly higher compared to PCA3 (0.544) (p=0.02), and tPSA (0.516) (p=0.003), age (0.53) (p= 0.02), but not %fPSA (0.60) and PSAD (0.57). Likewise, in the initial setting, AUC was highest for phi (0.68) followed by %fPSA (0.62) PCA3 (0.60), age (0.57), PSA (0.53), PSAD (0.641) and %fPSA (0.608). On the contrary, in the repeat setting, AUC was highest for PCA3 (0.67) compared to phi (0.60) %fPSA (0.55), tPSA (0.54) and age (0.64) even if no statistically significant difference was found. In the whole group, with a sensitivity set at 80%, specificity for phi and PCA3 was 36.15% and 20%, respectively. In the initial setting a 12.3% increase of phi compared to PCA3 was found. In the repeat setting, a 15.0% increase of specificity of PCA3 compared to phi was reported. At a specificity of 50%, sensitivity for phi and PCA3 were 74.5% and 62.5% in the initial setting and 63.3% and 62.8% in the repeat setting, respectively.

Conclusions:phi seems to be the strongest parameter to predict PBx outcome in the initial setting, while PCA3 seems to be more accurate than phi in the repeat setting.

Abstract 912; Monday, 27 February 2012

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