- Email: [email protected]
2102 PROSTATE-SPECIFIC ANTIGEN KINETICS AND BIOPSY PROGRESSION IN PATIENTS MANAGED BY ACTIVE SURVEILLANCE
Vol. 187, No. 4S, Supplement, Wednesday, May 23, 2012
THE JOURNAL OF UROLOGY姞
e847
PCa was significantly associated with decreasing age (OR 1.8, p⫽0.001) and PSA (OR 1.69, p⫽0.019) such as a decreasing number of positive cores (OR 1.58, p⫽0.009), respectively. CONCLUSIONS: In our study cohort about two third of patients would have been correctly identified to harbour organ confined and less aggressive prostate cancer. Moreover, age, PSA and the number of positive cores could improve risk stratification in regards of cancer aggressiveness within active surveillance patients. Source of Funding: None
2102 Source of Funding: M. Garcia is supported by: NIH NICHD K08 Grant. J. Marh is supported by NIH COBRA grant funds.
PROSTATE-SPECIFIC ANTIGEN KINETICS AND BIOPSY PROGRESSION IN PATIENTS MANAGED BY ACTIVE SURVEILLANCE Viacheslav Iremashvili*, Murugesan Manoharan, Soum Lokeshwar, Daniel L Rosenber, David Pan, Mark S Soloway, Miami, FL
Prostate Cancer: Markers I Podium Wednesday, May 23, 2012
8:00 AM-10:00 AM
2101 USING SPECIFIC ACTIVE SURVEILLANCE CRITERIA WITHIN A EUROPEAN MULTICENTRE REFERRAL COHORT TO IDENTIFY THE MOST APPROPRIATE CANDIDATES. Marco Auprich*, Herbert Augustin, Graz, Austria; Anton Ponholzer, Vienna, Austria; Raid Abdelghani, Hamburg, Germany; Oliver Pachernegg, Graz, Austria; Markus Graefen, Hamburg, Germany; Paul Schramek, Vienna, Austria; Karl Pummer, Graz, Austria; Hans Heinzer, Hamburg, Germany INTRODUCTION AND OBJECTIVES: Active surveillance (AS) might be an option to defer or avoid curative treatment in low risk prostate cancer (PCa) patients. Objective was to evaluate pathological features in patients which complied to specific AS criteria and to asses the ability to correctly predict tumour stage and aggressiveness. METHODS: We retrospectively assessed 4340 consecutive patients, who underwent radical prostatectomy (RP) within three tertiary referral centres (Hamburg, Vienna, Graz) from 01/2006-12/2010. All pathological specimens’ were assessed following ISUP 2005 guidelines. 592 of these patients complied specific clinically applicable criteria [PSA ⱕ 10ng/ml, T1c-cT2a, biopsy Gleason score (GS) ⱕ 6, ⱕ 2 positive biopsy-cores (3 if 24 cores were taken)]. Pathological features were evaluated to estimate the proportion of patients diagnosed with organ-confined (OC) and less aggressive (pathological GS eⱕ 6) diseases at RP. Moreover we assessed if stratification according to age (⬍65y vs. PSA ⱖ 65y), PSA (⬍4 vs. ⱖ4-10ng/ml), TRUS assessed prostate volume (⬍50ml vs. ⱖ 50ml), biopsy scheme (⬍10 vs. 10 -12 vs. ⬎12 cores) and number of positive cores (1 vs. 2 or 3) affects on the ability to correctly predict OC stage and well differentiated PCa. Logistic regression was used to estimate potential associations between risk factors and OC stage, path. GS ⱕ 6 (LGPCa). RESULTS: Median age, PSA and number of biopsy cores was 64.5y (40-76), 5.4ng/ml (0.4 – 10) and 10.0 (4-24), with a median of 1.0 (1-3) positive biopsy cores. In 88.9% patients presented with pT1c stage. Out of 592 patients, all complying the specific AS criteria, 561 (94.8%) were diagnosed with organ confined PCa, with pT2c stage in 434 (73.3%) patients. In contrast, 31 (5.3%) patients were diagnosed with non organ confined PCa (ECE). Gleason score ⱕ 6 (LG) was diagnosed in 392 (66.2%) patients. A favourable combination of OC and LGPCa was found within 382 (64.5%) of patients. Less aggressive
INTRODUCTION AND OBJECTIVES: Prostate-specific antigen (PSA) kinetics such as PSA velocity (PSAV) and PSA doubling time (PSADT) may reflect dynamic changes in prostate histology and therefore could be useful in predicting biopsy progression in active surveillance patients. In the current study we tested this possibility. METHODS: Our inclusion criteria for active surveillance are biopsy Gleason sum ⬍7, ⱕ2 positive biopsy cores, ⱕ20% tumor present in any core, and clinical stage T1-T2a. Changes in any of these parameters during the follow-up that went beyond these limits are considered to be progression. This study included 250 patients who had at least one surveillance biopsy, an available PSA measured no earlier than 3 months before diagnosis, and at least one PSA measurement before each surveillance biopsy. We evaluated the association between PSA kinetics and progression by any criterion or presence of Gleason 4/5 cancer at successive surveillance biopsies in different subgroups of patients by calculating the area under a receiver operative characteristics curve (AUC). RESULTS: Over a median follow-up of 3.0 years 64 (26%) patients progressed. 1,432 PSA measurements were used in the PSA kinetics calculations in the entire cohort, with a median of 5 measurements per patient (IQR 3-7 measurements, mean 5.728). PSADT was not associated with biopsy progression, while PSAV was only weakly associated with progression in certain subgroups (Table 1). However, incorporation of PSAV in models including total PSA resulted in a moderate increase in AUC only when the entire cohort was analyzed (Table 2). In other subgroups the predictive accuracy of total PSA was not significantly improved by adding PSAV. CONCLUSIONS: Our findings do not support using PSA kinetics in decision-making in patients with low-risk prostate cancer managed by active surveillance. Therefore, regular surveillance biopsies should remain as the principal method of monitoring cancer progression in these men.
e848
THE JOURNAL OF UROLOGY姞
Vol. 187, No. 4S, Supplement, Wednesday, May 23, 2012
Table 1. Predictive accuracy of prostate-specific antigen kinetics for biopsy progression and presence of Gleason 4/5 cancer in different groups of patients Area under the curve Restricted cubic splines
Progression
Area under the curve Untransformed values Presence of Gleason 4/5
Progression
Area under the curve Restricted cubic splines Presence of Gleason 4/5
PSAV (95%CI)
0.549 (0.467-0.630)
0.619 (0.528-0.710)
0.527 (0.447-0.607)
0.628 (0.535-0.721)
PSADT1 (95%CI)
0.493 (0.386-0.601)
0.511 (0.399-0.622)
0.525 (0.420-0.629)
0.596 (0.489-0.702)
Group
Area under the curve Untransformed values
Entire cohort
At least 3 PSA over at least 18 months PSAV (95%CI)
0.554 (0.459-0.649)
0.630 (0.527-0.734)
0.557 (0.463-0.655)
0.635 (0.531-0.738)
PSADT (95%CI)
0.550 (0.436-0.665)
0.566 (0.446-0.685)
0.597 (0.481-0.714)
0.529 (0.412-0.646)
First surveillance biopsy PSAV (95%CI)
0.527 (0.423-0.631)
0.546 (0.410-0.682)
0.646 (0.552-0.738)
0.689 (0.543-0.834)
PSADT (95%CI)
0.315 (0.164-0.466)
0.287 (0.085-0.488)
0.685 (0.536-0.834)
0.727 (0.525-0.928)
Second surveillance biopsy PSAV (95%CI)
0.538 (0.418-0.657)
0.567 (0.440-0.695)
0.555 (0.439-0.672)
0.576 (0.448-0.703)
PSADT (95%CI)
0.430 (0.279-0.581)
0.420 (0.269-0.572)
0.653 (0.509-0.796)
0.651 (0.505-0.796)
Third surveillance biopsy PSAV (95%CI)
0.452 (0.283-0.622)
0.656 (0.440-0.872)
0.565 (0.388-0.741)
0.665 (0.417-0.913)
PSADT (95%CI)
0.417 (0.156-0.678)
0.516 (0.189-0.843)
0.758 (0.544-0.972)
0.679 (0.433-0.925)
Forth and later biopsies PSAV (95%CI)
0.962 (0.904-1.000)
0.941 (0.863-1.000)
0.962 (0.904-1.000)
0.941 (0.863-1.000)
PSADT (95%CI)
0.915 (0.814-1.000)
0.917 (0.815-1.000)
0.962 (0.896-1.000)
0.926 (0.829-1.000)
Third surveillance biopsy2 PSAV (95%CI)
0.383 (0.219-0.546)
0.478 (0.209-0.747)
0.643 (0.485-0.801)
0.623 (0.396-0.850)
PSADT (95%CI)
0.383 (0.124-0.642)
0.356 (0.000-0.786)
0.724 (0.427-1.000)
0.815 (0.555-1.000)
Patients with PSA⬍ 4 ng/ml at diagnosis PSAV (95%CI)
0.547 (0.374-0.720)
0.614 (0.418-0.810)
0.637 (0.482-0.792)
0.614 (0.417-0.810)
PSADT (95%CI)
0.571 (0.371-0.772)
0.538 (0.325-0.750)
0.717 (0.554-0.881)
0.645 (0.458-0.832)
Patients with PSA ⱖ4 ng/ml at diagnosis PSAV (95%CI)
0.551 (0.457-0.645)
0.616 (0.509-0.723)
0.506 (0.416-0.596)
0.624 (0.516-0.732)
PSADT (95%CI)
0.557 (0.427-0.686)
0.527 (0.390-0.663)
0.653 (0.527-0.778)
0.596 (0.465-0.726)
1 ⫽ Calculated using only positive PSADT values; 2 ⫽ PSA kinetics calculated using PSA values obtained during the 24 months before the biopsy. PSAV ⫽ prostate-specific antigen velocity; CI ⫽ confidence interval; PSADT ⫽ prostatespecific antigen doubling time. Table 2. Predictive accuracy of models based on the last PSA before biopsy or a combination of the last PSA with PSA velocity before the same biopsy in different subgroups of patients
Entire cohort
Biopsy progression Area under the curve (95%CI) PSA -
Biopsy progression Area under the curve (95%CI) PSA⫹PSAV1 -
p
PREOPERATIVE PROSTATE-SPECIFIC ANTIGEN ISOFORM P2PSA AND ITS DERIVATES, %P2PSA AND PROSTATE HEALTH INDEX, PREDICT PATHOLOGIC OUTCOMES IN PATIENTS UNDERGOING RADICAL PROSTATECTOMY FOR PROSTATE CANCER Massimo Lazzeri*, Giovanni Lughezzani, Alessandro Larcher, Vincenzo Scattoni, Andrea Cestari, Nicolomaria Buffi, Luigi Broglia, Giulio Maria Gadda, Milan, Italy; Vittorio Bini, Perugia, Italy; Francesco Montorsi, Patrizio Rigatti, Giorgio Guazzoni, Milan, Italy INTRODUCTION AND OBJECTIVES: The current predictive models fail to assist clinical decision making. Thus, new biomarkers are needed. The aim of this study was to evaluate the predictive accuracy of PSA isoform p2PSA and its derivates, percentage of p2PSA to free PSA (%p2PSA) and the Beckman Coulter Prostate Health Index (PHI), in determining prostate cancer (PCa) characteristics at final pathology. METHODS: This study was an observational prospective study in a real clinical setting of 350 men diagnosed with clinically localized PCa who underwent radical prostatectomy (RP). We determined the predictive accuracy of serum total PSA (tPSA), free PSA (fPSA), fPSA to tPSA (%fPSA), p2PSA, %p2PSA ([p2PSA/fPSA] ⫻ 100), and PHI (p2PSA/fPSA ⫻ √tPSA) for five different end points: the presence of extracapsular disease (pT3); the presence of pathologic Gleason sum ⱖ7 PCa; the presence of Gleason sum upgrading, defined as an upgrading of Gleason sum from ⱕ6 to ⱖ7; the presence of tumor volume ⬍0.5 ml. All the prostate specimens were analyzed by a single expert genitourinary pathologist. All calculations were carried out with Predictive Analytic Software (PASW®) release 17.0.2, SPSS Inc., Chicago, USA, 2009. A two-sided p-value ⬍0.05 was considered significant. RESULTS: The %p2PSA and PHI levels were significantly higher in patients with pT3 disease, pathologic Gleason sum ⱖ7 and Gleason sum upgrading (all p values ⱕ0.001). Conversely, %p2PSA and PHI levels were significantly lower in patients with tumor volume ⬍0.5 ml (p ⬍ 0.001). In univariate analyses of the area under the receiver operating characteristic curve, both %p2PSA and PHI were the most accurate biomarkers when predicting the presence of pT3 disease, pathologic Gleason sum ⱖ7, Gleason sum upgrading and tumor volume ⬍0.5 ml. At multivariate analyses, the inclusion of both %p2PSA and PHI significantly increased the predictive accuracy of a base multivariate model (excluding the tumor volume prediction for both variables, and Gleason sum upgrading for model including %p2PSA) that included patient age, tPSA, fPSA, f/tPSA, Clinical Stage and Biopsy Gleason sum. CONCLUSIONS: We found p2PSA and its derivatives are predictors of PCa characteristics at final pathology after RP and are more accurate than currently available markers.
Presence of Gleason 4/5
Presence of Gleason 4/5
Area under the curve (95%CI) PSA 0.602 (0.508-0.696)
Area under the curve (95%CI) PSA⫹PSAV1 0.642 (0.549-0.734)
p 0.01
0.605 (0.501-0.709)
0.636 (0.531-0.742)
0.312
2104 PROSPECTIVE MULTICENTER EVALUATION OF PCA3 AND TMPRSS2-ERG GENE FUSIONS AS DIAGNOSTIC AND PROGNOSTIC BIOMARKERS FOR PROSTATE CANCER
Source of Funding: Beckman Coulter, Italy
At least 3 PSA over at least 18 months
-
-
First surveillance biopsy
0.653 (0.541-0.765)
0.744 (0.632-0.856)
0.07
0.663 (0.528-0.799)
0.748 (0.597-0.899)
0.196
Fourth and later biopsies
0.924 (0.838-1.000)
0.951 (0.887-1.000)
0.456
0.895 (0.784-1.000)
0.980 (0.943-1.000)
0.093
Patients with PSA ⱖ4 ng/ml at diagnosis
-
-
0.611 (0.501-0.722)
0.655 (0.546-0.764)
0.113
1 ⫽ restricted cubic splines CI ⫽ confidence interval; PSA ⫽ prostate-specific antigen; PSAV ⫽ prostate-specific antigen velocity.
Source of Funding: None
2103
Gisele Leyten, Daphne Hessels, Nijmegen, Netherlands; Erik Cornel, Hengelo, Netherlands; Theo de Reyke, Amsterdam, Netherlands; Henk Vergunst, Nijmegen, Netherlands; Paul Kil, Tilburg, Netherlands; Ben Knipscheer, Emmen, Netherlands; Sander Jannink, Frank Smit, Hans de Jong, Inge van Oort, Peter Mulders, Jack Schalken*, Nijmegen, Netherlands INTRODUCTION AND OBJECTIVES: In 2007 it was published that the combined use of urine markers PCA3 and TMPRSS2-ERG gene fusions (T2:ERG) increased diagnostic sensitivity for prostate cancer. The aim of this study was to evaluate the diagnostic and prognostic value of Progensa PCA3 and T2:ERG (as individual biomarkers and as a panel) in a prospective multicenter setting.
THE JOURNAL OF UROLOGY姞
e847
PCa was significantly associated with decreasing age (OR 1.8, p⫽0.001) and PSA (OR 1.69, p⫽0.019) such as a decreasing number of positive cores (OR 1.58, p⫽0.009), respectively. CONCLUSIONS: In our study cohort about two third of patients would have been correctly identified to harbour organ confined and less aggressive prostate cancer. Moreover, age, PSA and the number of positive cores could improve risk stratification in regards of cancer aggressiveness within active surveillance patients. Source of Funding: None
2102 Source of Funding: M. Garcia is supported by: NIH NICHD K08 Grant. J. Marh is supported by NIH COBRA grant funds.
PROSTATE-SPECIFIC ANTIGEN KINETICS AND BIOPSY PROGRESSION IN PATIENTS MANAGED BY ACTIVE SURVEILLANCE Viacheslav Iremashvili*, Murugesan Manoharan, Soum Lokeshwar, Daniel L Rosenber, David Pan, Mark S Soloway, Miami, FL
Prostate Cancer: Markers I Podium Wednesday, May 23, 2012
8:00 AM-10:00 AM
2101 USING SPECIFIC ACTIVE SURVEILLANCE CRITERIA WITHIN A EUROPEAN MULTICENTRE REFERRAL COHORT TO IDENTIFY THE MOST APPROPRIATE CANDIDATES. Marco Auprich*, Herbert Augustin, Graz, Austria; Anton Ponholzer, Vienna, Austria; Raid Abdelghani, Hamburg, Germany; Oliver Pachernegg, Graz, Austria; Markus Graefen, Hamburg, Germany; Paul Schramek, Vienna, Austria; Karl Pummer, Graz, Austria; Hans Heinzer, Hamburg, Germany INTRODUCTION AND OBJECTIVES: Active surveillance (AS) might be an option to defer or avoid curative treatment in low risk prostate cancer (PCa) patients. Objective was to evaluate pathological features in patients which complied to specific AS criteria and to asses the ability to correctly predict tumour stage and aggressiveness. METHODS: We retrospectively assessed 4340 consecutive patients, who underwent radical prostatectomy (RP) within three tertiary referral centres (Hamburg, Vienna, Graz) from 01/2006-12/2010. All pathological specimens’ were assessed following ISUP 2005 guidelines. 592 of these patients complied specific clinically applicable criteria [PSA ⱕ 10ng/ml, T1c-cT2a, biopsy Gleason score (GS) ⱕ 6, ⱕ 2 positive biopsy-cores (3 if 24 cores were taken)]. Pathological features were evaluated to estimate the proportion of patients diagnosed with organ-confined (OC) and less aggressive (pathological GS eⱕ 6) diseases at RP. Moreover we assessed if stratification according to age (⬍65y vs. PSA ⱖ 65y), PSA (⬍4 vs. ⱖ4-10ng/ml), TRUS assessed prostate volume (⬍50ml vs. ⱖ 50ml), biopsy scheme (⬍10 vs. 10 -12 vs. ⬎12 cores) and number of positive cores (1 vs. 2 or 3) affects on the ability to correctly predict OC stage and well differentiated PCa. Logistic regression was used to estimate potential associations between risk factors and OC stage, path. GS ⱕ 6 (LGPCa). RESULTS: Median age, PSA and number of biopsy cores was 64.5y (40-76), 5.4ng/ml (0.4 – 10) and 10.0 (4-24), with a median of 1.0 (1-3) positive biopsy cores. In 88.9% patients presented with pT1c stage. Out of 592 patients, all complying the specific AS criteria, 561 (94.8%) were diagnosed with organ confined PCa, with pT2c stage in 434 (73.3%) patients. In contrast, 31 (5.3%) patients were diagnosed with non organ confined PCa (ECE). Gleason score ⱕ 6 (LG) was diagnosed in 392 (66.2%) patients. A favourable combination of OC and LGPCa was found within 382 (64.5%) of patients. Less aggressive
INTRODUCTION AND OBJECTIVES: Prostate-specific antigen (PSA) kinetics such as PSA velocity (PSAV) and PSA doubling time (PSADT) may reflect dynamic changes in prostate histology and therefore could be useful in predicting biopsy progression in active surveillance patients. In the current study we tested this possibility. METHODS: Our inclusion criteria for active surveillance are biopsy Gleason sum ⬍7, ⱕ2 positive biopsy cores, ⱕ20% tumor present in any core, and clinical stage T1-T2a. Changes in any of these parameters during the follow-up that went beyond these limits are considered to be progression. This study included 250 patients who had at least one surveillance biopsy, an available PSA measured no earlier than 3 months before diagnosis, and at least one PSA measurement before each surveillance biopsy. We evaluated the association between PSA kinetics and progression by any criterion or presence of Gleason 4/5 cancer at successive surveillance biopsies in different subgroups of patients by calculating the area under a receiver operative characteristics curve (AUC). RESULTS: Over a median follow-up of 3.0 years 64 (26%) patients progressed. 1,432 PSA measurements were used in the PSA kinetics calculations in the entire cohort, with a median of 5 measurements per patient (IQR 3-7 measurements, mean 5.728). PSADT was not associated with biopsy progression, while PSAV was only weakly associated with progression in certain subgroups (Table 1). However, incorporation of PSAV in models including total PSA resulted in a moderate increase in AUC only when the entire cohort was analyzed (Table 2). In other subgroups the predictive accuracy of total PSA was not significantly improved by adding PSAV. CONCLUSIONS: Our findings do not support using PSA kinetics in decision-making in patients with low-risk prostate cancer managed by active surveillance. Therefore, regular surveillance biopsies should remain as the principal method of monitoring cancer progression in these men.
e848
THE JOURNAL OF UROLOGY姞
Vol. 187, No. 4S, Supplement, Wednesday, May 23, 2012
Table 1. Predictive accuracy of prostate-specific antigen kinetics for biopsy progression and presence of Gleason 4/5 cancer in different groups of patients Area under the curve Restricted cubic splines
Progression
Area under the curve Untransformed values Presence of Gleason 4/5
Progression
Area under the curve Restricted cubic splines Presence of Gleason 4/5
PSAV (95%CI)
0.549 (0.467-0.630)
0.619 (0.528-0.710)
0.527 (0.447-0.607)
0.628 (0.535-0.721)
PSADT1 (95%CI)
0.493 (0.386-0.601)
0.511 (0.399-0.622)
0.525 (0.420-0.629)
0.596 (0.489-0.702)
Group
Area under the curve Untransformed values
Entire cohort
At least 3 PSA over at least 18 months PSAV (95%CI)
0.554 (0.459-0.649)
0.630 (0.527-0.734)
0.557 (0.463-0.655)
0.635 (0.531-0.738)
PSADT (95%CI)
0.550 (0.436-0.665)
0.566 (0.446-0.685)
0.597 (0.481-0.714)
0.529 (0.412-0.646)
First surveillance biopsy PSAV (95%CI)
0.527 (0.423-0.631)
0.546 (0.410-0.682)
0.646 (0.552-0.738)
0.689 (0.543-0.834)
PSADT (95%CI)
0.315 (0.164-0.466)
0.287 (0.085-0.488)
0.685 (0.536-0.834)
0.727 (0.525-0.928)
Second surveillance biopsy PSAV (95%CI)
0.538 (0.418-0.657)
0.567 (0.440-0.695)
0.555 (0.439-0.672)
0.576 (0.448-0.703)
PSADT (95%CI)
0.430 (0.279-0.581)
0.420 (0.269-0.572)
0.653 (0.509-0.796)
0.651 (0.505-0.796)
Third surveillance biopsy PSAV (95%CI)
0.452 (0.283-0.622)
0.656 (0.440-0.872)
0.565 (0.388-0.741)
0.665 (0.417-0.913)
PSADT (95%CI)
0.417 (0.156-0.678)
0.516 (0.189-0.843)
0.758 (0.544-0.972)
0.679 (0.433-0.925)
Forth and later biopsies PSAV (95%CI)
0.962 (0.904-1.000)
0.941 (0.863-1.000)
0.962 (0.904-1.000)
0.941 (0.863-1.000)
PSADT (95%CI)
0.915 (0.814-1.000)
0.917 (0.815-1.000)
0.962 (0.896-1.000)
0.926 (0.829-1.000)
Third surveillance biopsy2 PSAV (95%CI)
0.383 (0.219-0.546)
0.478 (0.209-0.747)
0.643 (0.485-0.801)
0.623 (0.396-0.850)
PSADT (95%CI)
0.383 (0.124-0.642)
0.356 (0.000-0.786)
0.724 (0.427-1.000)
0.815 (0.555-1.000)
Patients with PSA⬍ 4 ng/ml at diagnosis PSAV (95%CI)
0.547 (0.374-0.720)
0.614 (0.418-0.810)
0.637 (0.482-0.792)
0.614 (0.417-0.810)
PSADT (95%CI)
0.571 (0.371-0.772)
0.538 (0.325-0.750)
0.717 (0.554-0.881)
0.645 (0.458-0.832)
Patients with PSA ⱖ4 ng/ml at diagnosis PSAV (95%CI)
0.551 (0.457-0.645)
0.616 (0.509-0.723)
0.506 (0.416-0.596)
0.624 (0.516-0.732)
PSADT (95%CI)
0.557 (0.427-0.686)
0.527 (0.390-0.663)
0.653 (0.527-0.778)
0.596 (0.465-0.726)
1 ⫽ Calculated using only positive PSADT values; 2 ⫽ PSA kinetics calculated using PSA values obtained during the 24 months before the biopsy. PSAV ⫽ prostate-specific antigen velocity; CI ⫽ confidence interval; PSADT ⫽ prostatespecific antigen doubling time. Table 2. Predictive accuracy of models based on the last PSA before biopsy or a combination of the last PSA with PSA velocity before the same biopsy in different subgroups of patients
Entire cohort
Biopsy progression Area under the curve (95%CI) PSA -
Biopsy progression Area under the curve (95%CI) PSA⫹PSAV1 -
p
PREOPERATIVE PROSTATE-SPECIFIC ANTIGEN ISOFORM P2PSA AND ITS DERIVATES, %P2PSA AND PROSTATE HEALTH INDEX, PREDICT PATHOLOGIC OUTCOMES IN PATIENTS UNDERGOING RADICAL PROSTATECTOMY FOR PROSTATE CANCER Massimo Lazzeri*, Giovanni Lughezzani, Alessandro Larcher, Vincenzo Scattoni, Andrea Cestari, Nicolomaria Buffi, Luigi Broglia, Giulio Maria Gadda, Milan, Italy; Vittorio Bini, Perugia, Italy; Francesco Montorsi, Patrizio Rigatti, Giorgio Guazzoni, Milan, Italy INTRODUCTION AND OBJECTIVES: The current predictive models fail to assist clinical decision making. Thus, new biomarkers are needed. The aim of this study was to evaluate the predictive accuracy of PSA isoform p2PSA and its derivates, percentage of p2PSA to free PSA (%p2PSA) and the Beckman Coulter Prostate Health Index (PHI), in determining prostate cancer (PCa) characteristics at final pathology. METHODS: This study was an observational prospective study in a real clinical setting of 350 men diagnosed with clinically localized PCa who underwent radical prostatectomy (RP). We determined the predictive accuracy of serum total PSA (tPSA), free PSA (fPSA), fPSA to tPSA (%fPSA), p2PSA, %p2PSA ([p2PSA/fPSA] ⫻ 100), and PHI (p2PSA/fPSA ⫻ √tPSA) for five different end points: the presence of extracapsular disease (pT3); the presence of pathologic Gleason sum ⱖ7 PCa; the presence of Gleason sum upgrading, defined as an upgrading of Gleason sum from ⱕ6 to ⱖ7; the presence of tumor volume ⬍0.5 ml. All the prostate specimens were analyzed by a single expert genitourinary pathologist. All calculations were carried out with Predictive Analytic Software (PASW®) release 17.0.2, SPSS Inc., Chicago, USA, 2009. A two-sided p-value ⬍0.05 was considered significant. RESULTS: The %p2PSA and PHI levels were significantly higher in patients with pT3 disease, pathologic Gleason sum ⱖ7 and Gleason sum upgrading (all p values ⱕ0.001). Conversely, %p2PSA and PHI levels were significantly lower in patients with tumor volume ⬍0.5 ml (p ⬍ 0.001). In univariate analyses of the area under the receiver operating characteristic curve, both %p2PSA and PHI were the most accurate biomarkers when predicting the presence of pT3 disease, pathologic Gleason sum ⱖ7, Gleason sum upgrading and tumor volume ⬍0.5 ml. At multivariate analyses, the inclusion of both %p2PSA and PHI significantly increased the predictive accuracy of a base multivariate model (excluding the tumor volume prediction for both variables, and Gleason sum upgrading for model including %p2PSA) that included patient age, tPSA, fPSA, f/tPSA, Clinical Stage and Biopsy Gleason sum. CONCLUSIONS: We found p2PSA and its derivatives are predictors of PCa characteristics at final pathology after RP and are more accurate than currently available markers.
Presence of Gleason 4/5
Presence of Gleason 4/5
Area under the curve (95%CI) PSA 0.602 (0.508-0.696)
Area under the curve (95%CI) PSA⫹PSAV1 0.642 (0.549-0.734)
p 0.01
0.605 (0.501-0.709)
0.636 (0.531-0.742)
0.312
2104 PROSPECTIVE MULTICENTER EVALUATION OF PCA3 AND TMPRSS2-ERG GENE FUSIONS AS DIAGNOSTIC AND PROGNOSTIC BIOMARKERS FOR PROSTATE CANCER
Source of Funding: Beckman Coulter, Italy
At least 3 PSA over at least 18 months
-
-
First surveillance biopsy
0.653 (0.541-0.765)
0.744 (0.632-0.856)
0.07
0.663 (0.528-0.799)
0.748 (0.597-0.899)
0.196
Fourth and later biopsies
0.924 (0.838-1.000)
0.951 (0.887-1.000)
0.456
0.895 (0.784-1.000)
0.980 (0.943-1.000)
0.093
Patients with PSA ⱖ4 ng/ml at diagnosis
-
-
0.611 (0.501-0.722)
0.655 (0.546-0.764)
0.113
1 ⫽ restricted cubic splines CI ⫽ confidence interval; PSA ⫽ prostate-specific antigen; PSAV ⫽ prostate-specific antigen velocity.
Source of Funding: None
2103
Gisele Leyten, Daphne Hessels, Nijmegen, Netherlands; Erik Cornel, Hengelo, Netherlands; Theo de Reyke, Amsterdam, Netherlands; Henk Vergunst, Nijmegen, Netherlands; Paul Kil, Tilburg, Netherlands; Ben Knipscheer, Emmen, Netherlands; Sander Jannink, Frank Smit, Hans de Jong, Inge van Oort, Peter Mulders, Jack Schalken*, Nijmegen, Netherlands INTRODUCTION AND OBJECTIVES: In 2007 it was published that the combined use of urine markers PCA3 and TMPRSS2-ERG gene fusions (T2:ERG) increased diagnostic sensitivity for prostate cancer. The aim of this study was to evaluate the diagnostic and prognostic value of Progensa PCA3 and T2:ERG (as individual biomarkers and as a panel) in a prospective multicenter setting.