- Email: [email protected]
2321 COMPARATIVE ANALYSIS OF PROSTATE CANCER ANTIGEN 3 MRNA EXPRESSION IN BENIGN PERIPHERAL PROSTATIC TISSUE, CANCER AND ISOLATED OR CANCER-ASSOCIATED HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA
e930
THE JOURNAL OF UROLOGY姞
CONCLUSIONS: PCA3 did not correlate with extra capsular extension or seminal vesicle invasion and its usefulness to predict aggressive disease (GS ⱖ7) at RP is clearly limited. Source of Funding: None
2319 A TMPRSS2:ERG GENE FUSION MOLECULAR URINE ASSAY CORRELATES WITH PATHOLOGIC STAGE AND PROSTATECTOMY GLEASON SCORE AND IS ASSOCIATED WITH BIOPSY-TO-PROSTATECTOMY GLEASON UPGRADING Alexander Haese*, Felix Chun, Hamburg, Germany; Sarah Meyer, Sheila Aubin, John Day, Jack Groskopf, San Diego, CA INTRODUCTION AND OBJECTIVES: An unmet need in PCa prognosis is the differentiation between indolent and significant PCa. Biochemical (e.g. PSA), clinical (e.g. clinical stage) or histological (BxGleason score) parameters, alone or combined, are not sufficiently accurate to aid in this critical distinction. On a genetic basis, a fusion between TMPRSS2 and the ETS family of transcription factors, found in 50 –70% of PCa, is the most common specific gene rearrangement identified to date among solid human malignancies. Studies have linked PCa gene fusions to indicators of significant PCA. In this prospective, ongoing study, we evaluated the correlation of a prototype quantitative TMPRSS2:ERG (T2:ERG) gene fusion urine assay with outcomes in men with PCa scheduled for RRP. METHODS: Post-DRE first-catch urine specimens were collected prior to RRP. T2:ERG mRNA copies were quantified using a transcription-mediated amplification assay and results normalized to PSA mRNA copies by calculating the ratio of TMPRSS2:ERG/PSA copies x 100,000 (T2:ERG Score). The prototype T2:ERG urine assay detects the gene fusion mRNA isoform corresponding to TMPRSS2 exon 1 to ERG exon 4. The T2:ERG Score was correlated with the presence or absence of pathologically organ (OC) vs. non-organconfined (NOC) PCa and the presence or absence of Bx-to-RRP Gleason upgrading. RESULTS: Of 74 subjects 28 (38%) had NOC-disease (ⱖpT3) and 69 (93%) had a RRP Gleason score ⱖ7. 21/26 subjects with BxGleason score of 6 were upgraded to Gleason Score ⱖ7 at RRP. Median T2:ERG Score was significantly higher in men with NOC vs. OC-PCa (80 vs. 9, p⫽0.002) and with RRP Gleason scores ⱖ7 vs. 6 (31 vs. 2, p⫽0.04). The median T2:ERG Score for subjects with vs without Bx-to-RRP-upgrading was 32 vs 2, respectively. CONCLUSIONS: The T2:ERG assay correlated significantly with pT-stage and RRPGleason score. Interestingly, subjects with Bx-to-RRP-upgrading showed a trend towards higher median T2:ERG Scores. These data suggest that a T2:ERG urine assay may be useful to decide when more aggressive treatment of PCa is necessary. Source of Funding: None
2320 INITIAL AND REPEAT PROSTATE BIOPSY: COMPARATIVE PERFORMANCE ANALYSIS OF PSA, %FPSA, PROSTATE VOLUME AND URINARY PCA3 INCLUDING DEVELOPMENT OF NOVEL PCA3 CUT-OFF THRESHOLDS Marco Auprich*, Graz, Austria; Hendrik van Poppel , Leuven, Belgium; Michael Marberger, Wien, Austria; Arnulf Stenzl, Tu¨bingen, Germany; Peter F. A. Mulders, Nijmegen, Netherlands; Hartwig Huland, Hamburg, Germany; Clement-Claude Abbou, Cre´teil, France; Alexander B. Stillebroer, Martin P. M. Q. van Gils, Jack A. Schalken, Nijmegen, Netherlands; Yves Fradet, Quebec City, Canada; Leonard S. Marks, Los Angeles, CA; Alexandre de la Taille, Cre´teil, France; William Ellis, Seattle, WA; Alan W. Partin, Baltimore, MD; Alexander Haese, Hamburg, Germany INTRODUCTION AND OBJECTIVES: We compared the performance characteristics of PSA, %fPSA, prostate volume (PV) and PCA3 as prostate cancer (PCa) risk factors at initial and repeat biopsy session and tested for novel PCA3 cut-offs.
Vol. 185, No. 4S, Supplement, Wednesday, May 18, 2011
METHODS: All 1606 patients underwent an extended initial or repeat biopsy. Indication was suspicious digital rectal examination (DRE) and/or persistently elevated age-specific total PSA cut-offs (2.56.5 ng/ml) and/or suspicious prior histology (ASAP/ ⱖ2 cores affected by HGPIN). PCA3 scores were assessed using the Progensa assay®. After stratification according to biopsy history [initial (IBX) vs. repeat (RBX)], a comparative analysis of all variables including calculation of sensitivity, specificity, positive and negative predictive value (PPV, NPV) such as proportion of avoided unnecessary repeat biopsies and avoided missed PCa compared to PSA at fixed sensitivity (80% and 90%) and specific (50% and 75%) thresholds were performed. Moreover, for each repeat biopsy scenario, comparisons of the area under the ROC- curve (AUC) were calculated. Finally novel cut-off threshold for IBX and RBX were developed using the Youdon-Index [sensitivity⫹ (specificity–1)] followed by graphical exploration. RESULTS: Overall, PCa was detected in 39.1% (n⫽628) of patients. Patients with PCa at the entire cohort presented a higher age, PSA and PCA3 score, suspicious DRE, and lower %fPSA and PV (all, p ⱕ 0.02). At IBX and a fixed sensitivity of 80%, specificity and PPV for PSA, %fPSA, PV and PCA3 was 27.3%, 33.7%, 37.2% and 54.4% and 48.6%, 49.1%, 52.2% and 59.7%, respectively. PCA3 was most informative in predicting PCa with an AUC of 0.74 and would have avoided 36.9% of unnecessary biopsies compared to PSA at 80%sensitivity. At IBX Youdon-Index (0.366) was highest for a PCA score of 29. At RBX and a fixed sensitivity of 80%, specificity and PPV for PSA, %fPSA, PV and PCA3 was 20.8%, 34.4%, 32.8% and 41.7% and 33.2%, 34.7%, 38.5% and 40.3%, respectively. PCA3 was most informative in predicting PCa with an AUC of 0.66 and would have avoided 26.4% of unnecessary biopsies compared to PSA at 80% sensitivity. At RBX Youdon-Index was highest for a PCA3 score of 29. CONCLUSIONS: Our findings demonstrate that PCA3 outperforming PSA, %fPSA and prostate volume in a head-to-head comparison and would have avoided up to 37% of unnecessary biopsies even at a high sensitivity (80%). Compared to the previously reported cut-off threshold of 35, our analyses revealed a lower vs. higher PCA3 cut-off at initial and repeat biopsy. Source of Funding: None
2321 COMPARATIVE ANALYSIS OF PROSTATE CANCER ANTIGEN 3 MRNA EXPRESSION IN BENIGN PERIPHERAL PROSTATIC TISSUE, CANCER AND ISOLATED OR CANCER-ASSOCIATED HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA M. Teresa Quiles, Maria Anto`nia Arbo´s, Ine´s M. de Torres, Carmen Bla´zquez, Juan M. Bastaro´s, Jose´ Placer, Andreas Doll, Jaume Revento´s, Juan Morote*, Barcelona, Spain INTRODUCTION AND OBJECTIVES: Prostate cancer antigen 3 (PCA3) score in urine after prostate-massage is a novel tool to increase prostate specific antigen (PSA) specificity especially in men with repeat prostate biopsy indication. Current data suggest a lower 1 efficacy of PCA3 score in men with HGPIN in the first biopsy . The objective of this study was to analyze the PCA3 gene expression in benign tissue (BT), cancer (CA) and HGPIN lesions (isolated: IHGPIN and cancer-associated: AHGPIN).
METHODS: Total mRNA was isolated and amplified from laserassisted microdissected foci of BT, CA and AHGPIN located in 15 radical prostatectomy frozen specimens and IHGPIN located in 13 radical cistoprostatectomy paraffin-embedded blocks from patients with bladder cancer. PCA3 mRNA amounts were measured by real-time qPCR (Sybr Green I chemistry). PCA3 mRNA amounts were normalized to two reference genes: small nucleolar RNA (SNORD) and Rho GTPase activating protein (ARHGAP). Target gene levels were determined using efficiency-corrected calibrator normalized relative quantification. Comparison among tissues was performed using non-parametric Friedman test followed by post-hoc Dunn’s multiple comparison test.
Vol. 185, No. 4S, Supplement, Wednesday, May 18, 2011
THE JOURNAL OF UROLOGY姞
e931
RESULTS: PCA3 mRNA expression was detected in 80% of BT samples, 86.7% of AHGPIN and 92.9% of CA tissues. PCA3 mean quantitative expression was 11.4 (p⫽0.009) and 20.7-fold increased (p⫽0.0002) in AHGPIN and CA related to BT samples. Qualitative PCA3 mRNA expression was detected in 61.5% of IHGPIN samples. CONCLUSIONS: We have demonstrated that PCA3 is not a specific gene of prostate cancer. PCA3 mRNA expression is significantly increased in cancer-associated HGPIN lesions as well as qualitatively expressed in isolated HGPIN lesions. After these findings and the previous clinical observation of a lower efficacy of PCA3 score in men with previous HGPIN1 we suggest that specific threshold of PCA3 score should be established in those men. 1. Morote et al. Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia. World J Urol. 2010 Jul 7. [Epub ahead of print] Source of Funding: Instituto de Salud Carlos III (FIS PI070536), Ministerio de Ciencia e Innovacio´n, Spain
2322 PCA3 VARIABILITY IN MEN WITH VERY LOW RISK PROSTATE CANCER Sergey Shikanov*, Gautam Jayram, Chicago, IL; Michael S. McGuire, Charles B. Brendler, Evanston, IL INTRODUCTION AND OBJECTIVES: Urinary PCA3 is considered a specific marker of prostate cancer tumor volume. We hypothesized that it will remain stable in patients with minimal disease without treatment. METHODS: 41 men with very low risk prostate cancer were enrolled in an IRB-approved active surveillance protocol. All men had clinical stage T1c, Gleason score 6, positive cores ⱕ3 and involvement of no positive core ⱖ50%. Urinary PCA3 was measured at enrollment and at 6 months. We assessed percent change ([enrollment PCA3– 6 months PCA3 /enrollment PCA3]x100%) and proportion of positive tests (PCA3 score ⬎35) at both time points. None of the patients had evidence of clinical progression during the observation period. RESULTS: Table 1 summarizes the cohort parameters. Median %PCA3 change was only 3%, and 46% of patients had positive PCA3 score both at enrollment and 6 months. However, compared to the enrollment PCA3 score, at 6 months the PCA3 score varied by more than 25% in 58% (n⫽24) and by more than 50% in 31% (n⫽13) of patients(Figure 1). When comparing PSA changes in the same population, PSA varied by more than 25% in only 41% (n⫽17) and by more than 50% in 7% (n⫽3) of patients. CONCLUSIONS: While urinary PCA3 scores on average change only slightly over 6 months in clinically stable men with very low risk prostate cancer, PCA3 scores vary significantly among individual patients. Given this variability, the usefulness of PCA3 in guiding treatment recommendations for the individual patient remains uncertain. Table 1. Cohort parameters, n⫽41 Positive cores 1
22 (54%)
2
15 (36%)
3
4 (10%)
Max. % of core involvement
5 (4 – 10)
Enrollment PCA3
31 (19 – 69)
6 month PCA3
34 (16 – 59)
% change PCA3 Enrollment PCA3 ⬎ 35
3 (⫺31 – 35) 19 (46%)
6 moths PCA3 ⬎ 35
19 (46%)
Enrollment PSA, ng/ml
4.2 (3.0 – 5.3)
6 months PSA, ng/ml
3.3 (2.9 – 5.5)
% change PSA 1 (⫺18 – 25) Continuous data presented as median (0.25– 0.75 quartile range), categorical data presented as count (% of total).
Source of Funding: Philanthropic Funds From NorthShore University Health System
2323 [-2]PROPSA PREDICTS BIOPSY RECLASSIFICATION IN MEN ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER Jeffrey Tosoian*, Sumit Isharwal, Zhaoyong Feng, Baltimore, MD; Danil Makarov, New Haven, CT; Patricia Landis, Robert Veltri, Bruce Trock, Jonathan Epstein, Alan Partin, Lori Sokoll, H.B. Carter, Stacy Loeb, Baltimore, MD INTRODUCTION AND OBJECTIVES: Previous studies have suggested an association between [-2]proPSA expression with prostate cancer risk and prognosis. Our objective was to examine the relationship between [-2]proPSA and disease progression among men enrolled in an active surveillance program. METHODS: In 167 men from our institutional active surveillance program, we used Cox proportional hazards models to examine the relationship between %[-2]proPSA ([-2]proPSA /fPSA) and annual surveillance biopsy results. The outcome of interest was disease reclassification based on biopsy (defined by Gleason score ⬎6, or ⬎2 positive biopsy cores, or ⬎50% involvement of any core with cancer). We also examined the association of biopsy results with %fPSA, [-2]proPSA/%fPSA, and the Beckman Coulter Prostate Health Index [phi⫽([-2]proPSA / fPSA) x (tPSA) (1/2)]. RESULTS: 63 (37.7%) men demonstrated disease reclassification at a median of 4.3 years from diagnosis, including 29 (17.4%) with reclassification based on upgrading to Gleason score ⬎6. Baseline and longitudinal %[-2]proPSA, %fPSA, [-2]proPSA/%fPSA, and phi measurements were significantly associated with disease reclassification. As shown in the table, a model including age, date and phi (baseline and longitudinal) had the greatest c-index for disease reclassification.
THE JOURNAL OF UROLOGY姞
CONCLUSIONS: PCA3 did not correlate with extra capsular extension or seminal vesicle invasion and its usefulness to predict aggressive disease (GS ⱖ7) at RP is clearly limited. Source of Funding: None
2319 A TMPRSS2:ERG GENE FUSION MOLECULAR URINE ASSAY CORRELATES WITH PATHOLOGIC STAGE AND PROSTATECTOMY GLEASON SCORE AND IS ASSOCIATED WITH BIOPSY-TO-PROSTATECTOMY GLEASON UPGRADING Alexander Haese*, Felix Chun, Hamburg, Germany; Sarah Meyer, Sheila Aubin, John Day, Jack Groskopf, San Diego, CA INTRODUCTION AND OBJECTIVES: An unmet need in PCa prognosis is the differentiation between indolent and significant PCa. Biochemical (e.g. PSA), clinical (e.g. clinical stage) or histological (BxGleason score) parameters, alone or combined, are not sufficiently accurate to aid in this critical distinction. On a genetic basis, a fusion between TMPRSS2 and the ETS family of transcription factors, found in 50 –70% of PCa, is the most common specific gene rearrangement identified to date among solid human malignancies. Studies have linked PCa gene fusions to indicators of significant PCA. In this prospective, ongoing study, we evaluated the correlation of a prototype quantitative TMPRSS2:ERG (T2:ERG) gene fusion urine assay with outcomes in men with PCa scheduled for RRP. METHODS: Post-DRE first-catch urine specimens were collected prior to RRP. T2:ERG mRNA copies were quantified using a transcription-mediated amplification assay and results normalized to PSA mRNA copies by calculating the ratio of TMPRSS2:ERG/PSA copies x 100,000 (T2:ERG Score). The prototype T2:ERG urine assay detects the gene fusion mRNA isoform corresponding to TMPRSS2 exon 1 to ERG exon 4. The T2:ERG Score was correlated with the presence or absence of pathologically organ (OC) vs. non-organconfined (NOC) PCa and the presence or absence of Bx-to-RRP Gleason upgrading. RESULTS: Of 74 subjects 28 (38%) had NOC-disease (ⱖpT3) and 69 (93%) had a RRP Gleason score ⱖ7. 21/26 subjects with BxGleason score of 6 were upgraded to Gleason Score ⱖ7 at RRP. Median T2:ERG Score was significantly higher in men with NOC vs. OC-PCa (80 vs. 9, p⫽0.002) and with RRP Gleason scores ⱖ7 vs. 6 (31 vs. 2, p⫽0.04). The median T2:ERG Score for subjects with vs without Bx-to-RRP-upgrading was 32 vs 2, respectively. CONCLUSIONS: The T2:ERG assay correlated significantly with pT-stage and RRPGleason score. Interestingly, subjects with Bx-to-RRP-upgrading showed a trend towards higher median T2:ERG Scores. These data suggest that a T2:ERG urine assay may be useful to decide when more aggressive treatment of PCa is necessary. Source of Funding: None
2320 INITIAL AND REPEAT PROSTATE BIOPSY: COMPARATIVE PERFORMANCE ANALYSIS OF PSA, %FPSA, PROSTATE VOLUME AND URINARY PCA3 INCLUDING DEVELOPMENT OF NOVEL PCA3 CUT-OFF THRESHOLDS Marco Auprich*, Graz, Austria; Hendrik van Poppel , Leuven, Belgium; Michael Marberger, Wien, Austria; Arnulf Stenzl, Tu¨bingen, Germany; Peter F. A. Mulders, Nijmegen, Netherlands; Hartwig Huland, Hamburg, Germany; Clement-Claude Abbou, Cre´teil, France; Alexander B. Stillebroer, Martin P. M. Q. van Gils, Jack A. Schalken, Nijmegen, Netherlands; Yves Fradet, Quebec City, Canada; Leonard S. Marks, Los Angeles, CA; Alexandre de la Taille, Cre´teil, France; William Ellis, Seattle, WA; Alan W. Partin, Baltimore, MD; Alexander Haese, Hamburg, Germany INTRODUCTION AND OBJECTIVES: We compared the performance characteristics of PSA, %fPSA, prostate volume (PV) and PCA3 as prostate cancer (PCa) risk factors at initial and repeat biopsy session and tested for novel PCA3 cut-offs.
Vol. 185, No. 4S, Supplement, Wednesday, May 18, 2011
METHODS: All 1606 patients underwent an extended initial or repeat biopsy. Indication was suspicious digital rectal examination (DRE) and/or persistently elevated age-specific total PSA cut-offs (2.56.5 ng/ml) and/or suspicious prior histology (ASAP/ ⱖ2 cores affected by HGPIN). PCA3 scores were assessed using the Progensa assay®. After stratification according to biopsy history [initial (IBX) vs. repeat (RBX)], a comparative analysis of all variables including calculation of sensitivity, specificity, positive and negative predictive value (PPV, NPV) such as proportion of avoided unnecessary repeat biopsies and avoided missed PCa compared to PSA at fixed sensitivity (80% and 90%) and specific (50% and 75%) thresholds were performed. Moreover, for each repeat biopsy scenario, comparisons of the area under the ROC- curve (AUC) were calculated. Finally novel cut-off threshold for IBX and RBX were developed using the Youdon-Index [sensitivity⫹ (specificity–1)] followed by graphical exploration. RESULTS: Overall, PCa was detected in 39.1% (n⫽628) of patients. Patients with PCa at the entire cohort presented a higher age, PSA and PCA3 score, suspicious DRE, and lower %fPSA and PV (all, p ⱕ 0.02). At IBX and a fixed sensitivity of 80%, specificity and PPV for PSA, %fPSA, PV and PCA3 was 27.3%, 33.7%, 37.2% and 54.4% and 48.6%, 49.1%, 52.2% and 59.7%, respectively. PCA3 was most informative in predicting PCa with an AUC of 0.74 and would have avoided 36.9% of unnecessary biopsies compared to PSA at 80%sensitivity. At IBX Youdon-Index (0.366) was highest for a PCA score of 29. At RBX and a fixed sensitivity of 80%, specificity and PPV for PSA, %fPSA, PV and PCA3 was 20.8%, 34.4%, 32.8% and 41.7% and 33.2%, 34.7%, 38.5% and 40.3%, respectively. PCA3 was most informative in predicting PCa with an AUC of 0.66 and would have avoided 26.4% of unnecessary biopsies compared to PSA at 80% sensitivity. At RBX Youdon-Index was highest for a PCA3 score of 29. CONCLUSIONS: Our findings demonstrate that PCA3 outperforming PSA, %fPSA and prostate volume in a head-to-head comparison and would have avoided up to 37% of unnecessary biopsies even at a high sensitivity (80%). Compared to the previously reported cut-off threshold of 35, our analyses revealed a lower vs. higher PCA3 cut-off at initial and repeat biopsy. Source of Funding: None
2321 COMPARATIVE ANALYSIS OF PROSTATE CANCER ANTIGEN 3 MRNA EXPRESSION IN BENIGN PERIPHERAL PROSTATIC TISSUE, CANCER AND ISOLATED OR CANCER-ASSOCIATED HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA M. Teresa Quiles, Maria Anto`nia Arbo´s, Ine´s M. de Torres, Carmen Bla´zquez, Juan M. Bastaro´s, Jose´ Placer, Andreas Doll, Jaume Revento´s, Juan Morote*, Barcelona, Spain INTRODUCTION AND OBJECTIVES: Prostate cancer antigen 3 (PCA3) score in urine after prostate-massage is a novel tool to increase prostate specific antigen (PSA) specificity especially in men with repeat prostate biopsy indication. Current data suggest a lower 1 efficacy of PCA3 score in men with HGPIN in the first biopsy . The objective of this study was to analyze the PCA3 gene expression in benign tissue (BT), cancer (CA) and HGPIN lesions (isolated: IHGPIN and cancer-associated: AHGPIN).
METHODS: Total mRNA was isolated and amplified from laserassisted microdissected foci of BT, CA and AHGPIN located in 15 radical prostatectomy frozen specimens and IHGPIN located in 13 radical cistoprostatectomy paraffin-embedded blocks from patients with bladder cancer. PCA3 mRNA amounts were measured by real-time qPCR (Sybr Green I chemistry). PCA3 mRNA amounts were normalized to two reference genes: small nucleolar RNA (SNORD) and Rho GTPase activating protein (ARHGAP). Target gene levels were determined using efficiency-corrected calibrator normalized relative quantification. Comparison among tissues was performed using non-parametric Friedman test followed by post-hoc Dunn’s multiple comparison test.
Vol. 185, No. 4S, Supplement, Wednesday, May 18, 2011
THE JOURNAL OF UROLOGY姞
e931
RESULTS: PCA3 mRNA expression was detected in 80% of BT samples, 86.7% of AHGPIN and 92.9% of CA tissues. PCA3 mean quantitative expression was 11.4 (p⫽0.009) and 20.7-fold increased (p⫽0.0002) in AHGPIN and CA related to BT samples. Qualitative PCA3 mRNA expression was detected in 61.5% of IHGPIN samples. CONCLUSIONS: We have demonstrated that PCA3 is not a specific gene of prostate cancer. PCA3 mRNA expression is significantly increased in cancer-associated HGPIN lesions as well as qualitatively expressed in isolated HGPIN lesions. After these findings and the previous clinical observation of a lower efficacy of PCA3 score in men with previous HGPIN1 we suggest that specific threshold of PCA3 score should be established in those men. 1. Morote et al. Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia. World J Urol. 2010 Jul 7. [Epub ahead of print] Source of Funding: Instituto de Salud Carlos III (FIS PI070536), Ministerio de Ciencia e Innovacio´n, Spain
2322 PCA3 VARIABILITY IN MEN WITH VERY LOW RISK PROSTATE CANCER Sergey Shikanov*, Gautam Jayram, Chicago, IL; Michael S. McGuire, Charles B. Brendler, Evanston, IL INTRODUCTION AND OBJECTIVES: Urinary PCA3 is considered a specific marker of prostate cancer tumor volume. We hypothesized that it will remain stable in patients with minimal disease without treatment. METHODS: 41 men with very low risk prostate cancer were enrolled in an IRB-approved active surveillance protocol. All men had clinical stage T1c, Gleason score 6, positive cores ⱕ3 and involvement of no positive core ⱖ50%. Urinary PCA3 was measured at enrollment and at 6 months. We assessed percent change ([enrollment PCA3– 6 months PCA3 /enrollment PCA3]x100%) and proportion of positive tests (PCA3 score ⬎35) at both time points. None of the patients had evidence of clinical progression during the observation period. RESULTS: Table 1 summarizes the cohort parameters. Median %PCA3 change was only 3%, and 46% of patients had positive PCA3 score both at enrollment and 6 months. However, compared to the enrollment PCA3 score, at 6 months the PCA3 score varied by more than 25% in 58% (n⫽24) and by more than 50% in 31% (n⫽13) of patients(Figure 1). When comparing PSA changes in the same population, PSA varied by more than 25% in only 41% (n⫽17) and by more than 50% in 7% (n⫽3) of patients. CONCLUSIONS: While urinary PCA3 scores on average change only slightly over 6 months in clinically stable men with very low risk prostate cancer, PCA3 scores vary significantly among individual patients. Given this variability, the usefulness of PCA3 in guiding treatment recommendations for the individual patient remains uncertain. Table 1. Cohort parameters, n⫽41 Positive cores 1
22 (54%)
2
15 (36%)
3
4 (10%)
Max. % of core involvement
5 (4 – 10)
Enrollment PCA3
31 (19 – 69)
6 month PCA3
34 (16 – 59)
% change PCA3 Enrollment PCA3 ⬎ 35
3 (⫺31 – 35) 19 (46%)
6 moths PCA3 ⬎ 35
19 (46%)
Enrollment PSA, ng/ml
4.2 (3.0 – 5.3)
6 months PSA, ng/ml
3.3 (2.9 – 5.5)
% change PSA 1 (⫺18 – 25) Continuous data presented as median (0.25– 0.75 quartile range), categorical data presented as count (% of total).
Source of Funding: Philanthropic Funds From NorthShore University Health System
2323 [-2]PROPSA PREDICTS BIOPSY RECLASSIFICATION IN MEN ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER Jeffrey Tosoian*, Sumit Isharwal, Zhaoyong Feng, Baltimore, MD; Danil Makarov, New Haven, CT; Patricia Landis, Robert Veltri, Bruce Trock, Jonathan Epstein, Alan Partin, Lori Sokoll, H.B. Carter, Stacy Loeb, Baltimore, MD INTRODUCTION AND OBJECTIVES: Previous studies have suggested an association between [-2]proPSA expression with prostate cancer risk and prognosis. Our objective was to examine the relationship between [-2]proPSA and disease progression among men enrolled in an active surveillance program. METHODS: In 167 men from our institutional active surveillance program, we used Cox proportional hazards models to examine the relationship between %[-2]proPSA ([-2]proPSA /fPSA) and annual surveillance biopsy results. The outcome of interest was disease reclassification based on biopsy (defined by Gleason score ⬎6, or ⬎2 positive biopsy cores, or ⬎50% involvement of any core with cancer). We also examined the association of biopsy results with %fPSA, [-2]proPSA/%fPSA, and the Beckman Coulter Prostate Health Index [phi⫽([-2]proPSA / fPSA) x (tPSA) (1/2)]. RESULTS: 63 (37.7%) men demonstrated disease reclassification at a median of 4.3 years from diagnosis, including 29 (17.4%) with reclassification based on upgrading to Gleason score ⬎6. Baseline and longitudinal %[-2]proPSA, %fPSA, [-2]proPSA/%fPSA, and phi measurements were significantly associated with disease reclassification. As shown in the table, a model including age, date and phi (baseline and longitudinal) had the greatest c-index for disease reclassification.