Original Article
Multiparametric Magnetic Resonance Imaging Outperforms the Prostate Cancer Prevention Trial Risk Calculator in Predicting Clinically Significant Prostate Cancer Simpa S. Salami, MD, MPH1; Manish A. Vira, MD1; Baris Turkbey, MD3; Mathew Fakhoury, BS1; Oksana Yaskiv, MD3; Robert Villani, MD4; Eran Ben-Levi, MD4; and Ardeshir R. Rastinehad, DO1,4
BACKGROUND: The Prostate Cancer Prevention Trial risk calculator for high-grade (PCPTHG) prostate cancer (CaP) was developed to improve the detection of clinically significant CaP. In this study, the authors compared the performance of the PCPTHG against multiparametric magnetic resonance imaging (MP-MRI) in predicting men at risk of CaP. METHODS: Men with an abnormal prostatespecific antigen (PSA) level or digital rectal examination (DRE) and a suspicious lesion on a 3-Tesla MP-MRI were enrolled prospectively. Three radiologists reviewed and graded all lesions on a 5-point Likert scale. Biopsy of suspicious lesion(s) was performed using a proprietary MRI/transrectal ultrasound fusion-guided prostate biopsy system, after which 12-core biopsy was performed. A genitourinary pathologist reviewed all pathology slides. The performance of PCPTHG was compared with that of MP-MRI in predicting clinically significant CaP. RESULTS: Of 175 men who were eligible for analysis, 64.6% (113 of 175 men) were diagnosed with CaP, including 93 of 113 men (82.3%) who had clinically significant disease. Age, abnormal DRE, PSA, PSA density, prostate size, extraprostatic extension on MRI, apparent diffusion coefficient value, and MRI lesion size were identified as significant predictors of high-grade CaP (all P 4 ng/mL) underwent MPMRI of the prostate. This was performed with a 3-Tesla Verio MRI (Siemens, Munich, Germany), a 16-channel cardiac coil (Sense; InVivo, Gainesville, Fla) placed on the anterior pelvis, and an endorectal coil (ERC) (BPX-30; Cancer
September 15, 2014
Medrad, Pittsburg, Pa) filled with PFC-770 (3M Corporation, St. Paul, Minn). The MRI sequences obtained included triplanar, T2-weighted (T2W), axial diffusionweighted imaging with apparent diffusion coefficient (ADC) mapping (with b values of 0, 500, 1000, 1500, and 2000) and dynamic contrast-enhanced MRI sequences (scan time, 26 minutes) (for MRI parameters, see online supporting information). Three radiologists (A.R.R., E.B.-L., and R.V.) reviewed all images and graded all lesions that were suspicious for CaP on a 5point Likert scale using the European Society of Urogenital Radiology guidelines,12 and the anatomic location of lesions was reported as defined by the National Institutes of Health prostate zones (Fig. 2). MR spectroscopy was not performed because of its cost, extra imaging time, and relatively poor sensitivity.9 Men who had suspicious lesion(s) on MP-MRI and were referred by their primary urologists for study evaluation were then consented and enrolled onto the trial. Exclusion criteria for these analyses included a previous history of CaP, radiation to the pelvis, and inability to tolerate prostate biopsy under local anesthesia or mild sedation. Demographic and clinical information, including age, race, biopsy history, family history of CaP, DRE 2877
Original Article
Figure 2. This is a pictorial representation of the National Institutes of Health prostate zones for reporting the anatomic location of lesions and the 5-point Likert scale (European Society of Urogenital Radiology [ESUR] guidelines) for classifying the overall suspicion level of prostate lesions (a indicates anterior; p, posterior; m, medial; L, lateral).
findings, serum PSA, and prior prostate imaging studies, were prospectively collected before patients underwent protocol prostate biopsy. Biopsy of suspicious prostate lesion(s) was performed using the UroNav MRI/TRUS fusion guided-prostate biopsy system (InVivo) to obtain 2 cores: 1 each in the axial and sagittal planes. A standard, 12-core, TRUS-guided prostate biopsy was then performed with the urologist now blinded to the location of the lesions by turning off the UroNav workstation (InVivo), where the MR images were processed. A genitourinary pathologist (O.Y.) reviewed all pathology slides. Statistical Analyses
Measures of central tendency and dispersion were used to describe demographics and participant characteristics, including age, race, PSA, DRE, family history, number of previous negative biopsies, and prostate MP-MRI results. For this analysis, a participant was classified as having cancer if either the MRI/TRUS fusion-guided biopsy or the standard 12-core biopsy was positive or if both were positive. Because this was a comparison with results from the PCPT, high-grade CaP was defined as a Gleason score 7, which was used in the development of the PCPTHG.7 However, exploratory analyses were performed using the Epstein criteria for clinically significant CaP.13 For 12-core biopsies, clinically significant CaP included a Gleason score 7 or a Gleason score of 6 with >2 cores and/or >50% of any core (no fusion biopsy cores were included in this classification). For fusion biopsies, clinically significant CaP included a Gleason score 7 and a Gleason score of 6 with a lesion volume >0.2 cm3 based on the Epstein criteria, which were developed 2878
using wholemount prostatectomy specimens. When both the MRI/TRUS fusion-guided biopsy and the standard 12-core biopsy were positive, the participant was assigned the higher risk classification. Comparisons between men diagnosed with high-grade CaP and those without CaP or with low-grade CaP were performed using the Fisher exact test for categorical variables and the Kruskal-Wallis test for continuous variables. We calculated the predicted risk of high-grade CaP using the PCPTHG (variables: age, PSA [ng/mL], African origin [yes vs no], DRE [normal vs suspicious], and history of prior negative biopsy [yes vs no]).6 Calibration was evaluated by comparing the observed proportions of high-grade CaP with the PCPTHG-predicted risks by deciles of risk. Receiver operating characteristic curves and corresponding AUCs were calculated to evaluate the discrimination of the PCPTHG. A cutoff for biopsy of 15%, as proposed by Nam et al14 as a decision point for biopsy, was evaluated, and its sensitivity and specificity were reported. Next, we compared the performance of the PCPTHG with that of MP-MRI in predicting clinically significant CaP (defined according to Gleason score and the Epstein criteria). Analyses were performed using the SAS statistical software package (version 9.3; SAS Institute Inc., Cary, NC), and 2-sided P values were reported. RESULTS Of the 51.7% (401 of 775) of men who had a suspicious lesion identified on MP-MRI during the study period, 175 men who met the inclusion criteria and consented to participate in the study were included in these analyses (Fig. 1). Nearly all 151 patients who were not referred for study evaluation were from urologists in private practices with the capability of performing fusion or cognitive biopsies. Demographic and clinical information about the cohort is provided in Table 1. The overall cancer detection rate (CDR) was 64.6% (113 of 175 men), and 47.4% (83 of 175 men) had high-grade CaP (Gleason 7). Eighty-two percent (93 of 113 men) of those diagnosed with CaP had clinically significant disease as defined by the Epstein criteria. The cohort included 113 men with a history of a previous negative biopsy and 62 men with no previous biopsy. The CDRs for these 2 cohorts were 64.6% (73 of 113 men) and 64.5% (40 of 62 men), respectively (P 5 .992). Men who were diagnosed with Gleason 7 CaP were more likely to be older and to have an abnormal DRE, elevated serum PSA, higher PSA density, smaller prostate size, extraprostatic extension on MRI, a lower ADC value, and a larger Cancer
September 15, 2014
MRI Outperforms the PCPT Risk Calculator/Salami et al
TABLE 1. Univariate Analyses of Variables Predicting High-Grade Prostate Cancer on Biopsy in the Cohort of 175 Men No. of Patients (%) or Median [IQR]a Variable Age, y African American Family history of CaP Abnormal DRE No. of previous biopsies PSA, ng/mL PSAD, ng/mL/cm3 MRI prostate volume, cm3 MRI lesion volume, cm3 ADC value of lesions, 31026 3 mm2/s EPE on MRI
Gleason 7, n 5 83
No CaP & Gleason
Multiparametric Magnetic Resonance Imaging Outperforms the Prostate Cancer Prevention Trial Risk Calculator in Predicting Clinically Significant Prostate Cancer Simpa S. Salami, MD, MPH1; Manish A. Vira, MD1; Baris Turkbey, MD3; Mathew Fakhoury, BS1; Oksana Yaskiv, MD3; Robert Villani, MD4; Eran Ben-Levi, MD4; and Ardeshir R. Rastinehad, DO1,4
BACKGROUND: The Prostate Cancer Prevention Trial risk calculator for high-grade (PCPTHG) prostate cancer (CaP) was developed to improve the detection of clinically significant CaP. In this study, the authors compared the performance of the PCPTHG against multiparametric magnetic resonance imaging (MP-MRI) in predicting men at risk of CaP. METHODS: Men with an abnormal prostatespecific antigen (PSA) level or digital rectal examination (DRE) and a suspicious lesion on a 3-Tesla MP-MRI were enrolled prospectively. Three radiologists reviewed and graded all lesions on a 5-point Likert scale. Biopsy of suspicious lesion(s) was performed using a proprietary MRI/transrectal ultrasound fusion-guided prostate biopsy system, after which 12-core biopsy was performed. A genitourinary pathologist reviewed all pathology slides. The performance of PCPTHG was compared with that of MP-MRI in predicting clinically significant CaP. RESULTS: Of 175 men who were eligible for analysis, 64.6% (113 of 175 men) were diagnosed with CaP, including 93 of 113 men (82.3%) who had clinically significant disease. Age, abnormal DRE, PSA, PSA density, prostate size, extraprostatic extension on MRI, apparent diffusion coefficient value, and MRI lesion size were identified as significant predictors of high-grade CaP (all P 4 ng/mL) underwent MPMRI of the prostate. This was performed with a 3-Tesla Verio MRI (Siemens, Munich, Germany), a 16-channel cardiac coil (Sense; InVivo, Gainesville, Fla) placed on the anterior pelvis, and an endorectal coil (ERC) (BPX-30; Cancer
September 15, 2014
Medrad, Pittsburg, Pa) filled with PFC-770 (3M Corporation, St. Paul, Minn). The MRI sequences obtained included triplanar, T2-weighted (T2W), axial diffusionweighted imaging with apparent diffusion coefficient (ADC) mapping (with b values of 0, 500, 1000, 1500, and 2000) and dynamic contrast-enhanced MRI sequences (scan time, 26 minutes) (for MRI parameters, see online supporting information). Three radiologists (A.R.R., E.B.-L., and R.V.) reviewed all images and graded all lesions that were suspicious for CaP on a 5point Likert scale using the European Society of Urogenital Radiology guidelines,12 and the anatomic location of lesions was reported as defined by the National Institutes of Health prostate zones (Fig. 2). MR spectroscopy was not performed because of its cost, extra imaging time, and relatively poor sensitivity.9 Men who had suspicious lesion(s) on MP-MRI and were referred by their primary urologists for study evaluation were then consented and enrolled onto the trial. Exclusion criteria for these analyses included a previous history of CaP, radiation to the pelvis, and inability to tolerate prostate biopsy under local anesthesia or mild sedation. Demographic and clinical information, including age, race, biopsy history, family history of CaP, DRE 2877
Original Article
Figure 2. This is a pictorial representation of the National Institutes of Health prostate zones for reporting the anatomic location of lesions and the 5-point Likert scale (European Society of Urogenital Radiology [ESUR] guidelines) for classifying the overall suspicion level of prostate lesions (a indicates anterior; p, posterior; m, medial; L, lateral).
findings, serum PSA, and prior prostate imaging studies, were prospectively collected before patients underwent protocol prostate biopsy. Biopsy of suspicious prostate lesion(s) was performed using the UroNav MRI/TRUS fusion guided-prostate biopsy system (InVivo) to obtain 2 cores: 1 each in the axial and sagittal planes. A standard, 12-core, TRUS-guided prostate biopsy was then performed with the urologist now blinded to the location of the lesions by turning off the UroNav workstation (InVivo), where the MR images were processed. A genitourinary pathologist (O.Y.) reviewed all pathology slides. Statistical Analyses
Measures of central tendency and dispersion were used to describe demographics and participant characteristics, including age, race, PSA, DRE, family history, number of previous negative biopsies, and prostate MP-MRI results. For this analysis, a participant was classified as having cancer if either the MRI/TRUS fusion-guided biopsy or the standard 12-core biopsy was positive or if both were positive. Because this was a comparison with results from the PCPT, high-grade CaP was defined as a Gleason score 7, which was used in the development of the PCPTHG.7 However, exploratory analyses were performed using the Epstein criteria for clinically significant CaP.13 For 12-core biopsies, clinically significant CaP included a Gleason score 7 or a Gleason score of 6 with >2 cores and/or >50% of any core (no fusion biopsy cores were included in this classification). For fusion biopsies, clinically significant CaP included a Gleason score 7 and a Gleason score of 6 with a lesion volume >0.2 cm3 based on the Epstein criteria, which were developed 2878
using wholemount prostatectomy specimens. When both the MRI/TRUS fusion-guided biopsy and the standard 12-core biopsy were positive, the participant was assigned the higher risk classification. Comparisons between men diagnosed with high-grade CaP and those without CaP or with low-grade CaP were performed using the Fisher exact test for categorical variables and the Kruskal-Wallis test for continuous variables. We calculated the predicted risk of high-grade CaP using the PCPTHG (variables: age, PSA [ng/mL], African origin [yes vs no], DRE [normal vs suspicious], and history of prior negative biopsy [yes vs no]).6 Calibration was evaluated by comparing the observed proportions of high-grade CaP with the PCPTHG-predicted risks by deciles of risk. Receiver operating characteristic curves and corresponding AUCs were calculated to evaluate the discrimination of the PCPTHG. A cutoff for biopsy of 15%, as proposed by Nam et al14 as a decision point for biopsy, was evaluated, and its sensitivity and specificity were reported. Next, we compared the performance of the PCPTHG with that of MP-MRI in predicting clinically significant CaP (defined according to Gleason score and the Epstein criteria). Analyses were performed using the SAS statistical software package (version 9.3; SAS Institute Inc., Cary, NC), and 2-sided P values were reported. RESULTS Of the 51.7% (401 of 775) of men who had a suspicious lesion identified on MP-MRI during the study period, 175 men who met the inclusion criteria and consented to participate in the study were included in these analyses (Fig. 1). Nearly all 151 patients who were not referred for study evaluation were from urologists in private practices with the capability of performing fusion or cognitive biopsies. Demographic and clinical information about the cohort is provided in Table 1. The overall cancer detection rate (CDR) was 64.6% (113 of 175 men), and 47.4% (83 of 175 men) had high-grade CaP (Gleason 7). Eighty-two percent (93 of 113 men) of those diagnosed with CaP had clinically significant disease as defined by the Epstein criteria. The cohort included 113 men with a history of a previous negative biopsy and 62 men with no previous biopsy. The CDRs for these 2 cohorts were 64.6% (73 of 113 men) and 64.5% (40 of 62 men), respectively (P 5 .992). Men who were diagnosed with Gleason 7 CaP were more likely to be older and to have an abnormal DRE, elevated serum PSA, higher PSA density, smaller prostate size, extraprostatic extension on MRI, a lower ADC value, and a larger Cancer
September 15, 2014
MRI Outperforms the PCPT Risk Calculator/Salami et al
TABLE 1. Univariate Analyses of Variables Predicting High-Grade Prostate Cancer on Biopsy in the Cohort of 175 Men No. of Patients (%) or Median [IQR]a Variable Age, y African American Family history of CaP Abnormal DRE No. of previous biopsies PSA, ng/mL PSAD, ng/mL/cm3 MRI prostate volume, cm3 MRI lesion volume, cm3 ADC value of lesions, 31026 3 mm2/s EPE on MRI
Gleason 7, n 5 83
No CaP & Gleason
