Michele Fascelli

Combined Biparametric Prostate Magnetic Resonance Imaging and Prostate-specific Antigen in the Detection of Prostate Cancer: A Validation Study in a Biopsy-naive Patient Population

OBJECTIVE To validate the use of biparametric (T2- and diffusion-weighted) magnetic resonance imaging (B-MRI) and prostate-specific antigen (PSA) or PSA density (PSAD) in a biopsy-naive cohort at risk for prostate cancer (PCa). METHODS All patients (n = 59) underwent PSA screening and digital rectal exam prior to a B-MRI followed by MRI or transrectal ultrasound fusion-guided targeted biopsy. Previously reported composite formulas incorporating screen positive lesions (SPL) on B-MRI and PSA or PSAD were developed to maximize PCa detection. For PSA, a patient was considered screen positive if PSA level + 6 × (the number of SPL) >14. For PSAD, screening was positive if PSAD × 14 + (the number of SPL) >4.25. These schemes were employed in this new test set to validate the initial formulas. Performance assessment of these formulas was determined for all cancer detection and for tumors with Gleason ≥3 + 4. RESULTS Screen positive lesions on B-MRI had the highest sensitivity (95.5%) and negative predictive value of 71.4% compared with PSA and PSAD. B-MRI significantly improved sensitivity (43.2-72.7%, P = .0002) when combined with PSAD. The negative predictive value of PSA increased with B-MRI, achieving 91.7% for B-MRI and PSA for Gleason ≥3 + 4. Overall accuracies of the composite equations were 81.4% (B-MRI and PSA) and 78.0% (B-MRI and PSAD). CONCLUSION Validation with a biopsy-naive cohort demonstrates the parameter SPL performed better than PSA or PSAD alone in accurately detecting PCa. The combined use of B-MRI, PSA, and PSAD resulted in improved accuracy for detecting clinically significant PCa.

Lymph Node Staging in Prostate Cancer

Nodal staging is important in prostate cancer treatment. While surgical lymph node dissection is the classic method of determining whether lymph nodes harbor malignancy, this is a very invasive technique. Current noninvasive approaches to identifying malignant lymph nodes are limited. Conventional imaging methods rely on size and morphology of lymph nodes and have notoriously low sensitivity for detecting malignant nodes. New imaging techniques such as targeted positron emission tomography (PET) imaging and magnetic resonance lymphography (MRL) with iron oxide particles are promising for nodal staging of prostate cancer. In this review, the strengths and limitations of imaging techniques for lymph node staging of prostate cancer are discussed.

The significance of anterior prostate lesions on multiparametric magnetic resonance imaging in African-American men

INTRODUCTION African-American (AA) men tend to harbor high-risk prostate cancer (PCa) and exhibit worse outcomes when compared to other groups. It has been postulated that AA men may harbor more anterior prostate lesions (APLs) that are undersampled by the standard transrectal ultrasound guided-biopsy (SBx), potentially resulting in greater degree of Gleason score (GS) upgrading at radical prostatectomy. We aimed to evaluate the detection rate of anterior PCa significance of APLs in AA men on multiparametric magnetic resonance imaging (mpMRI) and compare it to a matched cohort of White/Other (W/O) men. MATERIALS AND METHODS A review of 1,267 men who had an mpMRI with suspicious prostate lesions and who underwent magnetic resonance transrectal ultrasound fusion-guided biopsy (FBx) with concurrent SBx in the same biopsy session was performed. All AA men were matched to a control group of W/O using a 1:1 propensity score-matching algorithm with age, prostate-specific antigen, and prostate volume as matching variables. Logistic regression analysis was used to determine predictors of APLs in AA men. RESULTS Of the 195 AA men who underwent mpMRI, 93 (47.7%) men had a total of 109 APLs. Prior negative SBx was associated with the presence of APLs in AA men (Odds ratio = 1.81; 95% CI: 1.03-3.20; P = 0.04). On multivariate logistic regression analysis, smaller prostate (P = 0.001) and rising prostate-specific antigen (P = 0.007) were independent predictors of cancer-positive APLs in AA men. Comparative analysis of AA (93/195, 47.7%) vs. W/O (100/194, 52%) showed no difference in the rates of APLs (P = 0.44) or in cancer detection rate within those lesions or the distribution of GS within those cancers (P = 0.63) despite an overall higher cancer detection rate in AA men (AA: 124/195 [63.6%] vs. W/O: 97/194 [50.0%], P = 0.007). In cases where APLs were positive for PCa on FBx, the GS of APL was equal to the highest GS of the entire gland in 82.9% (29/35) and 90.9% (30/33) of the time in AA and W/O men, respectively. CONCLUSION Cancer-positive APLs represented the highest risk GS in most cases. AA men with prior negative SBx are twice as likely to harbor a concerning APL. In our cohort, AA and W/O men had comparable rates of APLs on mpMRI. Thus, differences in APLs do not explain the higher risk of AA men for deahth due to PCa. However, targeting of APLs via FBx can clinically improve PCa risk stratification and guide appropriate treatment options.

Reproducibility of Multiparametric Magnetic Resonance Imaging and Fusion Guided Prostate Biopsy: Multi-Institutional External Validation by a Propensity Score Matched Cohort

PURPOSE As the adoption of magnetic resonance imaging/ultrasound fusion guided biopsy expands, the reproducibility of outcomes at expert centers becomes essential. We sought to validate the comprehensive NCI (National Cancer Institute) experience with multiparametric magnetic resonance imaging and fusion guided biopsy in an external, independent, matched cohort of patients. MATERIALS AND METHODS We compared 620 patients enrolled in a prospective trial comparing systematic biopsy to fusion guided biopsy at NCI to 310 who underwent a similar procedure at Long Island Jewish Medical Center. The propensity score, defined as the probability of being treated outside NCI, was calculated using the estimated logistic regression model. Patients from the hospital were matched 1:1 for age, prostate specific antigen, magnetic resonance imaging suspicion score and prior negative biopsies. Clinically significant disease was defined as Gleason 3 + 4 or greater. RESULTS Before matching we found differences between the cohorts in age, magnetic resonance imaging suspicion score (each p <0.001), the number of patients with prior negative biopsies (p = 0.01), and the overall cancer detection rate and the cancer detection rate by fusion guided biopsy (each p <0.001). No difference was found in the rates of upgrading by fusion guided biopsy (p = 0.28) or upgrading to clinically significant disease (p = 0.95). A statistically significant difference remained in the overall cancer detection rate and the rate by fusion guided biopsy after matching. On subgroup analysis we found a difference in the overall cancer detection rate and the rate by fusion guided biopsy (p <0.001 and 0.003) in patients with prior negative systematic biopsy but no difference in the 2 rates (p = 0.39 and 0.51, respectively) in biopsy naïve patients. CONCLUSIONS Improved detection of clinically significant cancer by magnetic resonance imaging and fusion guided biopsy is reproducible by an experienced multidisciplinary team consisting of dedicated radiologists and urologists.

Preoperative multiparametric magnetic resonance imaging predicts biochemical recurrence in prostate cancer after radical prostatectomy

Objectives To evaluate the utility of preoperative multiparametric magnetic resonance imaging (MP-MRI) in predicting biochemical recurrence (BCR) following radical prostatectomy (RP). Materials/Methods From March 2007 to January 2015, 421 consecutive patients with prostate cancer (PCa) underwent preoperative MP-MRI and RP. BCR-free survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to identify clinical and imaging variables predictive of BCR. Logistic regression was performed to generate a nomogram to predict three-year BCR probability. Results Of the total cohort, 370 patients met inclusion criteria with 39 (10.5%) patients experiencing BCR. On multivariate analysis, preoperative prostate-specific antigen (PSA) (p = 0.01), biopsy Gleason score (p = 0.0008), MP-MRI suspicion score (p = 0.03), and extracapsular extension on MP-MRI (p = 0.03) were significantly associated with time to BCR. A nomogram integrating these factors to predict BCR at three years after RP demonstrated a c-index of 0.84, outperforming the predictive value of Gleason score and PSA alone (c-index 0.74, p = 0.02). Conclusion The addition of MP-MRI to standard clinical factors significantly improves prediction of BCR in a post-prostatectomy PCa cohort. This could serve as a valuable tool to support clinical decision-making in patients with moderate and high-risk cancers.

Should Hypoechoic Lesions on Transrectal Ultrasound Be Sampled During Magnetic Resonance Imaging-targeted Prostate Biopsy?

OBJECTIVE To determine whether supplemental biopsy of hypoechoic ultrasound lesions (HUL) incidentally found during magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion-targeted prostate biopsy results in improved prostate cancer (PCa) detection. METHODS Patients underwent MRI-TRUS-targeted biopsy as part of an ongoing prospective trial from August 2007 to February 2015. For men with HUL, the biopsy pathology of HUL and MRI lesions was classified according to the updated 2014 International Society of Urological Pathology (ISUP) grading system. The detection of PCa by MRI-targeted biopsy with and without HUL biopsy was compared. RESULTS Of 1260 men in the trial, 106 underwent biopsy of 119 HULs. PCa was diagnosed in 52 out of 106 men (49%) by biopsy of either MRI lesions or HUL. Biopsy of HUL in addition to MRI lesions resulted in 4 additional diagnoses of high-grade (ISUP grades 3-5) PCa versus biopsy of MRI lesions alone (20 vs 16 men, P = .046). Three of these cases were upgraded from lower grade (ISUP grades 1-2) PCa on MRI-guided biopsy alone, and only 1 case (1% of cohort) was diagnosed that would have been missed by MRI-guided biopsy alone. Supplemental biopsy of HUL did not change the PCa risk category in 96% (102 out of 106) of men with HUL. CONCLUSION Supplemental biopsy of HUL yields a small increase in the detection of higher grade PCa as compared with biopsy of MRI lesions alone. As upgrading is rare, routinely screening for HUL during MRI-targeted biopsy remains controversial.

The prostate cancer prevention trial risk calculator 2.0 performs equally for standard biopsy and MRI/US fusion-guided biopsy

Background:The Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC) is a widely used risk-based calculator used to assess a man’s risk of prostate cancer (PCa) before biopsy. This risk calculator was created from data of a patient cohort undergoing a 6-core sextant biopsy, and subsequently validated in men undergoing 12-core systematic biopsy (SBx). The accuracy of the PCPTRC has not been studied in patients undergoing magnetic resonance imaging/ultrasound (MRI/US) fusion-guided biopsy (FBx). We sought to assess the performance of the PCPTRC for straitifying PCa risk in a FBx cohort.Methods:A review of a prospective cohort undergoing MRI and FBx/SBx was conducted. Data from consecutive FBx/SBx were collected between August 2007 and February 2014, and PCPTRC scores using the PCPTRC2.0R-code were calculated. The risk of positive biopsy and high-grade cancer (Gleason ⩾7) on biopsy was calculated and compared with overall and high-grade cancer detection rates (CDRs). Receiver operating characteristic curves were generated and the areas under the curves (AUCs) were compared using DeLong’s test.Results:Of 595 men included in the study, PCa was detected in 39% (232) by SBx compared with 48% (287) on combined FBx/SBx biopsy. The PCPTRC AUCs for the CDR were similar (P=0.70) for SBx (0.69) and combined biopsy (0.70). For high-grade disease, AUCs for SBx (0.71) and combined biopsy (0.70) were slightly higher, but were not statistically different (P=0.55).Conclusions:In an MRI-screened population of men undergoing FBx, PCPTRC continues to represent a practical method of accurately stratifying PCa risk.

MP04-13 VALIDATION OF THE PROSTATE CANCER PREVENTION TRIAL RISK CALCULATOR 2.0 IN MULTIPARAMETRIC MRI ERA

INTRODUCTION AND OBJECTIVES: The Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC2.0) represents a widely used tool developed to identify men for PSA testing or prostate biopsy. PCPTRC2.0 has been assessed in previous trials with traditional methodologies for identifying prostate cancer (PCa). The accuracy of the PCPTRC2.0 in correctly identifying patients at risk for PCa has been called into question, particularly in patients undergoing MRI/US fusion prostate biopsies. We aim to assess the accuracy of the PCPTRC2.0 estimation in identifying PCa in an MRI-US fusion biopsy cohort. METHODS: A review of men studied prospectively with MRI/ US fusion biopsy was conducted. Between August 2007 and February 2014, 595 MRI/US fusion prostate biopsies were selected. Patients0 complete data was used to calculate their PCPTRC2.0 scores using the PCPTRC2.0 R-code. Risk of positive biopsy and high-grade (Gleason 7) cancer on biopsy was calculated for each patient. Receiver operating characteristic (ROC) curves were analyzed and areas under the curve (AUC) were compared using DeLong0s test. RESULTS: Of 595 men included in the study, cancer was detected in 39% (232) by systematic biopsy compared to 48% (287) on MRI-targeted biopsy alone. Median age was 62.3 years with a mean PSA of 12.0. The AUCs for overall cancer detection rate (CDR) were similar at 0.69 and 0.70 for systematic and MRI-targeted biopsy, respectively (p1⁄40.69) [Figure 1a]. For high-grade disease according to the PCPTRC2.0 calculator, AUCs increased to 0.71 and 0.73 for systematic and MRI-targeted biopsy, but remained not statistically different (p1⁄40.54) [Figure 1b]. CONCLUSIONS: PCPTRC2.0 represents a valid prostate cancer prediction tool in men undergoing multiparametric MRI and fusion-guided prostate biopsy. Source of Funding: None.

Multiparametric MRI (mpMRI): Guided Focal Therapy

Approximately one in seven men will be diagnosed with prostate cancer during his lifetime. PSA screening has been blamed for increased rates of cancer detection, leading to subsequent overtreatment of disease. Overuse of definitive therapy has produced significant burdens, including excess costs, increasing patient morbidities, and decreased quality of life. Thus, there has been an increasing interest in minimally invasive focal therapies to treat prostate cancer. Advances in image-guided therapy have begun to emerge—utilizing the accurate tumor localization and improved disease staging of multiparametric MRI (mpMRI). MpMRI-guided therapies can potentially achieve equivalent oncologic efficacy to traditional whole gland therapies such as surgery and radiation, while avoiding the side effects of conventional treatment. The purpose of this chapter is to review briefly the basis of various focal therapy techniques such as cryotherapy, high intensity focused ultrasound, and laser interstitial therapy, and to discuss the results of recent clinical trials that demonstrate early outcomes in patients with prostate cancer treated with these methods.

Multi-institutional evaluation of multiparametric MRI and fusion-guided prostate biopsy in a biopsy-naive population.

60 Background: Multiparametric MRI (mpMRI) and fusion biopsy (FB) has proven beneficial in men with a prior negative systematic biopsy (SB) or diagnosis of prostate cancer (CaP). The aim of the study was to evaluate mpMRI and FB in a biopsy-naive population. Methods: A multi-institutional review was performed on patients with no prior biopsy history who underwent mpMRI followed by concurrent FB and SB. Imaging protocol was standardized across institutions. Gleason score (GS) distribution/risk classifications were recorded. Univariate analysis was performed to compare FB versus SB. Results: A total of 361 biopsy-naive men were identified from 4 institutions. GS distribution/risk classification for FB and SB are presented in the table. Overall cancer detection rate (CDR) was 65.4%. In biopsy-naive men, FB detected a greater absolute number of high grade disease with 13% more high risk CaP than SB (78 vs 69). Additionally, FB detected 21% fewer cases of GS 6 CaP (57 vs 69). The CDR for FB alone was 57.3% wit...