Dima Raskolnikov

Use of serial multiparametric magnetic resonance imaging in the management of patients with prostate cancer on active surveillance

INTRODUCTION We evaluated the performance of multiparametric prostate magnetic resonance imaging (mp-MRI) and MRI/transrectal ultrasound (TRUS) fusion-guided biopsy (FB) for monitoring patients with prostate cancer on active surveillance (AS). MATERIALS AND METHODS Patients undergoing mp-MRI and FB of target lesions identified on mp-MRI between August 2007 and August 2014 were reviewed. Patients meeting AS criteria (Clinical stage T1c, Gleason grade ≤ 6, prostate-specific antigen density ≤ 0.15, tumor involving ≤ 2 cores, and ≤ 50% involvement of any single core) based on extended sextant 12-core TRUS biopsy (systematic biopsy [SB]) were included. They were followed with subsequent 12-core biopsy as well as mp-MRI and MRI/TRUS fusion biopsy at follow-up visits until Gleason score progression (Gleason ≥ 7 in either 12-core or MRI/TRUS fusion biopsy). We evaluated whether progression seen on mp-MRI (defined as an increase in suspicion level, largest lesion diameter, or number of lesions) was predictive of Gleason score progression. RESULTS Of 152 patients meeting AS criteria on initial SB (mean age of 61.4 years and mean prostate-specific antigen level of 5.26 ng/ml), 34 (22.4%) had Gleason score ≥ 7 on confirmatory SB/FB. Of the 118 remaining patients, 58 chose AS and had at least 1 subsequent mp-MRI with SB/FB (median follow-up = 16.1 months). Gleason progression was subsequently documented in 17 (29%) of these men, in all cases to Gleason 3+4. The positive predictive value and negative predictive value of mp-MRI for Gleason progression was 53% (95% CI: 28%-77%) and 80% (95% CI: 65%-91%), respectively. The sensitivity and specificity of mp-MRI for increase in Gleason were also 53% and 80%, respectively. The number needed to biopsy to detect 1 Gleason progression was 8.74 for SB vs. 2.9 for FB. CONCLUSIONS Stable findings on mp-MRI are associated with Gleason score stability. mp-MRI appears promising as a useful aid for reducing the number of biopsies in the management of patients on AS. A prospective evaluation of mp-MRI as a screen to reduce biopsies in the follow-up of men on AS appears warranted.

Multiparametric Magnetic Resonance Imaging and Image-Guided Biopsy to Detect Seminal Vesicle Invasion by Prostate Cancer

OBJECTIVES To evaluate the correlation between multiparametric prostate MRI (MP-MRI) suspicion for seminal vesicle invasion (SVI) by prostate cancer (PCa) and pathology on MRI/ultrasound (US) fusion-guided biopsy. PATIENTS AND METHODS From March 2007 to June 2013, 822 patients underwent MP-MRI at 3 Tesla and MRI/US fusion-guided biopsy. Of these, 25 patients underwent targeted biopsy of the seminal vesicles (SVs). In six patients, bilateral SVI was suspected, resulting in 31 samples. MP-MRI findings that triggered these SV biopsies were scored as low, moderate, or high suspicion for SVI based on the degree of involvement on MRI. Correlative prostate biopsy and radical prostatectomy (RP) pathology were reviewed by a single genitourinary pathologist. RESULTS At the time of MP-MRI, the median age was 64 years with a median prostate-specific antigen of 10.74 ng/mL. Of the 31 SV lesions identified, MP-MRI suspicion scores of low, moderate, and high were assigned to 3, 19, and 9 lesions, respectively. MRI/US fusion-guided biopsy detected SVI in 20/31 (65%) of cases. For the four patients who underwent RP after a preoperative assessment of SVI, biopsy pathology and RP pathology were concordant in all cases. CONCLUSIONS As this technology becomes more available, MP-MRI and MRI/US fusion-guided biopsy may play a role in the preoperative staging for PCa. Future work will determine if improved preoperative staging leads to better surgical outcomes.

The Role of Magnetic Resonance Image Guided Prostate Biopsy in Stratifying Men for Risk of Extracapsular Extension at Radical Prostatectomy

PURPOSE Magnetic resonance imaging detects extracapsular extension by prostate cancer with excellent specificity but low sensitivity. This limits surgical planning, which could be modified to account for focal extracapsular extension with image directed guidance for wider excision. In this study we evaluate the performance of multiparametric magnetic resonance imaging in extracapsular extension detection and determine which preoperative variables predict extracapsular extension on final pathology when multiparametric magnetic resonance imaging predicts organ confined disease. MATERIALS AND METHODS From May 2007 to March 2014, 169 patients underwent pre-biopsy multiparametric magnetic resonance imaging, magnetic resonance imaging/transrectal ultrasound fusion guided biopsy, extended sextant 12-core biopsy and radical prostatectomy at our institution. A subset of 116 men had multiparametric magnetic resonance imaging negative for extracapsular extension and were included in the final analysis. RESULTS The 116 men with multiparametric magnetic resonance imaging negative for extracapsular extension had a median age of 61 years (IQR 57-66) and a median prostate specific antigen of 5.51 ng/ml (IQR 3.91-9.07). The prevalence of extracapsular extension was 23.1% in the overall population. Sensitivity, specificity, and positive and negative predictive values of multiparametric magnetic resonance imaging for extracapsular extension were 48.7%, 73.9%, 35.9% and 82.8%, respectively. On multivariate regression analysis only patient age (p=0.002) and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy Gleason score (p=0.032) were independent predictors of extracapsular extension on final radical prostatectomy pathology. CONCLUSIONS Because of the low sensitivity of multiparametric magnetic resonance imaging for extracapsular extension, further tools are necessary to stratify men at risk for occult extracapsular extension that would otherwise only become apparent on final pathology. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy Gleason score can help identify which men with prostate cancer have extracapsular extension that may not be detectable by imaging.

Magnetic Resonance Imaging/Transrectal Ultrasonography Fusion Prostate Biopsy Significantly Outperforms Systematic 12-Core Biopsy for Prediction of Total Magnetic Resonance Imaging Tumor Volume in Active Surveillance Patients.

OBJECTIVE To correlate the highest percentage core involvement (HPCI) and corresponding tumor length (CTL) on systematic 12-core biopsy (SBx) and targeted magnetic resonance imaging/transrectal ultrasonography (MRI/TRUS) fusion biopsy (TBx), with total MRI prostate cancer (PCa) tumor volume (TV). PATIENTS AND METHODS Fifty patients meeting criteria for active surveillance (AS) based on outside SBx, who underwent 3.0T multiparametric prostate MRI (MP-MRI), followed by SBx and TBx during the same session at our institution were examined. PCa TVs were calculated using MP-MRI and then correlated using bivariate analysis with the HPCI and CTL for SBx and TBx. RESULTS For TBx, HPCI and CTL showed a positive correlation (R(2)=0.31, P<0.0001 and R(2)=0.37, P<0.0001, respectively) with total MRI PCa TV, whereas for SBx, these parameters showed a poor correlation (R(2)=0.00006, P=0.96 and R(2)=0.0004, P=0.89, respectively). For detection of patients with clinically significant MRI derived tumor burden greater than 500 mm(3), SBx was 25% sensitive, 90.9% specific (falsely elevated because of missed tumors and extremely low sensitivity), and 54% accurate in comparison with TBx, which was 53.6% sensitive, 86.4% specific, and 68% accurate. CONCLUSIONS HPCI and CTL on TBx positively correlates with total MRI PCa TV, whereas there was no correlation seen with SBx. TBx is superior to SBx for detecting tumor burden greater than 500 mm(3). When using biopsy positive MRI derived TVs, TBx better reflects overall disease burden, improving risk stratification among candidates for active surveillance.

The Role of Image Guided Biopsy Targeting in Patients with Atypical Small Acinar Proliferation

PURPOSE Men diagnosed with atypical small acinar proliferation are counseled to undergo early rebiopsy because the risk of prostate cancer is high. However, random rebiopsies may not resample areas of concern. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy offers an opportunity to accurately target and later retarget specific areas in the prostate. We describe the ability of magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy to detect prostate cancer in areas with an initial diagnosis of atypical small acinar proliferation. MATERIALS AND METHODS Multiparametric magnetic resonance imaging of the prostate and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy were performed in 1,028 patients from March 2007 to February 2014. Of the men 20 met the stringent study inclusion criteria, which were no prostate cancer history, index biopsy showing at least 1 core of atypical small acinar proliferation with benign glands in all remaining cores and fusion targeted rebiopsy with at least 1 targeted core directly resampling an area of the prostate that previously contained atypical small acinar proliferation. RESULTS At index biopsy median age of the 20 patients was 60 years (IQR 57-64) and median prostate specific antigen was 5.92 ng/ml (IQR 3.34-7.48). At fusion targeted rebiopsy at a median of 11.6 months 5 of 20 patients (25%, 95% CI 6.02-43.98) were diagnosed with primary Gleason grade 3, low volume prostate cancer. On fusion rebiopsy cores that directly retargeted areas of previous atypical small acinar proliferation detected the highest tumor burden. CONCLUSIONS When magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detects isolated atypical small acinar proliferation on index biopsy, early rebiopsy is unlikely to detect clinically significant prostate cancer. Cores that retarget areas of previous atypical small acinar proliferation are more effective than random rebiopsy cores.

Current Ability of Multiparametric Prostate Magnetic Resonance Imaging and Targeted Biopsy to Improve the Detection of Prostate Cancer

Introduction: Recent advancements in imaging technology have significantly increased the diagnostic accuracy of magnetic resonance imaging for prostate cancer. However, tissue diagnosis and grading remain the gold standard for diagnosis and prognostication. Because transrectal ultrasound guided prostate biopsy performs poorly, extensive research has been conducted into biopsy techniques that are guided by magnetic resonance imaging, including direct in‐bore, cognitive fusion and magnetic resonance imaging/ultrasound fusion guided biopsies. Methods: The PubMed® database was searched from inception until January 15, 2014 for criteria pertaining to targeted prostate biopsy. Results: Initial studies of the 3 types of targeted prostate biopsy yielded similar results. Most importantly, targeted biopsy detects a greater amount of clinically significant prostate cancer than does transrectal ultrasound guided biopsy. Magnetic resonance imaging/ultrasound fusion guided biopsy has generated the most interest, as it is an office based procedure that does not require a significant change from the current workflow of transrectal prostate biopsy. These techniques hold great promise in the areas of patient selection for definitive treatment, appropriate screening, active surveillance and focal therapy for prostate cancer. Conclusions: Targeted prostate biopsy has the potential to significantly improve the way patients are screened, treated and monitored in the setting of prostate cancer. These techniques allow for an individualized approach to each patient, which is a substantial improvement over the current practice of effectively random prostate biopsies. Large, multicenter studies are necessary to determine whether targeted prostate biopsy will become a definitive standard of care.

MP67-15 TARGETED MAGNETIC RESONANCE IMAGING/ULTRASOUND FUSION BIOPSY IS A SIGNIFICANTLY BETTER PREDICTOR OF TOTAL PROSTATE CANCER TUMOR VOLUME THAN RANDOM 12-CORE BIOPSY

INTRODUCTION AND OBJECTIVES: Tumor quantification with percent core and/or core length involvement is used to infer burden of disease for patients with prostate cancer (PCa). However, controversy exists regarding tumor quantification in random 12 core biopsies due to discrepancies in lesion targeting and overall needle core lengths obtained. Targeted magnetic resonance imaging/ultrasound (MRI/US) fusion biopsy allows for more optimal lesion targeting and interpretation of this parameter. We aim to correlate highest percentage core involvement and corresponding tumor length for both targeted fusion and random 12 core biopsies with total tumor volume. METHODS: Patients who underwent multiparametric MRI (MP MRI) with targeted MRI/US fusion biopsy at our institution between 2007 and 2013 were reviewed. MRI tumor volumes were calculated in fusion biopsy positive lesions and correlated with the highest percentage core involvement and corresponding tumor length in centimeters, for both targeted fusion biopsy and 12 core biopsy. Bivariate analysis was used to determine the empirical relationship between these variables and the correlative R2 value. RESULTS: 823 patients had MP MRI with MRI/US fusion biopsy, of which 100 patients had MRI tumor volumes quantified. Mean age was 62 years and mean PSA was 5.5ng/ml. For highest percentage core involvement, targeted biopsy showed a positive correlation (R1⁄40.54) whereas 12 core biopsy showed a poor correlation (R1⁄40.004) with total tumor volume (p<0.0001, p1⁄40.97 respectively). Similarly, for tumor length of the highest percentage core, targeted biopsy showed a positive correlation (R1⁄40.56) whereas 12 core biopsy showed a poor correlation (R1⁄40.06) with the total tumor volume (p<0.0001 and p1⁄40.59 respectively). (Figure 1) CONCLUSIONS: Highest percentage core involvement and tumor length on targeted MRI/US fusion biopsy positively correlate with total tumor volume. Targeted biopsy better predicts overall burden of disease and can aid in risk stratification of PCa patients.

MP7-17 DIFFERENTIAL DETECTION OF LESIONS ON MULTI-PARAMETRIC PROSTATE MRI WITH OR WITHOUT USE OF AN ENDORECTAL COIL BASED ON QUANTITATIVE MEASURES OF OBESITY

INTRODUCTION AND OBJECTIVES: Multiparametric 3T MRI (MP-MRI) with the use of an endorectal coil (ERC) provides improved signal to noise ratio for evaluation of prostatic lesions suspicious for prostate cancer. Herein, we aim to determine the degree of lesion identification lost by eliminating the use of an ERC based upon measures of obesity. METHODS: Prospectively collected data on 20 patients on an active surveillance protocol at the National Cancer Institute who have undergone non-ERC MP-MRI in 2013 following a prior ERC MP-MRI were analyzed. MP-MRI prostatic lesions suspicious for prostate cancer were identified and recorded on both ERC and non-ERC studies for each patient. Patient demographics including age, PSA, BMI, abdominal girth, waist circumference, and the drop distance from the anterior abdominal wall to the anterior aspect of the prostate were recorded. Quantitative measures of obesity were measured on T2-weighted MRI sequences. These parameters were analyzed using univariate and multivariable linear regression models individually with age and PSA to assess for significance in the decrease in number of lesions identified on followup studies without ERC use. RESULTS: The average number of lesions identified on ERC MP-MRI and followup non-ERC MP-MRI was 1.4 0.9 and 0.5 0.7, respectively. On univariate analysis, age and PSA were not significantly associated with a decrease in the number of lesions identified when the ERC was not used on followup MP-MRI. Of the quantitative parameters of obesity, on univariate analysis, greater BMI (p1⁄40.01) and abdominal girth (p1⁄40.0097) were significantly associated with a larger differential in the number of lesions identified. On multivariable linear regression models incorporating each of the measures of obesity with age and PSA, BMI (p1⁄40.026) and abdominal girth (p1⁄40.019) remained significant independent predictors of the difference in numbers of lesions identified between ERC and non-ERC studies. CONCLUSIONS: Typically more intraprostatic lesions are identified by MP-MRI performed with ERC due to the optimized signal to noise ratio. This difference is more dramatic in obese patients where the distance between body and surface coils and the prostate gland are increased. BMI and abdominal girth are predictors of significantly lower lesion identification when ERC is eliminated from the MP-MRI study. Since obesity has a negative impact on the detection of prostate cancer with non-ERC MRI, ERC use may be most important in this patient population.

OP3-04 DETECTION AND UPGRADING OF PROSTATE CANCER BY MRI/ULTRASOUND FUSION GUIDED BIOPSY ACROSS PSA-BASED CUTOFFS

INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is a treatment strategy for prostate cancer (CaP) involving close monitoring of men diagnosed with low-risk CaP to reduce overtreatment. We report here factors associated with disease progression while on AS in a large, single institution cohort. METHODS: We retrospectively reviewed the data of men enrolled in the University of California at San Francisco (UCSF) AS cohort between 1990 and 2012. Strict eligibility criteria were prostatespecific antigen (PSA) 33% cores. Factors associated with progression while on active surveillance were determined through multivariate Cox proportional hazards regression. RESULTS: Of 1,106 men enrolled in AS at UCSF, 764 men have consented to participate in research to date and have been followed on AS for a median of 57 months. Of these, 520 (68%) met strict criteria for AS while 244 (32%) did not. The median number of repeat biopsies was 3 (IQR 2-4). At 5 years after diagnosis, 53 % were progression-free and 40% of patients received local therapy. Overall survival was 94% among those not AS eligible and 99% among those AS eligible at 5 years. There were no CaP-related deaths. In multivariate analysis, PSA density (PSAD), total number of biopsies, and later year of diagnosis were positively associated with the risk of both biopsy progression (HR (95% CI): 1.58 (1.33-1.88); 0.82 (0.72-0.94); 1.17 (1.11-1.25) , respectively) and receiving treatment (HR (95%CI): 1.39 (1.20-1.61); 0.71 (0.64-0.78); 1.20 (1.15-1.25), respectively), all p<0.01. CONCLUSIONS: The majority of men who enrolled in this active surveillance cohort remained on AS after a median follow up of 57 months. While higher PSAD was associated with biopsy progression, additional predictive tools would improve selection and counseling of men for AS.