Faculty Bibliography

PURPOSE: Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA. PATIENTS AND METHODS: In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20). RESULTS: For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer. CONCLUSION: These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer.

OBJECTIVE: To evaluate the agreement in volumes of prostate tumors determined on multiparametric MRI (mpMRI) and histologic assessment, using detailed software-assisted co-registration. MATERIALS AND METHODS: 37 patients who underwent 3T mpMRI (T2WI, DWI/ADC, DCE) were included. A radiologist traced the borders of suspicious lesions on T2WI and ADC and assigned a suspicion score (SS) from 2-5; a uro-pathologist traced borders of tumors on histopathologic photographs. Software was used to co-register MRI and 3D digital reconstructions of RP specimens and compute imaging and histopathologic volumes. Agreement in volumes between MRI and histology was assessed using Bland-Altman plots and stratified by tumor characteristics. RESULTS: Among 50 tumors, mean difference and 95% limits of agreement on MRI relative to histology were -32% (-128% to +65%) on T2WI and -47% (-143% to +49%) on ADC. For all tumor subsets, volume under-estimation was more marked on ADC maps (mean difference ranging from -57% to -16%) than T2WI (mean difference ranging from -45% to +2%). 95% limits of agreement were wide for all comparisons, with lower 95% limit ranging between -77% and -143% across assessments. Volume under-estimation was more marked for tumors with Gleason score >/=7 or MRI SS 4 or 5. CONCLUSION: Volume estimates of PCa using MRI tended to substantially under-estimate histopathologic volumes, with wide variability in extent of under-estimation across cases. These findings have implications for efforts to use MRI to guide risk assessment.

AIM: To compare the size and shape of the prostate between in-vivo and fresh ex-vivo magnetic resonance imaging (MRI), in order to quantify alterations in the prostate resulting from surgical resection. MATERIAL AND METHOD: Ten patients who had undergone 3 T prostate MRI using a phased-array coil and who were scheduled for prostatectomy were included in this prospective study. The ex-vivo specimen underwent MRI prior to formalin fixation or any other histopathological processing. Prostate volume in vivo and ex vivo was assessed using planimetry. Prostate shape was assessed by calculating ratios between the diameters of the prostate in all three dimensions. RESULTS: Mean prostate volume was significantly smaller ex vivo than in vivo (39.7 +/- 18.6 versus 50.8 +/- 26.8 cm3; p = 0.008), with an average change in volume of -19.5%. The right-to-left (RL)/anteroposterior (AP) ratio of the prostate, representing the shape of the prostate within its axial plane, was significantly larger ex vivo than in vivo (1.33 +/- 0.14 versus 1.21 +/- 0.12; p = 0.015), with an average percent change in RL/AP ratio of the prostate of +12.2%. There was no significant difference between in-vivo and ex-vivo acquisitions in terms of craniocaudal (CC)/AP (p = 0.963, median change = -2.1%) or RL/CC (p = 0.265, median change = +1.3%) ratios. CONCLUSION: The observed volume and shape change following resection has not previously been assessed by comparison of in-vivo and fresh ex-vivo MRI and likely represents loss of vascularity and of connective tissue attachments in the ex-vivo state. These findings have implications for co-registration platforms under development to facilitate improved understanding of the accuracy of MRI in spatial localization of prostate tumours.

Introduction and Objectives: With improving accuracy of prostate cancer detection and localization using multi-parametric MRI (mpMRI), there is an increasing interest in mpMRI guidance of diagnosis and surveillance biopsy. Widespread application of such concept must address the challenging issues, including the ability to perform MRI-guided biopsy in realtime with adequate accuracy, and in the simple urology office environment. We propose and assess a new approach a new approach to directly coregister 2D standard TRUS to MRI. Materials and Methods: The developed concept is to use a raw 2D Ultrasound (US) (B&K 8848 device) prostate image and register it to the corresponding MRI slice. Pre-acquired MRI data represents the whole gland in 3D as an ordered collection of 2D MRI slices of known thickness. We have developed software for USMRI coregistration based on image intensity, texture, and boundaries. The power parameter P is directly proportional to algorithm speed and accuracy. The result is source US overlaying target MRI for visualization. The system was prospectively tested on 8 data sets corresponding to US images matching with prostate MRI. These data come from patients who underwent MRI prior to biopsy. Coregistration results were evaluated as success/failure by an expert urologist who interactively adjusted the transparency of US-MRI overlays and recorded the alignment of anatomical landmarks in both modalities, especially the veru montanum. Results: The system was able to find the matching slice of T2WI for all single 2D standard US slice. In all cases the location of the veru montanum confirmed the coregistration accuracy in axial plan. The median rank of the T2WI slice was the fifth one among median number of 10 T2WI slices. We tested the power parameter P=1; P=5 and P=20. Twenty three coregistrations over 23 were correct. There was a significant positive correlation between prostate volume and time of computation for each P value. The image similarity reached a 0.93 mean Dice index u!

Introduction and Objectives: Focal therapy (FT) is an emerging approach for treatment of localized prostate cancer. Multi-parametric (mp) MRI demonstrated capability to monitor the effect of FT procedures. At time of followup, the ablated zone (AZ) clearly undergoes local shrinkage. Accurate definition of AZ at follow-up will improve FT evaluation and oncologic safety. We analyzed the volume and shape changes of the gland between pre and post FT MRI by developing a 3D coregistration method to compensate for deformation of the gland in response to FT. Materials and Methods: We studied 10 patients who underwent FT (interstitial laser ablation and photodynamic therapy) within IRB approved trials. All patients underwent preoperative, early control and late postoperative 3T MRI which included T2, T1, diffusion and perfusion weighted sequences. We have developed image registration software to analyze, transfer and model shape changes using a deformable and a rigid body transformation. Alignment between pre- and post-op images of AZ was assessed using the overlap index or Dice index (Di) and the maximum boundary distance, or Hausdorff distance (HD). Correction for deformation was measured using the HD normalized by the volume to transform in mm/ cc and automated feature of the software. Results: There was a significant volume decrease D of the gland that averaged 6.49 cc (p=0.017) between preoperative and postoperative gland. D was directly correlated (=0.738, p=0.014) with the ablated volume (7.88, p=0.04). We successfully co registered pre operative to post operative MRI in each cases. There was a significant increase D computed with deformable versus rigid transform. Deformable model achieved a significantly more accurate match of pre- vs. post-FT AZ with deformable (Di=0.88, HD=1.98 mm) vs. rigid transformation (Di=0.95 HD=3.83mm). The deformable approach also yielded a higher (p=0.019) correction of deformation (0.72mm/cc) compared to the rigid model (0.15mm/cc). Conclusion: We described a novel !

PURPOSE: Optimization of prostate biopsy requires addressing the shortcomings of standard systematic transrectal ultrasound guided biopsy including false negative rates, incorrect risk stratification, detection of clinically insignificant disease, and the need for repetitive biopsy. MRI is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer (PCa) at the time of biopsy, thereby enhancing clinical risk assessment, and improving the ability to appropriately counsel patients regarding therapy. The purpose of this review is to 1) summarize the various sequences that comprise a prostate multiparametric MRI exam along with its performance characteristics in cancer detection, localization and reporting standards, 2) evaluate potential applications of MRI targeting in prostate biopsy among men with no previous biopsy, a negative previous biopsy, and those with low stage cancer and 3) describe the techniques of MRI-targeted biopsy and their comparative study outcomes MATERIALS AND METHODS: A bibliographic search covering the period up to October, 2013 was conducted using MEDLINE(R)/PubMed(R). Articles were reviewed and categorized based on which of the three objectives of this review was addressed. Data was extracted, analyzed, and summarized. RESULTS: Mp-MRI consists of anatomic T2-weighted imaging coupled with at least 2 functional imaging techniques and has demonstrated improved PCa detection sensitivity up to 80% in the peripheral zone and 81% in the transition zone. A PCa MRI suspicion score has been developed and is depicted using the Likert or PI-RADS scale for better standardization of MRI interpretation and reporting. Among men with no previous biopsy, MRI increases the frequency of significant cancer detection to 50% in low risk and 71% in high risk patients. In low risk men, the negative predictive valve of a combination of negative MRI with prostate volume parameters is nearly 98%, suggesting a potential role in avoiding a biopsy and reducing overdetection/overtreatment. Among men with previous negative biopsy, 72-87% of cancers detected by MRI guidance are clinically significant. Among men with known low risk cancer, repeat biopsy by MR-targeting demonstrates a high likelihood of confirming low risk disease in low suspicion score lesions and for upgrading in high suspicion score lesions. Techniques of MRI-targeted biopsy include visual estimation TRUS-guided biopsy, software co-registered MRI-US TRUS-guided biopsy, and in-bore MRI-guided biopsy. Although the improvement in accuracy and efficiency of visual estimation biopsy compared to systematic appears limited, both co-registered MRI-US biopsy and in-bore MRI-guided biopsy appears to increase cancer detection rates in conjunction with increasing suspicion score. CONCLUSIONS: Use of MRI for targeting prostate biopsies has potential to reduce the sampling error associate with conventional biopsy by providing better disease localization and sampling. More accurate risk stratification through improved cancer sampling may impact upon therapeutic decision-making. Optimal clinical application of MRI-targeted biopsy remains under investigation.

A modified Gleason grading system as proposed in the 2005 International Society of Urological Pathology (ISUP) consensus meeting is the current grading system for prostate cancer. With this modified ISUP Gleason grading system, many Gleason score (GS) 6 cancers by the old grading system are upgraded to GS7 cancers on biopsy diagnosis even with minimal quantity (