Faculty Bibliography

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.

The androgen receptor (AR) in stromal cells contributes significantly to the development and growth of prostate during fetal stages as well as during prostate carcinogenesis and cancer progression. During prostate development, stromal AR induces and promotes epithelial cell growth, as observed from tissue recombinant and mouse knockout studies. During prostate carcinogenesis and progression, the stromal cells begin to lose AR expression as early as at the stage of high-grade prostatic intraepithelial neoplasia. The extent of loss of stromal AR is directly proportional to the degree of differentiation (Gleason grade) and progression of prostate cancer (PCa). Co-culture studies suggested that stromal AR inhibits the growth of malignant epithelial cells, possibly through expression of certain paracrine factors in the presence of androgens. This functional reversal of stromal AR, from growth promotion during fetal prostate development to mediating certain growth-inhibiting effects in cancer, explains to some extent the reason that loss of AR expression in stromal cells may be crucial for development of resistance to androgen ablation therapy for PCa. From a translational perspective, it generates the need to re-examine the current therapeutic options and opens a fundamental new direction for therapeutic interventions, especially in advanced PCa.

PURPOSE: To evaluate pathologic outcomes and associations with MRI features in small renal masses measuring up to 20mm METHODS: 86 patients (61+/-13 years; 45M/41F) with 92 renal masses measuring up to 20mm that underwent MRI prior to tissue diagnosis were included. Two radiologists independently evaluated all masses for microscopic lipid, hemorrhage, T2-hyperintensity, T2-homogeneity, cystic/necrotic areas, hypervascularity, enhancement homogeneity, circumscribed margins, and predominantly exophytic location. These MRI features, as well as patient age, gender, and history of RCC, were compared with pathologic findings using Fisher's exact test, unpaired t-test, and multivariate logistic regression. RESULTS: 26.1% (24/92) of masses under 2cm were benign, only 32.6% (30/92) were clear-cell RCC, and only 7.6% (7/92) were high-grade. Among 16 masses measuring up to 1cm, only 12.5% (2/16) were clear-cell RCC, and none was high-grade. Within the entire cohort, no MRI or clinical feature showed a significant difference between benign and malignant lesions (p>/=0.053). However, for both readers, clear-cell RCC exhibited a significantly higher frequency of T2-hyperintensity, cystic/necrotic areas, and hypervascularity, and a significantly lower frequency of hemorrhage, T2-homogeneity, and enhancement homogeneity (p<0.001-0.036). Hypervascularity was a significant independent predictor of clear-cell RCC for both readers (p=0.002-0.007), as was T2-hyperintensity for reader 2 (p=0.007). CONCLUSION: A substantial fraction of small renal masses were benign, and when malignant, largely exhibited indolent pathologic characteristics, particularly when measuring under 1cm Although small benign and malignant masses could not be differentiated on MRI, hypervascularity showed a significant independent association with clear-cell RCC in comparison with other lesions.

INTRODUCTION: Tumor grade plays a critical role in the management of papillary non-invasive urothelial carcinoma (UC). Since grading of UC relies on morphologic criteria, variability in interpretation exists among pathologists. The objective of this study was to examine inter-observer variability in the grading of papillary non-invasive UC at a single academic medical center. MATERIALS AND METHODS: One general pathologist and two genitourinary pathologists were blinded to patient identity and graded 98 consecutive UC specimens using the 1973 and 2004 classification systems. Kappa statistics (kappa) were used to measure inter-observer reproducibility to account for agreement expected purely by chance. By convention, varkappa values from 0.21-0.4 represent "fair", from 0.41-0.6 represent "moderate", and > 0.6 represent "substantial" agreement. RESULTS: Raw percentage agreement among all three pathologists was only 26% using the 1973 system and 47% using the 2004 system. When measured by kappa, overall agreement was only "fair" for both systems and while higher for the 2004 system than the 1973, this was not significant (: 0.38 versus 0.26, respectively). There were no significant differences in agreement when comparing the specialists agreement between themselves with agreement between each specialist and the generalist (varkappa: 0.31-0.37 versus varkappa: 0.18-0.46). CONCLUSIONS: The current grading system continues to demonstrate challenges in reproducibility among general and specialized pathologists. The degree of variability has significant implications on management decisions for non-invasive UC. Our findings underscore the need to identify molecular markers that can provide a more objective and reliable risk stratification system to guide patient management.

BACKGROUND: Increasing evidence supports the use of magnetic resonance (MR)-targeted prostate biopsy. The optimal method for such biopsy remains undefined, however. OBJECTIVE: To prospectively compare targeted biopsy outcomes between MR imaging (MRI)-ultrasound fusion and visual targeting. DESIGN, SETTING, AND PARTICIPANTS: From June 2012 to March 2013, prospective targeted biopsy was performed in 125 consecutive men with suspicious regions identified on prebiopsy 3-T MRI consisting of T2-weighted, diffusion-weighted, and dynamic-contrast enhanced sequences. INTERVENTION: Two MRI-ultrasound fusion targeted cores per target were performed by one operator using the ei-Nav|Artemis system. Targets were then blinded, and a second operator took two visually targeted cores and a 12-core biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biopsy information yield was compared between targeting techniques and to 12-core biopsy. Results were analyzed using the McNemar test. Multivariate analysis was performed using binomial logistic regression. RESULTS AND LIMITATIONS: Among 172 targets, fusion biopsy detected 55 (32.0%) cancers and 35 (20.3%) Gleason sum >/=7 cancers compared with 46 (26.7%) and 26 (15.1%), respectively, using visual targeting (p=0.1374, p=0.0523). Fusion biopsy provided informative nonbenign histology in 77 targets compared with 60 by visual (p=0.0104). Targeted biopsy detected 75.0% of all clinically significant cancers and 86.4% of Gleason sum >/=7 cancers detected on standard biopsy. On multivariate analysis, fusion performed best among smaller targets. The study is limited by lack of comparison with whole-gland specimens and sample size. Furthermore, cancer detection on visual targeting is likely higher than in community settings, where experience with this technique may be limited. CONCLUSIONS: Fusion biopsy was more often histologically informative than visual targeting but did not increase cancer detection. A trend toward increased detection with fusion biopsy was observed across all study subsets, suggesting a need for a larger study size. Fusion targeting improved accuracy for smaller lesions. Its use may reduce the learning curve necessary for visual targeting and improve community adoption of MR-targeted biopsy.

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 (