Faculty Bibliography

Lower urinary tract symptoms (LUTS) secondary to benign prostatic hypertrophy (BPH) are among the most common medical issues for aging men. Population-based studies suggest that 13.8% of men in their 40s and more than 40% of men over age 60 have BPH. When LUTS are refractory to medical therapy and bothersome enough to warrant surgical intervention, transurethral resection of the prostate and open simple prostatectomy have been the historical reference-standard procedures for decades. Both procedures are highly effective and offer durable improvements in urinary functional outcomes. However, they also have the potential for considerable perioperative complications and morbidity. In an effort to limit surgical morbidity, a variety of minimally invasive surgical techniques to treat BPH have been introduced. Herein we present a comprehensive, evidence-based review of the efficacy and safety profile of modern minimally invasive treatments for large-gland BPH.

Laser interstitial thermal therapy (LITT) is a new therapeutic strategy being explored in prostate cancer (CaP), which involves focal ablation of organlocalized tumor via an interstitial laser fiber. While little is known about treatment-related changes following LITT, studying post-LITT changes via imaging is extremely significant for enabling early image-guided intervention and follow-up. In this work, we present the first attempt at examining focal treatment-related changes on a per-voxel basis via quantitative comparison of MRI features pre- and post-LITT, and hence identifying computerized MRI features that are highly sensitive as well as specific to post-LITT changes within the ablation zone in the prostate. A retrospective cohort of 5 patient datasets comprising both pre- and post-LITT T2-weighted (T2w) and diffusion-weighted (DWI) acquisitions was considered, where DWI MRI yielded an Apparent Diffusion Co-efficient (ADC) map. Our scheme involved (1) inter-protocol registration of T2w and ADC MRI, as well as inter-acquisition registration of pre- and post-LITT MRI, (2) quantitation of MRI parameters by correcting for intensity drift in order to examine tissuespecific response, and (3) quantification of the information captured by T2w MRI and ADC maps via texture and intensity features. Correction of parameter drift resulted in visually discernible improvements in highlighting tissue-specific response in different MRI features. Quantitative, voxel-wise comparison of the changes in different MRI features indicated that steerable and non-steerable gradient texture features, rather than the original T2w intensity and ADC values, were highly sensitive as well as specific in identifying changes within the ablation zone pre- and post-LITT. The highest ranked texture feature yielded a normalized percentage change of 186% within the ablation zone and 43% in a spatially distinct normal region, relative to its pre-LITT value. By comparison, both the original T2w intensity and ADC value demonstrated a markedly less sensitive and specific response to changes within the ablation zone. Qualitative as well as quantitative evaluation of co-occurrence texture features indicated the presence of LITT-related effects such as edema adjacent to the ablation zone, which were indiscernible on the original T2w and ADC images. Our preliminary results thus indicate great potential for non-invasive computerized MRI imaging features for determining focal treatment related changes, informing image-guided interventions, as well as predicting long- and short-term patient outcome.

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.

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.

Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.

PURPOSE: The authors describe their initial experience in implementing an integrated radiology reading room within a urologic oncology clinic, including the frequency and nature of clinician consultations and the perceived impact on patient management by clinicians. METHODS: A radiology reading room was established within an office-based urologic oncology clinic in proximity to the surgeon's work area. A radiologist was present in this reading room for a 3-hour shift each day. The frequency and nature of consultations during these shifts were recorded. Also, the clinic's staff completed a survey assessing perceptions of the impact of the integrated reading room on patient management. RESULTS: One hundred two consultations occurred during 57 included dates (average, 1.8 consultations per shift): 52% for review of external cases brought in by patients on discs, 43% for review of internal cases, and 5% for direct review by the radiologist of imaging with patients. The maximum number of consultations during a single shift was 8. All of the clinic's urologists indicated that >90% of consultations benefited patient care. The clinicians indicated tendencies to view consultations as affecting management in the majority of cases, to be more likely to seek consultation for outside imaging when the radiologist was on site, and to be less likely to repeat outside imaging when the radiologist was on site. CONCLUSIONS: The integrated reading room within the clinic has potential to improve the quality of care, for instance by facilitating increased review of outside imaging studies and thereby potentially reducing duplicate ordering and by enabling occasional direct image review with patients by radiologists.

PURPOSE: The prevalence of lower urinary tract symptoms increases with age and impairs quality of life. Radical prostatectomy has been shown to relieve lower urinary tract symptoms at short-term followup but the long-term effect of radical prostatectomy on lower urinary tract symptoms is unclear. MATERIALS AND METHODS: We performed a prospective cohort study of 1,788 men undergoing radical prostatectomy. The progression of scores from the self-administered AUASS (American Urological Association symptom score) preoperatively, and at 3, 6, 12, 24, 48, 60, 84, 96 and 120 months was analyzed using models controlling for preoperative AUASS, age, prostate specific antigen, pathological Gleason score and stage, nerve sparing, race and marital status. This model was also applied to patients stratified by baseline clinically significant (AUASS greater than 7) and insignificant (AUASS 7 or less) lower urinary tract symptoms. RESULTS: Men exhibited an immediate worsening of lower urinary tract symptoms that improved between 3 months and 2 years after radical prostatectomy. Overall the difference between mean AUASS at baseline and at 10 years was not statistically or clinically significant. Men with baseline clinically significant lower urinary tract symptoms experienced immediate improvements in lower urinary tract symptoms that lasted until 10 years after radical prostatectomy (13.5 vs 8.81, p <0.001). Men with baseline clinically insignificant lower urinary tract symptoms experienced a statistically significant but clinically insignificant increase in mean AUASS after 10 years (3.09 to 4.94, p <0.001). The percentage of men with clinically significant lower urinary tract symptoms decreased from baseline to 10 years after radical prostatectomy (p = 0.02). CONCLUSIONS: Radical prostatectomy is the only treatment for prostate cancer shown to improve and prevent the development of lower urinary tract symptoms at long-term followup. This previously unrecognized long-term benefit argues in favor of the prostate as the primary contributor to male lower urinary tract symptoms.