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Prostate cancer (PCa) is one of the most frequent causes of cancer death worldwide. Historically, diagnosis was based on physical examination, transrectal (TRUS) images, and TRUS biopsy resulting in overdiagnosis and overtreatment. Recently magnetic resonance imaging (MRI) has been identified as an evolving tool in terms of diagnosis, staging, treatment decision, and follow-up. In this review we provide the key studies and concepts of MRI as a promising tool in the diagnosis and management of prostate cancer in the general population and in challenging scenarios, such as anteriorly located lesions, enlarged prostates determining extracapsular extension and seminal vesicle invasion, and prior negative biopsy and the future role of MRI in association with artificial intelligence (AI).

The purpose of this review is to summarize the most current literature regarding the most important aspects to consider when developing a center of excellence for prostate imaging and biopsy. Multiparametric MRI (mp-MRI) has changed the way we diagnose and treat prostate cancer. This imaging modality allows for more precise identification of areas suspicious in terms of harboring prostate cancer, enabling performance of targeted mp-MRI-guided biopsies that have been demonstrated to yield superior cancer detection rates. Centers worldwide are increasingly adopting this technology. However, obtaining results comparable with those findings published in the literature can be challenging. The imaging and biopsy process entails the need for a multidisciplinary team including a dedicated radiologist, urologist, and pathologist. Adequate mp-MRI interpretation for accurate lesion identification, acquaintance with the biopsy technique selected, and precise characterization of Gleason Score/Grade Groupings are equal determinants of accurate biopsy results. Furthermore, all specialists are required to attain appropriate learning curves to ensure optimal results. In this review, we characterize crucial aspects to consider when developing a center of excellence for prostate imaging and biopsy as well as insights regarding how to implement them.

Between 5 and 10% of patients undergoing percutaneous nephrolithotomy (PCNL) develop postoperative sepsis 1, 2. Strategies to prevent infectious complications are based on information provided by preoperative midstream urine cultures (PMUC). The aim of this study is to evaluate the concordance of the microbiologic findings of PMUC, cultures of the renal stone (RSC) and urine obtained directly from the renal pelvis (RPUC) in patients undergoing PCNL. This is a multicenter prospective study. The study included all patients who underwent PCNL from May 2013 to July 2015 in three academic hospitals. All patients underwent a PMUC. Samples for RPUC were obtained by renal puncture for PCNL. Stone fragments extracted during the procedure were sent for culture (RSC). Clinical variables, stone configuration, burden and microbiology reports of cultures were recorded. We analyzed concordance between cultures and association with infectious complications. One hundred and twenty-two patients underwent PCNL. Twenty-four percent had positive culture, 3.2% (4/122) PMUC, 14.7% (18/122) RPUC and 13.9% (17/122) RSC. Positive PMUC demonstrated multidrug-susceptible Escherichia coli and Staphylococcus aureus, while RPUC showed multidrug-resistant pathogens and/or fungus. Seven patients (5.7%) developed postoperative infectious complications prior to discharge. There was a weak correlation between PMUC and intraoperative urine cultures (RPUC and RSC). Concordance rate between RPUC and RSC was 83.3%. The most common isolated pathogens were multidrug-resistant bacteria or fungus. PMUC did not reflect the microbiological environment found in stones and urine directly obtained from the renal pelvis. Patients with postoperative infectious complications had negative PMUC with positive RPUC or RSC. RPUC and RSC can help guide prompt and appropriate antibiotic treatment for patients who develop postoperative infectious complications after PCNL.

Multifocal and hereditary kidney cancers often require repeated ipsilateral nephron sparing procedures with higher blood loss and complication rates compared to first time renal surgery. Consequently, many surgeons avoid minimally invasive techniques in the setting. We present the characteristics, complications, and short-term renal functional outcomes of patients who underwent a repeat robotic partial nephrectomy (rRPNx).A database was retrospectively reviewed to identify patients who underwent robotic partial nephrectomies between January 2007 and December 2013. Selection criteria for the rRPNx cohort included patients who had undergone at least two ipsilateral renal surgeries, with the second procedure being an rRPNx. All other patients comprised the initial robotic partial nephrectomy (iRPNx) group.One hundred twenty-four patients who underwent robotic partial nephrectomy during the study period were identified. rRPNx constituted 26 (21%) of the total cases. Age of the rRPNx cohort was similar (p = 0.56), but number of tumors resected was two-fold greater in the rRPNx group (p = 0.44). Neither surgery time nor renal clamp time was significantly longer in either group (p = 0.18 and p = 0.65, respectively). Importantly, estimated blood loss (EBL) was significantly larger than in the iRPNx group (p = 0.01). Both groups had similar intravenous pain medication administration durations (p = 0.32), but postsurgical length of stay was greater for the rRPNx patients (p = 0.011). There were no significant differences in clavian complication rates (p = 0.17-0.39), with the exception of urine leak which occurred more frequently in the rRPNx group (p = 0.01). There was no difference in percent change in serum creatinine or estimated glomerular filtration rate (p = 0.89 and p = 0.67, respectively).rRPNx is safe and feasible in select patients. EBL, postoperative lengths of stay, and urine leak were the only factors significantly associated with rRPNx compared to iRPNx. Patient 3-month follow-up revealed excellent and comparable outcomes between the two groups.

To identify renal function outcomes after robotic multiplex partial nephrectomy (RMxPNx), we reviewed our institutional database at the National Institutes of Health, National Cancer Institute. To our knowledge, we present the largest series of RMxPNx renal function outcomes to date. Robotic partial nephrectomy has been employed for oncologic control and to prevent dialysis dependence in hereditary multifocal renal cell carcinoma conditions. We have termed robotic surgery on a single kidney with three or more lesions a RMxPNx.We evaluated patients from a prospectively maintained database at a single institution (NIH/NCI) that underwent RMxPNx from 2007 to 2013. Demographic and operative data were compiled with statistical analysis with T test performed to determine renal function outcomes.A total of 54 patients underwent RMxPNx. Mean number of tumors removed was 8.63 (range 3-52). Mean preoperative creatinine and eGFR were 1.02 ± 0.26 mg/dL and 85.4 ± 21.5 mL/min, respectively. Postoperatively, creatinine increased from baseline by 0.45 mg/dL (p 0.001). Similarly, a mean decrease in eGFR by 24.6 mL/min was observed (p 0.001). At 3-month follow-up, the creatinine increase from baseline was 0.05 mg/dL (p = 0.10) and mean decrease in eGFR was 3.01 mL/min (p = 0.21). When stratifying based on preoperative CKD stages I-III, similar results were observed.Robotic multiplex partial nephrectomy is a safe and feasible approach to patients with multifocal renal masses. These complex surgeries have a demonstrated learning curve, but this minimally invasive approach for nephron-sparing surgery allows patients to preserve renal function where they would otherwise require open surgery or a radical nephrectomy.

To identify the risk factors associated with development of postoperative elevation of creatine kinase (CK) and study its effect on renal function in patients who underwent complex multifocal partial nephrectomy (PN).Patients who underwent PN at National Cancer Institute between January 2007 and December 2012 were included in the study. Elevated serum CK was defined as2000 U/L. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR). Changes were reported as percent change from preoperative values and compared using the Wilcoxon test. Regression analysis was performed to identify the predictors of elevation in CK and decline in eGFR.From 407 total cases, 207 had adequate CK data for analysis. Median number of tumors removed was 3 (1-70). Median peak CK was 1458 (82-36,788). Forty-two percent developed CK elevation2000 U/L. Factors associated with postoperative elevation of CK 2000 were young age (p = 0.009), high BMI (p = 0.003) and operating room time (p 0.001). Although CK 2000 was associated with significantly greater decline in eGFR (37.4 vs. 20.3 %, p 0.001) in immediate postoperative period, this change largely resolved to a much less clinically relevant (9.2 vs 3.3 %, p = 0.040) change after 3 months. On multivariate analysis, postoperative elevation in CK was not found to be an independent factor determining renal function at 3 months.In our cohort, a significant proportion of patients developed CK elevations2000 U/L. While patients with elevated CK had more decline in eGFR in immediate postoperative period, postoperative elevations of CK did not appear to impact overall long-term renal function in patients undergoing PN.

PURPOSE: While the significance of circulating tumor cells in clinically localized cancer remains controversial, it has been reported that surgical tumor manipulation can increase circulating tumor cells, including during open prostatectomy. To our knowledge it is unknown whether this cell shedding also occurs during minimally invasive prostatectomy, which minimizes tumor palpation and uses earlier vascular control. We tested the impact of robotic assisted laparoscopic radical prostatectomy on intraoperative circulating tumor cell levels. MATERIALS AND METHODS: Circulating tumor cell counts were compared in peripheral blood specimens from 25 patients treated with robotic assisted laparoscopic radical prostatectomy preoperatively vs intraoperatively after prostate excision, in addition to 11 healthy blood donors. Circulating tumor cell detection was performed using EpCAM immunomagnetic enrichment and multiparametric flow cytometry quantification of viable EpCAM positive/prostate specific membrane antigen positive/CD45 negative cells. Intraoperative cell counts and increases were tested in univariable analyses for associations with perioperative variables, histopathology and postoperative progression. RESULTS: Circulating tumor cells were detected in 0% of healthy controls compared to 48% and 52% of prostatectomy cases preoperatively and intraoperatively, respectively (range 1 to 8 cells). There was no difference in the incidence or mean number of circulating tumor cells preoperatively vs intraoperatively. Of the patients 60% had no intraoperative change from preoperative levels. Intraoperative cell increases vs decreases were equally infrequent (each 20%) with no intraoperative increase greater than 1 circulating tumor cell. Intraoperative circulating tumor cell detection was not significantly associated with prostatectomy operative characteristics, histopathology or early postoperative progression at a median 21-month followup. CONCLUSIONS: Robotic assisted laparoscopic radical prostatectomy does not cause significant intraoperative increases in circulating tumor cells in contrast to historical reports of open prostatectomy. These findings may aid urologists in counseling candidates for robotic assisted laparoscopic radical prostatectomy regarding the possibility of intraoperative tumor cell shedding.

Prostate cancer remains the only solid tumor diagnosed using transrectal ultrasound-guided sampling of the gland, and not an image-based, lesion-directed approach. This technique has limitations in that it underdiagnoses clinically significant disease and overdiagnoses indolent tumors resulting in overtreatment of patients. Technical advances in MRI in the last decade have made this method the preferred imaging modality for prostate anatomy and for risk assessment of prostate cancer. As of 2018, the indications for MRI in the diagnosis and risk assessment of prostate cancer have expanded from preoperative evaluation to the pre-biopsy setting, as well as for surveillance protocols. This article summarizes the current role of multiparametric MRI in the diagnosis, risk assessment, and treatment of prostate cancer.

Purpose: Multiparametric magnetic resonance imaging may be beneficial in the search for rational ways to decrease prostate cancer intervention in patients on active surveillance. We applied a previously generated nomogram based on multiparametric magnetic resonance imaging to predict active surveillance eligibility based on repeat biopsy outcomes.Materials and Methods: We reviewed the records of 85 patients who met active surveillance criteria at study entry based on initial biopsy and who then underwent 3.0 Tesla multiparametric magnetic resonance imaging with subsequent magnetic resonance imaging/ultrasound fusion guided prostate biopsy between 2007 and 2012. We assessed the accuracy of a previously published nomogram in patients on active surveillance before confirmatory biopsy. For each cutoff we determined the number of biopsies avoided (ie reliance on magnetic resonance imaging alone without rebiopsy) over the full range of nomogram cutoffs.Results: We assessed the performance of the multiparametric...

Objective To compare cancer detection rates and concordance between magnetic resonance imaging and ultrasound (MRI-US) fusion-guided prostate biopsy cores obtained from axial and sagittal approaches. Patients and Methods Institutional records of MRI-US fusion-guided biopsy were reviewed. Detection rates for all cancers, Gleason ≥3 + 4 cancers, and Gleason ≥4 + 3 cancers were computed. Agreement between axial and sagittal cores for cancer detection, and frequency where one was upgraded the other was computed on a per-target and per-patient basis. Results In all, 893 encounters from 791 patients that underwent MRI-US fusion-guided biopsy in 2007–2013 were reviewed, yielding 4688 biopsy cores from 2344 targets for analysis. The mean age and PSA level at each encounter was 61.8 years and 9.7 ng/mL (median 6.45 ng/mL). Detection rates for all cancers, ≥3 + 4 cancers, and ≥4 + 3 cancers were 25.9%, 17.2%, and 8.1% for axial cores, and 26.1%, 17.6%, and 8.6% for sagittal cores. Per-target agreement was 88.6%, 93.0%, and 96.5%, respectively. On a per-target basis, the rates at which one core upgraded or detected a cancer missed on the other were 8.3% and 8.6% for axial and sagittal cores, respectively. Even with the inclusion of systematic biopsies, omission of axial or sagittal cores would have resulted in missed detection or under-characterisation of cancer in 4.7% or 5.2% of patients, respectively. Conclusion Cancer detection rates, Gleason scores, and core involvement from axial and sagittal cores are similar, but significant cancer may be missed if only one core is obtained for each target. Discordance between axial and sagittal cores is greatest in intermediate-risk scenarios, where obtaining multiple cores may improve tissue characterisation.

Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum.We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed.A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis.Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater.

Objective To describe the detection rate of anteriorly located prostate cancer (PCa) with the addition of magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided biopsy (FGB) to the standard transrectal ultrasonography (TRUS)-guided biopsy. Patients and Methods All patients, regardless of their biopsy history, who were referred for clinical suspicion of PCa (i.e elevated prostate-specific antigen (PSA) level and abnormal digital rectal examination) underwent 3T multiparametric-MRI (mpMRI) screening; and those with suspicious lesions in the anterior region of the prostate were identified. Patients then received a FGB of all suspicious lesions in addition to a systematic 12-core extended sextant TRUS-guided biopsy. We conducted a lesion-based analysis comparing cancer detection rates of anterior targets using FGB vs systematic cores taken from the same anatomic sextant within the prostate. Lengths of cancer in the most involved core were also compared between the two biopsy techniques used. Patients with only anterior targets were analysed separately. Results Of 499 patients undergoing FGB, 162 had a total of 241 anterior lesions. The mean age, PSA level and prostate volume in this group were 62 years, 12.7 ng/dL, and 57 mL, respectively. In total, PCa was diagnosed in 121 anterior lesions (50.2%) identified on mpMRI. Sixty-two (25.7%) of these anterior lesions were documented as positive for cancer on systematic 12-core TRUS-guided biopsy cores, while 97 (40.2%) were positive on the targeted FGB cores (P = 0.001). In lesions that were positive on both FGB and TRUS biopsy, the most involved core was 112% longer on FGB (3.7 vs 1.6 mm, P ≤ 0.01). Forty-two patients had only anterior lesions on mpMRI; of these, 24 (57.1%) were found to have cancer on the FGB + TRUS biopsy platform. Six patients were positive on FGB only and 13 were positive on both biopsy techniques; however, 7/13 patients were upgraded to a higher Gleason score after FGB. All five patients positive on TRUS biopsy only were candidates for active surveillance. Conclusion The results showed that FGB detects significantly more anteriorly located PCa than does TRUS-guided biopsy alone and it may serve as an effective tool for the subset of patients with such tumours.

Objectives To determine the diagnostic yield of analysing biparametric (T2- and diffusion-weighted) magnetic resonance imaging (B-MRI) for prostate cancer detection compared with standard digital rectal examination (DRE) and prostate-specific antigen (PSA)-based screening. Patients and Methods Review of patients who were enrolled in a trial to undergo multiparametric-prostate (MP)-MRI and MR/ultrasound fusion-guided prostate biopsy at our institution identified 143 men who underwent MP-MRI in addition to standard DRE and PSA-based prostate cancer screening before any prostate biopsy. Patient demographics, DRE staging, PSA level, PSA density (PSAD), and B-MRI findings were assessed for association with prostate cancer detection on biopsy. Results Men with detected prostate cancer tended to be older, with a higher PSA level, higher PSAD, and more screen-positive lesions (SPL) on B-MRI. B-MRI performed well for the detection of prostate cancer with an area under the curve (AUC) of 0.80 (compared with 0.66 and 0.74 for PSA level and PSAD, respectively). We derived combined PSA and MRI-based formulas for detection of prostate cancer with optimised thresholds. (i) for PSA and B-MRI: PSA level + 6 x (the number of SPL) > 14 and (ii) for PSAD and B-MRI: 14 × (PSAD) + (the number of SPL) >4.25. AUC for equations 1 and 2 were 0.83 and 0.87 and overall accuracy of prostate cancer detection was 79% in both models. Conclusions The number of lesions positive on B-MRI outperforms PSA alone in detection of prostate cancer. Furthermore, this imaging criteria coupled as an adjunct with PSA level and PSAD, provides even more accuracy in detecting clinically significant prostate cancer.

Purpose A magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided prostate biopsy increases detection rates compared to an extended sextant biopsy. The imaging characteristics and pathology outcomes of subsequent biopsies in patients with initially negative MRI-US fusion biopsies are described in this study. Materials and methods We reviewed 855 biopsy sessions of 751 patients (June 2007 to March 2013). The fusion biopsy consisted of two cores per lesion identified on multiparametric MRI (mpMRI) and a 12-core extended sextant transrectal US (TRUS) biopsy. Inclusion criteria were at least two fusion biopsy sessions, with a negative first biopsy and mpMRI before each. Results The detection rate on the initial fusion biopsy was 55.3%; 336 patients had negative findings. Forty-one patients had follow-up fusion biopsies, but only 34 of these were preceded by a repeat mpMRI. The median interval between biopsies was 15 months. Fourteen patients (41%) were positive for cancer on the repeat MRI-US fusion biopsy. Age, prostate-specific antigen (PSA), prostate volume, PSA density, digital rectal exam findings, lesion diameter, and changes on imaging were comparable between patients with negative and positive rebiopsies. Of the patients with positive rebiopsies, 79% had a positive TRUS biopsy before referral (P = 0.004). Ten patients had Gleason 3+3 disease, three had 3+4 disease, and one had 4+4 disease. Conclusion In patients with a negative MRI-US fusion prostate biopsy and indications for repeat biopsy, the detection rate of the follow-up sessions was lower than the initial detection rate. Of the prostate cancers subsequently found, 93% were low grade (≤ 3+4). In this low risk group of patients, increasing the follow-up time interval should be considered in the appropriate clinical setting.

Objective To assess the incidence and clinical significance of ‘skip lesions’ that are present in proximal but not in distal ureteric sections, which are occasionally found during the pathological examination of ureteric margins during radical cystectomy (RC). Patients and Methods We identified 660 patients who underwent a RC and had at least two permanent margins for a given ureter. In all, 1173 ureters were analysed and classified as follows: ‘normal’ (no tumour, reactive atypia, mild or moderate dysplasia) or ‘abnormal’ (severe dysplasia, carcinoma in situ (CIS), or tumour). Transitions from ‘normal’ distal pathology to ‘abnormal’ on proximal section(s) determined frequency of skip lesions. Fisher's exact test and the log-rank test were used to study correlations. Results Ureteric skip lesions were found in 4.8% patients (2.9% ureters). Pathology of skip lesions was CIS in 55.9%, transitional cell carcinoma in 23.5% and severe dysplasia in 20.6%. Skip lesions were associated with lymphovascular invasion (34.4% vs 13.7%, P = 0.004) and advanced pT stage (P = 0.007). On multivariate analysis, skip lesions correlated with lower median overall survival (OS) (inestimable vs 8.2 years, P = 0.014) in patients with pT0 or pTa disease and a trend towards lower OS (2.7 vs 8.8 years, P = 0.066) in pTis disease. Concordance between frozen distal margin and permanent proximal margin varied; sensitivity was 80% in those without and 20% in those with skip lesions. Conclusions The presence of a ureteric skip lesion may be associated with lower survival in patients with pT0, pTa or pTis urothelial carcinoma. Thus, while uncommon, ureteric skip lesions should be reported in pathological findings.

Patients with an enlarged prostate and suspicion of prostate cancer pose a diagnostic dilemma. The prostate cancer detection rate of systematic 12-core transrectal ultrasound guided biopsy is between 30% and 40%. For prostates greater than 40 cc this decreases to 30% or less. Magnetic resonance-ultrasound fusion biopsy has shown superior prostate cancer detection rates. We defined the detection rate of magnetic resonance-ultrasound fusion biopsy in men with an enlarged prostate gland.We retrospectively analyzed the records of patients who underwent multiparametric prostate magnetic resonance imaging followed by magnetic resonance-ultrasound fusion biopsy at our institution. Whole prostate volumes were calculated using magnetic resonance imaging reconstructions. Detection rates were analyzed with respect to age, prostate specific antigen and whole prostate volumes. Multivariable logistic regression was used to assess these parameters as independent predictors of prostate cancer detection.We analyzed 649 patients with a mean±SD age of 61.8±7.9 years and a median prostate specific antigen of 6.65 ng/ml (IQR 4.35-11.0). Mean whole prostate volume was 58.7±34.3 cc. The overall detection rate of the magnetic resonance-ultrasound fusion platform was 55%. For prostates less than 40 cc the detection rate was 71.1% compared to 57.5%, 46.9%, 46.9% 33.3%, 36.4% and 30.4% for glands 40 to 54.9, 55 to 69.9, 70 to 84.9, 85 to 99.9, 100 to 114.9 and 115 cc or greater, respectively (p0.0001). Multivariable logistic regression showed a significant inverse association of magnetic resonance imaging volume with prostate cancer detection, controlling for age and prostate specific antigen.Transrectal ultrasound guided and fusion biopsy cancer detection rates decreased with increasing prostate volume. However, magnetic resonance-ultrasound fusion biopsy had a higher prostate cancer detection rate compared to that of transrectal ultrasound guided biopsy in the literature. Magnetic resonance-ultrasound fusion biopsy represents a promising solution for patients with suspicion of prostate cancer and an enlarged prostate.

BACKGROUND Active surveillance (AS) is an attempt to avoid overtreatment of clinically insignificant prostate cancer (PCa); however, patient selection remains controversial. Multiparametric prostate magnetic resonance imaging (MP-MRI) may help better select AS candidates. METHODS We reviewed a cohort of men who underwent MP-MRI with MRI/Ultrasound fusion–guided prostate biopsy and selected potential AS patients at entry using Johns Hopkins criteria. MP-MRI findings were assessed, including number of lesions, dominant lesion diameter, total lesion volume, prostate volume, and lesion density (calculated as total lesion volume/prostate volume). Lesions were assigned a suspicion score for cancer by MRI. AS criteria were reapplied based on the confirmatory biopsy, and accuracy of MP-MRI in predicting AS candidacy was assessed. Logistic regression modeling and chi-square statistics were used to assess associations between MP-MRI interpretation and biopsy results. RESULTS Eighty-five patients qualified for AS with a mean age of 60.2 years and mean prostate-specific antigen level of 4.8 ng/mL. Of these, 25 patients (29%) were reclassified as not meeting AS criteria based on confirmatory biopsy. Number of lesions, lesion density, and highest MRI lesion suspicion were significantly associated with confirmatory biopsy AS reclassification. These MRI-based factors were combined to create a nomogram that generates a probability for confirmed AS candidacy. CONCLUSION As clinicians counsel patients with PCa, MP-MRI may contribute to the decision-making process when considering AS. Three MRI-based factors (number of lesions, lesion suspicion, and lesion density) were associated with confirmatory biopsy outcome and reclassification. A nomogram using these factors has promising predictive accuracy for which future validation is necessary. Cancer 2013;119:3359–66. Published 2013. This article is a U.S. Government work and is in the public domain in the USA

Hsp90 is a molecular chaperone and important driver of stabilization and activation of several oncogenic proteins that are involved in the malignant transformation of tumor cells. Therefore, it is not surprising that Hsp90 has been reported to be a promising target for the treatment of several neoplasias, such as non-small-cell lung cancer and HER2-positive breast cancer. Hsp90 chaperone function depends on its ability to bind and hydrolyze ATP and Hsp90 inhibitors have been shown to compete with nucleotides for binding to Hsp90. Multiple factors, such as co-chaperones and post-translational modification, are involved in regulating Hsp90 ATPase activity. Here, the impact of post-translational modifications and co-chaperones on the efficacy of Hsp90 inhibitors are reviewed.

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.

Administration of Bacillus Calmette-Guerin (BCG) has been shown to cause granulomatous prostatitis, a rare inflammatory process that can be mistaken for prostate cancer. We present a case of a 78-year-old man on active surveillance for prostate cancer with a subsequent diagnosis of high-grade urothelial carcinoma. After intravesical BCG therapy, he developed chronic granulomatous prostatitis. We present serial magnetic resonance imaging and biopsy data demonstrating the time interval between BCG administration and the manifestation of chronic granulomatous prostatitis.

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).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.For TBx, HPCI and CTL showed a positive correlation (R(2)=0.31, P0.0001 and R(2)=0.37, P0.0001, 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.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.

Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc. and Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, as well as other private donors. For a complete list, please visit the Foundation website at: http://fnih.org/work/education-training-0/ medical-research-scholars-program

INTRODUCTION AND OBJECTIVES: Central gland (CG) prostatic adenocarcinomas (CaP) are historically reported with lesser incidence, smaller tumor volume, and higher Gleason scores when compared to the peripheral zone (PZ). Additionally, index tumor lesions as defined by highest grade may be missed when residing in the CG. MRI/US fusion-guided biopsy allows targeting of lesions seen on MRI, potentially better identifying cancer outside the traditional TRUS biopsy template. METHODS: Retrospective review was performed of 1003 patients who underwent MR/US fusion-guided biopsy of 2119 suspicious lesions. Targets were stratified by zonal distribution of the lesion on multiparametric MRI (mpMRI) in the CG or PZ. Detection rates for Gleason 4þ3 cancers were tabulated by location and correlated with PSA, Gleason score, prostate volume and MRI suspicion. RESULTS: MR/US fusion-guided biopsy targeted lesions in the central (n1⁄4711, 34%) or peripheral (n1⁄41408, 66%) prostatic zones. Cancer detection rate was similar between zonal distributions, 35.2% in the CG compared to 33.6% in the PZ (p1⁄40.497) (Table 1). Cancer detection of clinically significant disease (Gleason 4þ3) was found to be similar in the CG and PZ (11.4% vs 11%, p1⁄40.128) despite a higher prostate volume in those with CG lesions (p1⁄4 0.004). In contrast to random 12-core TRUS biopsy, upgrading occurred in 18.5% of patients with CG lesions versus 13.3% for PZ targets (p1⁄40.024). When MRI detected suspicious lesions in the CG, 36.6% (77/210) of these represented the highest risk lesion. These CG index lesions translated to 13% (77/592) of the entire cohort of men with biopsy-proven CaP. CONCLUSIONS: Prostate cancer of the central gland occurs at a similar frequency than in peripheral zone. Targeted lesions of the CG were more likely to be upgraded from 12-core biopsy, frequently representing the index lesion as determined by Gleason grade. In all patients upgraded by a CG lesion, CG targeted cores constituted the highest Gleason grade index lesion in a third of all males with prostate cancer. Multiparametric MRI and fusion-guided biopsy aids in identifying clinically significant disease of the CG not captured on traditional TRUS biopsy. Source of Funding: This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research, and the Center for Interventional Oncology. NIH and Philips Healthcare have a cooperative research and development agreement. NIH and Philips share intellectual property in the field.

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.

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.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.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.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.

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.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.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.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.

To describe the detection rate of anteriorly located prostate cancer (PCa) with the addition of magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided biopsy (FGB) to the standard transrectal ultrasonography (TRUS)-guided biopsy.All patients, regardless of their biopsy history, who were referred for clinical suspicion of PCa (i.e elevated prostate-specific antigen (PSA) level and abnormal digital rectal examination) underwent 3T multiparametric-MRI (mpMRI) screening; and those with suspicious lesions in the anterior region of the prostate were identified. Patients then received a FGB of all suspicious lesions in addition to a systematic 12-core extended sextant TRUS-guided biopsy. We conducted a lesion-based analysis comparing cancer detection rates of anterior targets using FGB vs systematic cores taken from the same anatomic sextant within the prostate. Lengths of cancer in the most involved core were also compared between the two biopsy techniques used. Patients with only anterior targets were analysed separately.Of 499 patients undergoing FGB, 162 had a total of 241 anterior lesions. The mean age, PSA level and prostate volume in this group were 62 years, 12.7 ng/dL, and 57 mL, respectively. In total, PCa was diagnosed in 121 anterior lesions (50.2%) identified on mpMRI. Sixty-two (25.7%) of these anterior lesions were documented as positive for cancer on systematic 12-core TRUS-guided biopsy cores, while 97 (40.2%) were positive on the targeted FGB cores (P = 0.001). In lesions that were positive on both FGB and TRUS biopsy, the most involved core was 112% longer on FGB (3.7 vs 1.6 mm, P ≤ 0.01). Forty-two patients had only anterior lesions on mpMRI; of these, 24 (57.1%) were found to have cancer on the FGB + TRUS biopsy platform. Six patients were positive on FGB only and 13 were positive on both biopsy techniques; however, 7/13 patients were upgraded to a higher Gleason score after FGB. All five patients positive on TRUS biopsy only were candidates for active surveillance.The results showed that FGB detects significantly more anteriorly located PCa than does TRUS-guided biopsy alone and it may serve as an effective tool for the subset of patients with such tumours.

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.

INTRODUCTION AND OBJECTIVES: To overcome the wellknown prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. METHODS: A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasoundguided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. RESULTS: Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. CONCLUSIONS: mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Source of Funding: none

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

(40%), p

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

INTRODUCTION AND OBJECTIVES: In patients with prostate cancer (CaP), preoperative identification of extracapsular extension (ECE) can provide vital information for the surgical planning of robotassisted radical prostatectomy (RARP). Historically, MRI has had limited sensitivity for ECE. We aim to evaluate which parameters on multiparametric MRI (MP-MRI) and MRI/ultrasound (MRI/US) fusionguided biopsy aid in the pre-operative assessment of ECE. METHODS: Between May 2007 and August 2013, 299 patients at our institution underwent 3T MP-MRI, MRI/US fusion-guided biopsy with standard 12-core biopsy, and RARP. Visualized lesions were identified as low, moderate, or high suspicion for CaP according to the previously validated NIH scoring system. Findings were characterized as “presence of ECE,” “extracapsular bulge,” or neither. MP-MRI findings were correlated with biopsy results, final RARP pathology and margin status. Univariate analysis was performed to evaluate preoperative predictors of ECE on final pathology. RESULTS: MRI was positive for ECE in 27 patients and negative in 272, with a sensitivity of 17.2% and a specificity of 93.2% when compared to final pathology. In all patients, the rate of positive surgical margins was 15.1%. This rate increased to 22.2% in the subset of patients with MRIs that were positive for ECE, but increased to 31.1% in those patients whose MRIs were false negatives. In the group of patients with negative MRIs, PSA, MRI suspicion score, presence of bulge, and highest Gleason score on MRI/US fusion-guided biopsy were all associated with ECE on final pathology (p