Use of multiparametric magnetic resonance imaging and fusion-guided biopsies to properly select and follow African-American men on active surveillance.

OBJECTIVES: To determine the rate of Gleason Grade Group (GGG) upgrading in African-American (AA) men with a prior diagnosis of low-grade prostate cancer (GGG 1 or GGG 2) on 12-core systematic biopsy (SB) after multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB); and whether AA men who continued active surveillance (AS) after mpMRI and FB fared differently than a predominantly Caucasian (non-AA) population. PATIENTS AND METHODS: A database of men who had undergone mpMRI and FB was queried to determine rates of upgrading by FB amongst men deemed to be AS candidates based on SB prior to referral. After FB, Kaplan-Meier curves were generated for AA men and non-AA men who then elected AS. The time to GGG upgrading and time continuing AS were compared using the log-rank test. RESULTS: AA men referred with GGG 1 disease on previous SB were upgraded to GGG ≥3 by FB more often than non-AA men, 22.2% vs 12.7% (P = 0.01). A total of 32 AA men and 258 non-AA men then continued AS, with a median (interquartile range) follow-up of 39.19 (24.24-56.41) months. The median time to progression was 59.7 and 60.5 months, respectively (P = 0.26). The median time continuing AS was 61.9 months and not reached, respectively (P = 0.80). CONCLUSIONS: AA men were more likely to be upgraded from GGG 1 on SB to GGG ≥3 on initial FB; however, AA and non-AA men on AS subsequently progressed at similar rates following mpMRI and FB. A greater tendency for SB to underestimate tumour grade in AA men may explain prior studies that have shown AA men to be at higher risk of progression during AS.

mpMRI preoperative staging in men treated with antiandrogen and androgen deprivation therapy before robotic prostatectomy.

INTRODUCTION: Using multiparametric magnetic resonance imaging (mpMRI), we sought to preoperatively characterize prostate cancer (PCa) in the setting of antiandrogen plus androgen deprivation therapy (AA-ADT) prior to robotic-assisted radical prostatectomy (RARP). We present our preliminary findings regarding mpMRI depiction of changes of disease staging features and lesion appearance in treated prostate. METHODS: Prior to RARP, men received 6 months of enzalutamide and goserelin. mpMRI consisting of T2 weighted, b = 2,000 diffusion weighted imaging, apparent diffusion coefficient mapping, and dynamic contrast enhancement sequences was acquired before and after neoadjuvant therapy. Custom MRI-based prostate molds were printed to directly compare mpMRI findings to H&E whole-mount pathology as part of a phase II clinical trial (NCT02430480). RESULTS: Twenty men underwent imaging and RARP after a regimen of AA-ADT. Positive predictive values for post-AA-ADT mpMRI diagnosis of extraprostatic extension, seminal vesicle invasion, organ-confined disease, and biopsy-confirmed PCa lesions were 71%, 80%, 80%, and 85%, respectively. Post-treatment mpMRI correctly staged disease in 15/20 (75%) cases with 17/20 (85%) correctly identified as organ-confined or not. Of those incorrectly staged, 2 were falsely positive for higher stage features and 1 was falsely negative. Post-AA-ADT T2 weighted sequences best depicted presence of PCa lesions as compared to diffusion weighted imaging and dynamic contrast enhancement sequences. CONCLUSION: mpMRI proved reliable in detecting lesion changes after antiandrogen therapy corresponding to PCa pathology. Therefore, mpMRI of treated prostates may be helpful for assessing men for surgical planning and staging.

A comparison of outcomes for standard and multiplex partial nephrectomy in a solitary kidney: The National Cancer Institute experience.

OBJECTIVES: To study the short and intermediate surgical, renal functional, and oncologic outcomes of multiplex partial nephrectomy (mPN) and standard partial nephrectomy (sPN) in the setting of a solitary kidney. PATIENTS AND METHODS: Review of a prospectively maintained database of patients undergoing solitary kidney partial nephrectomy at our institution was performed. Patients were stratified into 2 cohorts: mPN-where 3 or more renal tumors were resected and sPN-where 1 or 2 tumors were resected. Perioperative, renal functional, and oncological outcomes were compared. RESULTS: Ninety-three patients with a solitary kidney underwent a total of 121 surgical procedures; 43 (35.5%) were sPN and 78 (64.4%) were mPN. The total and major (Clavien Grade III and IV) complication rates between sPN and mPN were similar (57.1% vs. 70.1%, P = 0.2; 31.0% vs. 35.1%, P = 0.3). At 12 months post-op, the percentage of patients with eGFR > 45 was similar in each group (sPN 87.0%, mPN 73.7%; P = 0.2), and long-term hemodialysis rates were 4.7% and 6.4%, respectively. Completion nephrectomy was performed in 2.3% of sPN and 2.6% of mPN. At a median follow-up of 40.1 months, the metastasis rate was 8.6% in the sPN group and 4.1% in the mPN group (P = 0.4). CONCLUSIONS: Partial nephrectomy in the setting of a solitary kidney can effectively preserve renal function. The renal functional and oncologic outcomes were similar in sPN and mPN, with low hemodialysis rates and complication rates within the expected range of these operations. Three or more tumors in a solitary kidney should not be a contraindication for nephron sparing surgery.

Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. METHODS: A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. RESULTS: Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. CONCLUSIONS: A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

Predicting Gleason Group Progression for Men on Prostate Cancer Active Surveillance: Role of a Negative Confirmatory Magnetic Resonance Imaging-Ultrasound Fusion Biopsy.

PURPOSE: Active surveillance has gained acceptance as an alternative to definitive therapy in many men with prostate cancer. Confirmatory biopsies to assess the appropriateness of active surveillance are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. We sought to determine the prognostic implications of negative multiparametric magnetic resonance imaging-transrectal ultrasound guided fusion biopsy consisting of extended sextant, systematic biopsy plus multiparametric magnetic resonance imaging guided targeted biopsy of suspicious lesions on magnetic resonance imaging. MATERIALS AND METHODS: All patients referred with Gleason Grade Group 1 or 2 prostate cancer based on systematic biopsy performed elsewhere underwent confirmatory fusion biopsy. Patients who continued on active surveillance after a positive or a negative fusion biopsy were followed. The baseline characteristics of the biopsy negative and positive cases were compared. Cox regression analysis was used to determine the prognostic significance of a negative fusion biopsy. Kaplan-Meier survival curves were used to estimate Grade Group progression with time. RESULTS: Of the 542 patients referred with Grade Group 1 (466) or Grade Group 2 (76) cancer 111 (20.5%) had a negative fusion biopsy. A total of 60 vs 122 patients with a negative vs a positive fusion biopsy were followed on active surveillance with a median time to Grade Group progression of 74.3 and 44.6 months, respectively (p <0.01). Negative fusion biopsy was associated with a reduced risk of Grade Group progression (HR 0.41, 95% CI 0.22-0.77, p <0.01). CONCLUSIONS: A negative confirmatory fusion biopsy confers a favorable prognosis for Grade Group progression. These results can be used when counseling patients about the risk of progression and for planning future followup and biopsies in patients on active surveillance.

Clinical implications of PET/CT in prostate cancer management.

Several imaging modalities exist for the investigation of prostate cancer (PCa). From ultrasound to computed tomography (CT) and magnetic resonance imaging (MRI), the role of imaging in detecting lesion foci, staging, and localizing disease after biochemical recurrence (BCR) is expanding. However, many of the conventional imaging modalities are suboptimal, particularly in the detection of metastasis. Positron emission tomography (PET) has recently emerged as a promising tool in PCa management. The ability to develop radiolabeled tracers for functional imaging based on characteristics of PCa cells can potentially provide more insight into management by utilizing key features of those cells, such as metabolic activity, increased proliferation, and receptor expression. 18-flurodeoxyglucose (FDG) is one of the earliest tracers used in PET imaging that takes advantage of increased metabolism of glucose. Its role in PCa has been somewhat limited due to poor resolution and confounders including noise resulting from the proximity of the prostate to the bladder. Choline, a precursor molecule for a major component of the cell membrane, phosphatidylcholine, shows increased uptake in cells with rapid proliferation. When compared to metabolic based imaging techniques with FDG, choline PET/CT was superior. Nevertheless, choline PET/CT was not equivocal to MRI in detection of local disease, but was superior to conventional imaging in localizing metastasis and lymph node metastasis (LNM). Fluciclovine is another novel marker that utilizes the increased proliferation seen in tumor cells. Studies have shown it to be superior to choline PET/CT in PCa management, particularly in patients with BCR. As with choline PET/CT, studies that have assessed the impact of fluciclovine on clinical practice have highlighted the impact of these new tracers on clinical decision making. Most recently, the newest molecular probe targeting prostate specific membrane antigen (PSMA) was developed. It offers higher detection rates compared to choline PET/CT and conventional imaging modalities and has shown promise in LNM and BCR. With the wide range of available PET tracers, this review aims to highlight the role of each in lesion foci detection, primary staging, disease recurrence and explore the potential clinical impact.

Incidental bladder cancers found on multiparametric MRI of the prostate gland: a single center experience.

PURPOSE: In the era of multiparametric magnetic resonance imaging (mpMRI) of the prostate gland, incidental findings are occasionally discovered on imaging. We aimed to report our experience of detecting incidental bladder cancers on mpMRI of the prostate in asymptomatic patients without irritative voiding symptoms or microscopic or gross hematuria. METHODS: A retrospective review was performed on a prospectively maintained database of all men who underwent prostate mpMRI at our institution from 2012 to 2018. Patients who were found to have incidental bladder lesions were identified and baseline demographics, imaging and histopathologic data were recorded. All patients with incidental bladder lesion detection on mpMRI, not attributable to extension of prostate cancer, underwent cystoscopy in addition to a biopsy and/or transurethral resection of bladder tumor (TURBT) if warranted on cystoscopy. RESULTS: There were 3147 prostate mpMRIs performed during this period and 25 cases (0.8%) of incidental bladder lesions were detected. These patients did not have any presenting symptoms such as gross or microscopic hematuria to prompt bladder lesion workup. The largest diameter of incidentally discovered bladder lesions ranged from 0.4 cm to 1.7 cm. Of the 25 cases of incidental bladder lesions, five were suspected to be due to prostate cancer invasion into the bladder. Only two of these five patients underwent biopsy, which confirmed prostate adenocarcinoma in both cases. Of the 20 patients without suspected prostate cancer invasion of the bladder, four had no suspicious lesions on cystoscopy to warrant a biopsy. The remaining 16 patients had bladder lesions seen on cystoscopy and underwent a biopsy and/or TURBT. Three of these patients had benign features on pathology (urachal remnant, amyloidosis and inflammation) and the remaining 13 had stage Ta urothelial carcinoma. Seven of these patients had low-grade Ta tumors and six had high-grade Ta tumors. All patients were treated with standard management of TURBT with or without intravesical BCG. There have been no reported cases of recurrence or progression in any of the patients in our cohort at the median follow-up of 26 months (interquartile range,19-40 months). CONCLUSION: mpMRI of the prostate may yield incidental findings, such as small bladder tumors. Awareness of the possibility of incidental bladder lesions is important as 65% of lesions reported in the bladder, not attributable to extension of prostate cancer, proved to be bladder cancer. This may allow for early intervention for asymptomatic patients with undetected bladder cancer prior to disease progression.

Comparison of Elastic and Rigid Registration during Magnetic Resonance Imaging/Ultrasound Fusion-Guided Prostate Biopsy: A Multi-Operator Phantom Study.

PURPOSE: The relative value of rigid or elastic registration during magnetic resonance imaging/ultrasound fusion guided prostate biopsy has been poorly studied. We compared registration errors (the distance between a region of interest and fiducial markers) between rigid and elastic registration during fusion guided prostate biopsy using a prostate phantom model. MATERIALS AND METHODS: Four gold fiducial markers visible on magnetic resonance imaging and ultrasound were placed throughout 1 phantom prostate model. The phantom underwent magnetic resonance imaging and the fiducial markers were labeled as regions of interest. An experienced user and a novice user of fusion guided prostate biopsy targeted regions of interest and then the corresponding fiducial markers on ultrasound after rigid and then elastic registration. Registration errors were compared. RESULTS: A total of 224 registration error measurements were recorded. Overall elastic registration did not provide significantly improved registration error over rigid registration (mean ± SD 4.87 ± 3.50 vs 4.11 ± 2.09 mm, p = 0.05). However, lesions near the edge of the phantom showed increased registration errors when using elastic registration (5.70 ± 3.43 vs 3.23 ± 1.68 mm, p = 0.03). Compared to the novice user the experienced user reported decreased registration error with rigid registration (3.25 ± 1.49 vs 4.98 ± 2.10 mm, p <0.01) and elastic registration (3.94 ± 2.61 vs 6.07 ± 4.16 mm, p <0.01). CONCLUSIONS: We found no difference in registration errors between rigid and elastic registration overall but rigid registration decreased the registration error of targets near the prostate edge. Additionally, operator experience reduced registration errors regardless of the registration method. Therefore, elastic registration algorithms cannot serve as a replacement for attention to detail during the registration process and anatomical landmarks indicating accurate registration when beginning the procedure and before targeting each region of interest.

Added Value of Multiparametric Magnetic Resonance Imaging to Clinical Nomograms for Predicting Adverse Pathology in Prostate Cancer.

PURPOSE: We examined the additional value of preoperative prostate multiparametric magnetic resonance imaging and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy when performed in combination with clinical nomograms to predict adverse pathology at radical prostatectomy. MATERIALS AND METHODS: We identified all patients who underwent 3 Tesla multiparametric magnetic resonance imaging prior to fusion biopsy and radical prostatectomy. The Partin and the MSKCC (Memorial Sloan Kettering Cancer Center) preradical prostatectomy nomograms were applied to estimate the probability of organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement using transrectal ultrasound guided systematic biopsy and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy Gleason scores. With radical prostatectomy pathology as the gold standard we developed multivariable logistic regression models based on these nomograms before and after adding multiparametric magnetic resonance imaging to assess any additional predictive ability. RESULTS: A total of 532 patients were included in study. When multiparametric magnetic resonance imaging findings were added to the systematic biopsy based MSKCC nomogram, the AUC increased by 0.10 for organ confined disease (p <0.001), 0.10 for extraprostatic extension (p = 0.003), 0.09 for seminal vesicle invasion (p = 0.011) and 0.06 for lymph node involvement (p = 0.120). Using Gleason scores derived from targeted biopsy compared to systematic biopsy provided an additional predictive value of organ confined disease (Δ AUC 0.07, p = 0.003) and extraprostatic extension (Δ AUC 0.07, p = 0.048) at radical prostatectomy with the MSKCC nomogram. Similar results were obtained using the Partin nomogram. CONCLUSIONS: Magnetic resonance imaging alone or in addition to standard clinical nomograms provides significant additional predictive ability of adverse pathology at the time of radical prostatectomy. This information can be greatly beneficial to urologists for preoperative planning and for counseling patients regarding the risks of future therapy.

"Super-active surveillance": MRI ultrasound fusion biopsy and ablation for less invasive management of prostate cancer.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate has allowed clinicians to better visualize and target suspicious lesions during biopsy. Targeted prostate biopsies give a more accurate representation of the true cancer volume and stage so that appropriate treatment or active surveillance can be selected. Advances in technology have led to the development of MRI and ultrasound fusion platforms used for targeted biopsies, monitoring cancer progression, and more recently for the application of focal therapy. Lesions visualized on mpMRI can be targeted for ablation with a variety of energy sources employed under both local and general anesthesia. Focal ablation may offer an alternative option for treating prostate cancer as compared to the well-established interventions of whole-gland radiation or prostatectomy. Focal ablation may also be an option for patients on active surveillance who wish to be even more "active" in their surveillance. In this review, we describe the advancements and development of fusion biopsies, the rationale behind focal therapy, and introduce focal ablative techniques for indolent prostate cancers ("super-active surveillance"), including cryoablation and focal laser ablation (FLA) and the subsequent MRI/biopsy surveillance.

Bilateral Ureteroenteric Strictures: A Case of the "Reverse 7".

Anastomotic stricture is a well-known complication of the urinary diversion that accompanies radical cystectomy. Management options range from endoscopic procedures to open surgeries, with a subset of the latter employing bowel as the interposing segment. In this report, we describe a rare patient, who successfully underwent a "Reverse 7" procedure, bypassing strictures at both anastomotic junctions between ureters and neobladder.

New therapies in nonmuscle invasive bladder cancer treatment.

INTRODUCTION: Nonmuscle invasive bladder cancer (NMIBC) remains a very challenging disease to treat with high rates of recurrence and progression associated with current therapies. Recent technological and biological advances have led to the development of novel agents in NMIBC therapy. METHODS: We reviewed existing literature as well as currently active and recently completed clinical trials in NMIBC by querying PubMed.gov and clinicaltrials.gov. RESULTS: A wide variety of new therapies in NMIBC treatment are currently being developed, utilizing recent developments in the understanding of immune therapies and cancer biology. CONCLUSION: The ongoing efforts to develop new therapeutic approaches for NMIBC look very promising and are continuing to evolve.