Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.

PURPOSE: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. EXPERIMENTAL DESIGN: This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. RESULTS: uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. CONCLUSIONS: uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.

Robotic simple prostatectomy plus panniculectomy and Giant umbilical hernia repair.

INTRODUCTION: Simple prostatectomy is the gold standard for prostates >80 grams, robotic system has proven to help into speed the recovery of the patient and in morbid obesity the advantages of the robotic system can help to perform a successful surgery. CASE: 80 years old male with morbid obesity (BMI 45) and several other comorbidities, with history of an umbilical hernia and obstructive lower urinary tract symptoms in acute urinary retention. PSA was 7 ng/dl, DRE demonstrates a >100gr prostate gland. A robotic simple prostatectomy, urethropexy, umbilical hernia repair and panniculectomy in Fleur-de-Lis was performed. RESULTS: Operative time (OT) and estimated blood loss (EBL) were 438 min and 160 ml respectively. A JP drain was placed in the pelvis and 2 additional were left in the abdominal cavity with several Penrose drains. No immediate or intraoperative complications were observed. The length of stay (LOS) was 6 days without complications. Pathology report showed prostate of 304gr and benign prostatic tissue. DISCUSSION: In patients with multiple comorbidities robot-assisted surgery provides advantages of shorter LOS, EBL, less transfusion and lower rate of complications. In patients with morbid obesity where the increased girth makes difficult the open approach, robotic surgery is an ideal way to provide definitive treatment; concomitant, Fleur-de-Lis panniculectomy can correct the abdominal contour in both vertical and horizontal orientation at the same time that provides a better plane for trocar insertion, an accurate location of the needle tip and a proper position of the remote center decreasing the possible complication of port placement.

Differentiation of Solid Renal Tumors with Multiparametric MR Imaging.

Characterization of renal tumors is critical to determine the best therapeutic approach and improve overall patient survival. Because of increased use of high-resolution cross-sectional imaging in clinical practice, renal masses are being discovered with increased frequency. As a result, accurate imaging characterization of these lesions is more important than ever. However, because of the wide array of imaging features encountered as well as overlapping characteristics, identifying reliable imaging criteria for differentiating malignant from benign renal masses remains a challenge. Multiparametric magnetic resonance (MR) imaging based on various anatomic and functional parameters has an important role and adds diagnostic value in detection and characterization of renal masses. MR imaging may allow distinction of benign solid renal masses from several renal cell carcinoma (RCC) subtypes, potentially suggest the histologic grade of a neoplasm, and play an important role in ensuring appropriate patient management to avoid unnecessary surgery or other interventions. It is also a useful noninvasive imaging tool for patients who undergo active surveillance of renal masses and for follow-up after treatment of a renal mass. The purpose of this article is to review the characteristic MR imaging features of RCC and common benign renal masses and propose a diagnostic imaging approach to evaluation of solid renal masses using multiparametric MR imaging. ©RSNA, 2017.

Scrotal Ultrasound for Pain: Low Frequency of Absolute Surgical Indications.

OBJECTIVE: To examine the results of scrotal ultrasounds (US) conducted for scrotal or testicular pain and review the pathologic findings of orchiectomies done for lesions that were suspicious for malignancy on US. MATERIALS AND METHODS: We retrospectively reviewed the indications and findings of all scrotal US completed at our institution from 2002 to 2014. If a patient underwent an orchiectomy for an intratesticular lesion that was concerning for malignancy on US, the pathology report was also reviewed. RESULTS: There were 18,593 scrotal US performed, with 7,668 (41.2%) conducted for scrotal pain. Of the US performed for pain, 80.4% revealed benign or normal findings, and only 2.2% demonstrated a finding that is an absolute indication for surgery (intratesticular lesion suspicious for malignancy 0.8%, abscess 0.7%, torsion 0.6%, infiltrative process such as lymphoma 0.1%). For those patients undergoing an orchiectomy, 75% had malignancy on pathologic analysis. CONCLUSION: The majority of the 7668 US performed to evaluate scrotal or testicular pain reveal normal or benign findings. A low percentage demonstrates a finding that necessitates urgent or emergent surgery.

Dramatic increase in the utilization of multiparametric magnetic resonance imaging for detection and management of prostate cancer.

PURPOSE: Multiparametric MRI (mpMRI) of the prostate is an evolving technology that provides functional information of the prostate that helps distinguish benign from malignant lesions. We hypothesized that mpMRI is rapidly adopted in the US to fill the unmet need for a non-invasive, accurate screening tool. The aim of this study is to assess the increasing utilization of mpMRI for the diagnosis and management of prostate cancer. METHODS: We conducted a retrospective review of an institutional clinical data repository of four million patients. Clinical information from all men undergoing mpMRI from October 2013 to December 2015 was collected in a prospectively designed database. Individual chart reviews were performed for each patient. RESULTS: 1521 mpMRI of the prostate were performed with an increase in the use of 486% over 26 months. The most common indication for mpMRI was abnormal screening (64%) and 47% of these men went on to prostate biopsy, either by cognitive mapping (65%) or MRI-US fusion targeting (35%). 261 men elected to defer prostate needle biopsy after informative decision-making with their urologist. 12.7% of mpMRI were performed for active surveillance, 7.5% for clinical staging, and 3.2% by radiation oncologists planning radiotherapy. 7% of mpMRI were performed to evaluate the pelvis for biochemical recurrence, a third of which identified a region of suspicion for targeted. CONCLUSION: Prostate mpMRI is increasingly performed for both the diagnosis and management of prostate cancer. As clinical utilization increases along with the diffusion of technology and radiologic expertise, MpMRI has the potential to influence clinical decision-making and fulfill the need for a non-invasive, accurate tool for the diagnosis and management of prostate cancer.

Extraprostatic Extension Is Extremely Rare for Contemporary Gleason Score 6 Prostate Cancer.

BACKGROUND: A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. OBJECTIVE: To assess pathologic stage of pure GS6 at radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: In the period 2003-2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a-b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. RESULTS AND LIMITATIONS: Of the 60 GS6 pT3a-b cases identified in the period 2003-2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. CONCLUSIONS: In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. PATIENT SUMMARY: GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles.

High-Risk of Adverse Pathologic Features in Patients With Clinical T1 High-Grade Bladder Cancer Undergoing Radical Cystectomy.

BACKGROUND: Radical cystectomy (RC) is used to treat select patients with T1 high-grade (T1HG) bladder cancer. However, population-level utilization trends and outcomes for these patients are not well-known. We sought to evaluate treatment patterns and clinicopathologic outcomes of RC for T1HG bladder cancer. PATIENTS AND METHODS: Using the National Cancer Data Base (NCDB) for 1998-2012, we conducted a retrospective cohort study of patients with clinical T1HG bladder cancer. The prevalence of RC used to treat T1HG bladder cancer from 1998-2012 was determined. For years 2010-2012, demographic and cancer-related factors were described and regression analysis was used to examine associations with RC. Oncologic outcomes of RC were described and related to mortality using Cox proportional hazards regression. RESULTS: Treatment of T1HG bladder cancer with RC nearly doubled, from 5.5% during 1998-2000 to 9.9%, during 2010-2012. For 2010-2012, 18,277 patients with T1HG bladder cancer were analyzed. Patients who underwent RC were younger, had fewer comorbidities, and were more often treated at an academic center than those who did not undergo RC. At the time of RC, 41% of patients with T1HG bladder cancer were upstaged (pT2 or greater) and 12.7% had lymph node metastases. The 1- and 3-year survival rates were 0.89 and 0.68, respectively. Extravesical (T3+) disease at RC had the strongest independent hazard (hazard ratio [HR], 2.32; 95% CI, 1.72-3.11) of death other than age of 82 years or older (HR, 3.40; 95% CI, 2.28-5.07). CONCLUSIONS: The use of RC for T1HG bladder cancer has increased in prevalence in recent years but is still not widely used. There are concerning pathologic outcomes in patients with clinical T1HG bladder cancer treated with RC, including high rates of pathologic upstaging and nodal metastases. Future studies are necessary to better risk-stratify patients with T1HG bladder cancer to best select those who will benefit from aggressive therapy with RC.

Genomic characterization of high-risk non-muscle invasive bladder cancer.

The genetic mechanisms associated with progression of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have not been described. We conducted selective next-generation sequencing (NGS) of HR-NMIBC and compared the genomic profiles of cancers that responded to intravesical therapy and those that progressed to muscle-invasive or advanced disease. DNA was extracted from paraffin-embedded sections from 25 HR-NMIBCs (22 with T1HG; 3 with TaHG with or without carcinoma in situ). Ten patients with HR-NMIBC developed progression (pT2+ or N+) ("progressors"). Fifteen patients had no progression ("non-progressors"). Tissue from 11 patients with metastatic bladder cancer (BC) were analyzed for comparison. We found no difference in frequency of mutations of TP53, PIK3CA, or KMT2D between the primary tumors of progressors compared to non-progressors and metastatic tumors. An increased frequency of deletions of CDKN2A/B was identified in tumors at progression (37%) compared to non-progressors (6%) (p = 0.10). We found a significant decrease in total mutational burden (TMB) that has been associated with immunotherapy response comparing non-progressors, progressors and metastatic tumors at 15, 10.1 and 5.1 mutations/MB respectively (p = 0.02). This association suggests more advanced tumors have decreased neoantigen burden and may explain the mechanism of BCG response in non-progressors. We found no novel genetic drivers in progressors and HR-NMIBC had many genetic features similar to metastatic BC. Loss of CDKN2A/B may occur late during invasion of BC and may represent an important step in progression. Further research is necessary to evaluate TMB and loss of CDKN2A/B locus as a biomarker for progression of NMIBC.

Complete Vesicourethral Anastomotic Disruption Following Prostatectomy.

Vesicourethral anastomotic (VUA) disruption with bladder displacement into the abdominal cavity following robot-assisted laparoscopic prostatectomy (RALP) is an exceedingly rare complication. There have been no cited case reports after robotic surgery but case reports after open radical prostatectomy have been noted. Other complications related to VUA include bleeding with or without pelvic hematoma, bladder neck contracture, or severe stress urinary incontinence. Following radical prostatectomy, studies estimate the rate of VUA leakage to be 1.4% and no exact rate of complete disruption is known given its rarity. However, the majority of these cases are managed conservatively and rarely require reoperation. To date, there are no published studies that describe complete VUA and bladder displacement secondary to a large pelvic hematoma following prostatectomy. We report a rare case of VUA disruption after RALP successfully managed with conservative treatment.

The Evolving Management of Patients With Clinical Stage I Seminoma.

OBJECTIVE: To determine trends in management and factors associated with men receiving either chemotherapy or radiation therapy post orchiectomy for clinical stage I (CSI) seminoma in a contemporary setting. PATIENTS AND METHODS: The National Cancer Data Base was queried for all patients with CSI seminoma from 1998 to 2012. Adjuvant treatment after orchiectomy was classified into 3 groups: surveillance, radiotherapy, and chemotherapy. Yearly trends in management are described. Subgroup analysis for the years 2010-2012 was completed using logistic regression to determine predictors of receiving treatment. RESULTS: Of 80,385 patients with testicular cancer, 16,931 had CSI seminoma. There was a progressive decline in the use of post-orchiectomy treatment from 1998 to 2012. In the years 2010-2012 (n = 5816), 59.9% of patients chose surveillance compared with 25.1% receiving radiotherapy and 15.0% receiving chemotherapy. Regression modeling demonstrated that men aged 18-30 were less likely (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.69-1.00, P = .048) to receive treatment than those aged 31-37. Increasing pathologic stage was associated with a greater likelihood of treatment (OR 1.77, 95% CI 1.52-2.06), whereas patients treated at academic hospitals were less likely to receive adjuvant therapy (OR 0.77, 95% CI 0.62-0.94). CONCLUSION: Despite a trend toward increased use of post-orchiectomy surveillance for patients with CSI seminoma, a significant portion of patients are still receiving treatment. Pathologic stage and treating hospital type have the strongest association with management decisions. Improved guideline adherence may reduce the potential for adverse effects after chemotherapy or radiation therapy for CSI seminoma.

Bladder Pneumatosis From a Catastrophic Vascular Event.

Air within the bladder wall, or bladder pneumatosis, is a very rare finding typically resulting from an infectious etiology, as in emphysematous cystitis (EC). However, there have been reports of bladder pneumatosis occurring without clear infectious origins. We present a case of a female patient found to have concurrent bladder and ileal pneumatosis secondary to a catastrophic vascular event. Prompt recognition of non-infectious etiologies of bladder pneumatosis is essential as this distinction may dramatically alter clinical decision-making.

Lower Urinary Tract Symptoms Secondary to Mass Lesion of the Brain: A Case Report and Review of the Literature.

Lower urinary tract symptoms (LUTS) secondary to neurologic disorders are well-established, but intracranial mass lesions are rare causes of LUTS with very few case reports described in the literature. We present a 28-year old man with urinary urgency, frequency and incontinence which were revealed to be secondary to a large thrombosed intracranial aneurysm. Any unusual clinical presentations of LUTS such as new onset neurologic symptoms need to be explored to rule out potentially treatable causes.

The Gender Divide: The Impact of Surgeon Gender on Surgical Practice Patterns in Urology.

PURPOSE: There is a perception in urology that female urologists encounter gender based role assignments and are often pigeonholed into caring for more female patients and female specific urological issues than their male colleagues. We assessed the influence of surgeon gender on patient gender demographics by exploring the surgical case logs of American urologists. MATERIALS AND METHODS: Six-month case logs of certifying urologists from 2003 to 2012 were obtained from the ABU (American Board of Urology). We reviewed case logs based on CPT codes of common urological procedures, focusing on 6 index gender neutral and gender specific procedure groups, including treatment of nephrolithiasis, nephrectomy, resection of bladder tumors, treatment of stress urinary incontinence, elective sterilization and treatment of prostate cancer. RESULTS: Among a cohort of 6,166 urologists 1,011,800 cases were logged. Female surgeons operated on a significantly higher percent of female patients than their male peers (54.4% vs 32.5%, p <0.01). Female surgeons performed significantly more female specific procedures, such as slings, than their male counterparts (18 vs 10 per year, p <0.001). Male urologists performed significantly more male specific procedures than their female colleagues, including 3 times as many vasectomies (32 vs 12 per year, p <0.001) and more than twice as many prostatectomies (15 vs 6 per year, p <0.001). These trends were consistent across all subspecialties and geographic regions (p <0.01). CONCLUSIONS: Female surgeon gender has a significant influence on patient gender demographics among index urological procedures. As the number of women in urology grows, increasing attention to gender biases is necessary to understand how these disparities will shape the clinical landscape.