Diagnostic miRNA Signatures in Paired Tumor, Plasma, and Urine Specimens From Renal Cell Carcinoma Patients.

BACKGROUND: The incidence of patients diagnosed with renal cell carcinoma (RCC) is increasing. There are no approved biofluid biomarkers for routine diagnosis of RCC patients. This retrospective study aims to identify cell-free microRNA (cfmiR) signatures in urine samples that can be utilized as biomarkers for early diagnosis of sporadic RCC patients. METHODS: Tissue, plasma, and urine samples (n = 221) from 56 sporadic RCC patients and respective normal healthy donors were profiled for 2083 microRNAs (miRs) using the next-generation sequencing-based HTG EdgeSeq miR Whole Transcriptome Assay. DESeq2 (FC |1.2|, false discovery rate <0.05) was performed to identify differentially expressed miRs. Data from RCC tissue samples of The Cancer Genome Atlas database were used for miR validation. RESULTS: We found a 10-miR signature that distinguished RCC tissues from remote normal kidney tissue or benign kidney lesion samples. Additionally, we identified subtype-specific miRs (miR-122-5p, miR-210-3p, and miR-21-3p) and miRs specific for all RCC subtypes (miR-106b-3p, miR-629-5p, and miR-885-5p). We observed that miR-155-5p was associated with tumor size. Using The Cancer Genome Atlas data sets, we validated the miRs found in RCC tissue samples. In plasma or urine analysis, we found cfmiRs that were consistently and significantly upregulated in RCC tissue samples. A 15-cfmiR signature was proposed in urine samples of RCC patients, of which miR-1275 was consistently upregulated in tissue, plasma, and urine samples. CONCLUSIONS: This integrative study found diagnostic miRs/cfmiRs for RCC patients, which were validated using The Cancer Genome Atlas data sets. Distinctive cfmiR signatures found in urine may have clinical utility for the diagnosis of RCC.

Two-stage classifiers that minimize PCA3 and the PSA proteolytic activity testing in the prediction of prostate cancer recurrence after radical prostatectomy.

INTRODUCTION: Early biochemical recurrence after prostate cancer surgery is associated with higher risk of aggressive disease and cancer specific death. Many new tests are being developed that will predict the presence of indicators of aggressive disease like early biochemical recurrence. Since recurrence occurs in less than 10% of patients treated for prostate cancer, validation of such tests will require expensive testing on large patient groups. Moreover, clinical application of the validated test requires that each new patient be tested. In this report we introduce a two-stage classifier system that minimizes the number of patients that must be tested in both the validation and clinical application of any new test for recurrence. MATERIALS AND METHODS: Expressed prostatic secretion specimens were prospectively collected from 450 patients prior to robot-assisted radical prostatectomy for prostate cancer. Patients were followed for 2.5 years for evidence of biochemical recurrence. Standard clinical parameters, the levels proteolytic activity of prostate specific antigen (PSA) and the levels of PCA3 RNA, PSA RNA and TMPRSS2:ERG fusion RNA were determined in each prospective patient specimen for subsequent correlation with biochemical recurrence. RESULTS: While levels of PCA3 and PSA proteolytic activity (PPA) in prostatic secretions provided an effective pre-surgical predictor of early biochemical recurrence in prostate cancer, application of the two-stage classifier shows that only 60% of the patients need these tests. CONCLUSION: Two-stage classifiers can provide a parsimonious approach to both the validation and clinical application of biomarker-based tests. Adoption of the two-stage neutral zone classifier can reduce unnecessary testing in prostate cancer treatment.

Ureteroenteric anastomotic revision as initial management of stricture after urinary diversion.

OBJECTIVE: To report our experience with ureteroenteric anastomotic revision as initial treatment of stricture after urinary diversion. METHODS: An institutional review board-approved retrospective study was carried out. A total of 41 patients who underwent primary ureteroenteric anastamotic revision were identified between 2007 and 2015. Data analyzed included patient characteristics, type of diversion, estimated blood loss, operative time, change in renal function, length of stay, postoperative complications and time with nephrostomy/stent. Success of revision was defined as an improvement in hydronephrosis on radiographic imaging and/or reflux during pouchogram. Predictors of length of stay and complications were analyzed using analysis of covariance. RESULTS: A total of 50 renal units were revised with a success rate of 100%. The median length of stay was 6 days (2-16 days). There were a total of 15 complications (one major, 14 minor) in 14 patients (33% 30-day complication rate). The most common were wound infection (n = 4) and arrhythmia (n = 4). Robotic revision (n = 5) had a median length of stay of 3 days (2-4) with no complications. CONCLUSIONS: Primary ureteroenteric anastomotic revisions have an excellent success rate at an experienced center and might obviate the need for multiple interventions. Open revision is associated with mostly minor complications. Robotic revision might reduce the morbidity of open revision in select cases.

Early and late complications of robot-assisted radical cystectomy: a standardized analysis by urinary diversion type.

PURPOSE: Minimally invasive surgical treatment for bladder cancer has gained popularity but standardized data on complications are lacking. Urinary diversion type contributes to complications and to our knowledge diversion types after minimally invasive cystectomy have not yet been compared. We evaluated perioperative complications stratified by urinary diversion type in patients treated with robot-assisted radical cystectomy. MATERIALS AND METHODS: We analyzed the records of 209 consecutive patients who underwent robot-assisted radical cystectomy at our institution from 2003 to 2012 with respect to perioperative complications, including severity, time period (early and late) and diversion type. All complications were reviewed by academic urologists. Urinary diversion was also done. As outcome measurements and statistical analysis, univariate and multivariate logistic regression models were used to determine predictors of various complications. RESULTS: The American Society of Anesthesiologists(®) (ASA) score was 3 or greater in 80% of patients and continent diversion was performed in 68%. Median followup was 35 months. Within 90 days 77.5% of patients experienced any complication and 32% experienced a major complication. The 90-day mortality rate was 5.3%. Most complications were gastrointestinal, infectious and hematological. On multivariate analysis patients with ileal conduit diversion had a decreased likelihood of complications compared to patients with Indiana pouch and orthotopic bladder substitute diversion despite the selection of a more comorbid population for conduit diversion. Continent diversion was associated with a higher likelihood of urinary tract infection. Our results are comparable to those of previously reported open and minimally invasive cystectomy series. CONCLUSIONS: Open or minimally invasive cystectomy is a complex, morbid procedure. Urinary diversion is a significant contributor to complications, as is patient comorbidity. Although patients with an ileal conduit had more comorbidities, they experienced fewer complications than those with an orthotopic bladder substitute or Indiana pouch diversion.

Pooled analysis of clinical outcomes with neoadjuvant cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer.

PURPOSE: Neoadjuvant chemotherapy for muscle invasive bladder cancer has been shown to confer a survival advantage in phase III studies. Although cisplatin and gemcitabine are often used in this setting, a comprehensive evaluation of this regimen is lacking. In this review we summarize the efficacy of neoadjuvant cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer based on currently published studies. MATERIALS AND METHODS: A systematic literature review was conducted in April 2012 searching MEDLINE® databases. Articles were selected if they included patients with muscle invasive bladder cancer, evaluated the combination of cisplatin and gemcitabine as neoadjuvant treatment, and reported pathological data after cystectomy. Cisplatin and gemcitabine dosing regimens and clinical data were further summarized using weighted averages. RESULTS: Seven studies encompassing 164 patients were published between 2007 and 2012. The majority of patients (79%) received cisplatin and gemcitabine on a 21-day cycle. A weighted average of 19.2 lymph nodes was obtained at cystectomy, and 29.7% of patients were found to have pN1 disease. Pathological down staging to pT0 and less than pT2 occurred in 42 (25.6%) and 67 (46.5%) patients, respectively. CONCLUSIONS: Neoadjuvant cisplatin and gemcitabine yield appreciable pathological response rates in patients with muscle invasive bladder cancer. Since pathological response has been implicated as a potential surrogate for survival in muscle invasive bladder cancer, these data suggest that neoadjuvant cisplatin and gemcitabine may warrant further prospective assessment.

Standardized comparison of robot-assisted limited and extended pelvic lymphadenectomy for prostate cancer.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Extended pelvic lymphadenectomy is the present standard of care according to European Association of Urology guidelines. Extended dissection improves staging, removes more metastatic lymph nodes, and potentially has therapeutic benefits. Previous reports have examined the morbidity of extended dissection compared with a more limited dissection in the open and laparoscopic setting. While some have suggested an increased complication rate with extended node dissection, others have not. This represents the first study focused on comparing the complications associated with the extent of node dissection using the modified Clavien system and Martin criteria in the literature on robot-assisted surgery. In a single surgeon series, we found no statistically significant differences in complications. With careful anatomic dissection, robot-assisted extended lymph node dissection can be performed safely and effectively, although operating time and length of hospital of stay are slightly increased. OBJECTIVES: To compare the perioperative course of patients undergoing robot-assisted limited lymph node dissection (LLND) or extended lymph node dissection (ELND) for prostate cancer. To examine the differential lymph node counts and rates of detection of lymph node metastases. PATIENTS AND METHODS: Between 2008 and 2012, 406 consecutive patients with D'Amico intermediate- or high-risk prostate cancer underwent either bilateral LLND (n = 204) or ELND (n = 202) and robot-assisted laparoscopic radical prostatectomy by a single surgeon. The region of dissection was the obturator fossa for LLND, while ELND included, in addition, the common iliac, external iliac and internal iliac lymph nodes. All complications within 90 days of surgery were recorded according to a modified Clavien system. Clinical variables were summarized and compared. Logistic regression was used to identify predictors of complications. RESULTS: There were no differences in demographics when comparing patients who underwent ELND with those who underwent LLND. The median operating time was 3.0 h for the ELND cohort and 2.8 h in the LLND cohort (P < 0.001). Intraoperative blood loss was 200 mL in both cohorts. Hospital stay was longer for a small percentage of patients in the ELND cohort, with 75% of ELND patients and 85% of LLND patients staying 1 day (P = 0.004). No significant difference was found in the overall or major complication rates between LLND (21.6% overall; 6.9% major) and ELND (22.8% overall; 4.5% major). No difference was seen in the symptomatic lymphocele rate between LLND and ELND, 2.9 vs 2.5%, respectively. Overall, the lymph-node-positive rate was 12% compared with 4% for the ELND and LLND groups, respectively (P = 0.002). A higher Charlson comorbidity index score was associated with the development of major complications. CONCLUSIONS: ELND at the time of robot-assisted radical prostatectomy can be performed safely with minimal additional morbidity. Long-term oncological and functional outcomes require further study.

Penile cancer: Clinical Practice Guidelines in Oncology.

Squamous cell carcinoma of the penis represents approximately 0.5% of all cancers among men in the United States and other developed countries. Although rare, it is associated with significant disfigurement, and only half of the patients survive beyond 5 years. Proper evaluation of both the primary lesion and lymph nodes is critical, because nodal involvement is the most important factor of survival. The NCCN Clinical Practice Guidelines in Oncology for Penile Cancer provide recommendations on the diagnosis and management of this devastating disease based on evidence and expert consensus.

Bladder cancer.

Bladder cancer is the fourth most common cancer in the United States. Urothelial carcinoma that originates from the urinary bladder is the most common subtype. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) provide recommendations on the diagnosis and management of non-muscle-invasive and muscle-invasive urothelial carcinoma of the bladder. This version of the guidelines provides extensive reorganization and updates on the principles of chemotherapy management.

Characterization of Lymph Node Tumor Burden in Node-Positive Prostate Cancer Patients after Robotic-Assisted Radical Prostatectomy with Extended Pelvic Lymph Node Dissection.

BACKGROUND: Prostate cancer (PCa) nodal staging does not account for lymph node (LN) tumor burden. The LN anatomical compartment involved with the tumor or the quantified extent of extranodal extension (ENE) have not yet been studied in relation to biochemical recurrence-free survival (BRFS). METHODS: Histopathological slides of 66 pN1 PCa patients who underwent extended pelvic lymph node dissection were reviewed. We recorded metrics to quantify LN tumor burden. We also characterized the LN anatomical compartments involved and quantified the extent of ENE. RESULTS: The median follow-up time was 38 months. The median number of total LNs obtained per patient was 30 (IQR 23-37). In the risk-adjusted cox regression model, the following variables were associated with BRFS: mean size of the largest LN deposit per patient (log2: adjusted hazard ratio (aHR) = 1.91, p < 0.001), the mean total span of all LN deposits per patient (2.07, p < 0.001), and the mean percent surface area of the LN involved with the tumor (1.58, p < 0.001). There was no significant BRFS association for the LN anatomical compartment or the quantified extent of ENE. CONCLUSION: LN tumor burden is associated with BRFS. The LN anatomical compartments and the quantified extent of ENE did not show significant association with BRFS.

Controlling the dorsal venous complex during robotic prostatectomy.

INTRODUCTION: The objective of our study was to determine whether dorsal venous complex (DVC) control technique influences positive apical margins following robotic assisted laparoscopic radical prostatectomy (RALRP). MATERIALS AND METHODS: One thousand fifty-eight patients who underwent RALRP at City of Hope from June 2007 to October 2009 were assessed. Endoscopic stapling and suture ligature of the DVC were compared. Positive apical margins were identified and compared based on DVC-control technique. Recurrence probability was estimated using the Kaplan-Meier method, and logistic regression analysis was used to predict the odds of positive apical margins. RESULTS: Of 1058 patients, 633 (60%) underwent endoscopic stapling, and 425 (40%) had suture ligature. The groups had similar baseline characteristics including age and body mass index. We observed a statistically different PSA (5.4 ng/mL versus 5.2 ng/mL, p = 0.03) and operative time (2.8 hours versus 2.7 hours, p = 0.02) between stapling and suture groups, but the actual difference was small. Operative time, Gleason score, pathologic stage, and overall positive margin rates were not significantly different between groups. Positive apical margins were observed in 39 (6%) and 27 (6%) patients in the staple and suture groups, respectively. Multivariate analysis showed that the positive apical margin rate was greater in patients with higher pathologic stage and final pathological Gleason score. CONCLUSIONS: During RALRP, there is no difference in positive apical margin rate when the DVC is controlled using either endoscopic stapling or suture ligature. However, patients with a higher pathologic stage and final pathologic Gleason score are at higher risk for positive apical surgical margins.

Urine Cell-Free MicroRNAs in Localized Prostate Cancer Patients.

Prostate cancer (PCa) is the most common cancer in men. Prostate-specific antigen screening is recommended for the detection of PCa. However, its specificity is limited. Thus, there is a need to find more reliable biomarkers that allow non-invasive screening for early-stage PCa. This study aims to explore urine microRNAs (miRs) as diagnostic biomarkers for PCa. We assessed cell-free miR (cfmiR) profiles of urine and plasma samples from pre- and post-operative PCa patients (n = 11) and normal healthy donors (16 urine and 24 plasma) using HTG EdgeSeq miRNA Whole Transcriptome Assay based on next-generation sequencing. Furthermore, tumor-related miRs were detected in formalin-fixed paraffin-embedded tumor tissues obtained from patients with localized PCa. Specific cfmiRs signatures were found in urine samples of localized PCa patients using differential expression analysis. Forty-two cfmiRs that were detected were common to urine, plasma, and tumor samples. These urine cfmiRs may have potential utility in diagnosing early-stage PCa and complementing or improving currently available PCa screening assays. Future studies may validate the findings.

Cryopreserved placental tissue allograft accelerates time to continence following robot-assisted radical prostatectomy.

Intra-operatively placed cryopreserved placental tissue allograft (CPTA) has shown promise in expediting the recovery urinary continence (UC) following robot-assisted radical prostatectomy (RARP). In this retrospective review of a prospectively maintained single-surgeon, single-institution RARP database, we compare three groups of patients: historical controls (C; N = 183 men) that received no allograft versus two different CPTA products (total CPTA N = 162 [A1 N = 81; A2 N = 81]). The CPTA product was intra-operatively placed as an onlay over the area of the neurovascular bundles during RARP. CPTA cases had significantly faster median time to UC (A1 = 1.4 months; A2 = 1.45 months) versus controls (1.64 months), p = 0.01. On multivariable analysis, use of A1 (HR 1.55, 95% CI [1.14-2.09], p = 0.005) and use of A2 (HR 1.53, CI [1.11-2.11], p = 0.01) were significantly associated with quicker return of UC. Older age (HR 0.97, CI [0.96-0.99], p = 0.001) and non-organ-confined clinical stage (HR 0.51, CI [0.26-1.0] p = 0.05), were significantly associated with slower return of UC. In a propensity score-matched analysis of 77 CPTA patients with sufficient follow-up versus controls, there was significantly less biochemical recurrence (BCR; p = 0.01). Our study indicates that CPTA use appears to accelerate time to UC in age- and performance status-matched men undergoing RARP without increased risk of BCR.

Robotic assisted laparoscopic salvage prostatectomy for radiation resistant prostate cancer.

PURPOSE: We report on outcomes of robotic assisted laparoscopic radical prostatectomy as salvage local therapy for radiation resistant prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the charts of all patients who underwent robotic assisted laparoscopic radical prostatectomy for biopsy proven prostate cancer after primary radiation treatment. Patient characteristics, intraoperative and perioperative data, and oncological and functional outcomes were assessed. RESULTS: A total of 18 patients were identified with a median followup of 18 months (range 4.5 to 40). Primary treatment was brachytherapy in 8 patients and external beam radiation in 8, while 2 underwent proton beam therapy. Median age at salvage robotic assisted laparoscopic radical prostatectomy was 67 years (range 53 to 76). Median preoperative prostate specific antigen was 6.8 ng/ml (range 1 to 28.9) and median time to surgery after primary treatment with radiation was 79 months (range 7 to 146). Median operative parameters for estimated blood loss, surgery length and hospital stay were 150 ml, 2.6 hours and 2 days, respectively. No patient required conversion to open surgery or a blood transfusion, or experienced a rectal injury. Perioperative complications occurred in 7 patients (39%) of which the most common was urine leak identified by postoperative cystogram. Five patients (28%) had a positive surgical margin. Although some patients had limited followup, 6 (33%) were continent and 67% were free of biochemical progression. CONCLUSIONS: Robotic assisted laparoscopic radical prostatectomy can be performed safely as salvage local therapy after failed radiation therapy. Outcomes are comparable to those of large series of open salvage prostatectomy.

Four-arm robotic partial nephrectomy for complex renal cell carcinoma.

OBJECTIVES: Laparoscopic partial nephrectomy (LPN) remains challenging to even experienced laparoscopists. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery (NSS). We represented our technique and results of robotic partial nephrectomy (RPN) for hilar, endophytic, and multiple renal tumors. MATERIALS AND METHODS: Between May 2006 and March 2008, 29 patients with complex renal tumors underwent RPN, including hilar (n = 14), endophytic (n = 12) and multiple tumors (n = 3).The hilar vessels were clamped with laparoscopic bulldog with warm ischemia. Follow-up ranged from 3 to 23 months (mean of 15 mo). The perioperative data and pathologic results were retrospectively reviewed. RESULTS: Robotic partial nephrectomy procedures were performed successfully without complications. The mean diameter of tumors was 3.0 cm (range 2.0-4.0). The mean operative time was 197 minutes (range 172-259), and the mean blood loss was 220 ml (range 100-370). The mean warm ischemia time (WIT) was 25 min (range 16-43). The hospital stay averaged 2.5 days (range 2-3). Histopathology confirmed clear-cell carcinoma (n = 21), chromophobe cell carcinoma (n = 4), hybrid oncocytic tumor (n = 2), oncocytoma (n = 1), and cystic renal cell carcinoma (n = 1). All cases had negative surgical margins. At the 3-23 months (mean of 15 mo) follow-up, no patients experienced a significant change of glomerular filtration rate compared to preoperative levels and there was no evidence of tumor recurrence. CONCLUSION: Robotic partial nephrectomy is a safe and feasible procedure. RPN is a preferred approach for complex renal tumors when NSS is indicated. For complex and technical challenging renal tumors, robotic assistance may provide patients the benefit of minimally invasive surgery.

Re-establishing the Role of Robot-assisted Radical Cystectomy After the 2020 EAU Muscle-invasive and Metastatic Bladder Cancer Guideline Panel Recommendations.

The EAU guidelines panel on muscle-invasive and metastatic bladder cancer (MIBC) recently recommended open radical cystectomy (ORC) as the best surgical approach for MIBC patients. We critically re-examine the indications for considering ORC as the first choice over robot-assisted radical cystectomy. To the best of our knowledge, this is not supported by trials or meta-analyses.

Performance of a single assay for both type III and type VI TMPRSS2:ERG fusions in noninvasive prediction of prostate biopsy outcome.

BACKGROUND: TMPRSS2:ERG fusions are promising prostate cancer biomarkers. Because they can occur in multiple forms in a single cancer specimen, we developed a quantitative PCR test that detects both type III and type VI TMPRSS2:ERG fusions. The assay is quantified from a standard curve determined with a plasmid-cloned type III TMPRSS2:ERG fusion target. METHODS: We collected expressed prostatic secretion (EPS) under an institutional review board-approved, blinded, prospective study from 74 patients undergoing transrectal ultrasound-guided biopsy for prostate cancer. We compared the characteristic performance of the test for type III and type VI TMPRSS2:ERG fusions in predicting biopsy outcome and distinguishing between high and low Gleason scores with similar tests for the expression of PCA3 and DNA methylation levels of the APC, RARB, RASSF1, and GSTP1 genes. We used logistic regression to analyze the effects of multiple biomarkers in linear combinations. RESULTS: Each test provided a significant improvement in characteristic performance over baseline digital rectal examination (DRE) plus serum prostate-specific antigen (PSA); however, the test for type III and type VI TMPRSS2:ERG fusions yielded the best performance in predicting biopsy outcome [area under the curve (AUC) 0.823, 95% CI 0.728-0.919, P < 0.001] and Gleason grade >7 (AUC 0.844, 95% CI 0.740-0.948, P < 0.001). CONCLUSIONS: Although each test appears to have diagnostic value, PSA plus DRE plus type III and type VI TMPRSS2:ERG provided the best diagnostic performance in EPS specimens.

The impact of prostate gland weight in robot assisted laparoscopic radical prostatectomy.

PURPOSE: We determined whether prostate weight has an impact on the pathological and operative outcomes of robot assisted laparoscopic radical prostatectomy. MATERIALS AND METHODS: We reviewed the records of 1,847 consecutive patients who underwent robot assisted laparoscopic radical prostatectomy at our institution. Variables were compared across quartile distributions of prostate size as defined by weight, including group 1-less than 30 gm, group 2-30 to 49.9, group 3-50 to 69.9 and group 4-70 or greater. Factors assessed in this analysis were patient age, body mass index, prostate specific antigen, Gleason score, pathological stage, margin status, operative time, blood loss, transfusion rate, length of stay and rehospitalization rate. RESULTS: Patients with a larger prostate (group 4) were older (mean age 66.2 years), had higher pretreatment prostate specific antigen (median 6.5 ng/ml), lower Gleason score (mean 6.3), longer operative time (mean 3.2 hours), higher estimated blood loss (median 250 cc) and longer hospital stay (p = 0.0002). There was a trend toward higher risk disease based on D'Amico risk stratification and positive margin status in group 1, although evidence of extracapsular extension was more common in groups 2 and 3. There was no association between prostate size and body mass index, lymph node status, blood transfusion rate, seminal vesicle involvement and rehospitalization rate. CONCLUSIONS: Robot assisted laparoscopic radical prostatectomy in patients with an enlarged prostate is feasible with slightly longer operative time, urinary leakage rates and hospital stay. Pathologically larger prostates are generally associated with lower Gleason score and risk group stratification. One-year continence rates and biochemical recurrence rates are similar across all groups.

Sentinel node evaluation in prostate cancer.

Sentinel lymph node (SLN) based pelvic lymph node dissection (PLND) in prostate cancer (PCa) is appealing over the time, cost and morbidity classically attributed to conventional PLND during radical prostatectomy. The initial report of feasibility of the SLN concept in prostate cancer was nearly 20 years ago. However, PLND based on the SLN concept, either SLN biopsy of a single node or targeted SLN dissection of multiple nodes, is still considered investigational in PCa. To better appreciate the challenges, and potential solutions, associated with SLN-based PLND in PCa, this review will discuss the rationale behind PLND in PCa and evaluate current SLN efforts in the most commonly diagnosed malignancy in men in the US.

Emerging Utility of Urinary Cell-free Nucleic Acid Biomarkers for Prostate, Bladder, and Renal Cancers.

CONTEXT: By 2020 the estimated incidence of genitourinary (GU) cancers (prostate, bladder, and kidney) will be over 2 million worldwide and responsible for ∼800 000 deaths. Current diagnosis and monitoring methods of GU cancer patients are often invasive and/or lack sensitivity and specificity. Given the utility of blood-based cell-free nucleic acid (cfNA) biomarkers, the development of urinary cfNA biomarkers may improve the sensitivity of urine assays utilizing urine sediment for GU cancers. This review of urinary cfNA in GU cancers identifies the current stage of research, potential clinical utility, and the next steps needed to enter clinical use. OBJECTIVE: To critically evaluate the literature of urinary cfNA in GU cancers for clinical utility in diagnosis, screening, and precision medicine. Furthermore, the strategy for future efforts to discover potential new urinary cfNA biomarkers will be described. EVIDENCE ACQUISITION: A PubMed database (2006 to current) search was performed according to Preferred Reporting Items for Systemic Review and Meta-analysis using key Medical Subject Headings terms. Additional studies were obtained by cross-referencing from the literature. EVIDENCE SYNTHESIS: The collective research publications in urinary cfNA of GU cancers present a promising alternative liquid biopsy approach compared with blood biopsies and urine sediment, particularly for early-stage GU diseases. CONCLUSIONS: Urinary cfNA as a liquid biopsy holds potential for a more sensitive alternative to blood biopsies and urine sediment-based tests for clinical use in GU cancers. Not only does urinary cfNA offer advantages including the potential for more frequent testing, monitoring, and home use, but also has applications in early-stage GU cancers. PATIENT SUMMARY: In this review, we evaluated the current status of urinary cell-free nucleic acid in genitourinary cancers. We identified the potential advantages of urinary cell-free nucleic acid over blood and urine sediment and its clinical use in genitourinary cancer.

Lymph Node Fluorescence During Robot-Assisted Radical Prostatectomy With Indocyanine Green: Prospective Dosing Analysis.

OBJECTIVE: To prospectively assess the ideal dosing and the value of fluorescent sentinel lymph node (LN) detection with indocyanine green (ICG) for the detection of LN metastases in intermediate- and high-risk patients undergoing robot-assisted prostatectomy and extended pelvic LN dissection (ePLND). PATIENTS AND METHODS: Twenty patients received transperineal prostatic injections of ICG. Patients were cycled through 5 doses (1.25, 2.5, 3.75, 5, and 7.5 mg) so optimal ICG dosing could be discovered early. RESULTS: ICG injection was able to identify fluorescent LN (FLN) packets in all 20 patients. Compared to the higher ICG doses, the 1.25 and 2.5 mg doses had fewer FLN packets and were abandoned after 1 dose each. The median number of FLN packets was 4.0, 6.0, and 4.5 for the respective doses of 3.75, 5.0, and 7.5 mg. The external iliac group was the most common site of fluorescence in 27.2% of patients, followed by the common iliac (21.3%), obturator (20.3%), internal iliac (18.5%), and node of Cloquet (7.7%). Seven (35%) of 20 patients had node-positive disease. Of the 5 patients that had fluorescent tissue outside of our ePLND template, 1 had a positive node present in the anterior bladder neck fat. Across all patients, ICG had 62% sensitivity, 50% specificity, 8% positive predictive value, and 95% negative predictive value in detecting LN metastases. CONCLUSION: The low sensitivity of ICG for the detection of LN metastases highlights why FLN dissection with ICG does not represent an alternative to ePLND.