The Association of Ischemia Type and Duration with Acute Kidney Injury after Robot-Assisted Partial Nephrectomy.

BACKGROUND: Acute kidney injury (AKI) after robot-assisted partial nephrectomy (RAPN) is a robust surrogate for chronic kidney disease. The objective of this study was to evaluate the association of ischemia type and duration during RAPN with postoperative AKI. MATERIALS AND METHODS: We reviewed all patients who underwent RAPN at our institution since 2011. The ischemia types were warm ischemia (WI), selective artery clamping (SAC), and zero ischemia (ZI). AKI was defined according to the Risk Injury Failure Loss End-Stage (RIFLE) criteria. We calculated ischemia time thresholds for WI and SAC using the Youden and Liu indices. Logistic regression and decision curve analyses were assessed to examine the association with AKI. RESULTS: Overall, 154 patients met the inclusion criteria. Among all RAPNs, 90 (58.4%), 43 (28.0%), and 21 (13.6%) were performed with WI, SAC, and ZI, respectively. Thirty-three (21.4%) patients experienced postoperative AKI. We extrapolated ischemia time thresholds of 17 min for WI and 29 min for SAC associated with the occurrence of postoperative AKI. Multivariable logistic regression analyses revealed that WIT ≤ 17 min (odds ratio [OR] 0.1, p < 0.001), SAC ≤ 29 min (OR 0.12, p = 0.002), and ZI (OR 0.1, p = 0.035) significantly reduced the risk of postoperative AKI. CONCLUSIONS: Our results confirm the commonly accepted 20 min threshold for WI time, suggest less than 30 min ischemia time when using SAC, and support a ZI approach if safely performable to reduce the risk of postoperative AKI. Selecting an appropriate ischemia type for patients undergoing RAPN can improve short- and long-term functional kidney outcomes.

Novel Classification for Upper Tract Urothelial Carcinoma to Better Risk-stratify Patients Eligible for Kidney-sparing Strategies: An International Collaborative Study.

BACKGROUND: The European Association of Urology risk stratification dichotomizes patients with upper tract urothelial carcinoma (UTUC) into two risk categories. OBJECTIVE: To evaluate the predictive value of a new classification to better risk stratify patients eligible for kidney-sparing surgery (KSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study including 1214 patients from 21 centers who underwent ureterorenoscopy (URS) with biopsy followed by radical nephroureterectomy (RNU) for nonmetastatic UTUC between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariate logistic regression analysis identified predictors of muscle invasion (≥pT2) at RNU. The Youden index was used to identify cutoff points. RESULTS AND LIMITATIONS: A total of 811 patients (67%) were male and the median age was 71 yr (interquartile range 63-77). The presence of non-organ-confined disease on preoperative imaging (p < 0.0001), sessile tumor (p < 0.0001), hydronephrosis (p = 0.0003), high-grade cytology (p = 0.0043), or biopsy (p = 0.0174) and higher age at diagnosis (p = 0.029) were independently associated with ≥pT2 at RNU. Tumor size was significantly associated with ≥pT2 disease only in univariate analysis with a cutoff of 2 cm. Tumor size and all significant categorical variables defined the high-risk category. Tumor multifocality and a history of radical cystectomy help to dichotomize between low-risk and intermediate-risk categories. The odds ratio for muscle invasion were 5.5 (95% confidence interval [CI] 1.3-24.0; p = 0.023) for intermediate risk versus low risk, and 12.7 (95% CI 3.0-54.5; p = 0.0006) for high risk versus low risk. Limitations include the retrospective design and selection bias (all patients underwent RNU). CONCLUSIONS: Patients with low-risk UTUC represent ideal candidates for KSS, while some patients with intermediate-risk UTUC may also be considered. This classification needs further prospective validation and may help stratification in clinical trial design. PATIENT SUMMARY: We investigated factors predicting stage 2 or greater cancer of the upper urinary tract at the time of surgery for ureter and kidney removal and designed a new risk stratification. Patients with low or intermediate risk may be eligible for kidney-sparing surgery with close follow-up. Our classification scheme needs further validation based on cancer outcomes.

Pretreatment Risk Stratification for Endoscopic Kidney-sparing Surgery in Upper Tract Urothelial Carcinoma: An International Collaborative Study.

BACKGROUND: Several groups have proposed features to identify low-risk patients who may benefit from endoscopic kidney-sparing surgery in upper tract urothelial carcinoma (UTUC). OBJECTIVE: To evaluate standard risk stratification features, develop an optimal model to identify ≥pT2/N+ stage at radical nephroureterectomy (RNU), and compare it with the existing unvalidated models. DESIGN, SETTING, AND PARTICIPANTS: This was a collaborative retrospective study that included 1214 patients who underwent ureterorenoscopy with biopsy followed by RNU for nonmetastatic UTUC between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed multiple imputation of chained equations for missing data and multivariable logistic regression analysis with a stepwise selection algorithm to create the optimal predictive model. The area under the curve and a decision curve analysis were used to compare the models. RESULTS AND LIMITATIONS: Overall, 659 (54.3%) and 555 (45.7%) patients had ≤pT1N0/Nx and ≥pT2/N+ disease, respectively. In the multivariable logistic regression analysis of our model, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.0-1.03, p = 0.013), high-grade biopsy (OR 1.81, 95% CI 1.37-2.40, p < 0.001), biopsy cT1+ staging (OR 3.23, 95% CI 1.93-5.41, p < 0.001), preoperative hydronephrosis (OR 1.37 95% CI 1.04-1.80, p = 0.024), tumor size (OR 1.09, 95% CI 1.01-1.17, p = 0.029), invasion on imaging (OR 5.10, 95% CI 3.32-7.81, p < 0.001), and sessile architecture (OR 2.31, 95% CI 1.58-3.36, p < 0.001) were significantly associated with ≥pT2/pN+ disease. Compared with the existing models, our model had the highest performance accuracy (75% vs 66-71%) and an additional clinical net reduction (four per 100 patients). CONCLUSIONS: Our proposed risk-stratification model predicts the risk of harboring ≥pT2/N+ UTUC with reliable accuracy and a clinical net benefit outperforming the current risk-stratification models. PATIENT SUMMARY: We developed a risk stratification model to better identify patients for endoscopic kidney-sparing surgery in upper tract urothelial carcinoma.

Functional Outcomes after Local Salvage Therapies for Radiation-Recurrent Prostate Cancer Patients: A Systematic Review.

PURPOSE: To assess the rate and severity of functional outcomes after salvage therapy for radiation recurrent prostate cancer. METHODS: This systematic review of the MEDLINE/PubMed database yielded 35 studies, evaluating salvage radical prostatectomy (RP), brachytherapy (BT), high-intensity focal ultrasound (HIFU) and cryotherapy (CT) after failure of primary radiation therapy. Data on pre- and post-salvage rates and severity of functional outcomes (urinary incontinence, erectile dysfunction, and lower urinary tract symptoms) were collected from each study. RESULTS: The rates of severe urinary incontinence ranged from 28-88%, 4.5-42%, 0-6.5%, 2.4-8% post salvage RP, HIFU, CT and BT, respectively. The rates of erectile dysfunction were relatively high reaching as much as 90%, 94.6%, 100%, 62% following RP, HIFU, CT and BT, respectively. Nonetheless, the high pre-salvage rates of ED preclude accurate estimation of the effect of salvage therapy. There was an increase in the median IPSS following salvage HIFU, BT and CT ranging from 2.5-3.4, 3.5-12, and 2, respectively. Extended follow-up showed a return-to-baseline IPSS in a salvage BT study. The reported data suffer from selection, reporting, publication and period of study biases, making inter-study comparisons inappropriate. CONCLUSIONS: local salvage therapies for radiation recurrent PCa affect continence, lower urinary tract symptoms and sexual functions. The use of local salvage therapies may be warranted in the setting of local disease control, but each individual decision must be made with the informed patient in a shared decision working process.

Pre-therapy serum albumin-to-globulin ratio in patients treated with neoadjuvant chemotherapy and radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: The accurate selection of patients who are most likely to benefit from neoadjuvant chemotherapy is an important challenge in oncology. Serum AGR has been found to be associated with oncological outcomes in various malignancies. We assessed the association of pre-therapy serum albumin-to-globulin ratio (AGR) with pathologic response and oncological outcomes in patients treated with neoadjuvant platin-based chemotherapy followed by radical nephroureterectomy (RNU) for clinically non-metastatic UTUC. METHODS: We retrospectively included all clinically non-metastatic patients from a multicentric database who had neoadjuvant platin-based chemotherapy and RNU for UTUC. After assessing the pretreatment AGR cut-off value, we found 1.42 to have the maximum Youden index value. The overall population was therefore divided into two AGR groups using this cut-off (low, < 1.42 vs high, ≥ 1.42). A logistic regression was performed to measure the association with pathologic response after NAC. Univariable and multivariable Cox regression analyses tested the association of AGR with OS and RFS. RESULTS: Of 172 patients, 58 (34%) patients had an AGR < 1.42. Median follow-up was 26 (IQR 11-56) months. In logistic regression, low AGR was not associated with pathologic response. On univariable analyses, pre-therapy serum AGR was neither associated with OS HR 1.15 (95% CI 0.77-1.74; p = 0.47) nor RFS HR 1.48 (95% CI 0.98-1.22; p = 0.06). These results remained true regardless of the response to NAC. CONCLUSION: Pre-therapy low serum AGR before NAC followed by RNU for clinically high-risk UTUC was not associated with pathological response or long-term oncological outcomes. Biomarkers that can complement clinical factors in UTUC are needed as clinical staging and risk stratification are still suboptimal leading to both over and under treatment despite the availability of effective therapies.

The Performance of Tumor Size as Risk Stratification Parameter in Upper Tract Urothelial Carcinoma (UTUC).

INTRODUCTION: The objective of this study was to evaluate the performance of different tumor diameters for identifying ≥ pT2 upper tract urothelial carcinoma (UTUC) at radical nephroureterectomy. PATIENTS AND METHODS: This was a multi-institutional retrospective study that included 932 patients who underwent radical nephroureterectomy for nonmetastatic UTUC between 2000 and 2016. Tumor sizes were pathologically assessed and categorized into 4 groups: ≤ 1 cm, 1.1 to 2 cm, 2.1 to 3 cm, and > 3 cm. We performed logistic regression and decision-curve analyses. RESULTS: Overall, 45 (4.8%) patients had a tumor size ≤ 1 cm, 141 (15.1%) between 1.1 and 2 cm, 247 (26.5%) between 2.1 and 3 cm, and 499 (53.5%) > 3 cm. In preoperative predictive models that were adjusted for the effects of standard clinicopathologic features, tumor diameters > 2 cm (odds ratio, 2.38; 95% confidence interval, 1.70-3.32; P < .001) and > 3 cm (odds ratio, 1.81; 95% confidence interval, 1.38-2.38; P < .001) were independently associated with ≥ pT2 pathologic staging. The addition of the > 2-cm diameter cutoff improved the area under the curve of the model from 58.8% to 63.0%. Decision-curve analyses demonstrated a clinical net benefit of 0.09 and a net reduction of 8 per 100 patients. CONCLUSION: The 2-cm cutoff appears to be most useful in identifying patients at risk of harboring ≥ pT2 UTUC. This confirms the current European Association of Urology guideline's risk stratification. Tumor size alone is not sufficient for optimal risk stratification, rather a constellation of features is needed to select the best candidate for kidney-sparing surgery.

Efficacy of Preoperative Chemotherapy for High Risk Upper Tract Urothelial Carcinoma.

PURPOSE: The impact of preoperative chemotherapy in patients with upper urinary tract urothelial carcinoma remains poorly investigated. We assessed the rates of pathological complete response (pT0N0/X) and downstaging (pT1N0/X or less) at radical nephroureterectomy after preoperative chemotherapy and evaluated their impact on survival. MATERIALS AND METHODS: This was an international observational study of patients who underwent preoperative chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma between 2005 and 2017. Multiple imputation of chained equations was applied to account for missing values. Logistic regression analyses were performed to identify predictors of pathological response. Cox proportional hazard regression models were used to estimate recurrence-free survival, cancer specific survival and overall survival. RESULTS: A total of 267 patients met our inclusion criteria. Among included patients 82 (31%) received methotrexate, vinblastine, doxorubicin and cisplatin; 123 (46%) gemcitabine and cisplatin; 25 (9%) gemcitabine and carboplatin; and 32 (12%) other regimens. The overall rates of pathological complete response and pathological downstaging were 10.1% and 44.9%, respectively. On multivariable analysis the use of gemcitabine and cisplatin, and gemcitabine and carboplatin was not statistically different from methotrexate, vinblastine, doxorubicin and cisplatin in achieving pathological complete response and pathological downstaging, respectively. The number of administered cycles did not appear to have an effect on pathological responses. Pathological downstaging was the strongest prognostic factor for recurrence-free survival (HR 0.2, p <0.001), cancer specific survival (HR 0.19, p <0.001) and overall survival (HR 0.40, p <0.001). CONCLUSIONS: Pathological downstaging after preoperative chemotherapy is a robust prognostic factor at radical nephroureterectomy and is associated with improved survival outcomes. Although preoperative chemotherapy appears to be effective, well designed prospective studies are still needed.

Performance of [68Ga] Ga-PSMA 11 PET for detecting prostate cancer in the lymph nodes before salvage lymph node dissection: a systematic review and meta-analysis.

BACKGROUND: Salvage lymph node dissection (sLND) for nodal recurrence in prostate cancer (PCa) patients with biochemical recurrence (BCR) is still not recommended in current guidelines, because of the diagnostic inaccuracy of current conventional imaging. To assess the performance of [68Ga] Ga-prostate-specific membrane antigen conjugate 11 positron emission tomography (PSMA-PET) in detecting PCa lymph node metastasis using pathologic confirmation through sLND. METHODS: Literature search was conducted using the MEDLINE, SCOPUS, Web of Science, and Cochrane Library on November 11th, 2018 to identify the eligible studies. Studies were eligible if they investigated the diagnostic performance of PSMA-PET before sLND in PCa patients with BCR and reported the number of true positive, false positive, false negative, and true negative on a lesion-based and/or field-based analyses to compare with histopathologic findings in sLND specimens. RESULTS: Fourteen studies published between 2015 and 2018 comprising 462 patients were selected in this systematic review and meta-analysis. The positive predictive value of PSMA-PET before sLND on a patient-based analysis ranged between 0.70 and 0.93. The pooled sensitivity using lesion-based and field-based analyses were 0.84 (95%CI: 0.61-0.95) and 0.82 (95%CI: 0.72-0.89), respectively. The pooled specificity using lesion-based and field-based analyses were 0.97 (95%CI: 0.95-0.99) and 0.95 (95%CI: 0.70-0.99), respectively. The diagnostic odds ratio using lesion-based and field-based analyses were 189 (95%CI: 39-920) and 82 (95%CI: 8-832), respectively. CONCLUSIONS: PSMA-PET before sLND provided highly accurate performance with clinically relevant high positive and negative predictive values for detecting lymph node disease in patients with BCR after local treatment with curative intent for PCa. PSMA-PET can identify the patients who are likely to benefit from sLND and possibly direct to lesion or region-based dissection.

Comparative Effectiveness in Perioperative Outcomes of Robotic versus Open Radical Cystectomy: Results from a Multicenter Contemporary Retrospective Cohort Study.

BACKGROUND: The comparative effectiveness of robotic-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) in terms of perioperative outcomes is still a matter of debate affecting payors, physicians, and patients. OBJECTIVE: To evaluate comparative perioperative and longer-term morbidity of RARC versus ORC in a multicenter contemporary retrospective cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter study included patients with bladder cancer treated with radical cystectomy at 10 academic centers between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Intraoperative outcomes including blood loss and operative time as well as postoperative outcomes including time to discharge, complication, readmission, reoperation, and mortality rates at 30 and 90 d were assessed. Multiple imputation and inverse probability of treatment weighting (IPTW) were used. IPTW-multivariable-adjusted regression and logistic analyses were performed to evaluate the associations of RARC versus ORC with perioperative outcomes at 30 and 90 d. RESULTS AND LIMITATIONS: Overall, 1887 patients (1197 RARC and 690 ORC) were included in the study. After IPTW-adjusted analysis, no differences between the groups in terms of preoperative characteristics were observed. RARC was associated with lower blood loss (p<0.001), shorter length of stay (p<0.001), and longer operative time (p=0.007). On IPTW-adjusted multivariable logistic regression analyses, no differences in terms of 30- and 90-d complications, reoperation, and mortality rates were observed. RARC was independently associated with a higher readmission rate at both 30 and 90 d. Limitations are mainly related to the retrospective nature of the study. CONCLUSIONS: While RARC was associated with less blood loss and shorter hospital stay, it also led to longer operation times and more readmissions. There were no differences in 30- and 90-d complications. Because there are no apparent differences in safety between ORC and RARC in expert centers, differences in oncologic and cost-effectiveness outcomes are likely to drive decision making regarding RARC utilization. PATIENT SUMMARY: In this study we investigated the differences between RARC and ORC in terms of perioperative outcomes. We found no difference in early and late complications. We concluded that, to date, differences in oncologic and cost-effectiveness outcomes should drive decision making regarding RARC utilization.

Diagnostic Value of 18F-fluorodeoxyglucose Positron Emission Tomography with Computed Tomography for Lymph Node Staging in Patients with Upper Tract Urothelial Carcinoma.

BACKGROUND: Presence of lymph node metastases (LNM) is an important prognostic factor for cancer-specific survival (CSS) in patients with upper tract urothelial carcinoma (UTUC). In various neoplasms, 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) is an established modality for preoperative lymph node (LN) staging. In UTUC, the diagnostic value of FDG-PET/CT for LN staging is unknown. OBJECTIVE: To determine the diagnostic value of FDG-PET/CT for LN staging in patients with UTUC. DESIGN, SETTING, AND PARTICIPANTS: Data of 152 patients with UTUC who underwent FDG-PET/CT followed by surgical treatment in eight centers between 2007 and 2017 were retrospectively collected. Patients receiving neoadjuvant chemotherapy were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: FDG-PET/CT results were compared with histopathology after lymph node dissection (LND). Recurrence-free survival (RFS), CSS, and overall survival (OS) were analyzed using Kaplan-Meier estimates, and compared for patients with and without suspicious LNs on FDG-PET/CT. RESULTS AND LIMITATIONS: We included 117 patients, of whom 62 underwent LND. Seventeen patients had LNM at histopathological evaluation. Sensitivity and specificity of FDG-PET/CT for diagnosis of LNM were 82% (95% confidence interval [CI]: 57-96) and 84% (95% CI: 71-94), respectively. RFS was significantly worse in patients with LN-positive FDG-PET/CT than in those with LN-negative FDG-PET/CT (p=0.03). CSS (p=0.11) and OS (p=0.5) were similar between groups. This study is limited by its retrospective design and by its sample size. Our results warrant further validation. CONCLUSIONS: FDG-PET/CT has 82% sensitivity and 84% specificity for the detection of LNM in patients with UTUC. Presence of suspicious LNs on FDG-PET/CT is associated with worse RFS. PATIENT SUMMARY: In patients with upper tract urothelial cancer, positron emission tomography with computed tomography (PET/CT) scans can detect lymph node metastases with noteworthy accuracy. Presence of suspicious lymph nodes on 18F-fluorodeoxyglucose PET/CT is associated with worse recurrence-free survival.

Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer.

PURPOSE: To investigate the prognostic role of expression of urokinase-type plasminogen activator system members, such as urokinase-type activator (uPA), uPA-receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). METHODS: Immunohistochemical staining for uPA system was performed on a tissue microarray of specimens from 3121 patients who underwent RP. Cox regression analyses were performed to investigate the association of overexpression of these markers alone or in combination with biochemical recurrence (BCR). Decision curve analysis was used to assess the clinical impact of these markers. RESULTS: uPA, uPAR, and PAI-1 were overexpressed in 1012 (32.4%), 1271 (40.7%), and 1311 (42%) patients, respectively. uPA overexpression was associated with all clinicopathologic characteristics of biologically aggressive PCa. On multivariable analysis, uPA, uPAR, and PAI-1 overexpression were all three associated with BCR (HR: 1.75, p < 0.01, HR: 1.22, p = 0.01 and HR: 1.20, p = 0.03, respectively). Moreover, the probability of BCR increased incrementally with increasing cumulative number of overexpressed markers. Decision curve analysis showed that addition of uPA, uPAR, and PAI-1 resulted in a net benefit compared to a base model comparing standard clinicopathologic features across the entire threshold probability range. In subgroup analyses, overexpression of all three markers remained associated with BCR in patients with favorable pathologic characteristics. CONCLUSION: Overexpression of uPA, uPAR, and PAI-1 in PCa tissue were each associated with worse BCR. Additionally, overexpression of all three markers is informative even in patients with favorable pathologic characteristics potentially helping clinical decision-making regarding adjuvant therapy and/or intensified follow-up.

Comparison of perioperative complications and health-related quality of life between robot-assisted and open radical cystectomy: A systematic review and meta-analysis.

To compare postoperative complications and health-related quality of life of patients undergoing robot-assisted radical cystectomy with those of patients undergoing open radical cystectomy. A systematic search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A pooled meta-analysis was carried out to assess the differences between robot-assisted radical cystectomy and open radical cystectomy according to randomized and non-randomized comparative studies, respectively. We identified six randomized comparative studies and 31 non-randomized comparative studies. Most robot-assisted radical cystectomy patients were treated with extracorporeal urinary diversion. Robot-assisted radical cystectomy was associated with longer operative times, and lower blood loss and transfusion rates compared with open radical cystectomy in both randomized comparative studies and non-randomized comparative studies. There was no significant difference between robot-assisted radical cystectomy and open radical cystectomy in the rate of patients with any or major complications within 90 days both in randomized comparative studies and non-randomized comparative studies. Non-randomized comparative studies reported a lower rate of complications at 30 days, mortality at 90 days and length of stay for patients treated with robot-assisted radical cystectomy, which were not confirmed in randomized comparative studies. Additionally, there were no differences in postoperative quality of life score assessment at 3 and 6 months between robot-assisted radical cystectomy and open radical cystectomy. Robot-assisted radical cystectomy is associated with less blood loss and lower transfusion rates. There is no difference in complications, length of stay, mortality, and quality of life between robot-assisted radical cystectomy and open radical cystectomy. Data from non-randomized comparative studies favor perioperative outcomes in robot-assisted radical cystectomy patients, the failure to confirm in randomized comparative studies, likely due to bias in study design and reporting. Further randomized comparative studies comparing postoperative complications and quality of life between robot-assisted radical cystectomy with intracorporeal urinary diversion and open radical cystectomy are required to assess potential differences between these two surgical approaches.

Oncologic outcomes after robot-assisted versus open radical cystectomy: a systematic review and meta-analysis.

PURPOSE: The efficacy of RARC in oncologic outcomes compared ORC is controversial. We assess potential differences in oncologic outcomes between robot-assisted radical cystectomy (RARC) and open radical cystectomy (ORC). METHODS: We performed the literature search systematically according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. A pooled meta-analysis was performed to assess the difference in oncologic outcomes between RARC and ORC, separately in randomized controlled trials (RCTs) and non-randomized studies (NRCTs). RESULTS: Five RCTs and 28 NRCTs were included in this systematic review and meta-analysis. There was no difference in the rate of overall positive surgical margin (PSM) in RCTs, while NRCTs showed a lower rate for RARC. There was no difference in the soft tissue PSM rate between RARC and ORC in both RCTs and NRCTs. There was no difference in the lymph node yield by standard and extended lymph node dissection between RARC and ORC in both RCTs and NRCTs. There was no significant difference in survival outcomes between RARC and ORC in both RCTs and NRCTs. CONCLUSIONS: Based on the current evidence, there is no difference in the rate of PSMs, lymph node yield, recurrence rate and location as well as short-term survival outcomes between RARC and ORC in RCTs. In NRCTs, only PSM rates were better for RARC compared to ORC, but this was likely due to selection and reporting bias which are inherent to retrospective study designs.

Optimal Management of Upper Tract Urothelial Carcinoma: an Unmet Need.

OPINION STATEMENT: Upper tract urothelial carcinoma (UTUC) is a rare genitourinary entity of the renal pelvis and the ureter characterized by a more aggressive disease phenotype when compared with urothelial carcinoma of the bladder (UCB) with more than half of UTUC cases presenting with invasive disease at diagnosis compared to 20% for bladder tumors. There is growing evidence suggesting that its distinct natural history from that of bladder cancer can be related to several genetic and epigenetic differences. Treatment of low-risk disease consists of kidney-sparing surgeries such as ureteroscopic and percutaneous treatments, segmental ureterectomy, and adjuvant topical and intracavitary chemo-immunotherapies. The standard of care for high-risk non-metastatic disease remains radical nephroureterectomy and bladder cuff excision with increasing utilization rates of minimally invasive approaches leading to reduced morbidity without compromising outcomes while the role of lymphadenectomy is still being investigated. The prognosis of UTUC has been stagnant over the past decade highlighting the need for further studies on the role of multimodal therapy (neoadjuvant/adjuvant chemotherapy, immunotherapy, targeted therapy) to optimize management and improve outcomes.

Endocavitary treatment for upper tract urothelial carcinoma: A meta-analysis of the current literature.

PURPOSE: To assess the oncologic impact of adjuvant endocavitary instillation after kidney-sparing surgery (KSS) in the treatment of upper tract urothelial carcinoma (UTUC). METHODS: A meta-analysis of the available literature was performed using PUBMED and MEDLINE on June 2018. No time or language restrictions were applied. All included participants were substratified into 2 groups: Ta/T1 UTUC and upper tract (UT) carcinoma in situ. Subjects with higher stage disease, involvement of the bladder, or urethra were excluded. Predefined endpoints of interest were rates of cytology response, UT recurrence, UT progression, cancer-specific survival, and overall survival. RESULTS: Overall, 27 eligible reports for a total of 438 patients were identified and 18 studies included for quantitative analyses. All included reports were nonrandomized observational case series. Among studies that reported on UT recurrence, 154 (35%) patients developed UT recurrence during a median follow-up of 30 months. The overall pooled estimates for adjuvant instillations in Ta-T1 patients were 40% for UT recurrence, 94% for cancer-specific survival, and 71% for OS. Subanalyses stratified by regimen used and instillation approach did not show any significant differences. In patients with UT carcinoma in situ treated with BCG, the pooled estimates for cytology response, UT recurrence, and progression were 84%, 34%, and 16%, respectively. Similarly, comparison between instillation approaches did not show any significant differences. CONCLUSIONS: In this meta-analysis of presumed nonmuscle invasive patients treated with kidney-sparing surgery, endocavitary instillations for noninvasive UTUC, did not reveal any differences between the regimens and instillations approaches. Patients with Ta-T1 UTUC had an UT recurrence rate comparable to that reported in the literature for nontreated patients. To date, the efficacy of endocavitary instillations in UTUC remains to be demonstrated. Upcoming novel drugs promise to change this paradigm.

Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy.

OBJECTIVE: To evaluate the incidence and survival outcomes of histological variants of upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analysed data from 1610 patients treated with RNU for clinically non-metastatic UTUC between 1990 and 2016 in several centres participating in the UTUC Collaboration. Histological variants were classified as micropapillary, squamous, sarcomatoid and other, including other rare variants (<10 cases for each). Multivariable competing risk analyses were conducted to assess the effect of variant histology on overall recurrence and cancer-specific mortality (CSM). RESULTS: Overall, 1460 patients (91%) had pure urothelial carcinoma (PUC), whereas 150 (9%) were diagnosed with a variant histology, including 89 (5.0%), 41 (2.0%), 10 (1.0%) and 10 (1.0%) cases of micropapillary, squamous, sarcomatoid and other tumours, respectively. Variant histology was associated with the presence of adverse pathological features compared with PUC, including non-organ-confined disease (59% vs 38%; P < 0.001), lymph node invasion (28% vs 24%; P = 0.02), high-grade disease (88% vs 71%; P < 0.001), tumour necrosis (28% vs 16%; P = 0.001) and positive surgical margins (15% vs 8%; P = 0.01). In competing risk analysis, micropapillary variant was the only factor associated with worse recurrence (sub-hazard ratio [SHR] 2.27, 95% confidence interval [CI] 1.25-4.79; P = 0.02) whereas sarcomatoid variant was associated with worse CSM (SHR 16.8, 95% CI 6.86-41.17; P < 0.001). CONCLUSION: We found that one out of 10 patients with UTUC treated with RNU had variant histology. Only micropapillary and sarcomatoid variants were associated with poorer oncological outcomes after adjusting for available confounding factors.

Perioperative blood transfusion affects oncologic outcomes after nephrectomy for renal cell carcinoma: A systematic review and meta-analysis.

AIM: To investigate the association of perioperative blood transfusion (PBT) with oncologic outcomes in patients with renal cell carcinoma (RCC), we conducted a systematic review and meta-analysis of the literature to clarify the long-term oncologic effect of PBT in patients undergoing nephrectomy for RCC. MATERIALS AND METHODS: We searched the MEDLINE, Web of Science, Cochrane Library and Scopus on 15th April 2018 to identify studies that compared patients who received PBT undergoing radical or partial nephrectomy for RCC to patients who did not with the aim of evaluating its impact on overall mortality (OM), cancer-specific mortality (CSM) and disease recurrence using multivariable cox regression analysis. RESULTS: A total of 19,681 patients in 7 studies matched the selection criteria for the systematic review and meta-analysis. All 7 studies were retrospective design and published between 1994 and 2018. Our study included low quality of eligible studies due to their retrospective design and showed a significant heterogeneity. PBT was associated with OM (pooled hazard ratio [HR], 1.49, 1.24-1.78), CSM (pooled HR, 1.46, 1.20-1.77), and disease recurrence (pooled HR, 1.80, 1.03-3.12). In a subgroup analysis of 3,664 patients with nonmetastatic RCC, PBT was remained associated with OM (pooled HR, 1.91; 1.06-3.41), but not anymore with CSM (pooled HR, 1.92, 0.94-3.91) or disease recurrence (pooled HR, 2.18, 0.86-5.55). CONCLUSIONS: PBT in patients undergoing nephrectomy for RCC is associated with worse overall survival. While PBT may be reflective of the underlying aggressiveness of the disease, it could be that its detrimental effect on outcomes is caused by its negative effect on the host's resilience.

A systematic review and meta-analysis of the impact of lymphovascular invasion in bladder cancer transurethral resection specimens.

The aim of the present review was to assess the prognostic impact of lymphovascular invasion (LVI) in transurethral resection (TUR) of bladder cancer (BCa) specimens on clinical outcomes. A systematic review and meta-analysis of the available literature from the past 10 years was performed using MEDLINE, EMBASE and Cochrane library in August 2017. The protocol for this systematic review was registered on PROSPERO (Central Registration Depository: CRD42018084876) and is available in full on the University of York website. Overall, 33 studies (including 6194 patients) evaluating the presence of LVI at TUR were retrieved. LVI was detected in 17.3% of TUR specimens. In 19 studies, including 2941 patients with ≤cT1 stage only, LVI was detected in 15% of specimens. In patients with ≤cT1 stage, LVI at TUR of the bladder tumour (TURBT) was a significant prognostic factor for disease recurrence (pooled hazard ratio [HR] 1.97, 95% CI: 1.47-2.62) and progression (pooled HR 2.95, 95% CI: 2.11-4.13), without heterogeneity (I2 = 0.0%, P = 0.84 and I2 = 0.0%, P = 0.93, respectively). For patients with cT1-2 disease, LVI was significantly associated with upstaging at time of radical cystectomy (pooled odds ratio 2.39, 95% CI: 1.45-3.96), with heterogeneity among studies (I2 = 53.6%, P = 0.044). LVI at TURBT is a robust prognostic factor of disease recurrence and progression in non-muscle invasive BCa. Furthermore, LVI has a strong impact on upstaging in patients with organ-confined disease. The assessment of LVI should be standardized, reported, and considered for inclusion in the TNM classification system, helping clinicians in decision-making and patient counselling.