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.

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.

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.

Prognostic Value of Concomitant Carcinoma In Situ in the Radical Cystectomy Specimen: A Systematic Review and Meta-Analysis.

PURPOSE: We investigated the prognostic impact of concomitant carcinoma in situ in radical cystectomy specimens. MATERIALS AND METHODS: We performed a systematic review and meta-analysis using MEDLINE®, Scopus®, Web of Science™ and The Cochrane Library to identify eligible studies published until October 2017. Studies were eligible for analysis if they compared patients with concomitant carcinoma in situ in radical cystectomy specimens for bladder cancer to patients without concomitant carcinoma in situ to determine its value to prognosticate overall mortality, recurrence-free survival, cancer specific mortality and ureteral involvement using multivariable analysis. The protocol for this systematic review was registered in PROSPERO (Prospective Register of Systematic Reviews, CRD42018086539) and is available in full on the University of York website. RESULTS: Overall 23 studies published between 2006 and 2017 including a total of 20,647 patients were selected for the systematic review and meta-analysis. Concomitant carcinoma in situ was reported in 39.4% of radical cystectomy specimens. In studies analyzing all patients the presence of concomitant carcinoma in situ was not associated with overall mortality (pooled HR 0.92, 0.77-1.10), recurrence-free survival (pooled HR 1.06, 0.99-1.13) or cancer specific mortality (pooled HR 1.00, 0.93-1.07). It was associated with ureteral involvement (pooled OR 4.51, 2.59-7.84). On subanalysis of studies restricted to patients with organ confined bladder cancer at radical cystectomy concomitant carcinoma in situ was associated with worse recurrence-free survival (pooled HR 1.57, 1.12-2.21) and cancer specific mortality (pooled HR 1.51, 1.001-2.280). CONCLUSIONS: Concomitant carcinoma in situ is significantly associated with ureteral involvement in patients treated with radical cystectomy. In patients with organ confined disease concomitant carcinoma in situ in the radical cystectomy specimen is a prognosticator of recurrence-free survival and cancer specific mortality.

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.

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.

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.

Development and external validation of a pathological nodal staging score for patients with clear cell renal cell carcinoma.

OBJECTIVES: To develop and externally validate a model that quantifies the likelihood that a pathologically node-negative patient with clear cell renal cell carcinoma (cRCC) has, indeed, no lymph node metastasis (LNM). PATIENTS AND METHODS: Data from 1389 patients treated with radical nephrectomy (RN) and lymph node dissection (LND) were analyzed. For external validation, we used data from 2270 patients in the Surveillance, Epidemiology and End Results (SEER) database. We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a pathological nodal staging score (pNSS), which represents the probability that a patient is correctly staged as node negative as a function of the number of examined lymph nodes (LNs). RESULTS: The mean and median number of LNs removed were 7.0 and 5.0 (standard deviation, SD 6.6; interquartile range, IQR 7.0) in the development cohort and 5.6 and 2.0 (SD 8.6, IQR 5.0) in the validation cohort, respectively. The probability of missing a positive LN decreased with increasing number of LNs examined. In both the validation and the development cohort, the number of LNs needed for correctly staging a patient as node negative increased with higher pathological tumor stage and Fuhrman grade. CONCLUSIONS: The number of examined LNs needed for adequate nodal staging in cRCC depends on pathological tumor stage and Fuhrman grade. We developed here and then externally validated a pNSS, which could help to refine patient counseling, decision-making regarding risk-stratified surveillance regimens and inclusion criteria for clinical trials of adjuvant therapy.

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.

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.

Is neutrophil-to-lymphocytes ratio a clinical relevant preoperative biomarker in upper tract urothelial carcinoma? A meta-analysis of 4385 patients.

BACKGROUND: Preoperative blood-based inflammatory biomarkers have been suggested to improve staging and prognostication in patients with upper-tract urothelial carcinoma (UTUC). Neutrophil-to-lymphocyte ratio (NLR) is the most studied blood-based biomarker. NLR is an indicator of systemic inflammation and has been shown to be associated with a poor prognosis in various malignancies. The aim of this study was to analyze the current evidence regarding the prognostic significance of preoperative NLR in patients undergoing radical nephroureterectomy (RNU) for UTUC to assess its prognostic potential. MATERIALS AND METHODS: A systematic search of Web of Science, Medline/PubMed and Cochrane library was performed on the 1st of October, 2017. Studies were deemed eligible if they compared patients with high NLR before surgical treatment for UTUC to patients with low NLR to determine its predictive value for survival using multivariable logistic regression analysis. We performed a formal meta-analysis for cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS). RESULTS: Nine studies including a total of 4385 patients assessing the importance of NLR were included in this meta-analysis. The cut-off NLR varied in the eligible studies ranging from 2 to 3. Increased pretreatment NLR predicted OS (pooled HR 1.64 95% CI; 1.23-2.17), RFS (pooled HR 1.60 95% CI; 1.16-2.20) and CSS (pooled HR 1.73 95% CI; 1.23-2.44) in multivariable analyses. CONCLUSION: In this meta-analysis, preoperative blood-based NLR is associated with worse prognosis in patients who underwent RNU for UTUC. NLR could be used to improve clinical decision making regarding RNU vs. kidney-sparing surgery, extent of lymphadenectomy, perioperative systemic therapy and follow-up schedule.

Accuracy and prognostic value of variant histology and lymphovascular invasion at transurethral resection of bladder.

OBJECTIVES: To evaluate the concordance rate of lymphovascular invasion (LVI) and variant histology (VH) of transurethral resection (TUR) with radical cystectomy (RC) specimens. Furthermore, to evaluate the value of LVI and VH at TUR for predicting non-organ confined (NOC) disease, lymph node metastasis, and survival outcomes. PATIENTS AND METHODS: Two hundred and sixty-eight patients who underwent TUR and subsequent RC were reviewed. Logistic regression analyses were performed to evaluate the association of LVI and VH with NOC and lymph node metastasis at RC. Cox regression analyses were used to estimate recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: LVI and VH were detected in 13.8 and 11.2% of TUR specimens, and in 30.2 and 25.4% of RC specimens, respectively. The concordance rate between LVI and VH at TUR and subsequent RC was 69.8 and 83.6%, respectively. They were both associated with adverse pathological features such as lymph node metastasis and advanced stage. TUR LVI and VH were both independently associated with lymph node metastasis and TUR VH was independently associated with NOC. On univariable Cox regression analyses, TUR LVI was associated with RFS and CSS while TUR VH was only associated with RFS. Only TUR LVI was independently associated with RFS. CONCLUSION: Detection of LVI is missed in a third of TUR specimens while VH seems more accurately identified. TUR LVI and VH are associated with more advanced disease and LVI predicts disease recurrence. Assessment and reporting of LVI and VH on TUR specimen are important for risk stratification and decision-making.

Oncologic outcomes after minimally invasive surgery for cT1 renal masses: a comprehensive review.

PURPOSE OF REVIEW: To evaluate current literature reporting oncologic outcomes after robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN). RECENT FINDINGS: Recently, there have been published first mid-term results after RAPN (5 years). To date, there are no randomized trials to guide decision-making regarding LPN or robotic partial nephrectomy (RPN), and such trials are unlikely to be forthcoming, given the rapid adoption of RAPN worldwide. We performed a literature search according to Cochrane guidelines up to 1 September 2017, including studies that had more than 40 months of oncologic follow-up. SUMMARY: A total of 2933 patients were included from 14 studies (1498 RAPN, 1525 LPN). RAPN had similar mid-term (5 years) oncologic outcomes as LPN. Large collaborative efforts are still necessary to provide solid long-term oncologic outcomes of open, laparoscopic, and RPN.

Robot-assisted partial nephrectomy: systematic review of functional results.

PURPOSE OF REVIEW: Various ischemia type during partial nephrectomy for renal cell cancer (RCC) resulted in different postoperative functional outcomes. Our objective was to systematically review the contemporary literature on robot-assisted partial nephrectomy (RPN) and investigate the association of ischemia type and tumor complexity with postoperative functional outcomes of the operated kidney and overall. RECENT FINDINGS: Forty-five of the 99 reports identified were selected for qualitative analysis. All included studies were observational and nonrandomized. Overall, we found that patients undergoing RPN with zero ischemia and selective artery clamping had a lower decrease in glomerular filtration rates of the operated kidney in comparison to both warm and cold ischemia. This association seems also to play a role in patients with bilateral kidneys harboring complex tumors. SUMMARY: Zero ischemia and selective artery clamping provide the best functional outcomes following robotic partial nephrectomy. This seems to be of particular relevance in patients with single kidney or tumors of high complexity. Whether these changes are statistically or clinically significant cannot be determined within this systematic review.

Frequency and Prognostic Value of PTEN Loss in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy.

PURPOSE: To our knowledge the frequency and prognostic significance of PTEN protein expression in upper tract urothelial carcinoma have not yet been investigated in large studies. We analyzed PTEN protein status and its association with disease recurrence and survival outcomes in a large, multi-institutional upper tract urothelial carcinoma cohort. MATERIALS AND METHODS: We retrospectively analyzed the records of 611 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy between 1991 and 2008 at a total of 7 institutions. Median followup was 23 months. Tissue microarrays and immunohistochemical PTEN staining (monoclonal antibody) were performed. Univariable and multivariable Cox regression models were created to address the association of PTEN protein expression with disease recurrence, and cancer specific and overall mortality. RESULTS: PTEN staining was absent in 45 cases (7.4%). Patients with PTEN loss had significantly advanced pathological tumor stage and grade (p <0.001), and higher rates of lymph node metastasis (p <0.01) and lymphovascular invasion (p <0.001) compared to patients with PTEN expression. PTEN loss was associated with disease recurrence, and cancer specific and overall mortality on univariable Cox regression analyses. However, on multivariable Cox regression analyses adjusted for the effect of standard clinicopathological features PTEN loss was only associated with overall mortality (HR 1.69, 95% CI 1.09-2.61, p = 0.02). CONCLUSIONS: In patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma loss of PTEN protein expression is rare but associated with features of biologically aggressive disease such as higher grade and stage as well as lymph node metastasis. Loss of PTEN expression was associated with overall mortality. PTEN loss seemed to promote worse outcomes in this relatively small group of patients.

Trends of lymphadenectomy in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy.

INTRODUCTION: To evaluate temporal trends in the delivery and extent of lymphadenectomy (LND) in radical nephroureterectomy (RNU) performed in upper tract urothelial carcinoma (UTUC) patients. METHODS: We evaluated a multi institutional collaborative database composed by 1512 consecutive patients diagnosed with UTUC treated with RNU between 1990 and 2016. Year of surgery were grouped in five periods: 1990-1996, 1997-2002, 2003-2007, 2008-2012 and 2013-2016. Data about LND were available for all patients and numbers of nodes removed and positive were reported by dedicate uropathologists. The Mann-Whitney and Chi square tests were used to compare the statistical significance of differences in medians and proportions, respectively. RESULTS: Five hundred forty-five patients (36.0%) received a concomitant LND while 967 (64.0%) did not; 41.9% of open RNU patients received a concomitant LND compared to 24.4% of laparoscopic RNU patients. The rate of concomitant LND increased with time in the overall, laparoscopic and open RNU patients (all p < 0.03). Patients treated with open RNU also had an increasing likelihood to receive an adequate concomitant LND (p < 0.001) while those undergoing a laparoscopic approach did not (p = 0.1). Patients treated with concomitant LND had a median longer operative time of 20 min (p = 0.01). There were no differences in perioperative outcomes and complications between patients who received a concomitant LND and those who did not (p > 0.1). CONCLUSION: Although an increased trend was observed, most patients treated with RNU did not receive LND. Surgeons using a laparoscopic RNU were less likely to perform a concomitant LND, and when done, they remove less nodes.

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.

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.

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.