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ObjectiveTo externally validate Yonsei nomogram. MethodsFrom 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR >= 60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage >= III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at . Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage >= III was assessed by calibration and discrimination analysis. Results and limitationMedian values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage >= III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study. ConclusionsThe largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up.

Context With the addition of active surveillance and thermal ablation (TA) to the urologist’s established repertoire of partial (PN) and radical nephrectomy (RN) as first-line management options for localized renal cell carcinoma (RCC), appropriate treatment decision-making has become increasingly nuanced. Objective To critically review the treatment options for localized, nonrecurrent RCC; to highlight the patient, renal function, tumor, and provider factors that influence treatment decisions; and to provide a framework to conceptualize that decision-making process. Evidence acquisition A collaborative critical review of the medical literature was conducted. Evidence synthesis We identify three key decision points when managing localized RCC: (1) decision for surveillance versus treatment, (2) decision regarding treatment modality (TA, PN, or RN), and (3) decision on surgical approach (open vs minimally invasive). In evaluating factors that influence these treatment decisions, we elaborate on patient, renal function, tumor, and provider factors that either directly or indirectly impact each decision point. As current nomograms, based on preselected patient datasets, perform poorly in prospective settings, these tools should be used with caution. Patient decision aids are an underutilized tool in decision-making. Conclusions Localized RCC requires highly nuanced treatment decision-making, balancing patient- and tumor-specific clinical variables against indirect structural influences to provide optimal patient care. Patient summary With expanding treatment options for localized kidney cancer, treatment decision is highly nuanced and requires shared decision-making. Patient decision aids may be helpful in the treatment discussion.

Radical nephrectomy (RN) is the gold standard treatment for large and locally advanced renal tumors. Although robot-assisted radical nephrectomy (RRN) is being increasingly adopted, it remains unclear whether it offers benefits over standard laparoscopic radical nephrectomy (LRN) or open radical nephrectomy (ORN).To compare the outcomes of robotic surgery to those of laparoscopic and open surgery in patients undergoing RN for renal cell carcinoma (RCC).A systematic search was performed across MEDLINE, EMBASE, and Web of Science for retrospective and prospective studies comparing RRN to LRN or ORN. A meta-analysis evaluated perioperative safety, effectiveness, survival, and cost-effectiveness outcomes. The weighted mean difference (WMD) and odds ratio (OR) were used to compare continuous and dichotomous variables, respectively. Quality was assessed using the Newcastle-Ottawa scale. Sensitivity analyses were performed to assess the robustness of the estimates.Twelve studies involving 64 221 patients were identified and included in the analysis. Compared to LRN, RRN was associated with statistically significant longer operative time (WMD 37.44 min; p = 0.03), shorter length of stay (WMD -0.84 days; p = 0.02) and higher total costs (WMD US$4700; p0.001). Compared to ORN, RRN was associated with shorter length of stay (WMD -3.06 days; p = 0.002), fewer overall complications (OR 0.56; p 0.001), lower estimated blood loss (WMD -702 ml; p = 0.01), and higher total hospital costs (WMD US$4520; p = 0.004). There was high heterogeneity across all analyses.In patients undergoing RN for RCC, RRN seems to offer some key advantages compared to ORN, including shorter hospitalization and fewer complications. Compared to LRN, RRN provides similar surgical outcomes but at higher total costs. These findings should be interpreted within the limitations of this type of analysis, given high heterogeneity between studies and poor robustness for most outcomes. Randomized clinical studies with long-term follow-up are needed to obtain more definitive results.In patients with renal cell carcinoma, robot-assisted radical nephrectomy shows perioperative advantages compared to open radical nephrectomy, but not compared to laparoscopic radical nephrectomy.

This case presents a 68-yr-old female patient with primary metastatic nonclear renal cell carcinoma (RCC) with multiple bone lesions. The patient underwent a single resection of skull bone lesion (diagnostic for poorly differentiated carcinoma of unknown origin) and cytoreductive nephrectomy. The pathology of the kidney specimen demonstrated an oncocytic papillary RCC. Within 3 mo, she developed skeletal progressive disease and was started on systemic therapy (sunitinib). After initial stabilization, bone metastasis progressed during the third cycle of sunitinib and required second-line therapy (cabozantinib). One of the major unmet needs in non-clear cell RCC is the lack of specific systemic therapy. Data on immunotherapy are still limited. Inclusion of these patients in clinical trials is strongly recommended. PATIENT SUMMARY: Patients with metastatic kidney cancer who present with the less common histological subtype (non-clear cell) have poor survival. In this case, the patient responded to second-line therapy. Very few therapies provide response to treatment. Patients should be offered participation in clinical trials testing combinations with immunotherapy.

Objective To evaluate the survival outcomes of patients with local recurrence after radical nephrectomy (RN) and to test the effect of surgery, as monotherapy or in combination with systemic treatment, on cancer-specific mortality (CSM). Methods Patients with local recurrence after RN were abstracted from an international dataset. The primary outcome was CSM. Cox’s proportional hazard models tested the main predictors of CSM. Kaplan–Meier method estimates the 3-year survival rates. Results Overall, 96 patients were included. Of these, 44 (45.8%) were metastatic at the time of recurrence. The median time to recurrence after RN was 14.5 months. The 3-year cancer-specific survival rates after local recurrence were 92.3% (± 7.4%) for those who were treated with surgery and systemic therapy, 63.2% (± 13.2%) for those who only underwent surgery, 22.7% (± 0.9%) for those who only received systemic therapy and 20.5% (± 10.4%) for those who received no treatment (p p = 0.001) or no treatment (HR: 5.63, 95% CI 2.21–14.92, p = 0.001) were both independently associated with higher CSM rates, even after multivariable adjustment. Following surgical treatment of local recurrence 8 (16.0%) patients reported complications, and 2/8 were graded as Clavien–Dindo ≥ 3. Conclusions Surgical treatment of local recurrence after RN, when feasible, should be offered to patients. Moreover, its association with a systemic treatment seems to warrantee adjunctive advantages in terms of survival, even in the presence of metastases.

Purpose To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). Materials and methods We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. Results pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6–37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p p = 0.002) compared to those with luminal papillary subtype. Conclusions While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

BACKGROUND: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved. OBJECTIVE: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN. DESIGN, SETTING, AND PARTICIPANTS: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC]). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores. RESULTS AND LIMITATIONS: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (

BACKGROUND: The aim of the study was to test the effect of active surveillance (AS) versus primary intervention (PI) on overall mortality (OM) in elderly patients diagnosed with SRM. METHODS: Elderly patients (75 years or older) diagnosed with SRMs (

Background Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. Objective We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. Design, setting, and participants Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). Outcome measurements and statistical analysis Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. Results and limitations Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08–1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38–5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08–2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03–0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20–7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era. Conclusions Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients. Patient summary We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications.

In the last years the incidence of renal neoplasms has been steadily increasing, along with the average age of patients at the time of diagnosis. Surgical management for localized disease is becoming more challenging because of patients’ frailty. We conducted a multi-center prospective study to evaluate the role of the G8 as a screening tool in the assessment of intra and post-operative complications of elderly patients (≥70 y.o.) undergoing surgery for kidney cancer. A total of 162 patients were prospectively enrolled between January 2015 to January 2019 and divided into two study groups (frail vs. not-frail) according to their geriatric risk profile based on G8 score. Several factors (i.e., age, CCI, ASA score, preoperative anemia, RENAL score, surgical procedures, and techniques) were analyzed to identify whether any of them would configure as a statistically significant predictor of surgical complications. According to the G8 Score, 90 patients were included in the frail group. A total of 52 frail patients vs. 4 non-frail patients developed a postoperative complication of any kind (p < 0.001). Of these, 11 were major complications and all occurred in the frail group. Our results suggest that the G8 screening tool is an effective and useful instrument to predict the risk of overall complications in elderly patients prior to renal surgery.

Background: The impact of warm ischemia time (WIT) on renal functional recovery remains controversial. We examined the length of WIT >30 min. on the long-term renal function following on-clamp partial nephrectomy (PN). Methods: Data from 23 centers for patients undergoing on-clamp PN between 2000 and 2018 were analyzed. We included patients with two kidneys, single tumor, cT1, minimum 1-year followup, and preoperative eGFR ≥60 ml/min/1.73m2. Patients were divided into two groups according to WIT length: group Ⅰ "WIT ≤30 min." and group Ⅱ "WIT >30 min.". A propensity-score matched analysis (1:1 match) was performed to eliminate potential confounding factors between groups. We compared eGFR values, eGFR (%) preservation, eGFR decline, events of chronic kidney disease (CKD) upgrading, and CKD-free progression rates between both groups. Cox regression analysis evaluated WIT impact on upgrading of CKD stages. Results: The primary cohort consisted of 3526 patients: group Ⅰ (n=2868) and group Ⅱ (n=658). After matching the final cohort consisted of 344 patients in each group. At last followup, there were no significant differences in median eGFR values at 1, 3, 5, and 10 years (P>0.05) between the matched groups. In addition, the median eGFR (%) preservation and absolute eGFR change were similar (89% in group Ⅰ vs. 87% in group Ⅱ, p=0.638) and (-10 in group Ⅰ vs. -11 in group Ⅱ, p=0.577), respectively. The 5 years new-onset CKD-free progression rates were comparable in the non-matched groups (79% in group Ⅰ vs. 81% in group Ⅱ, log-rank, p=0.763) and the matched groups (78.8% in group Ⅰ vs. 76.3% in group Ⅱ, log-rank, p=0.905). Univariable Cox regression analysis showed that WIT >30 min. was not a predictor of overall CKD upgrading (HR:0.953, 95%CI 0.829-1.094, p=0.764) nor upgrading into CKD stage ≥Ⅲ (HR:0.972, 95%CI 0.805-1.173, p=0.764). Retrospective design is a limitation of our study. Conclusions: Our analysis based on a large multicenter international cohort study suggests that WIT length during PN has no effect on the long-term renal function outcomes in patients having two kidneys and preoperative eGFR ≥60 ml/min/1.73m2.

Introduction and objectives: To evaluate the impact of the Controlling Nutritional Status (CONUT) score on perioperative morbidity and oncological outcomes of bladder cancer (BC) patients treated with radical cystectomy (RC). Materials and methods: We retrospectively analyzed a multi-institutional cohort of 347 patients treated with RC for clinical-localized BC between 2005 and 2019. The CONUT-score was defined as an algorithm including serum albumin, total lymphocyte count, and cholesterol. Multivariable logistic regression analyses were performed to evaluate the ability of the CONUT-score to predict any-grade complications, major complications and 30 days readmission. Multivariable Cox' regression models were performed to evaluate the prognostic effect of the CONUT-score on recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). Results: A cut-off value to discriminate between low and high CONUT-score was determined by calculating the receiver operating characteristic (ROC) curve. The area under the curve was 0.72 hence high CONUT-score was defined as ≥3 points. Overall, 112 (32.3%) patients had a high CONUT. At multivariable logistic regression analyses, high CONUT was associated with any-grade complications (OR 3.58, P = 0.001), major complications (OR 2.56, P = 0.003) and 30 days readmission (OR 2.39, P = 0.01). On multivariable Cox' regression analyses, high CONUT remained associated with worse RFS (HR 2.57, P < 0.001), OS (HR 2.37, P < 0.001) and CSS (HR 3.52, P < 0.001). Conclusions: Poor nutritional status measured by the CONUT-score is independently associated with a poorer postoperative course after RC and is predictive of worse RFS, OS, and CSS. This simple index could serve as a comprehensive personalized risk-stratification tool identifying patients who may benefit from an intensified regimen of supportive cares.

Background:: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. Objective:: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. Design, setting, and participants:: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. Outcome measurements and statistical analysis:: A nomogram for bladder cancer–specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. Results and limitations:: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2–52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4–2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3–2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7–4.6}; p < 0.001] and ypT3–4 [HR 5.9 {95 % CI: 3.8–9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1–82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. Conclusions:: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. Patient summary:: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability. We developed a nomogram predicting bladder cancer–specific mortality after neoadjuvant chemotherapy and radical cystectomy in a large, multi-institutional patient cohort.

Background Frailty has been recognized as a major risk factor for adverse perioperative and oncological outcomes in patients with genitourinary malignancies. Yet, the evidence supporting such an association in patients with renal cell carcinoma (RCC) is still sparse. Herein we provide an updated comprehensive overview of the impact of frailty on perioperative and oncologic outcomes in patients undergoing surgery or ablation for RCC. Evidence acquisition A systematic review of the English-language literature was conducted using the MEDLINE (Via PubMed), Web of Science and the Cochrane Library databases according to the principles highlighted by the EAU Guidelines Office and the PRISMA statement recommendations. The review protocol was registered on PROSPERO (CRD42021242516). The overall quality of evidence was assessed according to GRADE recommendations. Evidence synthesis Overall, 18 studies were included in the qualitative analysis. Most of these were retrospective single-centre series including patients undergoing surgery for non-metastatic RCC. The overall quality of evidence was low. A variety of measures were used for frailty assessment, including the Canadian Study of Health and Aging Frailty Index, the five-item frailty index, the Modified Rockwood's Clinical Frailty Scale Score, the Hopkins Frailty score, the Groningen Frailty Index, and the Geriatric nutritional risk index. Sarcopenia was defined based on the Lumbar skeletal muscle mass at cross-sectional imaging, the skeletal muscle index, the total psoas area, or the psoas muscle index. Overall, available studies point to frailty and sarcopenia as potential independent risk factors for worse perioperative and oncological outcomes after surgery or ablation for different RCC stages. Increased patient's frailty was indeed associated with higher risk of perioperative complications, healthcare resources utilization, readmission rates and longer hospitalization periods, as well as potentially lower cancer specific or overall survival. Conclusions Frailty has been consistently associated with worse outcomes after surgery for RCC, reinforcing the value of preoperative frailty assessment in carefully selected patients. Given the low quality of the available evidence (especially in the setting of tumour ablation), prospective studies are needed to standardize frailty assessments and to identify patients who are expected to benefit most from preoperative geriatric evaluation, aiming to optimize decision-making and postoperative outcomes in patients with RCC.

INTRODUCTION AND OBJECTIVE:The decompression of the upper urinary tract (UUT) in patients with ureteral obstruction may be performed through ureteral stenting (US) or percutaneous nephrostomy (PN)....

In the original article, the name of author Sia Daneshmand was incorrectly abbreviated as D. Daneshmand. The correct version is given in the above author list. Conflicts of interest: The authors have nothing to disclose.

Purpose Sunitinib is a vascular endothelial growth factor receptor (VEGFR) inhibitor with antitumor activity against bladder cancer. We hypothesized that treatment with sunitinib may decrease progression or recurrence in non-muscle invasive bladder cancer (NMIBC) refractory to intra-vesical BCG. Patients and Methods This is a single-arm phase II study of sunitinib in patients (pts) with NMIBC who progressed after BCG. Treatment included sunitinib 37.5 g daily for 12 weeks followed by 12± 2-week cystoscopy and surveillance for one year. The primary endpoint was the complete response rate at 12 months. Secondary endpoints included recurrence free survival (RFS), progression free survival (PFS), overall survival (OS), and safety of sunitinib. Correlative studies on effects of sunitinib on myeloid derived suppressor cells (MDSC) and humoral immune responses were also performed. This trial was registered on ClinicalTrials.gov, number NCT01118351. Results Between June 2011 and September 2011, 15/19 pts. completed 12 weeks of therapy. The remaining 4 pts. had treatment related adverse events leading to discontinuation of sunitinib with one patient withdrawing consent. On the 12-week cystoscopy, 44% (8/18) of the pts. showed remission, 50% (9/18) progression and 1/18 recurrence. Overall, 22% (4/18) of pts. remained free of progression for >12 months. Grade (G) 4 toxicities were noted in 2 pts. (anemia and thrombocytopenia) while G3 were noted in 58%. Sunitinib resulted in reversal of MDSC mediated immunosuppression. Conclusions In NMIBC refractory to BCG, treatment with sunitinib was safe but not associated with improved clinical outcomes. The immune effects of sunitinib deserve further investigation.

Background Despite definitive local therapy, patients with high-risk prostate cancer have a significant risk for local and distant failure. To date, no systemic therapy given prior to surgery has been shown to improve outcomes. The phosphatidilinositol 3-kinase/AKT/mTOR pathway is commonly dysregulated in men with prostate cancer. We sought to determine the clinical efficacy and safety of the mTOR/TORC1 inhibitor everolimus in men with high-risk prostate cancer undergoing radical prostatectomy. Methods This is a randomized phase II study of everolimus at two different doses (5 and 10 mg daily) given orally for 8 weeks before radical prostatectomy in men with high-risk prostate cancer. The primary endpoint was the pathologic response (histologic P0, margin status, extraprostatic extension) and surgical outcomes. Secondary endpoints included changes in serum PSA level and treatment effects on levels of expression of mTOR, p4EBP1, pS6 and pAKT. Results Seventeen patients were enrolled: nine at 10 mg dose and eight at 5 mg dose. No pathologic complete responses were observed and the majority of patients (88%) had an increase in their PSA values leading to this study being terminated early due to lack of clinical efficacy. Treatment-related adverse events were similar to those previously reported with the use of everolimus in other solid tumors and no additional surgical complications were observed. A significant decrease in the expression of p4EBP1 was noted in prostatectomy samples following treatment. Conclusions Neoadjuvant everolimus given at 5 mg or 10 mg daily for 8 weeks prior to radical prostatectomy did not impact pathologic responses and surgical outcomes of patients with high-risk prostate cancer. Trial registration NCT00526591 .

Context Management of locally recurrent renal cancer is complex. Objective In this systematic review we analyse the available literature on the management of local renal cancer recurrence. Evidence acquisition A systematic search (PubMed, Web of Science, CINAHL, Clinical Trials, and Scopus) of English literature from 2000 to 2017 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Evidence synthesis The search identified 1838 articles. Of those, 36 were included in the evidence synthesis. The majority of the studies identified were retrospective and not controlled. Local recurrence after thermal ablation (TA) may be managed with repeat TA. Alternatively, salvage nephrectomy is possible. However, a higher rate of complications should be expected than after primary nephrectomy. Salvage nephrectomy and TA represent treatment options for local recurrence after partial nephrectomy. Local retroperitoneal recurrence after radical nephrectomy is ideally treated with surgical resection, for which minimally invasive approaches might be applicable to select patients. For large recurrences, addition of intraoperative radiation may improve local control. Local tumour destruction appears to be more beneficial than systemic therapy alone for local recurrences. Conclusions Management of local renal cancer relapse varies according to the clinical course and prior treatments. The available data are mainly limited to noncontrolled retrospective series. After nephron-sparing treatment, TA represents an effective treatment with low morbidity. For local recurrence after radical nephrectomy, the low-level evidence available suggests superiority of surgical excision relative to systemic therapy or best supportive care. As a consequence, surgery should be prioritised when feasible and applicable. Patient summary In renal cell cancer, the occurrence and management of local recurrence depend on the initial treatment. This cancer is a disease with a highly variable clinical course. After initial organ-sparing treatment, thermal ablation offers good cancer control and low rates of complications. For recurrence after radical nephrectomy, surgical excision seems to provide the best long-term cancer control and it is superior to medical therapy alone.

Background: A non-negligible proportion of individuals diagnosed with cT1 renal cell carcinoma (RCC) are upstaged to pT3a at final pathology. Few data on oncological outcomes for these patients are available to determine whether partial nephrectomy (PN) might jeopardise cancer control. Objective: To assess, within an international multi-institutional collaboration, whether PN might undermine cancer control relative to radical nephrectomy (RN) in RCC patients with unexpected pT3a disease. Design, setting, and participants: International multi-institutional collaboration including patients with cT1abN0M0-pT3a RCC. Intervention: PN or RN. Outcome measurements and statistical analysis: We used Kaplan-Meier analyses, before and after propensity-score matching, to evaluate differences in metastatic progression (MP) and cancer-specific mortality (CSM) rates during follow-up. Univariable and multivariable Cox regression analyses were used to assess predictors of MP and CSM. Results and limitations: Overall, 309 patients with cT1abN0M0 RCC (cT1aN0M0, n = 107, 34.6%; cT1bN0M0, n = 202, 65.4%) had pT3a disease according to final pathology. Patients were treated with either PN (n = 71, 23%) or RN (n = 238, 77%). MP at 1, 2, and 5 yr was detected in 9.1%, 13.3%, and 24.1% of patients, respectively. CSM was 3.5%, 10.7%, and 18.4% at 1, 2, and 5 yr, respectively. After matching, no difference in terms of MP or CSM was observed between the PN and RN cohorts (both p>0.3). On multivariable analysis, type of surgery (PN vs RN) was not an independent predictor of either MP (p = 0.3) or CSM (p = 0.4). Limitations include the retrospective design. Conclusions: In patients with unexpected pT3a RCC at final pathology, PN does not appear to jeopardise cancer control with regard to MP and CSM. Patient summary: Cancer control is similar between patients treated with removal of the entire kidney and those with only partial removal, even if the final histology examination demonstrates a tumour that is unexpectedly not confined within the kidney. Partial nephrectomy does not undermine cancer control when unexpected pT3a renal cancer is identified at final pathology.

Introduction and objectives To evaluate the prognostic role of albumin-to-fibrinogen ratio (AFR) for the prediction of oncological outcomes in a multi-institutional cohort of bladder cancer (BC) patients treated with radical cystectomy (RC). Materials and methods We retrospectively analyzed a multicenter cohort of patients treated with upfront RC for localized (cT1-4aN0M0) BC. Multivariable logistic regression analyses were performed to evaluate the ability of AFR to predict non-organ confined (NOC) disease and lymph-node involvement (LNI) at time of RC. Multivariable Cox’ regression models were performed to evaluate the prognostic effect of AFR on Time-to-Progression (TTP), overall survival (OS), and cancer-specific survival (CSS). Results A cut-off value to discriminate between low and high AFR was determined by calculating the receiver operating characteristic (ROC) curve. The area under the curve was 0.73 with an optimal cut-off at 9.53. Data were available for 246 patients (91 with low AFR, 155 with high AFR). Low AFR was associated with characteristics of tumor aggressiveness and independently predicted NOC (OR 2.11, P = 0.02) and LNI (OR 1.58, P = 0.04) at final pathological report. On multivariable Cox’ regression analyses, preoperative low AFR was independently associated with worse TTP (HR 2.21, P = 0.02), OS (HR 2.24, P = 0.03), and CSS (HR 2.70, P = 0.01). Conclusion Preoperative low AFR is a prognostic biomarker for worse TTP, OS, CSS, and is independently associated with adverse tumor pathological features in BC patients undergoing RC. Our results suggest that especially patients with low AFR may be considered for neoadjuvant treatment.

Purpose: To investigate the natural history and follow-up after kidney tumor treatment of Von Hippel-Lindau (VHL) patients. Materials and methods: A multi-institutional European consortium of patients with VHL syndrome included 96 non-metastatic patients treated at 9 urological departments (1987–2018). Descriptive and survival analyses were performed. Results and limitations: Median age at VHL diagnosis was 34years (IQR 25–43). Two patients (2.1%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 60.4 vs. 68.7 vs. 30.2 vs. 15.6 vs. 15.6% of patients, respectively. 45% of patients had both CNS and pancreatic diseases alongside kidney. The median interval between VHL diagnosis and renal cancer treatment resulted 79months (IQR 0–132), and median index tumor size leading to treatment was 35.5mm (IQR 28–60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4cm. With a median follow-up of 8years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10years, respectively. Overall mortality was 4% and 7.5% at 5 and 10years, respectively. During the follow-up, 50% of patients did not receive a second active renal treatment. Finally, 25.3% of patients had CKD at last follow-up. Conclusions: Mean period between VHL diagnosis and renal cancer detection is roughly three years, with significant variability. Although, most renal tumors are small low-grade, clinical progression and mortality are not negligible. Moreover, kidney function represents a key issue in VHL patients.

INTRODUCTION Radical cystectomy (RC) is the current mainstay for muscle-invasive bladder cancer (MIBC). Concerns regarding morbidity, mortality and quality of life have favored the introduction of bladder sparing strategies. Trimodal therapy, combining transurethral resection, chemotherapy and radiotherapy is the current standard of care for bladder preservation strategies in selected patients with MIBC. EVIDENCE ACQUISITION A comprehensive search of the Medline and Embase databases was performed. A total of 19 studies were included in a systematic review of bladder sparing strategies in MIBC management was carried out following the preferred reporting items for systematic reviews and meta-analysis (PRISMA). EVIDENCE SYNTHESIS The overall median complete response rate after trimodal therapy (TMT) was 77% (55-93). Salvage cystectomy rate with TMT was 17% on average (8-30). For TMT, the 5-year cancer-specific survival and overall survival rates range from 42-82% and 32-74%, respectively. Currently data supporting neoadjuvant or adjuvant chemotherapy in bladder sparing approaches are emerging, but robust definitive conclusions are still lacking. Gastrointestinal toxicity rates are low around 4% (0.5-16), whereas genitourinary toxicity rates reached 8% (1-24). Quality of life outcomes are still underreported. CONCLUSIONS Published data and clinical experience strongly support trimodal therapy as an acceptable bladder sparing strategy in terms of oncological outcomes and quality of life in selected patients with MIBC. A strong need exists for specialized centers, to increase awareness among urologists, to discuss these options with patients and to stress the increased participation of patients and their families in treatment path decision-making.

INTRODUCTION AND OBJECTIVES: The role of cytoreductive nephrectomy (CN) in the setting of metastatic renal cell carcinoma (mRCC) is still object of great debate within the Urology community. In this regard, assessing the harms of CN is key to select patients most likely to benefit from this procedure. The aim of the study was to evaluate potential predictors of major complications (MC) after CN in a multicentre international cohort of patients with mRCC. METHODS: Data from patients with mRCC undergoing CN at 11 centers included in the REgistry of MetAstatic RCC (REMARCC) from January 2014 to December 2017 were retrospectively collected and analyzed. Patients with complete data on comorbidity profiles, intraoperative outcomes and perioperative complications formed the analytic cohort. Postoperative complications were assessed and graded using the modified Clavien-Dindo scale. MCs were defined as Clavien-Dindo grade 3 or more. Multivariable logistic regression analysiswas used to assess potential clinical predictors of 30-day readmission. RESULTS: Overall, 374 patients were included in the study. Twenty-three patients (6.1%) experienced MCs. Patient age, sex, BMI, Charlson comorbidity index, ECOG performance status, baseline Hb levels, estimated glomerular filtration rate, cT and cN status, as well as location of metastatic lesions, were comparable among patients who did and did not experience MCs. Conversely, median tumor size was significantly higher in patients experiencing MCs (11.0 vs 8.5 cm, p=0.002). Surgical approach was significantly different in the two study groups (87.0% of patients who experienced MCs were treated with open CN as compared to 65.4% of patients who did not; p=0.034). Performance of LDN was comparable among the study groups; on the contrary, removal of adjacent organs (43.5 % vs 23.4%, p=0.03), renal vein/vena cava thrombectomy (43.5% vs 17.4%, p=0.002) and metastasectomy at the time of CN (21.7% vs 7.1%, p=0.012) were significantly higher in patients who experienced MCs. Rate of hospital readmission within 30 days after surgery was significantly higher in patients who experienced MCs (11.1% vs 6.7%, p

Introduction: Percutaneous treatment of persistent urinary fistula after partial nephrectomy using N-butyl-2-cyanoacrylate and gelatin sponge (Spongostan®) is an effective and relatively non-invasive procedure that should be considered when a conservative approach fails. Three successful cases of percutaneous embolization by using N-butyl-2-cyanoacrylate have been reported in the literature. To our knowledge, the use of Spongostan for the treatment of urinary fistula after partial nephrectomy has not been previously described. Case report: We present the case of an 82-year old man who underwent percutaneous closure of a urinary fistula following partial nephrectomy by using gelatin sponge (Spongostan®) and N-butyl-2-cyanoacrylate.Conclusions: We encourage the use of this technique in selected cases. Collaboration amongst urologists and skilled interventional radiologist is strongly recommended.

Identification of reliable molecular biomarkers that can complement clinical practice represents a fascinating challenge in any cancer field. Urothelial carcinoma is a very heterogeneous disease and responses to systemic therapies, and outcomes after radical cystectomy are difficult to predict. Advances in molecular biology such as next generation sequencing and whole genome or transcriptomic analysis provide promising platforms to achieve a full understanding of the biology behind the disease and can identify emerging predictive biomarkers. Moreover, the ability to categorize patients' risk of recurrence after curative treatment, or even predict benefit from a conventional or targeted therapies, represents a compelling challenge that may reshape both selection for tailored treatment and disease monitoring. Progress has been made but currently no molecular biomarkers are used in the clinical setting to predict response to systemic agents in either neoadjuvant or adjuvant settings highlighting a relevant unmet need. Here, we aim to present the emerging role of molecular biomarkers in predicting response to systemic agents in urothelial carcinoma.

BACKGROUND To test the effect of active surveillance (AS) versus primary intervention (PI) on overall mortality (OM) in elderly patients diagnosed with SRM. METHODS Elderly patients (75 years or older) diagnosed with SRMs (< 4cm) and treated with either PI [i.e. partial nephrectomy or kidney ablation] or AS between 2009 and 2018 were abstracted from the REnal SURGery in the Elderly (RESURGE) and Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) datasets, respectively. OM rates were estimated among groups with Kaplan Meier method and Cox proportional hazards regression models after applying inverse probability of treatment weighting (IPTW). Multivariable logistic regression model was used to estimate IPTW. Covariates of interest were those unbalanced and/or significantly correlated with the treatment choice or with OM. RESULTS A total of 483 patients were included; 121 (25.1%) underwent AS. 60 patients (12.4%) died. Overall, 6.7% of all deaths were related to cancer. IPTW-Kaplan Meier curves showed a 5-year overall survival rates of 70.0 ± 3.5% and 73.2 ± 4.8% in AS and PI groups, respectively (IPTW-Log-rank p-value=0.308). IPTW-Cox regression model did not show meaningfully increased OM rates in AS group (HR=1.31, 95% CI: 0.69-2.49). CONCLUSIONS AS represents an appealing treatment option for very elderly patients presenting with SRM, as it avoids the risks of a PI while not compromising the survival outcomes of these patients.