Surgical metastasectomy for metastatic renal cell carcinoma in the era of targeted and immune therapy: a narrative review.

PURPOSE: Metastatic renal cell carcinoma (mRCC) still harbours a big propensity for future metastasis. Combinations of immune and targeted therapies are currently the cornerstone of management with a less clear role for surgical metastasectomy (SM). METHODS: We performed a narrative review of literature searching for the available evidence on the yield of surgical metastasectomy in the era of targeted and immune therapies. The review consisted of a PubMed search of relevant articles using the Mesh terms:" renal cell carcinoma", "surgery¼, «resection", "metastasectomy", "molecular targeted therapies", "immune checkpoint inhibitors" alone or in combination. RESULTS: In this review, we exposed the place of surgical metastasectomy within a multimodal treatment algorithm for mRCC Also, we detailed the patient selection criteria that yielded the best results when SM was performed. Finally, we discussed the feasibility and advantages of SM per organ site. CONCLUSION: Our work was able to show that SM could be proposed as a consolidation treatment to excise residual lesions that were deemed unresectable prior to a combination of systemic therapies. Contrastingly, it can be proposed as an upfront treatment, leaving systemic therapies as an alternative in case of future relapse. However, patient selection regarding their performance status, metastatic sites, number of lesions and tumorous characteristics is of paramount importance.

Contribution of canine olfaction in the diagnostic strategy of intermediate and high-risk prostate cancer: a double-blind validation study.

PURPOSE: Prostate cancer diagnosis is confirmed with a prostate biopsy, which is invasive and unpleasant. Adding canine olfaction into the diagnostic protocol could help avoid unnecessary biopsies. This study aims to determine whether dogs can identify ISUP (International Society of Urological Pathology) > 2 prostate cancer. MATERIALS AND METHODS: This double-blind, prospective, validation study included men with suspected prostate cancer between November 2022 and April 2023 in France. They were classified into two groups according to their prostate biopsy results; cases (ISUP > 2) and controls (ISUP < 1 or negative). Seven dogs analyzed their urine. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for canine olfactory detection of ISUP ≥ 2 prostate cancer were measured and compared with that of prostate MRI versus prostate biopsy. RESULTS: The seven dogs analyzed 151 urine samples, 78 from the case group and 73 from the control group. The minimal and maximal observed values were 54% and 86% for sensitivity, and 69% and 88% for specificity. Five dogs had a sensitivity above 73% and six dogs had a specificity above 75%. The kappa coefficient quantifying agreement between the biopsy result and the MRI PI-RADS ≥ 3 was 0.17 [- 0.14; 0.17], 0.20 [0.02-0.33] for PI-RADS ≥ 4 and 0.64 [0.5-0.75] for canine olfaction meaning there is a substantial agreement between the biopsy result and canine olfaction. CONCLUSIONS: Based on this study, the non-invasive and safe canine olfaction technique seems reliable for diagnosing ISUP ≥ 2 prostate cancer. Combined with prostate MRI, it may improve the decision-making process when choosing to perform prostate biopsies.

Open versus robotic partial nephrectomy in obese patients: a multi-institutional propensity score-matched analysis (UroCCR 43-Robese study).

INTRODUCTION: There is limited evidence on the outcomes of robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN) in obese patients (BMI ≥ 30 kg/m2). In this study, we aimed to compare perioperative and oncological outcomes of RPN and OPN. METHODS: We relied on data from patients who underwent PN from 2009 to 2017 at 16 departments of urology participating in the UroCCR network, which were collected prospectively. In an effort to adjust for potential confounders, a propensity-score matching was performed. Perioperative outcomes were compared between OPN and RPN patients. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Overall, 1277 obese patients (932 robotic and 345 open were included. After propensity score matching, 166 OPN and 166 RPN individuals were considered for the study purposes; no statistically significant difference among baseline demographic or tumor-specific characteristics was present. A higher overall complication rate and major complications rate were recorded in the OPN group (37 vs. 25%, p = 0.01 and 21 vs. 10%, p = 0.007; respectively). The length of stay was also significantly longer in the OPN group, before and after propensity-score matching (p < 0.001). There were no significant differences in Warm ischemia time (p = 0.66), absolute change in eGFR (p = 0.45) and positive surgical margins (p = 0.12). At a median postoperative follow-up period of 24 (8-40) months, DFS and OS were similar in the two groups (all p > 0.05). CONCLUSIONS: In this study, RPN was associated with better perioperative outcomes (improvement of major complications rate and LOS) than OPN. The oncological outcomes were found to be similar between the two approaches.

The Neuropilin-1/PKC axis promotes neuroendocrine differentiation and drug resistance of prostate cancer.

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a multi-resistant variant of prostate cancer (PCa) that has become a major challenge in clinics. Understanding the neuroendocrine differentiation (NED) process at the molecular level is therefore critical to define therapeutic strategies that can prevent multi-drug resistance. METHODS: Using RNA expression profiling and immunohistochemistry, we have identified and characterised a gene expression signature associated with the emergence of NED in a large PCa cohort, including 169 hormone-naïve PCa (HNPC) and 48 castration-resistance PCa (CRPC) patients. In vitro and preclinical in vivo NED models were used to explore the cellular mechanism and to characterise the effects of castration on PCa progression. RESULTS: We show for the first time that Neuropilin-1 (NRP1) is a key component of NED in PCa cells. NRP1 is upregulated in response to androgen deprivation therapies (ADT) and elicits cell survival through induction of the PKC pathway. Downmodulation of either NRP1 protein expression or PKC activation suppresses NED, prevents tumour evolution toward castration resistance and increases the efficacy of docetaxel-based chemotherapy in preclinical models in vivo. CONCLUSIONS: This study reveals the NRP1/PKC axis as a promising therapeutic target for the prevention of neuroendocrine castration-resistant variants of PCa and indicates NRP1 as an early transitional biomarker.

Machine-learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma (UroCCR-15).

OBJECTIVES: To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine-learning-based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging. MATERIALS AND METHODS: Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi-institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine-learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease-free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G-computation for pT3a tumours. RESULTS: A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a-upstaged RCC. The UroCCR-15 predictive model presented an area under the receiver-operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P > 0.9). CONCLUSIONS: Our study shows that machine-learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes.

Intraoperative complication of radical cystectomy for muscle-invasive bladder cancer: does the surgical approach matter? A retrospective multicenter study using the EAUiaiC classification.

PURPOSE: Despite surgical and anesthetic progress, radical cystectomy for bladder cancer remains one of the most morbid surgeries in urology. The objective of our study was to describe intraoperative complications and to assess the impact of surgical approach on morbidity. METHODS: We retrospectively reviewed medical records of patients treated by radical cystectomy for localized muscle invasive bladder cancer between 2015 and 2020, following the Martin et al. criteria for complications reports. All intraoperative adverse events were graded according to the EAUiaiC scores. Multivariate regression models were used to determine predicting factors of complications. RESULTS: A total of 318 patients were included for analysis. Among them, 17 patients (5.4%) presented an intraoperative complication. No preoperative oncological or clinical factor was associated with the occurrence of an intraoperative complication. Surgical approach had no impact on morbidity. Both overall survival (HR 2.02; CI95% 0.87-4.68; p = 0.101) and recurrence-free survival (HR 1.856; CI95% 0.804-4.284; p = 0.147) were not associated with intraoperative complication. CONCLUSION: Radical cystectomy remains a highly morbid surgery and surgical approach did not improve the complication rate. Perioperative morbidity has a significant impact on patient survival. The association between intraoperative and postoperative complications illustrates the cumulative effect of perioperative events that are associated with survival.

Association between overweight, obesity, and quality of life of patients receiving an anticancer treatment for prostate cancer: a systematic literature review.

BACKGROUND: Prostate cancer (PCa) and obesity are two ever-increasing public health issues that can independently impair the quality of life (QOL) of affected patients. Our objective was to evaluate the impact of overweight and obesity on the QOL of patients with PCa receiving an anticancer treatment. METHODS: We performed a systematic review of the literature using PubMed, Embase, Cochrane Library and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The search equation targeted studies that included PCa patients who had a body mass index (BMI) greater than 25 kg/m2, who were receiving anticancer therapy, and whose QOL was analyzed according to validated or non-validated scores. RESULTS: Of 759 identified articles, we selected 20 studies published between 2000 and 2019 of 12,529 patients treated for PCa, including 5549 overweight or obese patients. QOL assessment was performed using nine validated scales and two non-validated questionnaires. Of seven studies on radiotherapy, six found obesity to have a negative impact on patients' QOL (especially urinary, sexual, and bowel-related QOL). Thirteen studies assessed the QOL of patients who underwent radical prostatectomy, with a BMI > 25 kg/m2 having no observed impact. In obese patients under 65 years of age and without comorbidities, nerve-sparing surgery appeared to limit the deterioration of QOL. Four studies on brachytherapy found discordant results. One study showed greater QOL impairment in obese patients receiving first-generation hormone therapy than in those with normal or decreased BMI. No study evaluated the QOL of overweight or obese patients receiving other types of systemic treatment. CONCLUSION: Based on the published data, the level of evidence for an association between QOL and overweight or obesity in patients treated for PCa is not high. Prospective cohort studies including this type of patient population are warranted to answer this topical public health issue.

BR55 Ultrasound Molecular Imaging of Clear Cell Renal Cell Carcinoma Reflects Tumor Vascular Expression of VEGFR-2 in a Patient-Derived Xenograft Model.

Standard imaging cannot reliably predict the nature of renal tumors. Among malignant renal tumors, clear cell renal cell carcinoma (ccRCC) is the most common histological subtype, in which the vascular endothelial growth factor 2 (VEGFR-2) is highly expressed in the vascular endothelium. BR55, a contrast agent for ultrasound imaging, consists of gas-core lipid microbubbles that specifically target and bind to the extracellular portion of the VEGFR-2. The specific information provided by ultrasound molecular imaging (USMI) using BR55 was compared with the vascular tumor expression of the VEGFR-2 by immunohistochemical (IHC) staining in a preclinical model of ccRCC. Patients' ccRCCs were orthotopically grafted onto Nod-Scid-Gamma (NSG) mice to generate patient-derived xenografts (PdX). Mice were divided into four groups to receive either vehicle or axitinib an amount of 2, 7.5 or 15 mg/kg twice daily. Perfusion parameters and the BR55 ultrasound contrast signal on PdX renal tumors were analyzed at D0, D1, D3, D7 and D11, and compared with IHC staining for the VEGFR-2 and CD34. Significant Pearson correlation coefficients were observed between the area under the curve (AUC) and the CD34 (0.84, p < 10-4), and between the VEGFR-2-specific signal obtained by USMI and IHC (0.72, p < 10-4). USMI with BR55 could provide instant, quantitative information on tumor VEGFR-2 expression to characterize renal masses non-invasively.

Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells.

In early 2020, the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and rapidly propagated worldwide causing a global health emergency. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) protein for cell entry, followed by proteolytic cleavage of the Spike (S) protein by the transmembrane serine protease 2 (TMPRSS2), allowing fusion of the viral and cellular membranes. Interestingly, TMPRSS2 is a key regulator in prostate cancer (PCa) progression which is regulated by androgen receptor (AR) signaling. Our hypothesis is that the AR signaling may regulate the expression of TMPRSS2 in human respiratory cells and thus influence the membrane fusion entry pathway of SARS-CoV-2. We show here that TMPRSS2 and AR are expressed in Calu-3 lung cells. In this cell line, TMPRSS2 expression is regulated by androgens. Finally, pre-treatment with anti-androgen drugs such as apalutamide significantly reduced SARS-CoV-2 entry and infection in Calu-3 lung cells but also in primary human nasal epithelial cells. Altogether, these data provide strong evidence to support the use of apalutamide as a treatment option for the PCa population vulnerable to severe COVID-19.

[Alpha-blockers or hexanic extract of Serenoa repens for 6 months: sub-analysis of the PERSAT study]. / Alpha-bloquants ou extrait hexanique de Serenoa repens pendant 6 mois : sous-analyse de l'étude PERSAT.

OBJECTIVE: The objective of this sub-analysis of the PERSAT study was to evaluate the efficacy of hexanic extract of S. Repens (HESr) and alpha-blockers (AB), at 6 months in patients with moderate to severe LUTS/BPH. METHODS: The PERSAT observational study was conducted in France by general practitioners on patients with BPH with an IPSS≥12 score. The primary endpoint was the percentage of responders (decrease in total IPSS score ≥ 3) at 6 months. Improvement in quality of life (IPSS-QoL) as well as patient satisfaction were also measured. RESULTS: Of the 759 patients in the study, 324 treated with HESr and 309 with AB were reviewed at 6 months, with no change in treatment during follow-up. Characteristics at inclusion were globally similar with a mean IPSS of 18.2±4.9. The response rates at 6 months (IPSS-total decrease ≥ 3) were 93.7% and 94.8% for patients treated with HESr and AB, with a mean decrease in IPSS score of 10.1±5.6 points, which reached 13.6 and 14.8 points respectively, in severe patients (IPSS>19), without major difference between groups. More than 95% of HESr or AB patients reported a significant overall improvement in their LUTS/BPH. The most frequently reported adverse events with AB were ejaculation disorders (4.9%) and hypotension (4.2%) and with HESr digestive disorders (1.5%). CONCLUSION: This sub-analysis of the PERSAT cohort reported the clinical efficacy of HESr and AB as a first-line treatment in the management of moderate or severe LUTS/BPH patients.

Nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors as first-line treatment for metastatic clear-cell renal cell carcinoma (BIONIKK): a biomarker-driven, open-label, non-comparative, randomised, phase 2 trial.

BACKGROUND: We previously reported a 35-gene expression classifier identifying four clear-cell renal cell carcinoma groups (ccrcc1 to ccrcc4) with different tumour microenvironments and sensitivities to sunitinib in metastatic clear-cell renal cell carcinoma. Efficacy profiles might differ with nivolumab and nivolumab-ipilimumab. We therefore aimed to evaluate treatment efficacy and tolerability of nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors (VEGFR-TKIs) in patients according to tumour molecular groups. METHODS: This biomarker-driven, open-label, non-comparative, randomised, phase 2 trial included patients from 15 university hospitals or expert cancer centres in France. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had previously untreated metastatic clear-cell renal cell carcinoma. Patients were randomly assigned (1:1) using permuted blocks of varying sizes to receive either nivolumab or nivolumab-ipilimumab (ccrcc1 and ccrcc4 groups), or either a VEGFR-TKI or nivolumab-ipilimumab (ccrcc2 and ccrcc3 groups). Patients assigned to nivolumab-ipilimumab received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by intravenous nivolumab 240 mg every 2 weeks. Patients assigned to nivolumab received intravenous nivolumab 240 mg every 2 weeks. Patients assigned to VEGFR-TKIs received oral sunitinib (50 mg/day for 4 weeks every 6 weeks) or oral pazopanib (800 mg daily continuously). The primary endpoint was the objective response rate by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint and safety were assessed in the population who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02960906, and with the EU Clinical Trials Register, EudraCT 2016-003099-28, and is closed to enrolment. FINDINGS: Between June 28, 2017, and July 18, 2019, 303 patients were screened for eligibility, 202 of whom were randomly assigned to treatment (61 to nivolumab, 101 to nivolumab-ipilimumab, 40 to a VEGFR-TKI). In the nivolumab group, two patients were excluded due to a serious adverse event before the first study dose and one patient was excluded from analyses due to incorrect diagnosis. Median follow-up was 18·0 months (IQR 17·6-18·4). In the ccrcc1 group, objective responses were seen in 12 (29%; 95% CI 16-45) of 42 patients with nivolumab and 16 (39%; 24-55) of 41 patients with nivolumab-ipilimumab (odds ratio [OR] 0·63 [95% CI 0·25-1·56]). In the ccrcc4 group, objective responses were seen in seven (44%; 95% CI 20-70) of 16 patients with nivolumab and nine (50% 26-74) of 18 patients with nivolumab-ipilimumab (OR 0·78 [95% CI 0·20-3·01]). In the ccrcc2 group, objective responses were seen in 18 (50%; 95% CI 33-67) of 36 patients with a VEGFR-TKI and 19 (51%; 34-68) of 37 patients with nivolumab-ipilimumab (OR 0·95 [95% CI 0·38-2·37]). In the ccrcc3 group, no objective responses were seen in the four patients who received a VEGFR-TKI, and in one (20%; 95% CI 1-72) of five patients who received nivolumab-ipilimumab. The most common treatment-related grade 3-4 adverse events were hepatic failure and lipase increase (two [3%] of 58 for both) with nivolumab, lipase increase and hepatobiliary disorders (six [6%] of 101 for both) with nivolumab-ipilimumab, and hypertension (six [15%] of 40) with a VEGFR-TKI. Serious treatment-related adverse events occurred in two (3%) patients in the nivolumab group, 38 (38%) in the nivolumab-ipilimumab group, and ten (25%) patients in the VEGFR-TKI group. Three deaths were treatment-related: one due to fulminant hepatitis with nivolumab-ipilimumab, one death from heart failure with sunitinib, and one due to thrombotic microangiopathy with sunitinib. INTERPRETATION: We demonstrate the feasibility and positive effect of a prospective patient selection based on tumour molecular phenotype to choose the most efficacious treatment between nivolumab with or without ipilimumab and a VEGFR-TKI in the first-line treatment of metastatic clear-cell renal cell carcinoma. FUNDING: Bristol Myers Squibb, ARTIC.

Urethrectomy at the time of radical cystectomy for non-metastatic urothelial carcinoma of the bladder: a collaborative multicenter study.

INTRODUCTION: The optimal management of the urethra in patients planned for radical cystectomy (RC) remains unclear. We sought to evaluate the impact of urethrectomy on perioperative and oncological outcomes in patients treated with RC for non-metastatic urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: We assessed the retrospective data from patients treated with RC for UCB of five European University Hospitals. Associations of urethrectomy with progression-free (PFS), cancer-free (CSS), and overall (OS) survivals were assessed in univariable and multivariable Cox regression models. We performed a subgroup analysis in patients at high risk for urethral recurrence (UR) (urethral invasion and/or bladder neck invasion and/or multifocality and/or prostatic urethra involvement). RESULTS: A total of 887 non-metastatic UCB patients were included. Among them, 146 patients underwent urethrectomy at the time of RC. Urethrectomy was performed more often in patients with urethral invasion, T3/4 tumor stage, CIS, positive frozen section analysis of the urethra, and those who received neoadjuvant chemotherapy, underwent robotic RC, and/or received an ileal conduit urinary diversion (all p < 0.001). Estimated blood loss and the postoperative complication rate were comparable between patients who received an urethrectomy and those who did not. Urethrectomy during RC was not associated with PFS (HR 0.83, p = 0.17), CSS (HR 0.93, p = 0.67), or OS (HR 1.08, p = 0.58). In the subgroup of 276 patients at high risk for UR, urethrectomy at the time of RC decreased the risk of progression (HR 0.58, p = 0.04). CONCLUSION: In our study, urethrectomy at the time of RC seems to benefit only patients at high risk for UR. Adequate risk assessment of UCB patients' history may allow for better clinical decision-making and patient counseling.

Overexpression of Nucleolin and Associated Genes in Prostate Cancer.

Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer death in men worldwide. If local PCa presents a favorable prognosis, available treatments for advanced PCa display limiting benefits due to therapeutic resistances. Nucleolin (NCL) is a ubiquitous protein involved in numerous cell processes, such as ribosome biogenesis, cell cycles, or angiogenesis. NCL is overexpressed in several tumor types in which it has been proposed as a diagnostic and prognostic biomarker. In PCa, NCL has mainly been studied as a target for new therapeutic agents. Nevertheless, little data are available concerning its expression in patient tissues. Here, we investigated the expression of NCL using a new cohort from Mondor Hospital and data from published cohorts. Results were then compared with NCL expression using in vitro models. NCL was overexpressed in PCa tissues compared to the normal tissues, but no prognostic values were demonstrated. Nine genes were highly co-expressed with NCL in patient tissues and tumor prostate cell lines. Our data demonstrate that NCL is an interesting diagnostic biomarker and propose a signature of genes co-expressed with NCL.

A European Registry Evaluating Symptomatic Effectiveness of Pharmacologically Treated Patients with Lower Urinary Tract Symptoms due to Benign Prostatic Enlargement: Lessons Learned.

PURPOSE: We evaluated unmet needs of lower urinary tract symptoms-benign prostatic enlargement pharmacological treatment by measuring symptom improvement, persistence and deterioration in real life. A prospective registry was conducted for 24 months in 5 European countries and analyzed by the European Association of Urology Research Foundation. MATERIALS AND METHODS: Previously untreated and treated patients were enrolled to the registry in both primary care and urology referral centers in France, Germany, Italy, Spain and the UK. RESULTS: Overall, 2,175 patients were enrolled with 1,838 analyzed, consisting of 575 previously untreated lower urinary tract symptoms-benign prostatic enlargement patients (no alpha blockers for at least 1 month or no 5-alpha reductase inhibitors for at least 6 months) and 1,263 previously treated patients. During the registry 90% of patients adhered to the prescribed regimen. After 24 months, 70% of previously untreated and 42% of previously treated patients experienced symptom improvement (International Prostate Symptom Score [IPSS] reduction of ≥3 points). Symptomatic patients (IPSS ≥8) remained in both groups (59% in previously untreated and 61% in previously treated), with greater symptom deterioration (IPSS increase ≥3 points) in 18.9% in previously treated vs 7.8% in previously untreated patients. Both clinical lower urinary tract symptoms-benign prostatic enlargement progression and surgery rates were similar in untreated vs treated groups at 16% vs 17% and 5% vs 7%, respectively, at 24 months. CONCLUSIONS: This prospective registry confirmed lower urinary tract symptoms-benign prostatic enlargement pharmacological treatment effectiveness in a real-world setting, with low clinical progression observed in about 1 in 6 patients and lower surgery rates below 1 in 20, by 24 months.

Comorbidity and frailty assessment in renal cell carcinoma patients.

PURPOSE: Renal cell carcinoma (RCC) incidence has considerably increased during the last decades without any real impact on age-standardized mortality. It questions the relevance of aggressive treatments carrying potential side effects. Conservative management should be considered for frail patients. Comorbidity and frailty assessment in RCC patients is paramount before engaging a treatment. METHODS: Narrative, non-systematic review based on PubMed and EMBASE search with the terms "renal neoplasm", "elderly, frail", "comorbidities", "active surveillance", "metastatic". The selection was restricted to articles written in English. RESULTS: Comorbidity and frailty assessment go along with the cancer-specific aggressivity and intervention risks assessment. In localized disease, several standardized algorithms offer patient health evaluation to define how suitable the patient would be for curative treatment. The pre-operative American Society of Anesthesiologists and the age-adjusted Charlson's scores are the most widely used. At the metastatic stage, drug combinations based on immunotherapies and targeted therapies improved cancer outcomes at the price of significant toxicities. Frail patients are not always suitable for such strategies. Commonly used scores like the International Metastatic RCC Database Consortium or Memorial Sloan Kettering Cancer Center integrate features to define patients' risk groups, more specifically the Karnofsky Performance Score is an easy way to document the frailty. CONCLUSIONS: Comorbidity and frailty have to be assessed at any stage of the RCC disease based on a standardized scoring system to define the most suitable treatment strategy ranging from surveillance to aggressive treatment.

Preliminary assessment of patient and physician satisfaction with the use of teleconsultation in urology during the COVID-19 pandemic.

PURPOSE: Lockdown during the COVID-19 pandemic compelled urologists to change access to healthcare, especially for oncology patients. Teleconsultation is a safe way to receive medical advice without a risk of infection, and was implemented urgently in our academic centres. Our purpose was to evaluate patient and physician satisfaction with teleconsultation set up during the COVID-19 pandemic. METHODS: From March 16th 2020, all face-to-face consultations were cancelled in France, except for emergencies. Teleconsultation was started immediately by five senior urologists in two academic hospitals. All patients received an email survey including the validated Teleconsultation Satisfaction Questionnaire (TSQ) and demographic questions. Data were collected prospectively. Physicians also responded to the TSQ. Patient satisfaction was measured objectively with the validated 14-item TSQ. Each item was scored on a 5-point Likert scale. Factors associated with positive satisfaction with teleconsultation were assessed by multivariable logistic regression. RESULTS: Overall, 105 patients replied to the survey (91.3%). Median age was 66 years (IQR: 55‒71) and 95 were men (90.5%). Median overall TSQ score was 67 (IQR: 60‒69); teleconsultation was judged to be a good experience by 88 patients (83.8%) and four physicians (80%). Patients who met their surgeon for the first time were more likely to have a good experience (OR = 1.2 [95% CI 1.1‒1.5], p = 0.03). CONCLUSION: Introduced rapidly during the COVID-19 lockdown, urology teleconsultation attained a high level of satisfaction among both patients and physicians. A major change in telemedicine use is foreseen in the post COVID-19 era.

Neoadjuvant treatment with androgen receptor signaling inhibitors prior to radical prostatectomy: a systematic review.

CONTEXT: There is an urgent need to develop novel treatment strategies in patients with unfavorable intermediate- and high-risk localized prostate cancer (PCa) to optimize the outcome of these patients. Androgen receptor signaling inhibitors (ARSI) have demonstrated a survival benefit in metastatic hormonesensitive and castration-resistant PCa. A similar benefit might be expected in the localized setting. OBJECTIVE: To perform a systematic review about the role of neoadjuvant ARSI in unfavorable intermediate and high-risk localized PCa. EVIDENCE ACQUISITION: We performed a systematic review of the following databases: MEDLINE (PubMed), EMBASE, Cochrane Library and Web of Science. Publications of ASCO were consulted to identify meeting abstract with early results of ongoing trials. This systematic review was performed and reported in accordance with the PRISMA guidelines. EVIDENCE SYNTHESIS: Pathological complete response (pCR) following neoadjuvant ARSI treatment was observed in 4%-13% of the patients. Minimal residual disease response ranged from 36% to 73.9% when defined as residual cancer burden < 0.25 cm3 at final pathology and from 8% to 20% when defined as the diameter of the remaining tumor < 5 mm. Despite intense neoadjuvant ARSI treatment, residual pT3 disease was observed in 48%-76% of the patients. In contrast, positive surgical margins (PSM) were present in only 5%-22%. Only one trial reported BCR following neoadjuvant ARSI therapy (44% BCR at a median follow-up of 4 years). CONCLUSION: Despite intense neoadjuvant ARSI therapy, pCR is rarely attained and high proportions of pT3 disease are still observed at final pathology. In contrast, promising results are obtained in terms of PSMs. Long-term survival outcomes are eagerly awaited.

Comparison of the iliac, vaginal and umbilical graft extraction in robot-assisted laparoscopic living donor nephrectomy.

PURPOSE: To compare different extractions routes for robot-assisted living donor nephrectomy in terms of post-operative pain and renal function recovery. METHODS: Live donor kidney transplantation data from our institution were reviewed from November 2011 to March 2017. Postoperative pain was estimated using cumulative painkillers consumption. Variables were compared between the 3 groups with ANOVA for continuous data, χ2 test for categorial data. A survival analysis with Kaplan-Meier curve assessing time to transplant recipient nadir was performed to compare the renal function recovery. RESULTS: Sixty-three RLDN were performed (23 iliac, 23 vaginal and 17 umbilical extractions). There was no significant difference between the three groups in terms of operative time, blood lost, warm ischemia time, cumulative painkiller consumption and renal function recovery time. Postoperative complications for Umbilical, Vaginal and Iliac were, respectively, of 0, 3 and 1. No major difference was found between the 3 groups beside a slightly longer hospital stay in the iliac group. CONCLUSION: Iliac incision might impact post-operative pain with a moderate but significant longer hospital stay. Vaginal extraction is an option when cosmetic outcomes present a real demand. The three options appeared to be safe and should be discussed with the patient in regard of the surgeon experience.

Antitumor Activity and Mechanism of Action of Hormonotoxin, an LHRH Analog Conjugated to Dermaseptin-B2, a Multifunctional Antimicrobial Peptide.

Prostate cancer is the most common cancer in men. For patients with advanced or metastatic prostate cancer, available treatments can slow down its progression but cannot cure it. The development of innovative drugs resulting from the exploration of biodiversity could open new therapeutic alternatives. Dermaseptin-B2, a natural multifunctional antimicrobial peptide isolated from Amazonian frog skin, has been reported to possess antitumor activity. To improve its pharmacological properties and to decrease its peripheral toxicity and lethality we developed a hormonotoxin molecule composed of dermaseptin-B2 combined with d-Lys6-LHRH to target the LHRH receptor. This hormonotoxin has a significant antiproliferative effect on the PC3 tumor cell line, with an IC50 value close to that of dermaseptin-B2. Its antitumor activity has been confirmed in vivo in a xenograft mouse model with PC3 tumors and appears to be better tolerated than dermaseptin-B2. Biophysical experiments showed that the addition of LHRH to dermaseptin-B2 did not alter its secondary structure or biological activity. The combination of different experimental approaches indicated that this hormonotoxin induces cell death by an apoptotic mechanism instead of necrosis, as observed for dermaseptin-B2. These results could explain the lower toxicity observed for this hormonotoxin compared to dermaseptin-B2 and may represent a promising targeting approach for cancer therapy.

Effect of Extended Pelvic Lymph Node Dissection on Oncologic Outcomes in Patients with D'Amico Intermediate and High Risk Prostate Cancer Treated with Radical Prostatectomy: A Multi-Institutional Study.

PURPOSE: Pelvic lymph node dissection represents the gold standard of lymph node staging in patients with prostate cancer. We sought to assess the effect of extended pelvic lymph node dissection on oncologic outcomes in patients with characteristics of D'Amico intermediate or high risk prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: In a multi-institutional database of 4 centers we identified 9,742 patients who underwent radical prostatectomy from 2000 to 2017 with or without pelvic lymph node dissection. Only patients with a greater than 5% probability of lymph node invasion according to the Briganti nomogram were included in study. We performed 2:1 propensity score matching to account for potential differences between the 2 cohorts. Cox regression models were used to test the effect of pelvic lymph node dissection on biochemical recurrence, metastasis and cancer specific mortality. RESULTS: Overall 707 patients (7.3%) did not undergo pelvic lymph node dissection, of whom 520 and 187 harbored D'Amico intermediate and high risk characteristics, respectively. A median of 14 lymph nodes (IQR 8-21) were removed in the pelvic lymph node dissection cohort and 1,714 of these cases (19.0%) harbored lymph node metastasis. After propensity score matching the biochemical recurrence-free, metastasis-free and cancer specific mortality-free survival rates were 60.4% vs 65.6% (p=0.07), 87.0% vs 90.0% (p=0.06) and 95.2% vs 96.4% (p=0.2) for pelvic lymph node dissection vs no pelvic lymph node dissection 120 months after radical prostatectomy. Multivariable Cox regression models adjusted for postoperative and preoperative tumor characteristics revealed that pelvic lymph node dissection performed at radical prostatectomy was no independent predictor of biochemical recurrence, metastasis or cancer specific mortality (all p ≥0.1). CONCLUSIONS: There was no significant difference in oncologic outcomes in patients with D'Amico high or intermediate risk prostate cancer in whom pelvic lymph node dissection was or was not performed at radical prostatectomy. The therapeutic value of pelvic lymph node dissection remains unclear.