Value of perilesional biopsies in multiparametric magnetic resonance imaging-targeted biopsy and systematic biopsy in detection of prostate cancer: results of a prospective, non-randomized, surgeon-blinded study.

PURPOSE: The goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men. METHODS: This prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels < 20 ng/ml and ≥ one PI-RADS lesion (grades 3-5) per prostate lobe. Prostate biopsy was performed by two urologists. The first performed the MR-fusion biopsy with 3-5 targeted biopsies (TB) and 6 PB in a standardized pattern. The second performed the systematic (12-fold) biopsy (SB) without knowledge of the MR images. Primary outcome of this study is absence or presence of csPCa (≥ ISUP grade 2) comparing TB, PB and SB, using McNemar test. RESULTS: Analyses were performed for each PI-RADS lesion (n = 218). There was a statistically significant difference in csPC detection rate of TB + SB between PI-RADS 3, 4 and 5 lesions (18.0% vs. 42.5% vs. 82.6%, p < 0.001) and TB + PB (19.7% vs. 29.1% vs. 78.3%). Comparing only maximum ISUP grade per lesion, even SB plus TB plus PB did not detect more csPCa compared to SB plus TB (41.3% vs. 39.9%, p > 0.05). CONCLUSION: We present prospective study data investigating the role of perilesional biopsy in detection of prostate cancer. We detected no statistically significant difference in the detection of csPCa by the addition of PB. Therefore, we recommend continuing 12-fold bilateral SB in addition to TB.

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

PURPOSE: We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. MATERIALS AND METHODS: All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. RESULTS: In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. CONCLUSIONS: The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.

Clinical Impact and Management of Incidental Renal Findings on Pre-TAVI CT Scan from the Urologist's Perspective.

INTRODUCTION: The aim of the study was to investigate prevalence and impact of incidental renal masses (IRMs) accompanying increasing computed tomography (CT) work-up for symptomatic aortic valve stenosis (sAVS) of the elderly with regard to the relevance of urological consultation for overall survival (OS). METHODS: A retrospective analysis of pre-transcatheter aortic-valve implantations (TAVIs) CT scans of patients with sAVS (N = 1,253) harboring IRM was performed for 2014-2019. According to the clinical management, groups 1 (urologic consultation) and 2 (findings ignored) were formed and analyzed in terms of OS. RESULTS: The prevalence of IRM was 9% (119/1,253). In 19% (23/119), urological advice was sought (group 1). At baseline, group 1 showed a significantly higher rate of malignancy-specific lesions compared to 2 (p < 0.01). Other clinical parameters (e.g., age, cardiological scores, comorbidities) did not differ between groups (p > 0.05). In group 1, 4 (17%) findings were histologically confirmed, of which 3 (13%) underwent surgery. There was no significant difference in median OS at a median follow-up of 24.7 months between groups 1 and 2 with 35.7 (95% CI, 5.9; 65.4) and 47.4 months (95% CI, 33.0; 61.7), respectively (p = 0.4). In Cox regression analysis, chronic kidney disease but not urologic work-up or chronic obstructive pulmonary disease or heart failure emerged as an independent unfavorable predictor of OS (HR 2.44, 95% CI 1.37; 4.36, p = 0.003). CONCLUSION: For the first time, a TAVI population with IRM was analyzed from the urologist's perspective. Urologic co-evaluation and work-up does not confer a significant benefit in terms of OS in this particular population.

Understanding tumor localization in multiparametric MRI of the prostate-effectiveness of 3D printed models.

Introduction: Understanding tumor localization in multiparametric MRI (mpMRI) of the prostate is challenging for urologists but of great importance in mpMRI-fused prostate biopsy or radical prostatectomy. The aim was to evaluate the effectiveness of 3D printed models of the prostate to help urologists to locate tumors. Methods and Participants: 20 urologists from University Medical Center Mainz (Germany) were asked to plot the location of a cancer suspicious lesion (PI-RADS ≥ 4) on a total of 30 mpMRI on a prostate sector diagram. The following 3 groups (as matched triplets) were divided into: mpMRI only, mpMRI with radiological report and mpMRI with 3D printed model (scaled 1:1). Statistical analysis was performed using one-way and two-way ANOVA (with bonferroni post-test). Results: Overall, localization of the suspicious lesion was superior with the radiological report (median of max. 10 [IQR]: MRI 2 [IQR 1;5], MRI + report: 8 [6.3;9], MRI + 3D model 3 [1.3;5.8]; p < 0.001). Residents with <1 year of experience had a significantly higher detection rate using a 3D printed model [5 (5;5.8)] compared to mpMRI alone [1.5 (1;3.5)] (p < 0.05). Regarding the estimation of index lesion extension, the 3D model showed a significant benefit (mean percentage difference [95% CI]: MRI alone 234% [17.1;451.5], MRI + report 114% [78.5;149.6], MRI + 3D model 17% [-7.4;41.3] (p < 0.01). Conclusion: Urologists still need the written radiological report for a sufficient understanding of tumor localization. The effectiveness of the 3D printed model regarding tumor localization is particularly evident in young residents (<1 year) and leads to a better overall assessment of the tumor extension.

Change in Splenic Volume as a Surrogate Marker for Immunotherapy Response in Patients with Advanced Urothelial and Renal Cell Carcinoma-Evaluation of a Novel Approach of Fully Automated Artificial Intelligence Based Splenic Segmentation.

BACKGROUND: In the treatment of advanced urothelial (aUC) and renal cell carcinoma (aRCC), biomarkers such as PD-1 and PD-L1 are not robust prognostic markers for immunotherapy (IO) response. Previously, a significant association between IO and a change in splenic volume (SV) was described for several tumour entities. To the best of our knowledge, this study presents the first correlation of SV to IO in aUC and aRCC. METHODS: All patients with aUC (05/2017-10/2021) and aRCC (01/2012-05/2022) treated with IO at our academic centre were included. SV was measured at baseline, 3 and 9 months after initiation of IO using an in-house developed convolutional neural network-based spleen segmentation method. Uni- and multivariate Cox regression models for overall survival (OS) and progression-free survival (PFS) were used. RESULTS: In total, 35 patients with aUC and 30 patients with aRCC were included in the analysis. Lower SV at the three-month follow-up was significantly associated with improved OS in the aRCC group. CONCLUSIONS: We describe a new, innovative artificial intelligence-based approach of a radiological surrogate marker for IO response in aUC and aRCC which presents a promising new predictive imaging marker. The data presented implicate improved OS with lower follow-up SV in patients with aRCC.

Structured reporting in radiology enables epidemiological analysis through data mining: urolithiasis as a use case.

PURPOSE: To investigate the epidemiology and distribution of disease characteristics of urolithiasis by data mining structured radiology reports. METHODS: The content of structured radiology reports of 2028 urolithiasis CTs was extracted from the department's structured reporting (SR) platform. The investigated cohort represented the full spectrum of a tertiary care center, including mostly symptomatic outpatients as well as inpatients. The prevalences of urolithiasis in general and of nephro- and ureterolithasis were calculated. The distributions of age, sex, calculus size, density and location, and the number of ureteral and renal calculi were calculated. For ureterolithiasis, the impact of calculus characteristics on the degree of possible obstructive uropathy was calculated. RESULTS: The prevalence of urolithiasis in the investigated cohort was 72%. Of those patients, 25% had nephrolithiasis, 40% ureterolithiasis, and 35% combined nephro- and ureterolithiasis. The sex distribution was 2.3:1 (M:F). The median patient age was 50 years (IQR 36-62). The median number of calculi per patient was 1. The median size of calculi was 4 mm, and the median density was 734 HU. Of the patients who suffered from ureterolithiasis, 81% showed obstructive uropathy, with 2nd-degree uropathy being the most common. Calculus characteristics showed no impact on the degree of obstructive uropathy. CONCLUSION: SR-based data mining is a simple method by which to obtain epidemiologic data and distributions of disease characteristics, for the investigated cohort of urolithiasis patients. The added information can be useful for multiple purposes, such as clinical quality assurance, radiation protection, and scientific or economic investigations. To benefit from these, the consistent use of SR is mandatory. However, in clinical routine SR usage can be elaborate and requires radiologists to adapt.

Single-center, prospective phase 2 trial of high-intensity focused ultrasound (HIFU) in patients with unilateral localized prostate cancer: good functional results but oncologically not as safe as expected.

PURPOSE: Focal therapy (FT) for localized prostate cancer (PCa) is only recommended within the context of clinical trials by international guidelines. We aimed to investigate oncological follow-up and safety data of focal high-intensity focused ultrasound (HIFU) treatment. METHODS: We conducted a single-center prospective study of 29 patients with PCa treated with (focal) HIFU between 2016 and 2021. Inclusion criteria were unilateral PCa detected by mpMRI-US-fusion prostate biopsy and maximum prostate specific antigen (PSA) of 15 ng/ml. Follow-up included mpMRI-US fusion-re-biopsies 12 and 24 months after HIFU. No re-treatment of HIFU was allowed. The primary endpoint was failure-free survival (FFS), defined as freedom from intervention due to cancer progression. RESULTS: Median follow-up of all patients was 23 months, median age was 67 years and median preoperative PSA was 6.8 ng/ml. One year after HIFU treatment PCa was still detected in 13/ 29 patients histologically (44.8%). Two years after HIFU another 7/29 patients (24.1%) were diagnosed with PCa. Until now, PCa recurrence was detected in 11/29 patients (37.93%) which represents an FFS rate of 62%.One patient developed local metastatic disease 2 years after focal HIFU. Adverse events (AE) were low with 70% of patients remaining with sufficient erectile function for intercourse and 97% reporting full maintenance of urinary continence. CONCLUSION: HIFU treatment in carefully selected patients is feasible. However, HIFU was oncologically not as safe as expected because of progression rates of 37.93% and risk of progression towards metastatic disease. Thus, we stopped usage of HIFU in our department.

Impact of Blood Loss on Renal Function and Interaction with Ischemia Duration after Nephron-Sparing Surgery.

OBJECTIVES: Nephron-sparing surgery (NSS) exposes the kidney to ischemia-reperfusion injury. Blood loss and hypotension are also associated with kidney injury. We aimed to test the hypothesis that, during NSS, both ischemia duration and blood loss significantly affect postoperative renal function and that their effects interact. METHODS: Consecutive patients undergoing NSS were enrolled. The primary endpoint was renal function expressed as the absolute delta between preoperative and postoperative peak creatinine. We developed a generalized linear model with the ischemia duration and absolute hemoglobin difference as independent variables, their interaction term, and the RENAL score. The model was than expanded to include a history of hypertension (as a proxy for hypotension susceptibility) and related interaction terms. Further, we described the perioperative and mid-term oncological outcomes. RESULTS: A total of 478 patients underwent NSS, and 209 (43.7%) required ischemia for a mean of 10.9 min (SD 8). Both the ischemia duration (partial eta 0.842, p = 0.006) and hemoglobin difference (partial eta 0.933, p = 0.029) significantly affected postoperative renal function, albeit without evidence of a significant interaction (p = 0.525). The RENAL score also significantly influenced postoperative renal function (p = 0.023). After the addition of a previous history of hypertension, the effects persisted, with a significant interaction between blood loss and a history of hypertension (p = 0.02). CONCLUSIONS: Ischemia duration and blood loss had a similar impact on postoperative renal function, albeit without potentiating each other. While the surgical technique and ischemia minimization remain crucial to postoperative kidney function, increased awareness of conscious hemodynamic management appears warranted.

Comparative assessment of multiple-tract vs single-tract percutaneous nephrolithotomy.

INTRODUCTION: To investigate the efficacy and safety of multi-tract percutaneous nephrolithotomy (PNL) against the benchmark of the single-tract approach. METHODS: A retrospective analysis of 391 consecutive PNL procedures was conducted in our tertiary referral center between April 2016 and March 2020. Clinical outcome parameters such as stone-free rate, operation time, postoperative complications according to Clavien-Dindo, length of hospital stay and time to ipsilateral recurrence resulting in active treatment were assessed. RESULTS: Multi-tract PNL and single-tract PNL were performed in 37 (9%) and 354 (91%) cases respectively. At baseline, compared to single-tract PNL, multi-tract PNL cases were characterized by significantly larger stone burden (2.62 vs 0.97 cm3 , P < .00), lower Hounsfield units (HU) (751 vs 1017 HU, P < .01), a more complex S.T.O.N.E. (size, tract length, obstruction, number of calyces, essence) score (P < .00) and a higher rate of high-risk stone formers (59 vs 19%, P < .00). Analysis of outcome revealed shorter operation time and length of hospital stay for single-tract PNL compared to multi-tract PNL (P < .01). However, the difference in terms of stone-free rates (92% vs 88%), complication rates (43% vs 28%) and time to active retreatment due to ipsilateral recurrence was not statistically significant (P > .05). CONCLUSION: In this retrospective single-center analysis, a multi-tract PNL has been proved to be an efficient and safe expansion of single-tract PNL for large stone burden and complex kidney stone disease. Future prospective research should focus on the procedure's potential effectiveness in reducing the number of interventions until stone-free status in patients with massive stone disease.

Shikonin Inhibits Cell Growth of Sunitinib-Resistant Renal Cell Carcinoma by Activating the Necrosome Complex and Inhibiting the AKT/mTOR Signaling Pathway.

Therapy resistance remains a major challenge in treating advanced renal cell carcinoma (RCC), making more effective treatment strategies crucial. Shikonin (SHI) from traditional Chinese medicine has exhibited antitumor properties in several tumor entities. We, therefore, currently investigated SHI's impact on progressive growth and metastatic behavior in therapy-sensitive (parental) and therapy-resistant Caki-1, 786-O, KTCTL-26, and A498 RCC cells. Tumor cell growth, proliferation, clonogenic capacity, cell cycle phase distribution, induction of cell death (apoptosis and necroptosis), and the expression and activity of regulating and signaling proteins were evaluated. Moreover, the adhesion and chemotactic activity of the RCC cells after exposure to SHI were investigated. SHI significantly inhibited the growth, proliferation, and clone formation in parental and sunitinib-resistant RCC cells by G2/M phase arrest through down-regulation of cell cycle activating proteins. Furthermore, SHI induced apoptosis and necroptosis by activating necrosome complex proteins. Concomitantly, SHI impaired the AKT/mTOR pathway. Adhesion and motility were cell line specifically affected by SHI. Thus, SHI may hold promise as an additive option in treating patients with advanced and therapy-resistant RCC.

The timing of initial imaging in testicular cancer: impact on radiological findings and clinical decision making.

BACKGROUND: In testicular cancer determination of clinical stage and recommendation of therapeutic strategy after inguinal orchiectomy are based on primary imaging by CT-scan of the chest and CT- or MRI-abdomen. It has not been investigated so far whether the imaging should be performed before or after primary testicular surgery. Staging before surgery means exposing all patients to CT radiation irrespective of ensured histologic malignancy while postoperative staging could pose a risk in biased clinical decision making by increased presence of unspecific lymph node enlargement caused by postsurgical effects. Therefore, we aimed to investigate the association between the timing of initial staging and occurrence of unspecific lymph node enlargement and adjuvant therapies after inguinal orchiectomy. METHODS: We retrospectively evaluated clinical and radiological data from 236 patients who had undergone inguinal orchiectomy for testicular cancer at our department. Statistical analysis was performed to determine whether the occurrence of unspecific lymph node enlargement or the rate of adjuvant therapies were influenced by timing of initial staging (preoperative vs. postoperative). RESULTS: The postoperative imaging cohort showed significant more inguinal, pelvic and retroperitoneal unspecific lymph node enlargement than the preoperative imaging cohort. Simultaneous occurrence of inguinal or pelvic lymph node enlargement together with retroperitoneal enlargements could only be found in the postoperative imaging cohort. No difference regarding adjuvant therapies could be found. CONCLUSIONS: Timing of imaging affects the detection rate of unspecific lymph node enlargements but does not show a significant effect on the rate of adjuvant therapies.

Outcomes for Geriatric Urolithiasis Patients aged ≥80 Years Compared to Patients in Their Seventies.

BACKGROUND: Demographic changes are leading to an increase in geriatric urolithiasis patients aged ≥70 yr. Published data regarding their management remain sparse. In particular, for the subgroup of patients aged ≥80 yr there is a lack of evidence supporting the hypothesis that stone-removing treatment is effective, safe, and beneficial. OBJECTIVE: To examine the efficiency and safety of stone-removing treatment in geriatric urolithiasis patients aged ≥80 yr compared to their younger geriatric counterparts aged 70-79 yr against the background of their respective life expectancy. DESIGN, SETTING, AND PARTICIPANTS: Data for the study cohort were extracted from an institutional review board-approved retrospective database with 325 patients aged ≥70 yr (70-79 yr: n = 241; ≥80 yr: n = 84) consecutively admitted to hospital because of symptomatic urolithiasis from 2013 to 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics, outcome and follow-up data, and survival were compared using Wilcoxon-Mann-Whitney U tests, χ2 tests, Kaplan-Meier estimation, log-rank tests, and Cox regression. RESULTS AND LIMITATIONS: At baseline, the incidence of infected hydronephrosis was greater among patients aged ≥80 yr (p < 0.05), whereas the median stone burden and Charlson comorbidity index did not differ between the groups. Outcome analysis revealed no significant differences in terms of complication, stone-free, and 6-mo readmission rates (p > 0.05). Survival analysis for the two groups demonstrated a 2-yr overall survival (OS) rate of 0.91 (95% confidence interval [CI] 0.75-1) for patients aged ≥80 yr and 0.97 (95% CI 0.88-1), for those aged 70-79 yr (p < 0.01). Multivariable Cox analysis revealed age ≥80 yr (hazard ratio [HR] 3.3, 95% CI 1.3-8.5) and infected hydronephrosis (HR 2.8, 95% CI 1.0-7.8) as predictors of all-cause mortality (p < 0.05). The study is limited by its retrospective design. CONCLUSIONS: Stone-removing treatment for patients aged ≥80 yr proved to be as effective and safe as for patients in their seventies. Although characterized by shorter remaining life expectancy, excellent 2-yr OS for patients aged ≥80 yr supports the hypothesis of equal benefit from stone-removing treatment when compared to septuagenarians. PATIENT SUMMARY: There is a lack of evidence supporting the benefit of urinary stone-removing treatment for patients older than 80 yr. Our study included geriatric patients older than 70 yr with symptomatic urinary stone disease for which urinary drainage or stone removal is indicated. We compared treatment outcomes and survival between two age groups: patients aged 70-79 yr and those aged 80 yr or older. We found equivalent outcomes for the two groups and excellent 2-yr overall survival of 91% for those older than 80 yr. The study strengthens the evidence that active stone-removing therapy is safe and beneficial for these patients.

Co-administration of tyrosine kinase inhibitors with rottlerin in metastatic prostate cancer cells.

After prostatectomy due to prostate carcinoma, patients often develop metastases. Although prostate cancer is susceptible to hormonal manipulation, many patients become castration-resistant. Therefore, new therapies are the focus of investigations. We analyzed the effect of the tyrosine kinase inhibitors (TKIs), sorafenib and sunitinib, in combination with rottlerin, a PKCδ inhibitor, on metastatic mechanisms in prostate carcinoma cells. LNCaP and PC-3 prostate carcinoma cells were treated with sorafenib or sunitinib alone at various concentrations (1-20 µM) or in combination with rottlerin (10 µM) for 24 h. Then, cell toxicity (MTT test) and cell proliferation (BrdU incorporation assay) were quantified. The study demonstrated a dose-dependent inhibitory effect of sorafenib and sunitinib on PC-3 and LNCaP cell activity and proliferation. Both agents showed significantly stronger cytotoxic effects in LNCaP cells. At the highest concentrations, sorafenib and sunitinib inhibited the viability of LNCaP cells up to 2 % and 31 %, respectively, and the viability of PC-3 cell line up to 20 % and 43 %, respectively. The proliferation of both cell lines was significantly stronger inhibited by sorafenib than by sunitinib. In LNCaP cells, sorafenib and sunitinib at the highest concentrations inhibited cell proliferation up to 46 % and 49 %, respectively, and the proliferation of PC-3 line up to 40 % and 47 %, respectively. Rottlerin reduced the viability and proliferation of PC3 cells to 81 % and 42 %, whereas the viability and proliferation of LNCaP cells were reduced to 25 % and 57 %, respectively. Sorafenib and sunitinib at low concentrations partly neutralized the inhibitory effect of rottlerin on cell viability and proliferation. On the other hand, in PC-3 cells, rottlerin reduced the inhibitory effects of sorafenib and sunitinib at the highest concentrations on cell viability from 20 % to 30 % and from 43 % to 61 %, respectively. An additive effect on cell activity was observed after treating LNCaP cells with both sunitinib at high concentrations and rottlerin. This combination increased the cytotoxic effect from 31 % to 13 % at the highest sunitinib concentration. Our results showed that monotherapy with sorafenib was the most efficient in both PCa cell lines. A marginally additive effect of rottlerin was only observed in LNCaP cells treated with sunitinib at a high concentration. Sorafenib and sunitinib reduced cell migration in PC-3 cells to 10 % and 32 % of untreated cells, respectively. Co-treatment with sorafenib/sunitinib and rottlerin did not result in a significantly stronger anti-migratory effect than the treatment with each TKI alone. Given the strong cytotoxic effect of TKIs, especially sorafenib, on LNCaP cells, the results of the migration assay in this line were severely biased and not considered in the analysis. Unlike in other malignancies, combination therapy with TKI and rottlerin seems not beneficial in prostate cancer. More promising seems to be monotherapy with rottlerin, but further studies are needed to confirm this observation.

Robotic surgery can be safely performed for patients and healthcare workers during COVID-19 pandemic.

OBJECTIVES: To investigate the safety of robotic surgery during COVID-19 pandemic concerning new-acquired COVID-19 infections for patients and healthcare workers. PATIENTS: We performed a retrospective single-centre cohort study of patients undergoing robotic surgery in initial period of COVID-19 pandemic. Patients and healthcare workers COVID-19 infection status was assessed by structured telephone follow-up and/or repeated nasopharyngeal swabs. RESULTS: After 61 robotic surgeries (93,5% cancer surgery), one patient (1.6%) had COVID-19 infection. Sixty healthcare workers cumulatively exposed to 1187 h of robotic surgery had no infection. One patient with postoperative proof of SARS-CoV-2 had complete recovery. After this potentially contagious robotic surgery, eight healthcare workers had no COVID-19 infection after follow-up with each three nasopharyngeal swabs. CONCLUSIONS: Early clinical experience of robotic surgery during COVID-19 pandemic shows that robotic surgery can be safely performed for patients and healthcare workers. Despite our results we recommend elective surgery only for verified COVID-19 negative patients.

Global change of surgical and oncological clinical practice in urology during early COVID-19 pandemic.

OBJECTIVES: While the coronavirus disease 2019 (COVID-19) pandemic captures healthcare resources worldwide, data on the impact of prioritization strategies in urology during pandemic are absent. We aimed to quantitatively assess the global change in surgical and oncological clinical practice in the early COVID-19 pandemic. METHODS: In this cross-sectional observational study, we designed a 12-item online survey on the global effects of the COVID-19 pandemic on clinical practice in urology. Demographic survey data, change of clinical practice, current performance of procedures, and current commencement of treatment for 5 conditions in medical urological oncology were evaluated. RESULTS: 235 urologists from 44 countries responded. Out of them, 93% indicated a change of clinical practice due to COVID-19. In a 4-tiered surgery down-escalation scheme, 44% reported to make first cancellations, 23% secondary cancellations, 20% last cancellations and 13% emergency cases only. Oncological surgeries had low cancellation rates (%): transurethral resection of bladder tumor (27%), radical cystectomy (21-24%), nephroureterectomy (21%), radical nephrectomy (18%), and radical orchiectomy (8%). (Neo)adjuvant/palliative treatment is currently not started by more than half of the urologists. COVID-19 high-risk-countries had higher total cancellation rates for non-oncological procedures (78% vs. 68%, p = 0.01) and were performing oncological treatment for metastatic diseases at a lower rate (35% vs. 48%, p = 0.02). CONCLUSION: The COVID-19 pandemic has affected clinical practice of 93% of urologists worldwide. The impact of implementing surgical prioritization protocols with moderate cancellation rates for oncological surgeries and delay or reduction in (neo)adjuvant/palliative treatment will have to be evaluated after the pandemic.

Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis.

Although innovative therapeutic concepts have led to better treatment of advanced renal cell carcinoma (RCC), efficacy is still limited due to the tumor developing resistance to applied drugs. Artesunate (ART) has demonstrated anti-tumor effects in different tumor entities. This study was designed to investigate the impact of ART (1-100 µM) on the sunitinib-resistant RCC cell lines, Caki-1, 786-O, KTCTL26, and A-498. Therapy-sensitive (parental) and untreated cells served as controls. ART's impact on tumor cell growth, proliferation, clonogenic growth, apoptosis, necrosis, ferroptosis, and metabolic activity was evaluated. Cell cycle distribution, the expression of cell cycle regulating proteins, p53, and the occurrence of reactive oxygen species (ROS) were investigated. ART significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant RCC cells. In Caki-1, 786-O, and A-498 cell lines growth inhibition was associated with G0/G1 phase arrest and distinct modulation of cell cycle regulating proteins. KTCTL-26 cells were mainly affected by ART through ROS generation, ferroptosis, and decreased metabolism. p53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC.

Comparative assessment of docetaxel for safety and efficacy between hormone-sensitive and castration-resistant metastatic prostate cancer.

OBJECTIVE: To compare toxicity and response of docetaxel chemotherapy between metastatic hormone-sensitive prostate cancer (mHSPC) and castration-resistant metastatic prostate cancer (mCRPC) patients of the same therapeutic era for assessing of upfront docetaxel against the benchmark of docetaxel in the castrate resistant stage in the setting outside of clinical trials. METHODS: A prospectively collected database of real-world prostate cancer patients receiving docetaxel was divided in mHSPC and mCRPC cases and retrospectively analyzed. Principal objectives were toxicity measured by the common criteria of adverse events terminology and response characterized by Prostate specific antigen decline and radiographic progression-free disease at restaging. The prognostic value of suspected variables for grade 3 to 5 toxicity and response was investigated by logistic regression analysis. RESULTS: Of 72 patients 34 (47%) were treated for mHSPC and 38 (53%) for mCRPC. Patients with mCRPC were older and had worse performance status (P< 0.01). In mHSPC total number of grade 3 to 5 adverse events (24, median 0, interquartile range 0-1) was significantly less than in mCRPC (46, median 1, interquartile range 1-2) (P = 0.01). Multivariable analysis revealed age as independent predictive variable for grade 3 to 5 toxicity (P = 0.03) but not disease stage, Prostate specific antigen predocetaxel, volume of disease, and Eastern Cooperative Oncology Group performance status (P > 0.05). Objective response was significantly higher in mHSPC compared to mCRPC patients (P < 0.01). Multivariable analysis confirmed mHSPC stage as independent prognostic factor for radiographic progression free disease at restaging (P < 0.01). CONCLUSIONS: The association of age with toxicity and of mHSPC stage with response resulted in significantly fewer grade 3 to 5 adverse events but higher response rates for upfront docetaxel in mHSPC compared with docetaxel in the later mCRPC stage.

Cost-effectiveness analysis of robot-assisted vs. open partial nephrectomy.

BACKGROUND: The cost-effectiveness of robot-assisted partial nephrectomy (RAPN) vs. the open procedure is not established. METHODS: We estimated in-hospital complications and the cost of RAPN vs. open partial nephrectomy (OPN) using an economic model. Costs incurred both intraoperatively and in hospital were considered. US data were extracted from existing literature. RESULTS: Mean in-hospital costs were $14,824 (95% CI $13,368-$16,898) for RAPN and $15,094 (95% CI $13,491-$17,140) for OPN. Complications after RAPN occurred in 23.3% (95% CI 20.0-25.8%) and after OPN in 36.1% (95% CI 35.6-36.6%) of the patients. In a sensitivity analysis, limited centre experience was associated with relevant increase in RAPN cost and consequently in low cost-effectiveness. CONCLUSIONS: In this economic model based on US data, RAPN resulted in nominally lower cost but fewer perioperative complications than OPN. RAPN was not cost-effective in less experienced centres.

Prostate Cancer on the Web-Expedient Tool for Patients' Decision-Making?

Many patients diagnosed with cancer search for health information on the Web. We aimed to assess the quality and reliability of online health information on prostate cancer. Google, Yahoo, and Bing were searched for the term "prostate cancer." After selecting the most frequented websites, quality was measured by DISCERN score, JAMA benchmark criteria, and presence of HONcode certification. Popularity was assessed by Alexa tool, while accessibility, usability, and reliability were investigated by LIDA tool. Readability was analyzed by Flesch-Kincaid Reading Grade Level and Automated Readability Index. All 13 selected websites were rated as being of high quality according to the DISCERN instrument (76.5 ± 2.6 out of 80 points). JAMA benchmark criteria were fulfilled by 87 % of websites, whereas only 37 % were certified by the HONcode. Median Alexa Traffic Rank was 2718 ranging from 7 to 679,038. Websites received 2.3 ± 0.5 daily pageviews per visitor and users spent an average of 2 min 58 s ± 39 sec on the website. Accessibility (92 ± 5 %) and usability (92 ± 3 %) scores were high and reliability (88 ± 8 %) moderate according to the LIDA tool. Flesch-Kincaid Grade Level was 7.9 ± 2.2, and Automated Readability Index was 7.5 ± 2.4, rating the websites as fairly difficult to read. In conclusion, quality, accessibility, and usability of websites on prostate cancer provided a high rating in the current analysis. These findings are encouraging in view of the growing frequency of patients' access of health information online.