Publications by authors named "Tobias Klatte"

236 Publications

Outcome after resection of occult and non-occult lymph node metastases at the time of nephrectomy.

World J Urol 2021 Feb 25. Epub 2021 Feb 25.

Department of Urology, Renal Cancer Unit, Royal Free Hospital, London, UK.

Purpose: There is sparse evidence on outcomes of resected occult LN metastases at the time of nephrectomy (synchronous disease). We sought to analyse a large international cohort of patients and to identify clinico-pathological predictors of long-term survival.

Materials And Methods: We collected data of consecutive patients who underwent nephrectomy and LND for T cN0-1pN1 and cM0-1 RCC at 7 referral centres between 1988 and 2019. Patients were stratified into four clinico-pathological groups: (1) cN0cM0-pN1, (2) cN1cM0-pN1(limited, 1-3 positive nodes), (3) cN1cM0-pN1(extensive, > 3 positive nodes), and (4) cM1-pN1. Overall survival (OS) was estimated using the Kaplan-Meier method, and associations with all-cause mortality (ACM) were evaluated using Cox models with multiple imputations.

Results: Of the 4370 patients with LND, 292 patients with pN1 disease were analysed. Median follow-up was 62 months, during which 171 patients died. Median OS was 21 months (95% CI 17-30 months) and the 5-year OS rate was 24% (95% CI 18-31%). Patients with cN0cM0-pN1 disease had a median OS of 57 months and a 5-year OS rate of 43%. 5-year OS (median OS) decreased to 29% (33 months) in cN1cM0-pN1(limited) and to 23% (23 months) in cN1cM0-pN1(extensive) patients. Those with cM1-pN1 disease had the worst prognosis, with a 5-year OS rate of 13% (9 months). On multivariable analysis, age (p = 0.034), tumour size (p = 0.02), grade (p = 0.02) and clinico-pathological group (p < 0.05) were significant predictors of ACM.

Conclusion: Depending on clinico-pathological group, grade and tumour size, 5-year survival of patients with LN metastases varies from 13 to 43%. Patients with resected occult lymph node involvement (cN0/pN1 cM0) have the best prognosis with a considerable chance of long-term survival.
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http://dx.doi.org/10.1007/s00345-021-03633-5DOI Listing
February 2021

Prevalence, Disease-free, and Overall Survival of Contemporary Patients With Renal Cell Carcinoma Eligible for Adjuvant Checkpoint Inhibitor Trials.

Clin Genitourin Cancer 2021 Jan 7. Epub 2021 Jan 7.

Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, UCL Division of Surgical and Interventional Science, London, UK; Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address:

Introduction: Designing adjuvant trials is challenging because of uncertainties of prevalence and outcome of high-risk renal cell cancer (RCC) despite use of validated risk scores. Our objective is to investigate how differences in eligibility criteria may impact on potential study results in RCC adjuvant trials.

Patients And Methods: RECUR is a multicenter European database capturing patient and tumor characteristics, recurrence patterns, and survival of those curatively treated for non-metastatic RCC from 2006 to 2011 without any adjuvant therapy. We used RECUR to evaluate prevalence, disease-free survival (DFS), and overall survival (OS) according to eligibility criteria of immunotherapy-based adjuvant trials IMMotion 010 (NCT03024996), Checkmate 914 (NCT03138512), Keynote-564 (NCT03142334), RAMPART (NCT03288532), and PROSPER (NCT03055013).

Results: Of 3024 relevant patients in RECUR, 408 (13.5%), 725 (24%), 609 (20.1%), 1363 (45.1%), and 1071 (35.4%) met eligibility criteria for IMMotion-010, CheckMate-914, Keynote-564, RAMPART, and PROSPER, respectively. The median and 5-year DFS Kaplan-Meier estimates in RECUR corresponding to each trial eligibility criteria were: not reached and 69.6% for RAMPART; not reached and 64.5% for PROSPER; 109.3 months (95% confidence interval [CI], 83.9-134.6 months) and 57% for CheckMate-914; 75.8 months (95% CI, 52.7-98.8 months) and 54.3% for Keynote-564; and 43.6 months (95% CI, 30.8-56.4 months) and 45% for IMMotion-010. Our analysis may be limited by the retrospective design.

Conclusions: RECUR provides estimated DFS and OS benchmarks for placebo arms of adjuvant checkpoint inhibitor studies and hence likely time to trial reporting. Well-documented contemporary registries rather than past risk models should be used to design future adjuvant trials.
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http://dx.doi.org/10.1016/j.clgc.2020.12.005DOI Listing
January 2021

Clinical, surgical, pathological and follow-up features of kidney cancer patients with Von Hippel-Lindau syndrome: novel insights from a large consortium.

World J Urol 2021 Jan 8. Epub 2021 Jan 8.

Unit of Urology, University Vita-Salute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.

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 34 years (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 79 months (IQR 0-132), and median index tumor size leading to treatment was 35.5 mm (IQR 28-60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4 cm. With a median follow-up of 8 years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10 years, respectively. Overall mortality was 4% and 7.5% at 5 and 10 years, 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.
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http://dx.doi.org/10.1007/s00345-020-03574-5DOI Listing
January 2021

Development of a Novel Risk Score to Select the Optimal Candidate for Cytoreductive Nephrectomy Among Patients with Metastatic Renal Cell Carcinoma. Results from a Multi-institutional Registry (REMARCC).

Eur Urol Oncol 2020 Dec 29. Epub 2020 Dec 29.

Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain. Electronic address:

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 (<80%) and those with more than three metastases had also higher OM rates (p = 0.026 and 0.040, respectively). The C-index of the REMARCC model was higher than that of the MSKCC and IMDC models (66.4% vs 60.4% vs 60.3%). After stratification, 113 (22.0%) patients were classified to have a favorable (no risk factors), 202 (39.5%) an intermediate (one or two risk factors), and 197 (38.5%) a poor (more than two risk factors) prognosis. Moreover, 72 (17.2%) and 51 (13.9%) patients classified as having an intermediate and a poor prognosis according to MSKCC and IMDC categories, respectively, would be reclassified as having a good prognosis according to the REMARCC score.

Conclusions: Our findings confirm the relevance of tumor and patient features for the risk stratification of mRCC patients and clinical decision-making regarding CN. Further prospective external validations are required for the scoring system proposed herein.

Patient Summary: Current stratification systems for selecting patients for kidney removal when metastatic disease is shown are controversial. We suggest a system that includes tumor and patient features besides the systems already in use, which are based on blood tests.
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http://dx.doi.org/10.1016/j.euo.2020.12.010DOI Listing
December 2020

Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Nivolumab plus Cabozantinib Joins Immune Checkpoint Inhibition Combination Therapies for Treatment-naïve Metastatic Clear-Cell Renal Cell Carcinoma.

Eur Urol 2021 Mar 24;79(3):339-342. Epub 2020 Dec 24.

The Royal Free London NHS Foundation Trust, London, UK; UCL Division of Surgery and Interventional Science, University College London, London, UK; Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address:

Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. PATIENT SUMMARY: New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.
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http://dx.doi.org/10.1016/j.eururo.2020.12.005DOI Listing
March 2021

The Impact of Histological Subtype on the Incidence, Timing, and Patterns of Recurrence in Patients with Renal Cell Carcinoma After Surgery-Results from RECUR Consortium.

Eur Urol Oncol 2020 Oct 24. Epub 2020 Oct 24.

Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, UCL Division of Surgical and Interventional Science, London, UK; Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Background: Current follow-up strategies for patients with renal cell carcinoma (RCC) after curative surgery rely mainly on risk models and the treatment delivered, regardless of the histological subtype.

Objective: To determine the impact of RCC histological subtype on recurrence and to examine the incidence, pattern, and timing of recurrences to improve follow-up recommendations.

Design, Setting, And Participants: This study included consecutive patients treated surgically with curative intention (ie, radical and partial nephrectomy) for nonmetastatic RCC (cT1-4, M0) between January 2006 and December 2011 across 15 centres from 10 countries, as part of the euRopEan association of urology renal cell carcinoma guidelines panel Collaborative multicenter consortium for the studies of follow-Up and recurrence patterns in Radically treated renal cell carcinoma patients (RECUR) database project.

Outcome Measurements And Statistical Analysis: The impact of histological subtype (ie, clear cell RCC [ccRCC], papillary RCC [pRCC], and chromophobe RCC [chRCC]) on recurrence-free survival (RFS) was assessed via univariate and multivariate analyses, adjusting for potential interactions with important variables (stage, grade, risk score, etc.) Patterns of recurrence for all histological subtypes were compared according to recurrence site and risk criteria.

Results And Limitations: Of the 3331 patients, 62.2% underwent radical nephrectomy and 37.8% partial nephrectomy. A total of 2565 patients (77.0%) had ccRCC, 535 (16.1%) had pRCC, and 231 (6.9%) had chRCC. The median postoperative follow-up period was 61.7 (interquartile range: 47-83) mo. Patients with ccRCC had significantly poorer 5-yr RFS than patients with pRCC and chRCC (78% vs 86% vs 91%, p = 0.001). The most common sites of recurrence for ccRCC were the lung and bone. Intermediate-/high-risk pRCC patients had an increased rate of lymphatic recurrence, both mediastinal and retroperitoneal, while recurrence in chRCC was rare (8.2%), associated with higher stage and positive margins, and predominantly in the liver and bone. Limitations include the retrospective nature of the study.

Conclusions: The main histological subtypes of RCC exhibit a distinct pattern and dynamics of recurrence. Results suggest that intermediate- to high-risk pRCC may benefit from cross-sectional abdominal imaging every 6 mo until 2 yr after surgery, while routine imaging might be abandoned for chRCC except for abdominal computed tomography in patients with advanced tumour stage or positive margins.

Patient Summary: In this analysis of a large database from 15 countries around Europe, we found that the main histological subtypes of renal cell carcinoma have a distinct pattern and dynamics of recurrence. Patients should be followed differently according to subtype and risk score.
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http://dx.doi.org/10.1016/j.euo.2020.09.005DOI Listing
October 2020

Surgical Management and Outcomes of Renal Tumors Arising from Horseshoe Kidneys: Results from an International Multicenter Collaboration.

Eur Urol 2021 Jan 16;79(1):133-140. Epub 2020 Sep 16.

Department of Urology, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Background: Despite being the most frequent renal fusion anomaly, tumors arising from horseshoe kidneys (HSKs) are extremely rare and management guidance is lacking.

Objective: To evaluate the perioperative, oncological, and functional outcomes of surgically treated HSK tumors.

Design, Setting, And Participants: A retrospective, multicenter cohort study of 43 HSK tumors in 40 patients was conducted, and technical description of the surgical approach has been provided.

Surgical Procedure: Surgical resection of renal tumors arising from HSKs was performed either via open surgery or via minimally invasive surgery (MIS).

Measurements: We analyzed patient and tumor characteristics as well as surgical technique, and functional and oncological outcomes.

Results And Limitations: Eight patients were treated by MIS and 32 by open surgery. One patient (2.5%) experienced an intraoperative complication and 13 patients (32.5%) experienced postoperative complications, of which three (7.5%) were Clavien-Dindo ≥3 complications. Surgical margins were positive in two tumors (4.7%). The most frequent histology was clear-cell renal cell carcinoma (46.5%). The median follow-up was 51 (interquartile range [IQR] 17-73) mo. The 5-yr overall, cancer-specific, and recurrence-free survival rates were 81.2%, 86.8%, and 83.1%, respectively. The percent decreases in estimated glomerular filtration rate at discharge and the last follow-up were 15% (IQR 4-26%) and 17% (IQR 1-31%), respectively. Limitations include the cohort's retrospective nature, heterogeneity, and small sample size.

Conclusions: Surgical management of tumors in HSKs can be approached via both open surgery and MIS, with maximal preservation of functional renal parenchyma. In this cohort, rates of complications, positive surgical margins, and renal functional decrease were acceptable, considering the anatomical complexity of these kidneys and tumors. These tumors display great variation in histological subtypes. Meticulous presurgical planning, taking advantage of advanced imaging techniques, can aid in achieving good outcomes.

Patient Summary: We evaluated the surgical management of renal tumors in horseshoe kidneys, which are very rare. Although these procedures are highly complex, outcomes are acceptable. Modern imaging techniques are often required in presurgical planning.
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http://dx.doi.org/10.1016/j.eururo.2020.09.012DOI Listing
January 2021

Incidence and preoperative predictors for major complications following radical nephroureterectomy.

Transl Androl Urol 2020 Aug;9(4):1786-1793

Department of Surgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.

Background: Radical nephroureterectomy (RNU) is the referent standard for managing bulky, invasive, or high grade upper-tract urothelial carcinoma (UTUC). The UTUC patient population, however, generally harbor medical comorbidities thereby placing them at risk of surgical complications. This study reviews a large international cohort of RNU patients to define the risk of major complications and preoperative factors associated with their occurrence.

Methods: Patients undergoing RNU at 14 academic medical centers between 2002 and 2015 were retrospectively reviewed. Preoperative clinical, demographic, operative, and comorbidity indices were recorded. The modified Clavien-Dindo index was used to grade complications occurring within 30 days of surgery. The association between preoperative variables and major complications occurring after RNU was determined by multivariable logistic regression.

Results: One thousand two hundred and sixty-six patients (707 men; 559 women) with a median age of 70 years and BMI of 27 kg/m were included. Over three-quarters of the cohort was white, 50.1% had baseline chronic kidney disease (CKD) ≥ stage III, 22.4% had a Charlson comorbidity index (CCI) score >5, and 17.1% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Overall, 413 (32.6%) experienced a complication including 103 (8.1%) with a major event. Specific distribution of major complications included 49 Clavien III, 44 Clavien IV, and 10 Clavien V. On univariate analysis, patient age (P=0.006), hypertension (P=0.002), diabetes mellitus (P=0.023), CKD stage (P<0.001), American Society of Anesthesiologists (ASA) score (P=0.022), ECOG (P<0.001), and CCI (P<0.001) all were associated with major complications. On multivariate analysis, ECOG ≥2 (OR 2.38, 95% CI, 1.46-3.90), P=0.001), CCI >5 (OR 3.45, 95% CI, 1.41-8.33, P=0.007), and CKD stage ≥3 (OR 3.64, P=0.008) were independently associated with major complications.

Conclusions: Major complications following RNU occurred in almost 10% of patients. Impaired preoperative performance status and baseline CKD are preoperative variables associated with these major post-surgical adverse event. These easily measurable indices warrant consideration and discussion prior to proceeding with RNU.
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http://dx.doi.org/10.21037/tau.2020.01.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475660PMC
August 2020

[Current practice patterns of perioperative cystectomy management in Germany: a questionnaire survey].

Aktuelle Urol 2021 Feb 29;52(1):82-87. Epub 2020 Jul 29.

Charité Universitätsmedizin Berlin, Urologie, Berlin.

Objective:  Radical cystectomy (RCX) is the standard treatment for muscle-invasive and treatment-refractory non-invasive bladder cancer, but that is associated with high morbidity. We now survey current practice patterns on perioperative management among German urological departments of all sizes METHODS:  Members of the German Association of Urology and the German Society of Residents in Urology (GeSRU) were contacted by email and asked to answer a 24-item online questionnaire covering clinically relevant aspects of current guidelines and controversies.

Results:  Responses were obtained from at least 19 % of all German urological centers. About 60 % performed preoperative staging using CT urography and chest CT. The most common perioperative antibiotic prophylaxis was a third generation cephalosporin combined with metronidazole (46 %), administered for a median of 5 days. Stentograms for ileal conduit and neobladder are routinely performed in 38 % and 55 % of patients, respectively. Ureteral stents were usually removed 11 - 12 days after the procedure (ileal conduit and neobladder). Based on the surrogate parameters of preoperative bowel preparation, postoperative start of oral nutrition and use of nasogastric tube, fast-track concepts such as ERAS were not generally established (< 50 %). Robot-assisted cystectomy appears to be performed in 15 % of German urological centers and was associated with the number of performed cystectomies (p < 0.001).

Conclusions:  Most aspects of perioperative management in cystectomy patients - staging diagnostics, use of antibiotics, stent removal - are performed in accordance with current guidelines. Other clinical questions such as stent imaging before removal and fast track concepts are handled heterogeneously. Guideline-adherence was not associated with hospital size or number of procedures performed.
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http://dx.doi.org/10.1055/a-1025-2523DOI Listing
February 2021

Chronic Kidney Disease After Partial Nephrectomy in Patients With Preoperative Inconspicuous Renal Function - Curiosity or Relevant Issue?

Clin Genitourin Cancer 2020 Dec 20;18(6):e754-e761. Epub 2020 May 20.

Department of Urology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.

Background: Chronic kidney disease (CKD) is a severe long-term complication after partial nephrectomy (PN). Clinical and scientific focus lies on patients with impaired renal function at the time of surgery. Little data is available on patients with normal preoperative renal function (NPRF).

Patients And Methods: Patients who underwent PN with a preoperative estimated glomular filtration rate > 60 mL/min/1.73m were retrospectively examined at 8 European urologic centers. The occurrence of new onset CKD ≥ stage III after surgery (sCKD) was defined as the primary endpoint. Group comparisons and risk correlations were determined. Based on this data, a risk stratification model for sCKD was developed.

Results: Of the 1315 patients with NPRF included, 249 (18.9%) developed sCKD after a median follow-up of 44 months (range, 6-255 months). Pair analysis and univariable regression revealed age, arterial hypertension, American Society of Anesthesiologists score, tumor stage, surgical approach, intraoperative blood loss, perioperative blood transfusions and preoperative CKD stage as predictors for sCKD development. Multivariate analysis confirmed perioperative blood transfusion (hazard ratio [HR], 2.96; P ≤ .0001), age (≥ 55 years; HR, 2.60; P = .0002), tumor stage (> pT1; HR, 2.15; P = .025), and preoperative CKD stage (stage II vs. I; HR, 3.85; P ≤ .0001) as independent risk factors. A model that stratified patient risk for new onset CKD was highly significant (P < .0001).

Conclusion: Every fifth patient with NPRF developed sCKD following PN. Elderly patients with higher tumor stage and who require blood transfusion appear to be at increased risk. Based on our risk stratification, patients with ≥ 2 risk factors are candidates for an early, nephrologic follow-up.
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http://dx.doi.org/10.1016/j.clgc.2020.05.007DOI Listing
December 2020

The 1999 and 2010 WHO reference values for human semen analysis to predict sperm DNA damage: A comparative study.

Reprod Biol 2020 Sep 8;20(3):379-383. Epub 2020 Jun 8.

Department of Urology, Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, United Kingdom; Department of Surgery, University of Cambridge, Cambridge, United Kingdom.

Standard semen parameters are often used to predict male fertility, but whether the 2010 World Health Organization (WHO 2010) thresholds are better predictors than the 1999 thresholds has not been investigated. In this study, we addressed this issue using sperm DNA fragmentation (SDF) as a marker of male fertility in 134 subfertile male individuals. To compare the predictive value of the 1999 thresholds with the 2010 cutoffs, the Youden indices (YIs) of all possible thresholds were calculated using receiver operating characteristic (ROC) curves and compared to each other and to the respective YIs of optimal thresholds. We found that the area under the ROC curves of progressive motility and vitality was the highest among standard semen parameters, and that the YI of both parameters from the 2010 manual was comparable to the respective optimal YIs. In contrast, the threshold of sperm concentration and total sperm number from both WHO recommendations demonstrated low YIs, with substantial differences to the respective optimal YIs. The YIs of normal morphology cutoffs from both WHO manuals were slightly different from each other and from the respective optimal YIs. In conclusion, the 2010 thresholds for progressive motility and vitality are superior to the 1999 thresholds in predicting SDF, whereas the cutoff value of sperm concentration, total sperm number and normal morphology may need further revisions to increase their accuracy.
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http://dx.doi.org/10.1016/j.repbio.2020.04.008DOI Listing
September 2020

Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors.

Genome Med 2020 02 28;12(1):23. Epub 2020 Feb 28.

Cancer Research UK Major Centre - Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.

Background: Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established.

Methods: Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine.

Results: Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings.

Conclusions: These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.
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http://dx.doi.org/10.1186/s13073-020-00723-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048087PMC
February 2020

Partial nephrectomy versus thermal ablation for clinical T1 renal tumours.

Ann Transl Med 2019 Dec;7(Suppl 8):S363

Department of Surgery, University of Cambridge, Cambridge, UK.

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http://dx.doi.org/10.21037/atm.2019.09.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976424PMC
December 2019

Deferred Cytoreductive Nephrectomy Following Presurgical Vascular Endothelial Growth Factor Receptor-targeted Therapy in Patients with Primary Metastatic Clear Cell Renal Cell Carcinoma: A Pooled Analysis of Prospective Trial Data.

Eur Urol Oncol 2020 04 16;3(2):168-173. Epub 2020 Jan 16.

Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, UCL Division of Surgical and Interventional Science, London, UK. Electronic address:

Background: Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) concluded that sunitinib alone is not inferior to cytoreductive nephrectomy (CN) followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in patients with metastatic renal cell carcinoma. It remains uncertain whether deferred CN is beneficial in this setting.

Objective: The aim of this study was to compare outcome in patients treated with presurgical VEGFR-TKI followed by CN (deferred CN) with that in patients receiving CN followed by VEGFR-TKI (upfront CN).

Design, Setting, And Participants: Pooled data from prospective trials in which a strategy of deferred CN in the absence of disease progression was investigated were compared with a retrospective dataset of upfront CN.

Outcome Measurements And Statistical Analysis: Overall survival (OS) in the Memorial Sloan-Kettering Cancer Center (MSKCC) intermediate-risk group.

Results And Limitations: Patients were treated between 2006 and 2016. In the MSKCC intermediate-risk group, 144 patients with a strategy of deferred CN after systemic therapy were compared with 131 patients treated with upfront CN. OS in the deferred cohort was 33.0 mo (95% confidence interval [CI] 25.0-51.0) compared with 22.8 mo (95% CI 17.9-30.6) after upfront CN (hazard ratio 0.72 [95% CI 0.52-0.996], p = 0.047). This study is limited by retrospective comparison of data, subgroup analysis, and a lack of intention-to-treat data for the upfront CN cohort.

Conclusions: In MSKCC intermediate-risk patients, a strategy of deferred CN in the absence of progression yields OS, which compares favourably with upfront CN and published trial data from CARMENA. This warrants a formal individual patient data analysis of CARMENA, SURTIME, and single-arm prospective studies to define the role and timing of deferred CN in intermediate-risk patients.

Patient Summary: In this study, we report outcomes in patients with metastatic renal cell cancer treated with targeted therapy followed by nephrectomy, which compared favourably with nephrectomy followed by targeted therapy and results from published studies.
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http://dx.doi.org/10.1016/j.euo.2019.12.004DOI Listing
April 2020

Chest computed tomography for staging renal tumours: validation and simplification of a risk prediction model from a large contemporary retrospective cohort.

BJU Int 2020 04 8;125(4):561-567. Epub 2020 Feb 8.

Department of Urology, Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, UK.

Objectives: To externally validate a nomogram recently proposed by Larcher et al. (BJU Int. 2017; 120: 490) and to develop a simplified model with comparable accuracy to guide on the need for staging chest computed tomography (CT) for patients with new renal masses.

Patients And Methods: We analysed the data of 1082 consecutive patients with unilateral enhancing renal masses referred to urology multidisciplinary team meetings at two centres between 2011 and 2017. All patients underwent a staging chest CT at diagnosis. We fitted multivariable logistic regression models and tested the Larcher model performance using area under the receiver-operating curve (AUC), calibration and decision curve analysis.

Results: Forty-two patients (3.9%) had a positive chest CT. The Larcher nomogram had an AUC of 83.8% (95% confidence interval [CI] 77.1-90.6), but was only moderately well calibrated (calibration-in-the-large = -0.61, slope = 0.82). Specifically, the nomogram overestimated the risk of positive chest CT, and the magnitude of miscalibration increased with increasing predicted risks. Using a stepwise backward approach, a new model was developed including tumour size, nodal stage and systemic symptoms. Compared with the Larcher model, the new model had a similar AUC (82.7% [95% CI 75.5-90.0]), but improved calibration and clinical net benefit. The predicted risk of positive chest CT was <1% in the low-risk group and 1.9-79.9% in the high-risk group.

Conclusion: The Larcher nomogram is an accurate prediction tool that was moderately well calibrated with our dataset. However, our simplified model has similar accuracy and uses more objective variables available from referral, so may be easier to incorporate into clinical practice. The low-risk group from our model (tumour size ≤4 cm and no systemic symptoms) had a risk of positive chest CT <1%, suggesting these patients may forego chest CT.
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http://dx.doi.org/10.1111/bju.15001DOI Listing
April 2020

Standard Semen Parameters Sperm Kinematics to Predict Sperm DNA Damage.

World J Mens Health 2021 Jan 17;39(1):116-122. Epub 2019 Oct 17.

Department of Urology, Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, United Kingdom.

Purpose: The aims of this study were to associate sperm kinematics and standard semen parameters with sperm DNA damage and to evaluate whether the addition of sperm kinematics improve the multivariable prediction of sperm DNA fragmentation compared to standard semen parameters alone.

Materials And Methods: We evaluated sperm kinematics, standard semen parameters, and DNA fragmentation index (DFI) in 122 men. Univariate and multivariate logistic regression models were fitted to evaluate the association of sperm kinematics and standard semen parameters with pathologically damaged sperm DNA (DFI≥26%), and receiver operating characteristics (ROC) curves were calculated for these models.

Results: On univariate analyses, average velocity, curvilinear velocity, straight-line velocity, straightness (STR), beat-cross frequency (BCF), and the percentage of progressive motile sperm cells (PPMS) were significantly associated with pathologically damaged sperm DNA. Likewise, among standard semen parameters, sperm concentration, progressive motility, normal morphology, and vitality were found to be linked with sperm DNA damage. On the multivariate analysis, vitality was the strongest predictor of pathologically damaged sperm DNA with an area under the ROC curve (AUROC) of 88.3%. Adding STR, BCF, and PPMS to vitality increased the AUROC to the significant extent of 91.5%.

Conclusions: Sperm vitality is the most accurate routine-based laboratory test for the prediction of pathologically damaged sperm DNA, but the addition of sperm kinematics increases its accuracy. Both standard semen parameters and sperm kinematics are complementary in predicting pathologically damaged sperm DNA, and might serve as a new tool to screen for fertile men.
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http://dx.doi.org/10.5534/wjmh.190095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752507PMC
January 2021

The association of seminal leucocytes, interleukin-6 and interleukin-8 with sperm DNA fragmentation: A prospective study.

Andrologia 2019 Dec 22;51(11):e13428. Epub 2019 Oct 22.

Department of Urology, Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, UK.

The effect of seminal leucocytes on sperm DNA integrity has been discussed controversially in literatures. Moreover, the studies investigating the in vivo effect of pro-inflammatory cytokines interleukin-6 and interleukin-8 on sperm DNA fragmentation are scarce and inconsistent. The association of standard sperm parameters with sperm DNA fragmentation is also a matter of ongoing discussion. Hence, the aims of this study were, first, to evaluate the effect of seminal leucocytes, interleukin-6 and interleukin-8 on sperm DNA integrity and, second, to examine whether standard semen parameters are associated with sperm DNA fragmentation. Seminal leucocytes, interleukin-6, interleukin-8 and standard semen parameters, including total sperm number, sperm concentration, progressive motility, nonprogressive motility, immotility and normal morphology, were determined in 134 consecutive men. The concentrations of seminal leucocytes, interleukin-6 and interleukin-8, did not correlate with sperm DNA fragmentation. In contrast, total sperm number, sperm concentration, progressive motility, nonprogressive motility and normal morphology exhibited significant inverse correlations with sperm DNA fragmentation. Immotile spermatozoa were directly correlated with sperm DNA fragmentation. In conclusion, seminal leucocytes, interleukin-6 and interleukin-8, are not associated with sperm DNA fragmentation. Poor standard semen parameters are significantly related to the high levels of sperm DNA fragmentation.
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http://dx.doi.org/10.1111/and.13428DOI Listing
December 2019

Impact of Resection Technique on Perioperative Outcomes and Surgical Margins after Partial Nephrectomy for Localized Renal Masses: A Prospective Multicenter Study.

J Urol 2020 03 14;203(3):496-504. Epub 2019 Oct 14.

Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Purpose: The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury).

Materials And Methods: We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement.

Results: Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement.

Conclusions: Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.
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http://dx.doi.org/10.1097/JU.0000000000000591DOI Listing
March 2020

The VENUSS prognostic model to predict disease recurrence following surgery for non-metastatic papillary renal cell carcinoma: development and evaluation using the ASSURE prospective clinical trial cohort.

BMC Med 2019 10 3;17(1):182. Epub 2019 Oct 3.

Department of Urology, Addenbrooke's Hospital, Cambridge, UK.

Background: The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery.

Methods: We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1-4, N0-1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups.

Results: We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups.

Conclusions: We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials.
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http://dx.doi.org/10.1186/s12916-019-1419-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775651PMC
October 2019

A Decision Analysis Evaluating Screening for Kidney Cancer Using Focused Renal Ultrasound.

Eur Urol Focus 2019 Sep 14. Epub 2019 Sep 14.

Cambridge Centre for Health Services Research, University of Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge, UK; Health Economics Group, Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address:

Background: Screening for renal cell carcinoma (RCC) has been identified as a key research priority; however, no randomised control trials have been performed. Value of information analysis can determine whether further research on this topic is of value.

Objective: To determine (1) whether current evidence suggests that screening is potentially cost-effective and, if so, (2) in which age/sex groups, (3) identify evidence gaps, and (4) estimate the value of further research to close those gaps.

Design, Setting, And Participants: A decision model was developed evaluating screening in asymptomatic individuals in the UK. A National Health Service perspective was adopted.

Intervention: A single focused renal ultrasound scan compared with standard of care (no screening).

Outcome Measurements And Statistical Analysis: Expected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), discounted at 3.5% per annum.

Results And Limitations: Given a prevalence of RCC of 0.34% (0.18-0.54%), screening 60-yr-old men resulted in an ICER of £18 092/QALY (€22 843/QALY). Given a prevalence of RCC of 0.16% (0.08-0.25%), screening 60-yr-old women resulted in an ICER of £37327/QALY (€47 129/QALY). In the one-way sensitivity analysis, the ICER was <£30000/QALY as long as the prevalence of RCC was ≥0.25% for men and ≥0.2% for women at age 60yr. Given the willingness to pay a threshold of £30000/QALY (€37 878/QALY), the population-expected values of perfect information were £194 million (€244 million) and £97 million (€123 million) for 60-yr-old men and women, respectively. The expected value of perfect parameter information suggests that the prevalence of RCC and stage shift associated with screening are key research priorities.

Conclusions: Current evidence suggests that one-off screening of 60-yr-old men is potentially cost-effective and that further research into this topic would be of value to society.

Patient Summary: Economic modelling suggests that screening 60-yr-old men for kidney cancer using ultrasound may be a good use of resources and that further research on this topic should be performed.
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http://dx.doi.org/10.1016/j.euf.2019.09.002DOI Listing
September 2019

Evaluation of the prognostic role of co-morbidities on disease outcome in renal cell carcinoma patients.

World J Urol 2020 Jun 13;38(6):1525-1533. Epub 2019 Sep 13.

Department of Urology, University Medicine at the Ernst-Moritz-Arndt-University Greifswald, F. Sauerbruch Str, 17475, Greifswald, Germany.

Background: Co-morbidities may induce local and systemic tumor progression of renal cell carcinoma (RCC); however, the prognostic impact of co-morbidities has not yet been well characterized.

Patients And Methods: RCC patients (n = 2206) surgically treated at three academic institutions in the US and Europe were included in the analysis. Presence of diabetes mellitus, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, and hypothyroidism were investigated for their association with clinicopathological features and cancer-specific survival.

Results: Hypertension was associated with less advanced T stages (p = 0.025), a lower risk of lymph-node (p = 0.026) and distant metastases (p = 0.001), and improved cancer specific survival in univariable analysis (HR 0.81 95% CI 0.69-0.96, p = 0.013). However, hypertension was not an independent prognostic factor after adjustment for TNM stages, grading, and ECOG performance status (HR 0.95, 95% CI 0.80-1.12; p = 0.530). A correlation between the use of concomitant anti-hypertensive medications and improved survival outcome was not identified. All other investigated co-morbidities did not show significant associations with clinicopathological features or cancer-specific survival.

Conclusion: Although the investigated co-morbidities are capable or inducing pathophysiological changes that are predisposing factors for tumor progression, none is an independent prognostic factor in patients with RCC.
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http://dx.doi.org/10.1007/s00345-019-02930-4DOI Listing
June 2020

External validation of a postoperative nomogram for the prediction of disease-specific survival in patients with papillary renal cell carcinoma using a large multicenter database.

Int J Clin Oncol 2020 Jan 30;25(1):145-150. Epub 2019 Aug 30.

Department of Urology, LMU Munich, Grosshadern, Munich, Germany.

Purpose: Based on data retrieved from a comprehensive multicenter database, we externally validated a published postoperative nomogram for the prediction of disease-specific survival (DSS) in patients with papillary renal cell carcinoma (papRCC).

Methods: A multicenter database containing data of 2325 patients with surgically treated papRCC was used as validation cohort. After exclusion of patients with missing data and patients included in the development cohort, 1372 patients were included in the final analysis. DSS-probabilities according to the nomogram were calculated and compared to actual DSS-probabilities. Subsequently, calibration plots and decision curve analyses were applied.

Results: The median follow-up was 38 months (IQR 11.8-80.7). Median DSS was not reached. The c-index of the nomogram was 0.71 (95% CI 0.60-0.83). A sensitivity analysis including only patients operated after 1998 delivered a c-index of 0.84 (95% CI 0.77-0.92). Calibration plots showed slight underestimation of nomogram-predicted DSS in probability ranges below 90%: median nomogram-predicted 5-year DSS in the range below 90% was 55% (IQR 20-80), but the median actual 5-year DSS in the same group was 58% (95% CI 52-65). Decision-curve analysis showed a positive net-benefit for probability ranges between a DSS probability of 5% and 85%.

Conclusions: The nomogram performance was satisfactory for almost all DSS probabilities; hence it can be recommended for application in clinical routine and for counseling of patients with papRCC.
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http://dx.doi.org/10.1007/s10147-019-01530-xDOI Listing
January 2020

Systematic Review and Pooled Analysis of the Impact of Renorrhaphy Techniques on Renal Functional Outcome After Partial Nephrectomy.

Eur Urol Oncol 2019 09 9;2(5):572-575. Epub 2018 Dec 9.

Department of Urology, San Raffaele Scientific Institute, Milan, Italy; Division of Experimental Oncology/Unit of Urology, URI, IRCCS San Raffaele Hospital, Milan, Italy.

Despite the important relationship between renorrhaphy and functional outcomes of partial nephrectomy, the urological guidelines do not provide recommendations about the optimal renorrhaphy technique. We carried out the first pooled literature analysis of the impact of suture technique on ultimate renal function after partial nephrectomy. Three studies comparing interrupted versus running suture including data on glomerular filtration rate (GFR) were included, for a total of 124 versus 269 patients. No significant differences were found between pre- and postoperative GFR in either patients who received an interrupted suture (weighted mean difference, -4.88ml/min, 95% confidence interval [CI] -11.38; 1.63, p=0.14) or those who received a running suture (-3.42ml/min, 95% CI -9.96; 3.12, p=0.31). Three studies comparing single- versus double-layer renorrhaphy included data on GFR (321 vs 199 patients). A benefit in functional outcomes favored single-layer technique (-3.19ml/min, 95% CI -8.09; 1.70, p=0.2 vs -6.07ml/min, 95% CI -10.75; -1.39, p=0.01). In conclusion, our quantitative synthesis suggests a renal functional benefit of the single-layer closure during partial nephrectomy. PATIENT SUMMARY: The available studies on renal functional data included in the present review suggest that "less is more" for renorrhaphy after partial nephrectomy. The single-layer renorrhaphy technique showed advantages in renal functional outcomes compared with the double-layer technique.
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http://dx.doi.org/10.1016/j.euo.2018.11.008DOI Listing
September 2019

Urinary expression of genes involved in DNA methylation and histone modification for diagnosis of bladder cancer in patients with asymptomatic microscopic haematuria.

Oncol Lett 2019 Jul 7;18(1):57-62. Epub 2019 May 7.

Department of Urology, Medical University of Vienna, A-1090 Vienna, Austria.

The aim of the present study was to identify and test a urine marker panel of genes involved in DNA methylation and histone modification for the detection of urothelial carcinoma of the bladder (UCB). RNA samples obtained from the voided urine of 227 patients with asymptomatic microscopic haematuria (AMH) were analysed. Gene array analysis was performed on 18 randomly selected cDNA samples, which revealed that histone deacetylase 9 () and were differentially expressed between patients with UCB and control subjects. Subsequently, reverse transcription-quantitative polymerase chain reaction analysis was employed to test the performance of the identified four-gene panel on the remaining 209 cDNA samples. In this targeted discovery cohort, all four genes were significantly associated with UCB on univariable analyses [each odds ratio (OR) >2, P<0.05], but only was significant following multivariable analysis (OR=2.8, P=0.011). The addition of to a base risk factor model improved its accuracy by 1.4%. These data suggest that urinary is associated with the presence of UCB in patients with AMH; however, improved the accuracy of the established risk factors only to a marginal extent.
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http://dx.doi.org/10.3892/ol.2019.10330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540417PMC
July 2019

The Role of Ablation and Minimally Invasive Techniques in the Management of Small Renal Masses.

Eur Urol Oncol 2018 10 24;1(5):395-402. Epub 2018 Sep 24.

Unit of Urology, Division of Experimental Oncology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Milan, Italy.

Context: Nephron-sparing approaches are increasingly recommended for incidental small renal masses. Herein, we review the current literature regarding the safety and efficacy of focal therapy, including percutaneous ablation, for small renal masses.

Objective: To summarize the application of ablative therapy in the management of small renal masses.

Evidence Acquisition: PubMed and Medline database search was performed to look for findings published since 2000 on focal therapy for small renal masses. After literature review, 64 articles were selected and discussed.

Evidence Synthesis: Radiofrequency ablation and cryotherapy are the most widely used procedures with intermediate-term oncological outcome comparable with surgical series. Cost effectiveness seems excellent and side effects appear acceptable. To date, no randomized trial comparing percutaneous focal therapy with standard surgical approach or active surveillance has been performed.

Conclusions: Focal ablative therapies are now accepted as effective treatment for small renal tumors. For tumors <3cm, oncological effectiveness of ablative therapies is comparable with that of partial nephrectomy. Percutaneous ablation has fewer complications and a better postoperative profile when compared with minimally invasive partial nephrectomy.

Patient Summary: Focal ablative therapies are now accepted as effective treatment for small renal tumors. For tumors <3cm, oncological effectiveness of ablative therapies is comparable with that of partial nephrectomy.
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http://dx.doi.org/10.1016/j.euo.2018.08.029DOI Listing
October 2018

Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?

Cancers (Basel) 2019 Mar 25;11(3). Epub 2019 Mar 25.

Clinical Division of Oncology, Department of Medicine I & Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.

Renal cell carcinoma (RCC) with sarcomatoid differentiation belongs to the most aggressive clinicopathologic phenotypes of RCC. It is characterized by a high propensity for primary metastasis and limited therapeutic options due to its relative resistance to established systemic targeted therapy. Most trials report on a poor median overall survival of 5 to 12 months. Sarcomatoid RCC can show the typical features of epithelial-mesenchymal transition (EMT) and may contain epithelial and mesenchymal features on both the morphological and immunhistochemical level. On the molecular level, next-generation sequencing confirmed differences in driver mutations between sarcomatoid RCC and non-sarcomatoid RCC. In contrast, mutational profiles within the epithelial and sarcomatoid components of sarcomatoid RCC were shown to be identical, with TP53 being the most frequently altered gene. These data suggest that both epithelial and sarcomatoid components of RCC originate from the same progenitor cell, segregating primarily according to the underlying histologic epithelial subtype of RCC (clear cell, papillary or chromophobe). Current studies have shown that sarcomatoid RCC express programmed death 1 (PD-1) and its ligand (PD-L1) at a much higher level than non-sarcomatoid RCC, suggesting that blockade of the PD-1/PD-L1 axis may be an attractive new therapeutic strategy. Preliminary results of clinical trials evaluating checkpoint inhibitors in patients with sarcomatoid RCC showed encouraging survival data and objective response and complete response rates of up to 62% and 18%, respectively. These findings may establish a new standard of care in the management of patients with sarcomatoid RCC.
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http://dx.doi.org/10.3390/cancers11030422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468799PMC
March 2019

Disagreement in risk groups for metastatic renal cancer.

Nat Rev Urol 2019 Jun;16(6):332-333

Department of Surgery, University of Cambridge, Cambridge, UK.

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http://dx.doi.org/10.1038/s41585-019-0174-6DOI Listing
June 2019

Therapeutic rationale of targeting BCG and immune checkpoints in non-muscle-invasive bladder cancer: Is this the Future?

Urol Oncol 2019 06 28;37(6):343-345. Epub 2019 Feb 28.

Medical University Innsbruck, Department of Urology, Innsbruck, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.urolonc.2019.02.001DOI Listing
June 2019

A urinary microRNA (miR) signature for diagnosis of bladder cancer.

Urol Oncol 2018 12 12;36(12):531.e1-531.e8. Epub 2018 Oct 12.

Department of Urology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Electronic address:

Introduction: Bladder cancer (BC) is diagnosed by cystoscopy, which is invasive, costly and causes considerable patient discomfort. MicroRNAs (miR) are dysregulated in BC and may serve as non-invasive urine markers for primary diagnostics and monitoring. The purpose of this study was to identify a urinary miR signature that predicts the presence of BC.

Methods: For the detection of potential urinary miR markers, expression of 384 different miRs was analyzed in 16 urine samples from BC patients and controls using a Taqman™ Human MicroRNA Array (training set). The identified candidate gene signature was subsequently validated in an independent cohort of 202 urine samples of patients with BC and controls with microscopic hematuria. The final miR signature was developed from a multivariable logistic regression model.

Results: Analysis of the training set identified 14 candidate miRs for further analysis within the validation set. Using backward stepwise elimination, we identified a subset of 6 miRs (let-7c, miR-135a, miR-135b, miR-148a, miR-204, miR-345) that distinguished BC from controls with an area under the curve of 88.3%. The signature was most accurate in diagnosing high-grade non-muscle invasive BC (area under the curve = 92.9%), but was capable to identify both low-grade and high-grade disease as well as non-muscle and muscle-invasive BC with high accuracies.

Conclusions: We identified a 6-gene miR signature that can accurately predict the presence of BC from urine samples, independent of stage and grade. This signature represents a simple urine assay that may help reducing costs and morbidity associated with invasive diagnostics.
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http://dx.doi.org/10.1016/j.urolonc.2018.09.006DOI Listing
December 2018