Publications by authors named "Arnulf Stenzl"

554 Publications

Oncological validation of bone turnover markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) in patients with prostate cancer and bone metastases.

Transl Androl Urol 2021 Oct;10(10):4000-4008

Department of Urology, Eberhard-Karls University Tübingen, Tübingen, Germany.

Background: Bone formation markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) were reported to be increased in patients with prostate cancer (PC) and bone metastases. The objective of the presented study was to investigate the utility of serum 1CTP and P1NP values in the diagnosis of bone metastases and in predicting oncological outcome in patients with PC.

Methods: In total, serum samples of 186 patients were included retrospectively including 53 (28.50%) benign prostatic hyperplasia (BPH) patients and 133 (71.50%) PC-patients. The group of patients with PC consisted of 58 patients with non-metastatic PC (cM0) (43.61%) and 70 (52.63%) patients with bone metastases (cM1b). Serum 1CTP and P1NP were measured by radioimmunoassay (RIA). Results were compared to clinical variables including oncologic follow-up data by univariate and multivariate analyses.

Results: Median 1CTP concentrations were significantly higher in patients with PC compared to the BPH group [5.08 (range, 1.73-158.00) . 4.00 (range, 2.18-34.19) µg/L, P=0.019]. However, no significant difference of P1NP levels could be shown for these groups. With median values of 6.04 (1.73-158.00) and 3.91 µg/L (2.04-34.51) for 1CTP and 48.60 (9.12-1,074.37) and 33.90 (8.72-149.30) for P1NP both markers were altered in cM1b patients compared to cM0 patients (P=0.001 each). Furthermore, cancer-specific survival (CSS) and overall survival (OS) were significantly shorter in cM1b patients with higher 1CTP concentrations (P=0.037 and P=0.019, respectively), whereas no associations of P1NP and outcomes were observed.

Conclusions: The present study confirms that increased levels of 1CTP and P1NP concentrations are associated with presence of metastatic disease in the bone. Moreover, these markers are able to predict clinical course in PC patients with bone metastases. The potential use of these markers for treatment selection in advanced PC remains to be determined.
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http://dx.doi.org/10.21037/tau-20-1120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575559PMC
October 2021

A Non-Inferiority Comparative Analysis of Micro-Ultrasound and MRI Targeted Biopsy in Men at Risk of Prostate Cancer.

BJU Int 2021 Nov 13. Epub 2021 Nov 13.

Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Objective: To compare the efficacy of multiparametric magnetic resonance imaging (mpMRI) directed and micro-ultrasound (micro-US) directed biopsy for detecting clinically significant (Grade Group >1) prostate cancer (csPCa).

Materials And Methods: 203 patients were prospectively enrolled at 3 institutions across Germany and Austria in the period from January 2019 to December 2019. During each biopsy, the urologist was blinded to the mpMRI report until after micro-US targets had been assessed. After unblinding, targets were then sampled using software-assisted fusion, followed by systematic samples. The primary outcome measure was non-inferiority of micro-US to detect csPCa with a detection ratio of at least 80% of mpMRI.

Results: 79 csPCa cases were detected overall (39%). Micro-US targeted biopsy detected 58/79 (73%), while mpMRI targeted biopsy detected 60/79 (76%) and non-targeted (completion sampling) samples detected 45/79 (57%). mpMRI targeted samples alone detected 7/79 (9%) csPCa cases which were missed by Micro-US targets and non-targeted samples. 3/7 of these were anterior lesions with 2/7 in the transition zone. Micro-US targeted samples alone detected 5/79 (6%) and completion sampling alone detected 4/79 (5%). Micro-US was noninferior to mpMRI and detected 97% csPCa compared to mpMRI targeted biopsy (95% CI 80-116%, p=0.023) CONCLUSIONS: This is the first multi-center prospective study comparing micro-US targeted biopsy with mpMRI targeted biopsy and it provides further evidence that micro-US can reliably detect cancer lesions and suggests that micro-US biopsy might be as effective as mpMRI for detection of csPCA. This result has significant implications for increasing accessibility, reducing costs and expediting diagnosis.
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http://dx.doi.org/10.1111/bju.15635DOI Listing
November 2021

Conventional white light imaging-assisted transurethral resection of bladder tumour (TURBT) versus IMAGE1S-assisted TURBT in non-muscle-invasive bladder cancer patients: trial protocol and 18 months results.

World J Urol 2021 Nov 6. Epub 2021 Nov 6.

Department of Urology, Istanbul Medipol Mega University Hospital, Istanbul, Turkey.

Purpose: White light (WL) is the traditional imaging modality for transurethral resection of bladder tumour (TURBT). IMAGE1S is a likely addition. We compare 18-mo recurrence rates following TURBT using IMAGE1S versus WL guidance.

Methods: Twelve international centers conducted a single-blinded randomized controlled trial. Patients with primary and recurrent non-muscle-invasive bladder cancer (NMIBC) were randomly assigned 1:1 to TURBT guided by IMAGE1S or WL. Eighteen-month recurrence rates and subanalysis for primary/recurrent and risk groups were planned and compared by chi-square tests and survival analyses.

Results: 689 patients were randomized for WL-assisted (n = 354) or IMAGE1S-assisted (n = 335) TURBT. Of these, 64.7% had a primary tumor, 35.3% a recurrent tumor, and 4.8%, 69.2% and 26.0% a low-, intermediate-, and high-risk tumor, respectively. Overall, 60 and 65 patients, respectively, completed 18-mo follow-up, with recurrence rates of 31.0% and 25.4%, respectively (p = 0.199). In patients with primary, low-/intermediate-risk tumors, recurrence rates at 18-mo were significantly higher in the WL group compared with the IMAGE1S group (31.9% and 22.3%, respectively: p 0.035). Frequency and severity of adverse events were comparable in both treatment groups. Immediate and adjuvant intravesical instillation therapy did not differ between the groups. Potential limitations included lack of uniformity of surgical resection, central pathology review, and missing data.

Conclusion: There was not difference in the overall recurrence rates between IMAGE1S and WL assistance 18-mo after TURBT in patients with NMIBC. However, IMAGE1S-assisted TURBT considerably reduced the likelihood of disease recurrence in primary, low/intermediate risk patients.

Registration: ClinicalTrials.gov Identifier NCT02252549 (30-09-2014).
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http://dx.doi.org/10.1007/s00345-021-03866-4DOI Listing
November 2021

Impact of enzalutamide on patient-reported fatigue in patients with prostate cancer: data from the pivotal clinical trials.

Prostate Cancer Prostatic Dis 2021 Sep 13. Epub 2021 Sep 13.

Urology, University of Montréal Hospital Center, Montréal, QC, Canada.

Background: Fatigue is a multifactorial symptom commonly reported by patients with prostate cancer as a result of disease and treatment. This study assesses the impact enzalutamide has on patient-reported fatigue ("fatigue") by using patient-reported outcomes from four pivotal, placebo-controlled trials of enzalutamide (ARCHES (NCT02677896), PROSPER (NCT02003924), PREVAIL (NCT01212991), and AFFIRM (NCT00974311)).

Methods: Fatigue was assessed in the individual studies using the Functional Assessment of Cancer Therapy-Prostate item GP1 at baseline, weeks 13 or 17, and every 12 weeks until disease progression. Longitudinal changes were assessed using mean scores and mixed-model repeated measures.

Results: The fatigue rates at baseline were higher in patients with later-stage disease (metastatic and/or castration-resistant prostate cancer (CRPC)) and among patients who had already received prior treatment lines; rates ranged between 58% in PROSPER (nonmetastatic CRPC) and 86% in AFFIRM (post-docetaxel metastatic CRPC). Irrespective of disease state, initiation of enzalutamide or placebo resulted in an early increase of fatigue (by weeks 13 or 17), with fatigue levels stabilizing thereafter. At last assessment, ≥55% of patients reported fatigue improvement or stabilization in all trials compared to baseline. More patients reported fatigue worsening by ≥1 or ≥2 units with enzalutamide plus androgen deprivation therapy (ADT) than with placebo plus ADT in ARCHES, PROSPER, and PREVAIL, but the between-group difference was <10% in all trials.

Conclusions: The levels of fatigue were greater in mCRPC and lower in earlier states of disease. In all trials, patients reported a small increase in fatigue for the first 13-17 weeks after starting enzalutamide or placebo, with slightly greater fatigue with enzalutamide in all studies except AFFIRM, but fatigue stabilized or improved thereafter. This suggests a role for clinical management of fatigue to help patients cope early in treatment.
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http://dx.doi.org/10.1038/s41391-021-00447-9DOI Listing
September 2021

On the probability of lymph node negativity in pN0-staged prostate cancer-a theoretically derived rule of thumb for adjuvant needs.

Strahlenther Onkol 2021 Sep 2. Epub 2021 Sep 2.

Department of Radiation Oncology, Eberhard Karls University, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Purpose: The extent of lymphadenectomy and clinical features influence the risk of occult nodes in node-negative prostate cancer. We derived a simple estimation model for the negative predictive value (npv) of histopathologically node-negative prostate cancer patients (pN0) to guide adjuvant treatment.

Methods: Approximations of sensitivities in detecting lymph node metastasis from current publications depending on the number of removed lymph nodes were used for a theoretical deduction of a simplified formulation of npv assuming a false node positivity of 0.

Results: A theoretical formula of npv = p(N0IpN0) = (100 - prevalence) / (100 - sensitivity × prevalence) was calculated (sensitivity and preoperative prevalence in %). Depending on the number of removed lymph nodes (nLN), the sensitivity of pN0-staged prostate cancer was derived for three sensitivity levels accordingly: sensitivity = f(nLN) = 9 × nLN /100 for 0 ≤ nLN ≤ 8 and f(nLN) = (nLN + 70) /100 for 9 ≤ nLN ≤ 29 and f(nLN) = 1 for nLN ≥ 30.

Conclusion: We developed a theoretical formula for estimation of the npv in pN0-staged prostate cancer patients. It is a sine qua non to use the formula in a clinically experienced context before deciding to electively irradiate pelvic lymph nodes or to intensify adjuvant systemic treatment.
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http://dx.doi.org/10.1007/s00066-021-01841-xDOI Listing
September 2021

[eUrology].

Authors:
Arnulf Stenzl

Urologe A 2021 Sep 25;60(9):1115-1116. Epub 2021 Aug 25.

Klinik für Urologie, Universitätsklinik Tübingen, Hoppe-Seyler-Str. 4-6, 72076, Tübingen, Deutschland.

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http://dx.doi.org/10.1007/s00120-021-01613-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386147PMC
September 2021

[The 73rd congress of the German Society of Urology : eUrology].

Authors:
Arnulf Stenzl

Urologe A 2021 Sep 24;60(Suppl 1):1-2. Epub 2021 Aug 24.

Klinik für Urologie, Universitätsklinikum Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Deutschland.

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http://dx.doi.org/10.1007/s00120-021-01625-2DOI Listing
September 2021

Efficacy of enzalutamide in subgroups of men with metastatic hormone-sensitive prostate cancer based on prior therapy, disease volume, and risk.

Prostate Cancer Prostatic Dis 2021 Aug 21. Epub 2021 Aug 21.

Eberhard Karls University of Tübingen, Tübingen, Germany.

Background: While enzalutamide plus androgen deprivation therapy (ADT) significantly reduces the risk of radiographic progression-free survival (rPFS) and improves overall survival in metastatic hormone-sensitive prostate cancer (mHSPC), the efficacy in clinically relevant subgroups of patients based on prior local and systemic therapy, disease volume, and risk has not been analyzed to date. These post hoc analyses of the phase 3 ARCHES trial (NCT02677896) evaluated the efficacy of enzalutamide plus ADT according to prior local and systemic treatment, disease volume, and risk, assessed at trial baseline.

Methods: In ARCHES, a global, double-blind, placebo-controlled, phase 3 study, 1150 patients with mHSPC were randomized 1:1 to receive enzalutamide (160 mg/day) plus ADT or placebo plus ADT, stratified by prior docetaxel therapy and disease volume. Primary endpoint was rPFS. Secondary endpoints included time to prostate-specific antigen progression, symptomatic skeletal events, and prostate-specific antigen and radiographic responses. Analyses of clinical endpoints were completed by prior local therapy, prior docetaxel exposure, CHAARTED (NCT00309985)-defined disease volume, and LATITUDE (NCT01715285)-defined risk groups.

Results: Patients were randomized to enzalutamide plus ADT (n = 574) and placebo plus ADT (n = 576). Enzalutamide plus ADT significantly improved rPFS (hazard ratio: 0.39; p < 0.0001), with similar improvements reported in all subgroups based on prior local and docetaxel treatment, disease volume, and risk. Treatment benefits were observed with enzalutamide plus ADT in multiple secondary clinical endpoints in the overall population and all subgroups.

Conclusions: Enzalutamide plus ADT demonstrated clinical benefit across all patients with mHSPC, irrespective of prior local and systemic treatment, disease volume, and risk.
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http://dx.doi.org/10.1038/s41391-021-00436-yDOI Listing
August 2021

Prostate-specific Antigen Testing as Part of a Risk-Adapted Early Detection Strategy for Prostate Cancer: European Association of Urology Position and Recommendations for 2021.

Eur Urol 2021 Dec 15;80(6):703-711. Epub 2021 Aug 15.

Department of Urology, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany.

Background: Recommendations against prostate-specific antigen (PSA) testing in 2012 have increased advanced-stage diagnosis and prostate cancer-specific mortality rates.

Objective: To present the position of the European Association of Urology (EAU) in 2021 and provide recommendations for the use of PSA testing as part of a risk-adapted strategy for the early detection of prostate cancer.

Evidence Acquisition: The authors combined their review of relevant literature, including the EAU prostate cancer guidelines 2021 update, with their own knowledge to provide an expert opinion, representing the EAU's position in 2021.

Evidence Synthesis: The EAU has developed a risk-adapted early prostate cancer detection strategy for well-informed men based on PSA testing, risk calculators, and multiparametric magnetic resonance imaging, which can differentiate significant from insignificant prostate cancer. This approach largely avoids the overdiagnosis/overtreatment of men unlikely to experience disease-related symptoms during their lifetime and facilitates an early diagnosis of men with significant cancer to receive active treatment. It also reduces advanced-stage diagnosis, thereby potentially reducing prostate cancer-specific mortality and improving quality of life. Education is required among urologists, general practitioners, radiologists, policy makers, and healthy men, including endorsement by the European Commission to adapt the European Council's screening recommendations in its 2022 plan and requests to individual countries for its incorporation into national cancer plans.

Conclusions: This risk-adapted approach for the early detection of prostate cancer will reverse current unfavourable trends and ultimately save lives.

Patient Summary: The European Association of Urology has developed a patient information leaflet and algorithm for the early diagnosis of prostate cancer. It can identify men who do not need magnetic resonance imaging or a biopsy and those who would not show any symptoms versus those with more aggressive disease who require further tests/treatment. We need to raise awareness of this algorithm to ensure that all well-informed men at risk of significant prostate cancer are offered a prostate-specific antigen test.
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http://dx.doi.org/10.1016/j.eururo.2021.07.024DOI Listing
December 2021

Robotic Transrectal Computed Tomographic Ultrasound with Artificial Neural Network Analysis: First Validation and Comparison with MRI-Guided Biopsies and Radical Prostatectomy.

Urol Int 2021 Aug 17:1-7. Epub 2021 Aug 17.

Department of Urology, Eberhard Karls University, Tübingen, Germany.

Introduction: There is still a lack of availability of high-quality multiparametric magnetic resonance imaging (mpMRI) interpreted by experienced uro-radiologists to rule out clinically significant PC (csPC). Consequently, we developed a new imaging method based on computed tomographic ultrasound (US) supported by artificial neural network analysis (ANNA).

Methods: Two hundred and two consecutive patients with visible mpMRI lesions were scanned and recorded by robotic CT-US during mpMRI-TRUS biopsy. Only significant index lesions (ISUP ≥2) verified by whole-mount pathology were retrospectively analyzed. Their visibility was reevaluated by 2 blinded investigators by grayscale US and ANNA.

Results: In the cohort, csPC was detected in 105 cases (52%) by mpMRI-TRUS biopsy. Whole-mount histology was available in 44 cases (36%). In this subgroup, mean PSA level was 8.6 ng/mL, mean prostate volume was 33 cm3, and mean tumor volume was 0.5 cm3. Median PI-RADS and ISUP of index lesions were 4 and 3, respectively. Index lesions were visible in grayscale US and ANNA in 25 cases (57%) and 30 cases (68%), respectively. Combining CT-US-ANNA, we detected index lesions in 35 patients (80%).

Conclusions: The first results of multiparametric CT-US-ANNA imaging showed promising detection rates in patients with csPC. US imaging with ANNA has the potential to complement PC diagnosis.
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http://dx.doi.org/10.1159/000517674DOI Listing
August 2021

Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial.

Lancet Oncol 2021 09 10;22(9):1250-1264. Epub 2021 Aug 10.

Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.

Background: Poly(ADP-ribose) polymerase (PARP) inhibitors have antitumour activity against metastatic castration-resistant prostate cancers with DNA damage response (DDR) alterations in genes involved directly or indirectly in homologous recombination repair (HRR). In this study, we assessed the PARP inhibitor talazoparib in metastatic castration-resistant prostate cancers with DDR-HRR alterations.

Methods: In this open-label, phase 2 trial (TALAPRO-1), participants were recruited from 43 hospitals, cancer centres, and medical centres in Australia, Austria, Belgium, Brazil, France, Germany, Hungary, Italy, the Netherlands, Poland, Spain, South Korea, the UK, and the USA. Patients were eligible if they were men aged 18 years or older with progressive, metastatic, castration-resistant prostate cancers of adenocarcinoma histology, measurable soft-tissue disease (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]), an Eastern Cooperative Oncology Group performance status of 0-2, DDR-HRR gene alterations reported to sensitise to PARP inhibitors (ie, ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C), had received one or two taxane-based chemotherapy regimens for metastatic disease, and progressed on enzalutamide or abiraterone, or both, for metastatic castration-resistant prostate cancers. Eligible patients were given oral talazoparib (1 mg per day; or 0·75 mg per day in patients with moderate renal impairment) until disease progression, unacceptable toxicity, investigator decision, withdrawal of consent, or death. The primary endpoint was confirmed objective response rate, defined as best overall soft-tissue response of complete or partial response per RECIST 1.1, by blinded independent central review. The primary endpoint was assessed in patients who received study drug, had measurable soft-tissue disease, and had a gene alteration in one of the predefined DDR-HRR genes. Safety was assessed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, NCT03148795, and is ongoing.

Findings: Between Oct 18, 2017, and March 20, 2020, 128 patients were enrolled, of whom 127 received at least one dose of talazoparib (safety population) and 104 had measurable soft-tissue disease (antitumour activity population). Data cutoff for this analysis was Sept 4, 2020. After a median follow-up of 16·4 months (IQR 11·1-22·1), the objective response rate was 29·8% (31 of 104 patients; 95% CI 21·2-39·6). The most common grade 3-4 treatment-emergent adverse events were anaemia (39 [31%] of 127 patients), thrombocytopenia (11 [9%]), and neutropenia (ten [8%]). Serious treatment-emergent adverse events were reported in 43 (34%) patients. There were no treatment-related deaths.

Interpretation: Talazoparib showed durable antitumour activity in men with advanced metastatic castration-resistant prostate cancers with DDR-HRR gene alterations who had been heavily pretreated. The favourable benefit-risk profile supports the study of talazoparib in larger, randomised clinical trials, including in patients with non-BRCA alterations.

Funding: Pfizer/Medivation.
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http://dx.doi.org/10.1016/S1470-2045(21)00376-4DOI Listing
September 2021

Micro-Ultrasound: a way to bring imaging for prostate cancer back to urology.

Prostate Int 2021 Jun 18;9(2):61-65. Epub 2021 Jan 18.

Department of Urology, University Hospital Tübingen, Tübingen, Germany.

Only a decade ago, there were insufficient imaging options for the detection and local staging of prostate cancer. However, the introduction of multiparametric magnetic resonance imaging (mpMRI) has advanced a much-needed tool for this scope of application. The possibilities and limitations of mpMRI have been well studied. Imaging must be acquired and evaluated using a standardized protocol (the latest version of Prostate Imaging-Reporting and Data System). Sensitivity has been shown to increase with higher grades and larger tumors, and while the detection rate on a per patient basis is relatively high, the per-lesion detection rate is far inferior. Various specialists have attempted to elevate the use of transrectal ultrasound, a tool frequently used by all urologists. Encouragement for this idea comes from a recently introduced system of high frequency transrectal ultrasound. The level of evidence supporting its use in the detection and staging of prostate cancer is not comparable with mpMRI yet, but initial prospective studies indicate good potential. The sensitivity of micro-ultrasound and mpMRI for clinically significant prostate cancer ranges from 94% to 100% and from 88% to 90%, respectively. Further areas of application, such as local staging for prostate and bladder cancer, are currently being evaluated. In summary, microultrasound presents a promising technology for further improving urological imaging and allows for the possibility of returning prostate cancer imaging to urologists. This review will summarize the current scientific basis for the use of micro-ultrasound in the detection of prostate cancer.
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http://dx.doi.org/10.1016/j.prnil.2020.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322825PMC
June 2021

Comparison of the metabolome in urine prior and eight weeks after radical prostatectomy uncovers pathologic and molecular features of prostate cancer.

J Pharm Biomed Anal 2021 Oct 31;205:114288. Epub 2021 Jul 31.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian, 116023, China. Electronic address:

Prostate cancer (PCa) is associated with cellular metabolism alterations leading to changes of the metabolome. So far, studies investigating these alterations mainly focused on comparisons of metabolite profiles of PCa patients and healthy controls. In the present study we compared for the first time metabolite profiles in a significant number of paired urine samples collected before and eight weeks after radical prostatectomy (rPX) in 34 patients with PCa. Our comprehensive non-targeted liquid chromatographic-mass spectrometric metabolomics approach covered > 3000 metabolite ion masses. We annotated 23 metabolites showing significant changes eight weeks after rPX. While the levels of uridine and six acylcarnitines in urine were increased before surgery, lower levels were detected for 16 metabolites, like e.g. citrate, phenyl-lactic acid, choline, myo-inositol, emphasizing a relevant pathophysiological role of these biomarkers and the associated metabolic pathways. These results have important implications for potential use of metabolome analyses for detection of prostate cancer and related pathologic and molecular features.
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http://dx.doi.org/10.1016/j.jpba.2021.114288DOI Listing
October 2021

Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence.

Int J Mol Sci 2021 Jun 5;22(11). Epub 2021 Jun 5.

Center of Medical Research, Department of Urology at UKT, Eberhard-Karls-University, 72076 Tuebingen, Germany.

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI.
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http://dx.doi.org/10.3390/ijms22116092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201285PMC
June 2021

Evaluation of carbonic anhydrase IX as a potential therapeutic target in urothelial carcinoma.

Urol Oncol 2021 08 1;39(8):498.e1-498.e11. Epub 2021 Jun 1.

Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.

Objective: Carbonic anhydrase IX (CA9) is important in the regulation of intra- and extracellular pH in solid tumors, contributing to cell growth and invasion. In urothelial carcinoma (UC), CA9 has been identified as a urinary marker for disease detection, but its biologic role is unknown. To date, differential gene expression patterns of CA9 in various molecular subtypes and potential effects of CA9 inhibition in UC cells are unknown. We aimed to investigate the function of CA9 and the effects of CA9 inhibition in invasive UC.

Methods: Immunohistochemistry was used to assess CA9 expression in a cohort of 153 patients undergoing radical cystectomy. CA9 expression was correlated with molecular subtype by analysis of the TCGA data and of our own cohort of 223 patients with invasive UC receiving neoadjuvant chemotherapy. CA9 expression was assessed in a panel of 12 UC cell lines by Western Blot and qPCR, and multiple siRNAs were used to silence CA9 in 2 cell lines. Effects of CA9 silencing on cell growth, migration, and invasion were assessed. We also used the small molecule inhibitor U-104 to inhibit CA9 in vitro and in an orthotopic xenograft model.

Results: CA9 expression was higher in cancer tissue compared to benign urothelium and was particularly highly expressed in luminal papillary and basal squamous tumors. CA9 expression did not correlate with outcome after neoadjuvant chemotherapy and/or radical cystectomy. Silencing of CA9 by siRNA diminished invasion but did not induce a consistent change of cell growth and migration. Treatment with U-104 led to cell growth reduction only at high concentrations in vitro and failed to have a significant effect on tumor growth in vivo.

Conclusions: The present study confirms over-expression of CA9 in UC and for the first time shows a correlation with molecular subtypes. However, CA9 expression showed no association with the outcome of patients with muscle invasive bladder cancer and inhibition of CA9 did not lead to a consistent inhibition of tumor growth. Based on these data, CA9 exhibits a role neither as a predictive or prognostic marker nor as a therapeutic target in invasive UC.
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http://dx.doi.org/10.1016/j.urolonc.2021.04.011DOI Listing
August 2021

Thrombospondin-2 and LDH Are Putative Predictive Biomarkers for Treatment with Everolimus in Second-Line Metastatic Clear Cell Renal Cell Carcinoma (MARC-2 Study).

Cancers (Basel) 2021 May 25;13(11). Epub 2021 May 25.

Department of Urology and Pediatric Urology, Saarland University, Kirrberger Street, 66421 Homburg/Saar, Germany.

There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC-2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second-line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis-related protein thrombospondin-2 (TSP-2) at baseline (≤665 parts per billion, ppb) identified therapy responders with longer median progression-free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, < 0.001). Baseline TSP-2 levels had a stronger relation to PFS (HR 0.36, = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP-2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF-targeted therapy in patients with clear cell mRCC.
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http://dx.doi.org/10.3390/cancers13112594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199288PMC
May 2021

KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer.

Future Oncol 2021 Aug 28;17(23):3017-3026. Epub 2021 May 28.

Hoppe-Seylerstrasse 3, University of Tuebingen Medical Center, Tuebingen, D-72076, Germany.

Current treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) are noncurative, and median survival upon development of mCRPC is approximately 3 years. The novel hormonal agent enzalutamide has an established role in the mCRPC treatment paradigm, and emerging evidence suggests potential synergism with enzalutamide and the PD-1 inhibitor pembrolizumab in men with mCRPC. Here, we describe the design and rationale for the multicenter, randomized, double-blind, Phase III KEYNOTE-641 study, which will be conducted to compare the efficacy and safety of pembrolizumab plus enzalutamide with that of enzalutamide plus placebo in mCRPC. NCT03834493 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2020-1008DOI Listing
August 2021

Pembrolizumab for the treatment of renal cell carcinoma.

Expert Opin Biol Ther 2021 Sep 3;21(9):1157-1164. Epub 2021 Jun 3.

Department of Urology, University of Tübingen, Tuebingen, Germany.

Introduction: The acquisition of resistance to VEGF-inhibiting therapies has prompted research toward immunotherapy for the treatment of metastatic renal cell carcinoma (mRCC). Among several, checkpoint inhibitors including PD-1 and PD-L1 inhibitors are the most promising approach.

Areas Covered: This review addresses the clinical efficacy of the anti-PD-1 monoclonal antibody pembrolizumab in first- and second-line treatment for mRCC regarding the most recent and significant published and ongoing studies. Attention is also given to its pharmacological characteristics as well as adverse events and its impact on patients' quality of life.

Expert Opinion: Immunotherapy has become the backbone for the treatment of advanced RCC. With the approval of several therapeutic options, research needs now to focus on defining the appropriate therapy for each patient. Axitinib plus pembrolizumab belongs to the combinations of tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors for the first-line treatment of metastatic RCC. New combinations of pembrolizumab plus TKI for the evaluation in first- and second-line treatment of mRCC available. However, studies directly comparing the various treatment regimens using predictive biomarkers and long-term endpoints, including treatment-free survival, are lacking.
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http://dx.doi.org/10.1080/14712598.2021.1935856DOI Listing
September 2021

Receptor Activator of NF Kappa B (RANK) Expression Indicates Favorable Prognosis in Patients with Muscle-invasive Bladder Cancer.

Eur Urol Focus 2021 May 4. Epub 2021 May 4.

Department of Urology, University Hospital, Tübingen, Germany; Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Clinical Trials Unit, Studienpraxis Urologie, Nürtingen, Germany. Electronic address:

Background: Receptor activator of NF kappa B (RANK) and its ligand have an essential role in T-cell regulation and the development of bone metastases. The role of RANK expression in muscle-invasive bladder cancer (MIBC) is unknown.

Objective: To assess the relevance of RANK expression in patients with MIBC.

Design, Setting, And Participants: Expression of RANK was assessed via immunohistochemistry of benign urothelium, MIBC tissue, and lymph node metastases from 153 patients undergoing radical cystectomy. Expression data from The Cancer Genome Atlas (TCGA) cohort were analyzed for potential associations with molecular subtypes and outcome.

Outcome Measurements And Statistical Analysis: RANK expression was correlated with clinical and pathological parameters and to individual data for the clinical course of MIBC.

Results And Limitations: Expression of RANK was significantly higher in both primary tumors (p = 0.02) and lymph node metastases (p = 0.01) compared to normal urothelium. In tumor tissue, RANK expression was significantly lower in patients with locally advanced disease and lymph node involvement compared to those with organ-confined disease (p = 0.0009) and node-negative MIBC (p = 0.0002). In univariable and multivariable analyses, high expression of RANK was associated with a longer time to recurrence (p = 0.0005 and 0.01) and better cancer-specific (p = 0.0004 and 0.007) and overall survival (p = 0.002 and 0.04). High expression of RANK was associated with better outcome for patients with luminal infiltrated tumors in the TCGA cohort.

Conclusions: RANK expression is increased in bladder cancer tissue compared to benign urothelium, with higher expression in organ-defined compared to locally advanced disease. High RANK expression indicates a favorable prognosis in MIBC. The prognostic role differs in tumors of different molecular subtypes.

Patient Summary: Expression of a protein involved in bone turnover regulation (RANK) is higher in bladder cancer tissue than in benign bladder tissue. However, high levels of RANK on tumor cells indicate favorable prognosis for patients with bladder cancer that invades the muscle layer of the bladder.
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http://dx.doi.org/10.1016/j.euf.2021.04.015DOI Listing
May 2021

Enzalutamide with androgen deprivation therapy in Japanese men with metastatic hormone-sensitive prostate cancer: A subgroup analysis of the phase III ARCHES study.

Int J Urol 2021 07 6;28(7):765-773. Epub 2021 May 6.

Eberhard Karls University of Tübingen, Tübingen, Germany.

Objective: To evaluate the efficacy and safety of enzalutamide plus androgen deprivation therapy in Japanese men with metastatic hormone-sensitive prostate cancer.

Methods: A post-hoc analysis of the Japanese subgroup in the phase III, randomized, multinational ARCHES study (NCT02677896) was carried out. Patients with metastatic hormone-sensitive prostate cancer were randomized to receive enzalutamide or a placebo, plus androgen deprivation therapy, stratified by disease volume and prior docetaxel therapy. The primary end-point was radiographic progression-free survival. Secondary end-points included time to prostate-specific antigen progression and overall survival.

Results: Of 1150 patients, 92 Japanese patients were randomized to enzalutamide (n = 36) or a placebo (n = 56), plus androgen deprivation therapy; none received prior docetaxel. Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression or death in Japanese patients by 61% versus the placebo, similar to the overall population. Similar results were observed with secondary end-points, showing clinical benefit of enzalutamide plus androgen deprivation therapy in Japanese patients. Overall survival data were immature. Grade 3-4 adverse events were reported in 47% and 25% of the enzalutamide and placebo groups, respectively. Nasopharyngitis, hypertension and abnormal hepatic function were reported more frequently in Japanese patients versus the overall population.

Conclusions: Enzalutamide plus androgen deprivation therapy has clinical benefit with a tolerable safety profile in Japanese men with metastatic hormone-sensitive prostate cancer, consistent with the overall population.
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http://dx.doi.org/10.1111/iju.14568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360194PMC
July 2021

Treatment of Stress Urinary Incontinence with Muscle Stem Cells and Stem Cell Components: Chances, Challenges and Future Prospects.

Int J Mol Sci 2021 Apr 12;22(8). Epub 2021 Apr 12.

Department of Urology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.

Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges.
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http://dx.doi.org/10.3390/ijms22083981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069473PMC
April 2021

Injection of Porcine Adipose Tissue-Derived Stromal Cells by a Novel Waterjet Technology.

Int J Mol Sci 2021 Apr 12;22(8). Epub 2021 Apr 12.

Department of Urology, University Hospital Tübingen, Waldhörnlestrasse 22, 72072 Tübingen, Germany.

Previously, we developed a novel, needle-free waterjet (WJ) technology capable of injecting viable cells by visual guided cystoscopy in the urethral sphincter. In the present study, we aimed to investigate the effect of WJ technology on cell viability, surface markers, differentiation and attachment capabilities, and biomechanical features. Porcine adipose tissue-derived stromal cells (pADSCs) were isolated, expanded, and injected by WJ technology. Cell attachment assays were employed to investigate cell-matrix interactions. Cell surface molecules were analyzed by flow cytometry. Cells injected by Williams Needle (WN), normal cannula, or not injected cells served as controls. Biomechanical properties were assessed by atomic force microscopy (AFM). pADSCs injected by the WJ were viable (85.9%), proliferated well, and maintained their in vitro adipogenic and osteogenic differentiation capacities. The attachment of pADSCs was not affected by WJ injection and no major changes were noted for cell surface markers. AFM measurements yielded a significant reduction of cellular stiffness after WJ injections ( < 0.001). WJ cell delivery satisfies several key considerations required in a clinical context, including the fast, simple, and reproducible delivery of viable cells. However, the optimization of the WJ device may be necessary to further reduce the effects on the biomechanical properties of cells.
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http://dx.doi.org/10.3390/ijms22083958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070533PMC
April 2021

Utility of pT3 substaging in lymph node-negative urothelial carcinoma of the bladder: do pathologic parameters add to prognostic sub-stratification?

World J Urol 2021 Nov 21;39(11):4021-4027. Epub 2021 Apr 21.

Department of Urology, University Hospital, Tübingen, Germany.

Purpose: The value of bladder cancer (BC) substaging into macroscopic (pT3b) and microscopic (pT3a) perivesical fat extension in lymph node (Ln)-negative patients is controversially discussed and limited evidence for prognostic relevance of additional histopathological factors in pT3 BC exists. We evaluated the prognostic value of pT3 substaging and established pathological and clinical parameters with focus on tumor invasive front (TIF) and tumor size.

Methods: Specimens of 52 patients treated with radical cystectomy (RC) for pT3 a/b muscle-invasive BC were reviewed and re-evaluated by a pathologist specialized in uropathology. Clinical variables and standard histopathologic characteristics were assessed including TIF and tumor size. Their value as prognosticators for overall survival (OS) and recurrence-free survival (RFS) was evaluated.

Results: Mean age of patients was 67.55 years. Tumors were staged pT3a in 28 patients (53.8%) and pT3b in 24 (46.8%). Median OS was 34.51 months. Median tumor size was 3.2 cm, median TIF was 11.0 mm. Differences in OS between pT3a and pT3b were not significant (p = 0.45). Carcinoma in situ (CIS) and lymphovascular invasion (LVI) were significantly associated with pT3b tumors. Univariate analysis could not identify pathological prognosticators like TIF or tumor size for OS and RFS (p for all > 0.05).

Conclusion: No significant differences in OS or RFS were observed comparing Ln-negative pT3 BC following radical cystectomy. Additional pathologic variables like TIF could not be identified as prognosticator. Relevance of pT3 BC substaging needs reevaluation in larger prospective cohorts.
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http://dx.doi.org/10.1007/s00345-021-03697-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571207PMC
November 2021

Minimal-invasive management of urological complications after kidney transplantation.

Int Urol Nephrol 2021 Jul 2;53(7):1267-1277. Epub 2021 Mar 2.

Department of Urology, University Hospital Tübingen, Eberhard Karls University, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Kidney transplantation represents the gold standard treatment option for patients with end-stage renal disease. Improvements in surgical technique and pharmacologic treatment have continuously prolonged allograft survival in recent years. However, urological complications are frequently observed, leading to both postoperative morbidity and putative deterioration of allograft function. While open redo surgery in these patients is often accompanied by elevated surgical risk, endoscopic management of urological complications is an alternative, minimal-invasive option. In the present article, we reviewed the literature on relevant urological postoperative complications after kidney transplantation and describe preventive approaches during the pre-transplantation assessment and their management using minimal-invasive approaches.
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http://dx.doi.org/10.1007/s11255-021-02825-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192401PMC
July 2021

The prognostic value of fat invasion and tumor expansion in the hilar veins in pT3a renal cell carcinoma.

World J Urol 2021 Sep 27;39(9):3367-3376. Epub 2021 Feb 27.

Department of Urology, University of Tuebingen, Tübingen, Germany.

Purpose: The 7th TNM classification summarizes renal cell carcinoma (RCC) with perirenal (PFI) and/or sinus fat invasion (SFI) as well as hilar vein involvement (RVI) as pT3a tumors. In this study, we aimed to determine the prognostic value of fat invasion (FI) in the different compartments and RVI for medium-term cancer-specific-survival (CSS) in pT3a RCC.

Materials And Methods: Patients with pT3a RCC were identified using an institutional database. All original pathological reports were reclassified according to the 7th TNM edition. The prognostic value of FI as well as divided into PFI, SFI, combined PFI + SFI, and RVI for CSS was assessed using univariate and multivariate Cox-regression analysis. Survival was estimated using the Kaplan-Meier method.

Results: Median follow-up in 184 pT3a tumors was 38 months. FI was detectable in 153 patients (32.7% PFI, 45.1% SFI, 22.2% PFI + SFI), 31 patients showed RVI alone. Combined PFI + SFI increased the risk of cancer-related death compared to PFI (HR 3.11, p < 0.01), SFI (HR 1.84, p = 0.023) or sole RVI (HR 2.12, p = 0.025). In multivariate analysis, a combined PFI + SFI vs. PFI or SFI as the only compartment involved was confirmed as independent prognostic factor (HR 1.83, p = 0.029). Patients with FI and simultaneous RVI had significantly shorter CSS (HR 2.63, p < 0.01). In an unweighted model, the difference between patients with combined PFI + SFI and RVI and those with PFI alone was highest (HR 4.01, p = 0.029).

Conclusions: These results underline the subdivision of pT3a RCC depending on the location of FI and RVI for patient stratification.
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http://dx.doi.org/10.1007/s00345-021-03638-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510928PMC
September 2021

Versatility and clinical effectiveness of a synthetic sealing hemostatic patch as alternative to parenchyma suturing in laparoscopic partial nephrectomy.

Surg Endosc 2021 Feb 16. Epub 2021 Feb 16.

Department of Urology, Medical Faculty and University Hospital, Eberhard-Karls-University Tuebingen, Tübingen, Germany.

Background: Improvements in laparoscopic partial nephrectomy (LPN) in order to minimize perioperative warm ischemia time (WIT), complications, and consequently patient outcome are desirable. Veriset™ is a ready-to-use hemostatic patch of absorbable oxidized cellulose and hydrogel components that has earlier been implemented in vascular and hepatic surgery. We report our experience using this device in LPN.

Methods: Patients with a solitary malignant renal mass suspicious for renal cancer underwent LPN with either the use of Veriset™ hemostatic patch (n = 40) or conventional suture technique (n = 40). Patient characteristics, operation time and WIT, postoperative course and complications were recorded retrospectively. Tumor complexity was calculated according to the R.E.N.A.L. score. Outcome was determined according to the "trifecta" criteria (negative surgical margin, WIT < 25 min, no complications within 30 days).

Results: No significant differences with regard to clinical parameters and median R.E.N.A.L. score (6) were observed between both groups. Operation time (mean 127.1 min vs. 162. 8 min; p = 0.001) and WIT were both lower in the Veriset™ group (14.6 min vs. 20.6 min; p = 0.01). No differences in surgical margins (p = 0.602) and overall complication rates at 30 (p = 0.599) and 90 days (p = 0.611) postoperatively were noticed. The surgical outcome according to "trifecta" was achieved in 65% of patients using Veriset™ and in 57.5% of patients by suture closure, respectively.

Conclusion: The hemostatic Veriset™ patch can successfully be implemented in LPN. Handling and application appear favorable, thereby reducing operation time and WIT. The present results suggest that the device may represent an alternative to parenchyma suturing in LPN.
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http://dx.doi.org/10.1007/s00464-021-08333-0DOI Listing
February 2021

Combination of immune checkpoint inhibitors and tyrosine kinase inhibitors for the treatment of renal cell carcinoma.

Expert Opin Biol Ther 2021 Sep 27;21(9):1215-1226. Epub 2021 Feb 27.

Department of Urology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, Tübingen, Germany.

Introduction: We have experienced several paradigm shifts and substantial changes in the treatment of metastatic renal cell carcinoma (mRCC) over the last two decades. Combination therapy with immune checkpoint inhibitors (ICI) as a dual combination (ICI-ICI) or with VEGFR-tyrosine kinase inhibitors (VEGF-TKI) has shown remarkable efficacy in mRCC patients and has become the standard of care in first-line therapy.

Areas Covered: In this review, we will discuss the background as well as the benefits of combining ICI with TKI compared to ICI-ICI combination therapy for mRCC treatment and will also briefly highlight biomarkers for patient selection on therapies to improve patient outcomes and limit toxicities.

Expert Opinion: Due to the mediated additional anti-tumor effects, there is a strong rationale to combine ICIs and TKIs for mRCC therapy. When comparing first-line therapy options, the exceptionally higher ORR and PFS for the ICI-TKI combinations should be highlighted, whereas, nevertheless, the complete response rate is slightly higher for the ICI-ICI combination. In terms of an individualized therapeutic approach, biomarkers predicting the success or failure of an anti-VEGF-based regimen or ICI therapy as a corresponding mono - or combination therapy are lacking so far, however, gene expression signatures can be a landmark in this field.
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http://dx.doi.org/10.1080/14712598.2021.1890713DOI Listing
September 2021

Retrospective German claims data study on initial treatment of bladder carcinoma (BCa) by transurethral bladder resection (TURB): a comparative analysis of costs using standard white light- (WL-) vs. blue light- (BL-) TURB.

World J Urol 2021 Aug 10;39(8):2953-2960. Epub 2021 Feb 10.

Department of Urology, University of Tuebingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany.

Purpose: Photodynamic diagnosis using hexaminolevulinate (HAL)-guided BL-TURB may reduce the recurrence risk in non-muscle invasive BCa compared to standard WL-TURB due to more sensitive tumor detection. The impact of the initial use of WL- vs. BL-TURB on follow-up costs was evaluated in this real-world data analysis.

Methods: Anonymous claims data of German statutory health insurances (GKV) from 2011 to 2016 were analyzed in a primary and adjusted study population. Selection criteria included five quarters before enrolment, one index quarter (InQ) of initial TURB and BCa diagnosis, either within two years for the primary analysis or within four years for the adjusted analysis, and a follow-up period (FU) of either eleven or three quarters, respectively.

Results: In the primary analysis (n = 2331), cystectomy was identified as an important cost driver masking potential differences between cohorts. Therefore, patients undergoing cystectomy (InQ + FU) were excluded from the adjusted study population of n = 4541 patients (WL: 79%; BL: 21%). Mean total costs of BL-TURB were initially comparable to WL-TURB (WL: EUR 4534 vs. BL: EUR 4543) and tended to be lower compared to WL-TURB in the first two quarters of FU. After one year (3rd FU quarter), costs equalized. Considering total FU, mean costs of BL-TURB were significantly lower compared to WL-TURB (WL: EUR 7073 vs BL: EUR 6431; p = 0.045).

Conclusion: This retrospective analysis of healthcare claims data highlights the comparability of costs between BL-TURB and WL-TURB.
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http://dx.doi.org/10.1007/s00345-020-03587-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405483PMC
August 2021

Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma: Final Overall Survival Analysis of the Phase 3 PROTECT Trial.

Eur Urol 2021 03 15;79(3):334-338. Epub 2021 Jan 15.

Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.

Most studies indicate no benefit of adjuvant therapy with VEGFR tyrosine kinase inhibitors in advanced renal cell carcinoma (RCC). PROTECT (NCT01235962) was a randomized, double-blind, placebo-controlled phase 3 study to evaluate adjuvant pazopanib in patients with locally advanced RCC at high risk of relapse after nephrectomy (pazopanib, n = 769; placebo, n = 769). The results of the primary analysis showed no difference in disease-free survival between pazopanib 600 mg and placebo. Here we report the final overall survival (OS) analysis (median follow-up: pazopanib, 76 mo, interquartile range [IQR] 66-84; placebo, 77 mo, IQR 69-85). There was no significant difference in OS between the pazopanib and placebo arms (hazard ratio 1.0, 95% confidence interval 0.80-1.26; nominal p > 0.9). OS was worse for patients with T4 disease compared to those with less advanced disease and was better for patients with body mass index (BMI) ≥30 kg/m compared to those with lower BMI. OS was significantly better for patients who remained diseasefree at 2 yr after treatment compared with those who relapsed within 2 yr. These findings are consistent with the primary outcomes from PROTECT, indicating that adjuvant pazopanib does not confer a benefit in terms of OS for patients following resection of locally advanced RCC. PATIENT SUMMARY: In the randomized, double-blind, placebo-controlled phase 3 PROTECT study, overall survival was similar for patients with locally advanced renal cell carcinoma (RCC) at high risk of relapse after nephrectomy who received adjuvant therapy with pazopanib or placebo. Pazopanib is not recommended as adjuvant therapy following resection of locally advanced RCC. This trial is registered at Clinicaltrials.gov as NCT01235962.
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http://dx.doi.org/10.1016/j.eururo.2020.12.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407394PMC
March 2021
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