Objective: To investigate the predictors of biochemical recurrence (BCR) in patients with positive surgical margins (PSMs) after radical prostatectomy (RP). Methods: The data of patients who underwent open RP between 2003 and 2011 were reviewed. Only patients with PSM and negative lymph node invasion were considered for further analysis. Multivariable Cox regression analysis was performed to evaluate the correlation between clinicopathologic criteria and BCR. Results: Out of 116 patients, 80 (69%) developed BCR with a median (interquartile range [IQR]) time to recurrence of 19 (9-50) months. Median (IQR) time of follow-up in non recurrent patients was 121 (47-148) months. The 5- and 10-year BCR-free survival rates were 43% and 28%, respectively. Complete data regarding margin parameters were available only for 98 patients, of which 71 (72%) developed BCR. Univariable analysis demonstrated that prostate volume (PV) (HR 0.97, 95% CI 0.95-0.99, P = .005), highest Gleason grade (GG) at the margin (HR 1.73, 95% CI: 1-2.83, P = .028 for GG 4-5 vs. 3), tumor GG group 2 (HR [Hazard Ratio] 2, 95% CI 1.09-3.94, P = .025) and 4-5 (HR 2.34, 95% CI 1-4.98, P = .028) were significant predictors of BCR. In multivariable analysis, only PV remained an independent predictor of BCR (HR 0.98, 95% CI 0.96-0.99, P = .03). Conclusion: In patients with PSM after RP, smaller prostates have a higher probability of BCR. Further studies are needed to investigate this association. The highest GG at the margin has important predictive accuracy and should be reported in the pathol ogy report. Cite this article as: Mahmuod O, Al-Nader M, Grevendieck A, et al. Predictors of biochemical recurrence in patients with positive surgical margin after radical prostatectomy. Urol Res Pract. 2025;51(5):198-202.

Introduction The MemoKathTM-051 (MK) is a thermo-expandable spiral stent for the treatment of benign or malignant ureteral obstruction. Existing studies on outcome measurements, like complication rate or time to stent exchange for MK differ significantly. In this retrospective analysis, we investigated the supposed superiority of the MK over conventional tumor ureteral stent (TUS) insertion. Material and methods In this monocentric retrospective analysis, 72 consecutive patients with benign or malignant extrinsic ureteral stenosis who either underwent insertion of a MK or TUS between 03/2008 and 12/2018 were analyzed. Indications for stent insertion were either chronic benign or malignant extrinsic obstruction in patients who were unsuitable for or refused definitive surgery. Patients who underwent urinary diversion were excluded. We compared the indwelling time, the complication rates and the time to occurrence of complications using Mann-Whitney-U-test and chi 2 test for categorical variables. Complication rates of both, the MK and the TUS were compared using Fishers test. Complications were classified according to Clavien-Dindo Classification (CDC). Results The total number of ureteral units analyzed was 171, including 89 MK stents and 82 TUSs. No significant differences between both groups regarding age, stent indications, and stricture characteristics occurred. At a median follow-up of 32 and 27 months in the MK and TUS groups, postoperative complications occurred in 82 (92%) and 19 (23%) patients, respectively (p = 0.01). Almost all complications were major (CDC grade 3b) that required stent removal or replacement, with the exception of one patient in the MK group. Median time to complications was significantly longer for the MK group, 5.6 months, compared to 3.5 months in the TUS group (p = 0.01), and median time to stent replacement was 8 months for the MK group vs 5.2 months for the TUS group (p <0.001). Conclusions Although the MemoKathTM is designed for a long indwelling time of up to years, it is associated with higher complication rates and premature replacement. However, compared to the TUS, the MK still has a significantly longer indwelling time. Further studies are needed to determine the predictors of failure and the best candidates for both stents.

Temsirolimus has long been the only approved first-line standard of care (SOC) with overall survival (OS) benefit in poor-risk patients with advanced or metastatic renal cell cancer (mRCC). However, tyrosine kinase inhibitors are also commonly used in clinical practice. Pazopanib is an SOC for first-line mRCC treatment, but for poor-risk patients data are scarce. The FLIPPER (First-Line Pazopanib in Poor-Risk Patients with Metastatic Renal Cell Carcinoma) study aimed to assess efficacy and safety of first-line pazopanib in poor-risk mRCC patients. FLIPPER was a single-arm, multicenter, Phase IV trial. Key inclusion criteria were treatment-naive clear cell, inoperable advanced or mRCC, poor-risk according to MSKCC with slight modification, Karnofsky performance status (KPS) >= 60% and adequate organ function. Oral pazopanib 800 mg was given daily. Primary endpoint was the 6-month progression-free survival rate (PFS6). Secondary endpoints included PFS, OS, overall response rate (ORR), duration of response (DOR) and safety. For analysis, descriptive statistics were used. Between 2012 and 2016, 60 patients had been included. Forty-three patients qualified for safety analyses, 34 for efficacy. Median age was 66 years, 64.7% of patients were poor-risk, 82.4% had a KPS <= 70%. PFS6 was 35.3% (95% CI, 19.7-53.5). Median PFS and OS were 4.5 months (95% CI, 3.6-7.8) and 9.3 months (95% CI, 6.6-22.2), respectively. ORR was 32.4% (95% CI, 17.4-50.5), median DOR 9.7 months (95% CI, 1.8-12.4). The most common treatment-related grade 3/4 adverse event reported in 4.7% of patients was hypertension. No treatment-related death occurred. Since pazopanib is active and well tolerated in poor-risk patients with clear cell mRCC, our results support its use as first-line treatment in this setting.

Various types of human cancers were characterized by an altered expression of epithelial or stromal caveolin-1 (CAV1). However, the clinical significance of CAV1 expression in penile cancer remains largely unknown. Here the expression patterns of CAV1 were analyzed in a retrospective cohort (n=43) of penile squamous cell carcinomas (SCC). Upon penile cancer progression, significantly increased CAV1-levels were determined within the malignant epithelium, whereas within the tumor stroma, namely the fibroblastic tumor compartment harboring activated and/or cancer associated fibroblasts, CAV1 levels significantly decline. Concerning the clinicopathological significance of CAV1 expression in penile cancer as well as respective epithelial-stromal CAV1 distributions, high expression within the tumor cells as well as low expression of CAV1 within the stromal compartment were correlated with decreased overall survival of penile cancer patients. Herein, CAV1 expressions and distributions at advanced penile cancer stages were independent of the immunohistochemically proven tumor protein p53 status. In contrast, less differentiated p16-positive tumor epithelia (indicative for human papilloma virus infection) were characterized by significantly decreased CAV1 levels. Conclusively, we provide further and new evidence that the characteristic shift in stromal‐epithelial CAV1 being functionally relevant to tumor progression even occurs in penile SCC.

Objective: Patients with bladder cancer (BC) are at risk of developing upper tract urothelial carcinoma (UTUC). Therefore, CT urography is recommended for follow-up. To avoid intravenous contrast agents, retrograde pyelography (RPG) is an alternative. However, it is still unclear whether RPG increases the incidence of UTUC. The aim of this study was to investigate the impact of RPG in the presence of BC on the risk of developing UTUC. Patients and Methods: Retrospectively analysing a total of 3,680 RPGs between 2009 and 2016, all patients with simultaneous BC (group 1) and those without synchronous BC (group 2) during RPG were compared. All patients were risk stratified according to the EORTC bladder calculator. In patients without BC during RPG, risk stratification was based on the worst prior tumour characteristics. Results: A total of 145 patients with a history of BC were analysed. Of these, 112 patients underwent RPG with simultaneous BC. UTUC developed in 6 of 112 patients (5.4%) and 58.9% (66/112) had high-risk BC according to the EORTC bladder calculator. In the control group, one out of 33 (3%) patients with metachronous high-risk BC developed UTUC. Conclusions: Using RPG in the presence of BC did not increase the risk of UTUC. Due to the predominant number of high-risk/high-grade tumours, individual tumour biology appears to be the primary driver for the development of UTUC.

OBJECTIVES:To assess the impact of the presence of bland thrombus (BT) on prognosis of patients treated with resection of renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVCTT). MATERIALS AND METHODS:The medical records of a total of 145 consecutive postsurgical RCC patients with level I-IV IVCTT were reviewed from January 2008 to August 2018. Associations of BT with clinicopathological variables were estimated by chi-square test or Student's t-test. Kaplan-Meier method and multivariate Cox proportional hazard model were used. The eighth TNM staging system, "Spiess PE" model, University of California at Los Angeles Integrated Staging System and Stage, Size, Grade, and Necrosis (SSIGN) score were selected to assess whether BT could improve their predictive abilities. RESULTS:BT was observed in 34 (23.4%) patients and was significantly associated with increased levels of IVCTT (P = 0.004) and invasion of IVC wall (P = 0.030). Multivariable Cox analyses revealed that tumor grade, T stage, M stage, tumor thrombus consistency and BT were independent risk factors for both progression-free survival and overall survival. The concordance indexes ranged from a low of 0.652 in TNM to a high of 0.731 in SSIGN, and integrating BT into each base model led to an increased predictive accuracies of 6.2% for TNM (P = 0.025), 4.0% for "Spiess PE" model (P = 0.069), 2.1% for University of California at Los Angeles Integrated Staging System (P = 0.149) and 1.2% for SSIGN (P = 0.290), respectively. CONCLUSIONS:Presence of BT was independently associated with survival in postsurgical patients with RCC-IVCTT. Routine consideration of BT as an adjunct to TNM staging system may be suggested.

Background The proteoglycan syndecan-1 is involved in cell proliferation, adhesion and angiogenesis. It was shown to be involved in cancer progression in different tumor entities. So far, the role of syndecan-1 in renal cell carcinoma (RCC), one of the most common diseases in urologic oncology, was little described. Purpose of the present study was to obtain serum concentrations and tissue expression levels of syndecan-1 in a cohort of patients diagnosed with RCC. Methods Clinical and follow-up data were obtained from 413 RCC patients. SDC1 levels were determined in serum samples of 100 patients by enzyme-linked immunosorbent assay and tissue SDC1 expression was measured by immunohistochemistry (IHC) in 343 cases. Results were correlated with clinicopathological and follow-up data. Results Five and ten years overall and cancer specific survival were 67% and 56% [overall survival (OS)] and 79% and 76% [cancer-specific survival (CSS)]. In female patients and locally advanced disease (≥T3), tissue SDC1 expression was decreased (female 85.6% vs. male 71.1% low tissue SDC1 expression, P=0.0153 and ≤T2 70.0% vs. ≥T3 87.2% low tissue SDC1 expression, P=0.0055) compared to male patients and organ confined disease. Locally advanced tumor stage, presence of lymph node or distant metastases, high Fuhrman grading and clear cell carcinoma as histopathological subtype were independent prognostic factors for reduced CSS and OS. There was no impact of serum SDC1 (sSDC1) serum concentration or SDC1 tissue protein expression on OS, CSS or recurrence free survival (RFS) in uni- or multivariable analysis. Conclusions sSDC1 concentration or SDC1 tissue protein expression levels had no influence on patients’ prognosis in the present cohort of patients diagnosed with RCC.

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP84)1 Apr 2020MP84-12 CHANGE IN SEXUAL ATTRACTION AND SEXUAL PARTNERSHIP WITHIN THE INDIVIDUAL TRANSITION PROCESS IN TRANSWOMEN Jochen Hess*, Anja Breidenstein, Andrej Panic, Stephan Tschirdewahn, Sefik Tagay, Martin Teufel, and Boris Hadaschik Jochen Hess*Jochen Hess* More articles by this author , Anja BreidensteinAnja Breidenstein More articles by this author , Andrej PanicAndrej Panic More articles by this author , Stephan TschirdewahnStephan Tschirdewahn More articles by this author , Sefik TagaySefik Tagay More articles by this author , Martin TeufelMartin Teufel More articles by this author , and Boris HadaschikBoris Hadaschik More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000976.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Male to female (MtF) gender affirming surgery (GAS) comprises the resection of the testes and the erectile tissue and formation of a functional and aesthetic vaginal cavity capable for sexual intercourse with a sensitive neoclitoris. Interviews after GAS mostly refer to surgical outcomes and complications, subjective satisfaction and general or health related quality of life. Aspects of sexuality however have often been neglected. METHODS: In total 158 trans*-women (median age 49.5 years), who had undergone MtF GAS at the Department of Urology of the University Hospital Essen between 1995 and 2015, were surveyed using open questions and validated questionnaires (e.g. sexual orientation questionnaire FSO, Kinsey-Scale, partnership questionnaire short form PFB-K). Median time since surgery was 6.6 years. Results of the PFB-K were compared with a non-transsexual cohort. RESULTS: Respondents stated that their overall quality of life improved steadily during their individual transition process (coming out [CO] – start hormone intake – surgery – last four weeks), which was highly significant (p<0.001). At the time of survey (SUR) a total of 96.2% perceived themselves as female or rather female. Pursuant to the Kinsey-Scale 30.6% of participants were exclusively heterosexual, 31.8% were bisexual and 22.3% were exclusively homosexual referring to their perceived gender with 12.3% denying any sexual contacts. Sexual attraction changed in 23.6% after start of hormone replacement therapy and in 31.3% after GAS. Sexual attraction only to men was 11.5% at the time of coming out (CO) and 24.8% at the time of survey (SUR). In contrast exclusive attraction to women was 45.9% (CO) and 25.5% (SUR) respectively. In the same manner the rate of sexual relationships only to men changed from 11.5% (CO) to 24.2% (SUR) and from 52.2% (CO) to 28.0% (SUR) regarding relationships only to women. Whereas the proportion of women without any sexual attraction (8.9% CO versus 7.6% SUR) remained at a constant level, the percentage of those who felt attracted by both males and females increased from 3.8% (CO) to 12.1% (SUR). Sexual life as a whole impaired in 19.7%, improved in 49.7% and remained unaltered in 27.4%. At the time of interrogation nearly half of women (46.5%) lived in a firm relationship of whom 43.5% were allied with the same partner since coming out. In total 35.0% were partnered with a woman (3.2% with a trans*-woman) and 17.2% with a man (1.3% with a trans*-man). The women in the study population were significantly more satisfied with their partnership (according to PFB-K) compared to women of a non-transsexual cohort (mean 20.6 versus 18.4; p<0.001). CONCLUSIONS: In contrast to a rather stable gender identity we found a distinct fluidity of sexual orientation and change in sexual relationships during transition process. Sexual attraction does not necessarily reflect sexual contacts. Satisfaction with partnership was higher compared to a non-transsexual cohort. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1269-e1269 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jochen Hess* More articles by this author Anja Breidenstein More articles by this author Andrej Panic More articles by this author Stephan Tschirdewahn More articles by this author Sefik Tagay More articles by this author Martin Teufel More articles by this author Boris Hadaschik More articles by this author Expand All Advertisement PDF downloadLoading ...

Clinic for Medical Oncology and Clinic for Urology, West-German Cancer Center, University Hospital Essen, Essen, Germany Correspondence to: Viktor Grünwald, MD. Professor for Interdisciplinary Genitourinary Oncology, Clinic for Medical Oncology and Clinic for Urology, West-German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. Email: viktor.gruenwald@uk-essen.de. Provenance: This is an invited article commissioned by the Section Editor Dr. Xiao Li (Department of Urology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China). Comment on: Dudani S, Graham J, Wells JC, et al. First-line Immuno-Oncology Combination Therapies in Metastatic Renal-cell Carcinoma: Results from the International Metastatic Renal-cell Carcinoma Database Consortium. Eur Urol 2019;76:861-7.

INTRODUCTION AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsies improve detection of significant prostate cancer (sPC). However, the optimal number of cores being applied to a target is still under debate. Here, we assess cancer detection rates of two different target-dependent MRI/transrectal ultrasonography (TRUS) fusion-guided biopsy approaches (targeting compared to target saturation) in comparison to extended systematic biopsies. METHODS: Retrospective single-centre outcome of transperineal MR/TRUS fusion-guided biopsies of 221 men with MRI lesions, prospectively collected between 2016 and 2018. All men underwent transperineal targeted biopsy (TB) with 2-4 cores, followed by a median of 24 systematic biopsies (SB). Cancer detection rates and sPC, (ISUP grade group ≥ 2) detection rates were analysed. TB was compared to target saturation (TS) with 9 cores per target, calculated by the Barzell scheme and using the combination of TB and SB, including the lesion and the “penumbra” of the lesion. Cancer and sPC detection rates were calculated for SB, TB and TS on both, lesion and patient level. Combination of SB and TB served as reference. Statistical differences in sPC detection between the groups were calculated using McNemar`s tests. RESULTS: On a lesion basis, TS detected 95% of 128 sPC lesions which was significant more compared to TB (87%, p=0.003) and SB (82%, p<0.001). SB detected 33% more low-risk PC lesions compared to TB (p<0.001) and 11% more compared to TS (p=0.01). On a patient basis, 98% of men harboring sPC were detected by TS. This was significantly higher compared to both TB and SB (each 88%, p<0.001). CONCLUSIONS: The target saturation approach detected significantly more sPC compared to TB as well as extended SB. Given that 95% of sPC lesions and 98% of men harbouring sPC were identified by saturating the target lesion, this approach allows to omit systematic biopsy cores without compromising sPC detection. Source of Funding: None

BACKGROUND:Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsies (TBs) facilitate accurate detection of significant prostate cancer (sPC). However, it remains unclear how many cores should be applied per target. OBJECTIVE:To assess sPC detection rates of two different target-dependent magnetic resonance imaging (MRI)/transrectal ultrasonography (TRUS)-fusion biopsy approaches (TB and target saturation [TS]) compared with extended systematic biopsies (SBs). DESIGN, SETTING, AND PARTICIPANTS:Retrospective single-centre outcome of transperineal MRI/TRUS-fusion biopsies of 213 men was evaluated. All men underwent TB with a median of four cores per MRI lesion, followed by a median of 24 SBs, performed by experienced urologists. Cancer and sPC (International Society of Urological Pathology grade group ≥2) detection rates were analysed. TB was compared with SB and TS, with nine cores per target, calculated by the Ginsburg scheme and using individual cores of the lesion and its "penumbra". OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Cancer detection rates were calculated for TS, TB, and SB at both lesion and patient level. Combination of SB + TB served as a reference. Statistical differences in prostate cancer (PC) detection between groups were calculated using McNemar's tests with confidence intervals. RESULTS AND LIMITATIONS:TS detected 99% of 134 sPC lesions, which was significantly higher than the detection by TB (87%, p = 0.001) and SB (82%, p < 0.001). SB detected significantly more of the 72 low-risk PC lesions than TB (99% vs 68%, p < 0.001) and 10% (p = 0.15) more than that detected by TS. At a per-patient level, 99% of men harbouring sPC were detected by TS. This was significantly higher than that by TB and SB (89%, p = 0.03 and 81%, p = 0.001, respectively). Limitations include limited generalisability, as a transperineal biopsy route was used. CONCLUSIONS:TS detected significantly more cases of sPC than TB and extended SB. Given that both 99% of sPC lesions and men harbouring sPC were identified by TS, the results suggest that this approach allows to omit SB cores without compromising sPC detection. PATIENT SUMMARY:Target saturation of magnetic resonance imaging-suspicious prostate lesions provides excellent cancer detection and finds fewer low-risk tumours than the current gold standard combination of targeted and systematic biopsies.

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I (MP29)1 Apr 2020MP29-09 SPACING TECHNIQUE“ FOR CREATION OF NEOVAGINAL CANAL IN MALE TO FEMALE GENDER AFFIRMING SURGERY Jochen Hess*, Cordelia Kaspar, Alexander Henkel, Andrej Panic, Stephan Tschirdewahn, and Boris Hadaschik Jochen Hess*Jochen Hess* More articles by this author , Cordelia KasparCordelia Kaspar More articles by this author , Alexander HenkelAlexander Henkel More articles by this author , Andrej PanicAndrej Panic More articles by this author , Stephan TschirdewahnStephan Tschirdewahn More articles by this author , and Boris HadaschikBoris Hadaschik More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000868.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The creation of the neovaginal canal is one of the most demanding steps in male to female (MtF) gender affirming surgery (GAS). Problems can occur in defining the correct layer of tissue. Here we describe the new “spacing technique” that simplifies the creation of the neovaginal canal. METHODS: Under transrectal ultrasound guidance we placed a standard TSK-Supra-Needle (20 Gauge, 120 mm length) ventral to the fascia of Denonvillier between rectum and prostate gland. Injection of 40 – 60 ml of normal saline under direct visual control into the space between the prostate and rectum pushes the structures apart and positions the anterior rectal wall temporarily away from the prostate. For better intraoperative visualization we dyed the hydrodistensed space with a few drops of methylenblue. Results of patients with spacing technique (ST) were compared with the last 50 patients of standard vaginoplasty (SV) operated on by the same surgeon. RESULTS: Spacing technique was performed in 43 patients immediately prior to GAS. Patients in both groups did not differ in age (SV 37.58 ± 13.94, range 16 - 67 years vs. ST 37.47 ± 13.70, range 19 - 65 years, p=0.97) or BMI (SV 25.7 ± 5.1 vs. ST 28.3 ± 12.6 kg/m2; p=0.18). Vaginal depth and width were larger in ST patients compared to SV patients (14.5 ± 0.7 cm vs. 13.2 ± 2.2 cm; p=0.001 and 4.0 ± 0.2 cm vs. 3.7 ± 0.4 cm; p<0.001 respectively). There was no statistically significant difference in occurrence of intraoperative rectal perforation (SV: n= 1, ST: n=0; p=0.357). However total OR-time could be reduced when hydrodistension was performed before vaginoplasty (SV: 224.3 ± 33.3 min. vs. 200.8 ± 30.8 min.; p=0.001). CONCLUSIONS: Spacing technique is a promising easy to perform technique which allows a good insight view of the anatomical region of the most delicate step in vaginoplasty and can facilitate preparation of neovaginal canal during male to female gender affirming surgery. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e432-e432 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jochen Hess* More articles by this author Cordelia Kaspar More articles by this author Alexander Henkel More articles by this author Andrej Panic More articles by this author Stephan Tschirdewahn More articles by this author Boris Hadaschik More articles by this author Expand All Advertisement PDF downloadLoading ...

Tissue protein expression of IMP3 is emerging as a promising prognostic factor in renal cell carcinoma (RCC). The most commonly used immunohistochemical (IHC) antibody has been criticized for its low specificity. In addition, blood levels of IMP3 have not yet been analyzed in RCC. Therefore, we compared the prognostic performance of two different IMP3 IHC antibodies and assessed the prognostic relevance of IMP3 plasma levels in RCC. IMP3 levels were assessed in an overall number of 425 RCC (344× clear cell [ccRCC], 63× papillary [pRCC], 18× chromophobe [chRCC]) patients in three partly overlapping cohorts. Plasma IMP3 concentrations were determined by ELISA in 98 RCC (79× ccRCC, 15× pRCC, 4× chRCC) patients and 20 controls. IMP3 mRNA expression levels were analyzed in 73 frozen tissue samples (55× ccRCC, 12× pRCC, 6× chRCC), while protein expressions were assessed in 366 FFPE samples (294× ccRCC, 56× pRCC, 16× chRCC) using the M3626 and N‐19 antibodies. IMP3 plasma and mRNA expression levels were significantly higher in patients compared to controls and in high‐grade compared to low‐grade tumors. In addition, IMP3 plasma and tissue protein levels (by M3626) were higher and IMP3 mRNA expression levels tended to be higher in patients with distant metastasis. Multivariate analyses in clear cell RCC revealed high IMP3 plasma concentration and mRNA expression as independent predictors of disease‐specific survival. IMP3 immunostainings by M3626 but not by N‐19 were independently associated with poor overall and disease‐specific survival. High plasma and tissue levels of IMP3 are independently associated with poor RCC prognosis. The applied antibody significantly impacts the prognostic performance of analysis. IMP3 analysis may improve risk‐stratification of RCC patients and therefore could help to optimize therapeutic and follow‐up decisions.

Metastatic renal cell carcinoma (RCC) remains largely incurable. Up to 30% of patients show metastasis at the time of the initial diagnosis. Prognostic criteria developed by the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) and MSKCC (Memorial Sloan Kettering Cancer Center) are used to classify patients based on certain pretreatment factors. The prognosis of patients with metastatic disease varies depending on these risk factors. Anti-angiogenic agents targeting the vascular endothelial growth factor (VEGF) and its receptors are standard treatments based on improved clinical outcomes in randomized phase III trials. Standard of care therapies now include multitargeted tyrosine kinase inhibitors (TKIs) such as sunitinib, axitinib, pazopanib, and cabozantinib, as well as the mTOR inhibitors temsirolimus and everolimus. Tumor-associated PD-L1 expression has been detected in RCC and is associated with a worse prognosis. Immune checkpoint inhibitors such as the PD-1 inhibitor nivolumab have shown promising results in treatment of the metastatic disease. Future developments including novel combinations and attempts to find the optimal position of immunotherapy in the disease pathway are subject of ongoing clinical trials.

Tumour resistance to chemo- and radiotherapy, as well as molecularly targeted therapies, limits the effectiveness of current cancer treatments. We previously reported that the radiation response of human prostate tumours is critically regulated by CAV1 expression in stromal fibroblasts and that loss of stromal CAV1 expression in advanced tumour stages may contribute to tumour radiotherapy resistance. Here we investigated whether fibroblast secreted anti-apoptotic proteins could induce radiation resistance of prostate cancer cells in a CAV1-dependent manner and identified TRIAP1 (TP53 Regulated Inhibitor of Apoptosis 1) as a resistance-promoting CAV1-dependent factor. TRIAP1 expression and secretion was significantly higher in CAV1-deficient fibroblasts and secreted TRIAP1 was able to induce radiation resistance of PC3 and LNCaP prostate cancer cells in vitro, as well as of PC3 prostate xenografts derived from co-implantation of PC3 cells with TRIAP1-expressing fibroblasts in vivo. Immunohistochemical analyses of irradiated PC3 xenograft tumours, as well as of human prostate tissue specimen, confirmed that the characteristic alterations in stromal-epithelial CAV1 expression were accompanied by increased TRIAP1 levels after radiation in xenograft tumours and within advanced prostate cancer tissues, potentially mediating resistance to radiation treatment. In conclusion, we have determined the role of CAV1 alterations potentially induced by the CAV1-deficient, and more reactive, stroma in radio sensitivity of prostate carcinoma at a molecular level. We suggest that blocking TRIAP1 activity and thus avoiding drug resistance may offer a promising drug development strategy for inhibiting resistance-promoting CAV1-dependent signals.

BackgroundTo compare the outcomes of robot‐assisted (RAPN) and open partial nephrectomy (OPN) for completely endophytic renal tumors.MethodsConsecutive patients undergoing OPN or RAPN for entirely endophytic tumors in four high‐volume centers between 2008 and 2016 were identified. Endophytic masses were identified based on sectional imaging. Patient characteristics and surgical outcome were compared using Mann‐Whitney‐U‐test and chi‐squared‐tests. Uni‐ and multivariate analyses were performed to identify predictors of TRIFECTA achievement and excisional volume loss.ResultsOut of 1128 patients, 10.9% (64) of RAPN and 13.9% (76) of OPN underwent surgery for entirely endophytic tumors. Operative time was longer for RAPN (169 vs 140 min, P = 0.03) while ischemia time was shorter (13 vs 18 min, P = 0.001). Complication rates were comparable (21% OPN vs 22% RAPN, P = 0.91) and TRIFECTA achievement was not different between the groups (68% OPN vs 75% RAPN, P = 0.39). In multivariate analyses type of surgery was not associated with TRIFECTA achievement or excisional volume loss. Here, only tumor complexity (OR 0.48, P = 0.001) and size (OR 1.01, P = 0.002) were independent predictors.ConclusionFor entirely endophytic tumors, both RAPN and OPN offer good TRIFECTA achievement. This encourages the use of NSS even for these highly complex tumors using the surgeon's preferred approach.

Despite good treatment results in localized prostate tumors, advanced disease stages usually have a pronounced resistance to chemotherapy and radiotherapy. The membrane protein caveolin-1 (Cav1) functions here as an important oncogene. Therefore we examined the impact of stromal Cav1 expression for tumor growth and sensitivity to ionizing radiation (IR). Silencing of Cav1 expression in PC3 cells resulted in increased tumor growth and a reduced growth delay after IR when compared to tumors generated by Cav1-expressing PC3 cells. The increased radiation resistance was associated with increasing amounts of reactive tumor stroma and a Cav1 re-expression in the malignant epithelial cells. Mimicking the human situation these results were confirmed using co-implantation of Cav1-silenced PC3 cells with Cav1-silenced or Cav1-expressing fibroblasts. Immunohistochemically analysis of irradiated tumors as well as human prostate tissue specimen confirmed that alterations in stromal-epithelial Cav1 expressions were accompanied by a more reactive Cav1-reduced tumor stroma after radiation and within advanced prostate cancer tissues which potentially mediates the resistance to radiation treatment. Conclusively, the radiation response of human prostate tumors is critically regulated by Cav1 expression in stromal fibroblasts. Loss of stromal Cav1 expression in advanced tumor stages may thus contribute to resistance of these tumors to radiotherapy.