Impact of primary resistance to front-line targeted therapy in metastatic renal cell carcinoma on subsequent immune-checkpoint-inhibition.

INTRODUCTION: Synergistic effects have been discussed for tyrosine kinase (TKI) and immune checkpoint inhibitors (ICI). Primary resistance to TKI might disturb subsequent ICI effectiveness. The objective was to investigate, if primary resistance to 1st line TKI monotherapy predicts response to ICI in subsequent therapy lines and impacts overall survival (OS) in advanced renal cell carcinoma (aRCC). MATERIALS AND METHODS: Retrospectively, aRCC patients which received front-line TKI from 2016 to 2019 were analyzed for the outcomes primary resistance (1LR), response to sequential ICI therapy, progression free survival (PFS) and overall survival (OS). Kaplan-Meier-estimates, Cox proportional hazards and logistic regression were used. RESULTS: Primary resistance to front-line TKI was observed in 27 (53%) of 51 patients. Groups with disease control (DC) and 1st line TKI resistance (1LR) were not different at baseline with regard to clinicopathological features. Median duration on 1st line therapy was significantly shorter in the 1LR (5.1 months) than in the DC (14.7 months) group (p = 0.01). Sequential therapy was started in 21 (75%) and 12 (52%) patients of 1LR and DC groups using nivolumab in 16 (76%) vs. 11 (92%) cases (p > 0.05). Logistic regression revealed that 1LR status, neutrophil-to-lymphocyte ratio < 3, IMDC favorable prognosis and clear cell histology had no significant impact on responsiveness to ICI in subsequent therapy lines. Cox proportional hazards demonstrated no significant association of 1LR status with PFS and OS in patients who received subsequent ICI treatment. CONCLUSION: Primary TKI resistance of aRCC was neither significantly associated with responsiveness to ICI during sequential therapy nor with PFS and OS. This adds the evidence for ICI based sequential therapy in primary TKI resistant aRCC.

First Comparison of Retroperitoneal Versus Transperitoneal Robot-Assisted Nephroureterectomy with Bladder Cuff: A Single Center Study.

INTRODUCTION: After recent presentation of the first complete robot-assisted retroperitoneal nephroureterectomy with bladder cuff (RRNU) for patients with upper tract urothelial cancer (UTUC), we aimed to compare this new surgical technique with robot-assisted transperitoneal nephroureterectomy (TRNU) representing the current standard of care. METHODS: Robot-assisted nephroureterectomies (NUs) were retrospectively analyzed and compared based on two groups: transperitoneal versus retroperitoneal approach. Baseline data were collected for patient demographics, tumor characteristics, intra- (EAUiaiC) and postoperative (Clavien-Dindo) complications, and perioperative variables. Tumor characteristics included grade of malignancy, clinical stage, and surgical margin status. Short-term follow-up data including 30-day readmission rates were collected. Statistical analyses were performed assuming a significant p-value of < 0.05. RESULTS: The analysis includes perioperative patient data after proven UTUC of 24 TRNU versus 12 RRNU (mean age: 70 versus 71 years; BMI: 25.9 versus 26.1 kg/m2; CCI score ≥ 4: 83% versus 75%; ASA score ≥ 3: 37% vs 33%). Intraoperative (16.4% vs 0%, p = 0.35) and postoperative (25% vs 12.5%, p = 0.64) complications demonstrated no significant discrepancy. Notably, RRNU demonstrated significantly shorter surgery time (p < 0.05) and length of stay (p < 0.05). There was no significant difference in histopathological tumor characteristics, whereas significantly more lymph nodes were removed through RRNU (11.0±3.3 vs. 6.4±5.1, p < 0.05). Finally, no statistical difference was shown in short-term follow-up. CONCLUSION: We report the first head-to-head comparison between RRNU and TRNU. RRNU proves to be a safe and feasible approach which appears to be non-inferior to TRNU. RRNU expands the spectrum of minimally invasive treatment options, particularly for patients with major previous abdominal surgery.

Assessment of a novel smartglass-based point-of-care fusion approach for mixed reality-assisted targeted prostate biopsy: A pilot proof-of-concept study.

Purpose: While several biopsy techniques and platforms for magnetic resonance imaging (MRI)-guided targeted biopsy of the prostate have been established, none of them has proven definite superiority. Augmented and virtual reality (mixed reality) smartglasses have emerged as an innovative technology to support image-guidance and optimize accuracy during medical interventions. We aimed to investigate the benefits of smartglasses for MRI-guided mixed reality-assisted cognitive targeted biopsy of the prostate. Methods: For prospectively collected patients with suspect prostate PIRADS lesions, multiparametric MRI was uploaded to a smartglass (Microsoft® Hololens I), and smartglass-assisted targeted biopsy (SMART TB) of the prostate was executed by generation of a cognitive fusion technology at the point-of-care. Detection rates of prostate cancer (PCA) were compared between SMART TB and 12-core systematic biopsy. Assessment of SMART-TB was executed by the two performing surgeons based on 10 domains on a 10-point scale ranging from bad (1) to excellent (10). Results: SMART TB and systematic biopsy of the prostate were performed for 10 patients with a total of 17 suspect PIRADS lesions (PIRADS 3, n = 6; PIRADS 4, n = 6; PIRADS 5, n = 5). PCA detection rate per core was significant (p < 0.05) higher for SMART TB (47%) than for systematic biopsy (19%). Likelihood for PCA according to each core of a PIRADS lesion (17%, PIRADS 3; 58%, PIRADS 4; 67%, PIRADS 5) demonstrated convenient accuracy. Feasibility scores for SMART TB were high for practicality (10), multitasking (10), execution speed (9), comfort (8), improvement of surgery (8) and image quality (8), medium for physical stress (6) and device handling (6) and low for device weight (5) and battery autonomy (4). Conclusion: SMART TB has the potential to increase accuracy for PCA detection and might enhance cognitive MRI-guided targeted prostate biopsy in the future.

First completely robot-assisted retroperitoneal nephroureterectomy with bladder cuff: a step-by-step technique.

INTRODUCTION: While various surgical techniques have been reported for open and minimally invasive treatment of upper tract urothelial cancer (UTUC), the procedure of robot-assisted nephroureterectomy (NU) with bladder cuff has never been reported using only retroperitoneum without entering abdominal cavity. We developed a novel port placement and technique allowing to perform robot-assisted NU by a unique retroperitoneal approach. METHODS: Between February and June 2021 patients with history of UTUC were treated by robot-assisted NU completely restricted to retroperitoneal space using a singular trocar placement and a two-step docking without relocation of the surgical robot. Patient characteristics, perioperative outcomes and short-term follow-up were prospectively analyzed. RESULTS: The analysis included five patients [median age: 73 years; BMI: 27.2 kg/m2; Charlson comorbidity index 5]. All five patients had UTUC with a mean tumor size of 3.02 cm (range 0.9-6.0). UTUC was localized to distal ureter in two and to kidney in three cases. No positive surgical margins were noted for all patients with UTUC [1 low-grade and 4 high-grade]. Retroperitoneal lymphadenectomy in three patients did not reveal positive nodes. No intraoperative adverse events exceeding EAUiaiC classification ≥ 2 were observed, while median EBL was 150 ml (IQR 100-250). No patient experienced postoperative complications exceeding Clavien-Dindo classification ≥ 3a. Median hospital stay was 5.4d without any 30-d readmission. CONCLUSION: We demonstrate safety and feasibility of the first entire robot-assisted retroperitoneal nephroureterectomy (RRNU) with bladder cuff. This surgical technique is easily reproducible, while surgical outcomes are similar to other established techniques.

[Quality of care criteria in the treatment of penile cancer]. / Qualitätskriterien in der Therapie des Peniskarzinoms.

BACKGROUND: Penile cancer is a rare malignancy and the wide range of quality of care associated with it often results in inferior oncologic and functional treatment outcomes. OBJECTIVES: Assessment of the current healthcare situation in clinical routine and identification of the relevant key features and reference values for quality of care. MATERIALS AND METHODS: Search for relevant peer-reviewed articles and published congress abstracts in Medline, Embase and other databases as well as Google web search engine. RESULTS: Key quality features of penile cancer management include organ-sparing surgery of the primary tumor, invasive inguinal lymph node staging and systemic treatment. Adherence to treatment guidelines is currently low. Centralization of care has already led to a considerable improvement in the quality of care in some areas and increasing conformity with the guidelines' recommendations. CONCLUSION: Centralization of care and networks based on this can significantly improve patient outcomes. Thus, reference values for core parameters of quality cancer care can be generated and validated. Moreover, organ-sparing surgery, invasive lymph node staging and systemic therapy should be increasingly utilized. As a reference value, 90% adherence to the guidelines for these three features is recommended. However, before centralization of care can be introduced, aspects relevant to practical implementation must be addressed, such as the reimbursement of travel costs for those affected, infrastructure costs and instruments to measure quality of life and patient satisfaction after centralization.

Robot-assisted simple prostatectomy versus open simple prostatectomy: a single-center comparison.

PURPOSE: Open simple prostatectomy (OSP) is a standard surgical technique for patients with benign prostatic hyperplasia with prostate size larger than 80 ml. As a minimally invasive approach, robot-assisted simple prostatectomy (RASP) emerged as a feasible surgical alternative. Currently, there are no definite recommendations for the standard use of RASP. Therefore, we aimed at investigating various clinical outcomes comparing RASP with OSP. METHODS: In this retrospective single-center study, we evaluated clinical data from 103 RASP and 31 OSP patients. Both cohorts were compared regarding different clinical characteristics with and without propensity score matching. To detect independent predictive factors for clinical outcomes, multivariate logistic regression analysis was performed. RESULTS: Robot-assisted simple prostatectomy patients demonstrated a lower estimated blood loss and need for postoperative blood transfusions as well as less postoperative complications. OSP had a shorter operative time (125 min vs. 182 min) longer hospital stay (11 days vs. 9 days) and longer time to catheter removal (8 days vs. 6 days). In the multivariate analysis, RASP was identified as an independent predictor for longer operative time, lower estimated blood loss, shorter length of hospital stay, shorter time to catheter removal, less postoperative complications and blood transfusions. CONCLUSION: Robot-assisted simple prostatectomy is a safe alternative to OSP with less perioperative and postoperative morbidity. Whether OSP (shorter operative time) or RASP (shorter length of hospital stay) has a more favorable economic impact depends on the particular conditions of different health care systems. Further prospective comparative research is warranted to define the value of RASP in the current surgical management of benign prostatic hyperplasia.

Contemporary role of palliative cystoprostatectomy or pelvic exenteration in advanced symptomatic prostate cancer.

OBJECTIVE: To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC). PATIENTS AND METHODS: Twenty-five men with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien-Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis. RESULTS: Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (p = 0.2). Median follow-up was 15 months (range 3-41) for the entire cohort with a median survival of 15 months (95% CI 10.1-19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62-17.23, p = 0.164). CONCLUSION: Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome.

The PT2D-Score: a novel tool to predict complications and economic outcome after radical cystectomy.

BACKGROUND: Radical cystectomy (RC) has a high morbidity and leads to a significant socio-economic burden. We aimed to investigate pre-, intra-, and post-operative variables to create a novel score predicting both post-operative clinical (complications) and economic (length of hospital stay) outcome after RC. METHODS: We retrospectively evaluated clinical and histopathological data of 317 patients after RC. We performed univariate and multivariate logistic regression analyses to identify variables associated with post-operative clinical (30-day morbidity according to Clavien-Dindo complications) and economic (length of hospital stay) outcome. RESULTS: In multivariate analysis, a high number of intraoperative transfusions (T) of packed red blood cells predicted major complications (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.10-2.58, p = 0.017), preoperative potassium (P) level predicted three or more complications (OR for high preoperative potassium 0.71, 95% CI 0.52-0.98, p = 0.037), and high drain (D) loss on post-operative day 1 predicted a longer hospital stay ≥ 22 days (OR 1.57, 95% CI 1.04-2.35, p = 0.003). The PT2D-Score was able to predict three or more complications (area under the curve: 0.70, 95% CI 0.61-0.78, p < 0.001) and a hospital stay of ≥ 22 days in patients after radical cystectomy (area under the curve: 0.63, 95% confidence interval 0.53-0.72, p = 0.012). CONCLUSIONS: The novel PT2D-Score combines preoperative potassium level, intraoperative blood transfusion, and post-operative drain loss to predict both clinical (30-day morbidity) and economic (length of hospital stay) outcome for patients undergoing RC. After validation in a larger cohort, the novel PT2D-Score might serve as an additional criterion to identify patients for intensified monitoring after RC.

Prognostic models for predicting overall survival in metastatic castration-resistant prostate cancer: a systematic review.

PURPOSE: Prognostic models are developed to estimate the probability of the occurrence of future outcomes incorporating multiple variables. We aimed to identify and summarize existing multivariable prognostic models developed for predicting overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: The protocol was prospectively registered (CRD42017064448). We systematically searched Medline and reference lists up to May 2018 and included experimental and observational studies, which developed and/or internally validated prognostic models for mCRPC patients and were further externally validated or updated. The outcome of interest was overall survival. Two authors independently performed literature screening and quality assessment. RESULTS: We included 12 studies that developed models including 8750 patients aged 42-95 years. Models included 4-11 predictor variables, mostly hemoglobin, baseline PSA, alkaline phosphatase, performance status, and lactate dehydrogenase. Very few incorporated Gleason score. Two models included predictors related to docetaxel and mitoxantrone treatments. Model performance after internal validation showed similar discrimination power ranging from 0.62 to 0.73. Overall survival models were mainly constructed as nomograms or risk groups/score. Two models obtained an overall judgment of low risk of bias. CONCLUSIONS: Most models were not suitable for clinical use due to methodological shortcomings and lack of external validation. Further external validation and/or model updating is required to increase prognostic accuracy and clinical applicability prior to their incorporation in clinical practice as a useful tool in patient management.

Trend analysis and regional tumor incidence in Germany for testicular cancer between 2003 and 2014.

BACKGROUND: Testicular germ cell tumor (TGCT) is one the most common solid tumors in men between the age of 15 and 35 with an overall incidence rate of 1-1.5 %. Epidemiologic studies have demonstrated different incidence patterns in western civilized countries with overall rising incidence trends. OBJECTIVE: To analyze differences in regional tumor incidence rates for TGCT and perform a trend analysis for TGCT between 2003 and 2014 in Germany. MATERIAL AND METHODS: TGCT cases in Germany which were diagnosed between 2003 and 2014 were provided by the Robert-Koch-Institute, Berlin. For statistical analysis, cluster and spatial scan tests according to Kulldorff were used for cases with seminoma and non-seminoma. Results are presented in administrative districts and graphically illustrated. We performed a trend-analysis in order to evaluate age-adjusted incidence trends in Germany. Tests were two-sided with a level of significance of α=0.05. RESULTS: In total we included 35,066 patients. Overall, 22,634 cases had newly diagnosed seminoma and 12,432 were diagnosed as non-seminoma. Maximum incidence of seminoma and non-seminoma was observed for age-group 38-40 years and 26-28 years, respectively. No second peak for the incidences of seminoma and non-seminoma with respect to age were observed. Cluster analysis revealed areas with high and low incidence rates as well as slightly different spatial distribution in Germany between seminoma and nonseminoma. Furthermore, there was no significant increase in age-adjusted incidence rates over the reviewed time period in both cohorts. DISCUSSION: In this study differences in reginal tumor incidence rates for seminoma and non-seminoma are reported with both tumor entities revealing distinct clusters. Furthermore, tumor incidence trends for seminoma and nonseminoma between 2003 and 2014 were stable which might indicate the beginning of a plateau phase for TGCT incidence rates in Germany. CONCLUSION: In this analysis we were able to identify regions with significantly higher tumor incidence rates for both seminoma and non-seminoma which were specific for these two subtypes. Furthermore, trend analysis revealed a steady incidence rate for testicular cancer in Germany.

[Natural language processing in radiology : Neither trivial nor impossible]. / Natural Language Processing in der Radiologie : Weder trivial noch unerreichbare Magie.

BACKGROUND: The need for application expertise in natural language processing (NLP) is increasing in radiology. This way, in a complementary fashion to structured reporting using templates, the necessary database for quality assurance and continuous process optimization can be generated. OBJECTIVE: Possibilities and challenges of the application of NLP from the radiology point of view are explained. MATERIALS AND METHODS: The requirements and expectations for NLP systems are identified and demonstrated using a case study. RESULTS: For an effective use of this technology, NLP tasks for the interpretation of text using RadLex, an intuitive usage and feedback option as well as transparent quality of the NLP results are important. DISCUSSION: Using suitable NLP systems, targeted information can be extracted from large amounts of free text with manageable manual effort and high quality.

Substantial utilization of Facebook, Twitter, YouTube, and Instagram in the prostate cancer community.

PURPOSE: To measure the usage rate of social media (SoMe) resources in the prostate cancer community, we performed a comprehensive quantitative and qualitative assessment of SoMe activity on the topic of PCa on the four most frequented platforms. METHODS: We scanned the SoMe platforms Facebook, Twitter, YouTube, and Instagram for "prostate cancer" as a cross-sectional analysis or during a defined time period. Sources were included if their communication centered on PCa by title and content. We assessed activity measurements for each SoMe source and classified the sources into six functional categories. RESULTS: We identified 99 PCa-related Facebook groups that amassed 31,262 members and 90 Facebook pages with 283,996 "likes". On YouTube, we found 536 PCa videos accounting for 43,966,634 views, 52,655 likes, 8597 dislikes, and 12,393 comments. During a 1-year time period, 32,537 users generated 110,971 tweets on #ProstateCancer on Twitter, providing over 544 million impressions. During a 1-month time period, 638 contributors posted 1081 posts on Instagram, generating over 22,000 likes and 4,748,159 impressions. Among six functional categories, general information/support dominated the SoMe landscape on all SoMe platforms. CONCLUSION: SoMe activity on the topic of PCa on the four most frequented platforms is high. Facebook groups, YouTube videos, and Twitter tweets are mainly used for giving general information on PCa and education. High SoMe utilization in the PCa community underlines its future role for communication of PCa.

[Systemic immune checkpoint inhibition : A promising treatment for urological tumors?] / Systemische Immuncheckpoint-Inhibition : Eine vielversprechende Therapie urologischer Tumoren?

Improved understanding of the immunomodulatory interactions between tumor cells and immune cells has led to new and promising systemic therapeutic approaches in the first- and second-line therapy of urological tumors. Particularly in the case of urothelial carcinoma, for the first time in 20 years, checkpoint inhibitors (PD-1 and PDL-1 inhibitors) provide well-tolerated therapy that achieves response rates of >20% that can be sustained over the long term. This review explains the approach of immunotherapy and summarizes the current phase III clinical situation on urothelial carcinoma and renal cell carcinoma. The current immunomodulatory therapeutic approaches for prostate cancer are discussed. Finally, we highlight new immunomodulatory therapeutic approaches in basic research.

[Splice variant AR-V7 : Is it time for its routine use as a predictive marker in prostate cancer?] / Spleißvariante AR-V7 : Ist die Zeit reif für ihre routinemäßige Anwendung als prädiktiver Marker beim Prostatakarzinom?

Androgen receptor splice variants (AR-Vs), if overexpressed, lack the ligand-binding domain conveying metastasized castration-resistant prostate cancer with a therapeutic resistance to androgen receptor signaling inhibitors. Particularly AR-V7 has recently been proposed as a potential predictive biomarker to identify patients who would probably benefit most from taxane-based cytotoxic treatment. Several assays to substantiate or quantify AR-V7 expression have recently been proposed. However, their broad clinical value is still debatable. This contemporary update aims to shed light on the current evidence in the field and draw distinct practical conclusions.

Feasibility and safety of augmented reality-assisted urological surgery using smartglass.

PURPOSE: To assess the feasibility, safety and usefulness of augmented reality-assisted urological surgery using smartglass (SG). METHODS: Seven urological surgeons (3 board urologists and 4 urology residents) performed augmented reality-assisted urological surgery using SG for 10 different types of operations and a total of 31 urological operations. Feasibility was assessed using technical metadata (number of photographs taken/number of videos recorded/video time recorded) and structured interviews with the urologists on their use of SG. Safety was evaluated by recording complications and grading according to the Clavien-Dindo classification. Usefulness of SG for urological surgery was queried in structured interviews and in a survey. RESULTS: The implementation of SG use during urological surgery was feasible with no intrinsic (technical defect) or extrinsic (inability to control the SG function) obstacles being observed. SG use was safe as no grade 3-5 complications occurred for the series of 31 urological surgeries of different complexities. Technical applications of SG included taking photographs/recording videos for teaching and documentation, hands-free teleconsultation, reviewing patients' medical records and images and searching the internet for health information. Overall usefulness of SG for urological surgery was rated as very high by 43 % and high by 29 % of surgeons. CONCLUSIONS: Augmented reality-assisted urological surgery using SG is both feasible and safe and also provides several useful functions for urological surgeons. Further developments and investigations are required in the near future to harvest the great potential of this exciting technology for urological surgery.

[Urolithiasis 2016 : Reliable, effective and low radiation exposure]. / Steindiagnostik 2016 : Zuverlässig, effektiv und strahlungsarm.

BACKGROUND: Urolithiasis is a widespread disease. Diagnostic imaging plays an important role in the evaluation and management of patients with suspected urolithiasis. Furthermore, modern imaging methods may provide information on stone location, size, fragility and composition aiding the urologist to determine the appropriate treatment modality. PURPOSE: Based on the current literature and guidelines, this review reports on the various new and established diagnostic imaging modalities. RESULTS: Ultrasound should always be the initial imaging modality. Following ultrasound, noncontrast CT-principally using a low-dose protocol-is the imaging modality of choice in the evaluation of patients with acute flank pain and suspected urolithiasis. New imaging modalities like dual energy CT, Uro Dyna CT and digital tomosynthesis are currently under investigation but not yet part of daily clinical practice. Magnetic resonance imaging can be used to detect obstruction caused by urinary stones but is not a first-line imaging modality.

[Prevention of postprostatectomy incontinence: etiology and risk factors]. / Verhinderung der Postprostatektomieinkontinenz: Ätiologie und Risikofaktoren.

The prevention of postprostatectomy incontinence has always been a challenge for urologists. Improved understanding of male continence and changes in pelvic anatomy after radical prostatectomy and the implementation of new surgical techniques raised hope of reduced incontinence rates. Despite using the full potential of continence-sparing techniques and atraumatic robot-assisted surgery, postprostatectomy incontinence still occurs in 5-20 % of cases. Recently published data showed a trend of improved early return to continence using anterior suspension or posterior reconstruction in robot-assisted prostatectomy. Postprostatectomy incontinence has a negative impact on quality of life and causes high costs of treatment. Therefore, further research in the amelioration of postoperative continence is mandatory.