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.

[Virtual and augmented reality in urology]. / Virtual und Augmented Reality in der Urologie.

Although continuous technological developments have optimized and evolved medical care throughout time, these technologies were mostly still comprehensible for users. Driven by immense financial efforts, modern innovative products and technical solutions are transforming medicine today and will do so even more in the future: virtual and augmented reality. This review critically summarizes the current literature and future uses of virtual and augmented reality in the field of urology.