Expression patterns of the immune checkpoint ligand CD276 in urothelial carcinoma.

BACKGROUND: CD276 is an immune checkpoint molecule. Elevated CD276 expression by urothelial carcinoma is associated with poor prognosis, but little is known about its expression across different tumor stages. We therefore investigated CD276 expression in bladder cancer (BC) cells and in tissue samples of BC stages from pT2 to pT4. METHODS: CD276 expression was explored in 4 urothelial cancer cell lines and 4 primary normal urothelial cell populations by quantitative RT-PCR, Western blot and flow cytometry. CD276 was investigated in bladder tumors from 98 patients by immunohistochemistry using a score (0-300) incorporating both, staining intensity and area of CD276 staining. Normal appearing urothelium in the bladder of the same patients served as controls. RESULTS: The urothelial carcinoma cell lines expressed significantly higher levels of CD276 on transcript (p < 0.006), total protein levels (p < 0.005), and on the cell surface (p < 0.02) when compared to normal urothelial cells. In pT2-T4 tumor tissue samples, CD276 was overexpressed (median score 185) when compared to corresponding healthy tissues from the same patients (median score 50; p < 0.001). No significant differences in CD276 expression were recorded in late, locally advanced ≥ pT3a tumors (median score 185) versus organ-confined < pT3a tumors (median score 190), but it was significantly lower in the normal urothelial tissue associated with ≥ pT3a tumors (median score 40) versus < pT3a tumors (median score 80; p < 0.05). CONCLUSION: CD276 expression is significantly elevated in urothelial carcinoma cells in all stages but varies between individuals considerably. Reduced CD276 expression in normal urothelial cells may imply that these cells would be protected from CD276-mediated immuno therapies.

68Ga-PSMA-PET/CT-directed IGRT/SBRT for oligometastases of recurrent prostate cancer after initial surgery.

Background: We evaluated efficacy and toxicity of 68Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (SBRT/IGRT) for oligometastases of prostate cancer recurrences after previous surgery.Methods: Nineteen patients were analyzed within a prospective PET-registry study (064/2013BO1) and retrospectively analyzed (807/2017BO2) fulfilling the following inclusion criteria: biochemical recurrence after radical prostatectomy, ≤five 68Ga-PSMA-PET/CT positive lesions. Biochemical control was evaluated with EORTC (European Organization for Research and Treatment of Cancer)- and Phenix-definitions. Toxicity was scored according to CTCAE-criteria v. 4.03.Results: A total of 38 oligometastases (19 patients, 2 with re-treatment) were treated with SBRT/IGRT from October 2014 to July 2017. 68Ga-PSMA-PET/CT-positive lesions were detected on average 39 months (5-139) after prostatectomy (pT2b-3b pN0-1 cM0). Mean PSA (Prostate-specific antigen)-level at time of imaging reached 2.2 ng/mL (range 0.2-10.1). PET/CT-positive lesions were treated with different fractionation schedules reaching biological equivalent doses (BED) of 116.7-230.0 Gy. Concomitant androgen deprivation therapy (ADT) was given in seven patients. After a median follow-up of 17 months (4-42) all patients were alive. Estimated 1-year PSA- control (n = 19) reached 80.8% (Phenix) and 67.5% (EORTC). A PSA-decline (≥50%) was detected in 16/19 patients after radiotherapy. Higher graded G3+-acute toxicity did not occur. Temporary late G3-proctitis was detected in one patient.Conclusions: Reaching of nadir ≤0.1 or 0.2 ng/mL was associated by improved DMFS (distant metastases free survival) and could serve as a surrogate endpoint for RT of oligometastases after initial prostatectomy. Short term effects of 68Ga-PSMA-PET/CT-based ablative radiotherapy for oligometastases demonstrated an acceptable toxicity profile and favorable biochemical response.

Rare and changeable as a chameleon: paraneoplastic syndromes in renal cell carcinoma.

INTRODUCTION: Paraneoplastic syndromes (PNS) in renal cell carcinoma (RCC) are important to be recognized by the treating physician, because they may lead to diagnosis of underlying malignant disease. On the other hand, PNS may dominate the clinical picture and can hide the true disorder like a chameleon. When realized, a PNS can be used as a 'neoplastic tumour marker', especially in case of recurrence. Their occurrence can even be linked to prognosis of disease. METHODS: A PubMed search combining the MeSH terms renal cell carcinoma and paraneoplastic syndrome was executed in April 2015. All hits concerning these MeSH terms have been taken into account when writing this review. RESULTS: There is a big gap between reporting and incidence of paraneoplastic syndromes in renal cell carcinoma. Most of the articles in Medline are case reports and reviews of research done in the 1950s-1990s. One problem is that a clear definition of a paraneoplastic syndrome is still lacking. The most important PNS in RCC are hypercalcemia. It is important that PNS are not only arising in advanced stages of renal cell carcinoma; in contrast, a PNS can often be the first symptom of RCC. CONCLUSION: Paraneoplastic syndromes are often unrecognized but are important biomarkers in RCC. Further research into the underlying pathomechanisms of PNS may improve our understanding of the RCC tumour biology and is urgently needed.

First report of robot-assisted transperineal fusion versus off-target biopsy in patients undergoing repeat prostate biopsy.

PURPOSE: To clarify the value of targeted versus off-target biopsies in men with a suspicion of prostate cancer (PC) and a visible lesion in multi-parametric magnetic resonance imaging (mpMRI) using transperineal robot-assisted biopsy. METHODS: Fifty-five consecutive men with one non-palpable suspicious lesion in mpMRI after negative 12-core transrectal ultrasound-guided biopsy were enrolled in 2014-2015. Lesions were scored using the Prostate Imaging Reporting and Data System. A robot-assisted system was utilized to collect four robot-assisted targeted transperineal biopsy cores (RA-TB) within the lesion using mpMRI-TRUS elastic fusion. Untargeted transperineal 14-core biopsy was performed only outside the lesion (RA-UB). Histological grade was compared in biopsies and available prostatectomy specimens. RESULTS: Overall, 34 of 55 patients (62%) were diagnosed with PC based on biopsy. 85% of cancers were clinically significant PC (csPC) defined as GS ≥ 7. 85% of biopsy-proven cancers were detected with RA-TB alone. RA-UB identified only one additional patient with csPC and lead to upgrading in five biopsy cases (14.7%). Pathological evaluation of 14 prostatectomy specimens showed upgrading in 2 patients (14.3%), while all other patients were correctly classified by RA-TB without need of additional RA-UB. Mean procedure duration was 43 (±6) min, and only minor complications according to Clavien-Dindo were recorded during 30-day follow-up. CONCLUSIONS: This is the first report of transperineal robot-assisted elastic mpMRI-TRUS fusion biopsy. RA-TB of positive MR lesions enabled reliable detection of csPC, while RA-UB in MRI-negative regions is of minor importance.

Prostate cancer gene 3 (PCA3) is of additional predictive value in patients with PI-RADS grade III (intermediate) lesions in the MR-guided re-biopsy setting for prostate cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) improves diagnostic accuracy in re-biopsies of men with prostate cancer (PC) suspicion, but predictive value is limited despite the use of the new Prostate Imaging Reporting and Data System (PI-RADS). Prognostic value of the PC-specific biomarker prostate cancer gene 3 (PCA3) added to the PI-RADS score was evaluated. METHODS: The study was a retrospective analysis of the institutional database for men with MR-guided biopsy (MR-GB) for suspicious lesion in mpMRI and who had an additional pre-MR-GB PCA3 testing for ongoing PC suspicion. All men had ≥ 1 negative ultrasound GB. Lesions were retrospectively scored by PI-RADS in three MRI sequences (T2w, DCE, and DWI). PCA3 was analyzed with cutoffs of 25 and 35. The prognostic value of mpMRI and PCA3 and the additional value of both were explored. RESULTS: Tumor detection rate (49 men, mean PSA 10 ng/ml, lesion size 40 mm(2)) was 45 % (22/49 patients). In the subgroup of PI-RADS IV°, 17/17 patients had PC; in PI-RADS III° (intermediate) 5/15 had PC, and all 5 had a PCA3 > 35. PCA3 > 35 had no additional prognostic value in the whole cohort. Out of the 10/15 PC negative patients (PI-RADS III°), PCA3 was < 35 in 6. The inclusion of PCA3 value in PI-RADS III° patients improved predictive accuracy to 91.8 %. CONCLUSION: MpMRI and subsequent grading to PI-RADS significantly improves PC detection in the re-biopsy setting. The diagnostic uncertainty in the PI-RADS intermediate group can be ameliorated by the addition of PCA3 cutoff of 35 to avoid potential unnecessary biopsies.

Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended follow-up from the phase III randomised CheckMate 9ER trial.

BACKGROUND: Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score. PATIENTS AND METHODS: Patients with treatment-naïve aRCC received NIVO 240 mg every 2 weeks plus CABO 40 mg once daily or SUN 50 mg for 4 weeks (6-week cycles), until disease progression/unacceptable toxicity (maximum NIVO treatment, 2 years). Primary endpoint was progression-free survival (PFS) per blinded independent central review (BICR). Secondary endpoints were overall survival (OS), objective response rate (ORR) per BICR, and safety and tolerability. RESULTS: Overall, 323 patients were randomised to NIVO + CABO and 328 to SUN. Median PFS was improved with NIVO + CABO versus SUN [16.6 versus 8.4 months; hazard ratio (HR) 0.59; 95% confidence interval (CI) 0.49-0.71]; median OS favoured NIVO + CABO versus SUN (49.5 versus 35.5 months; HR 0.70; 95% CI 0.56-0.87). ORR (95% CI) was higher with NIVO + CABO versus SUN [56% (50% to 62%) versus 28% (23% to 33%)]; 13% versus 5% of patients achieved complete response, and median duration of response was 22.1 months versus 16.1 months, respectively. PFS and OS favoured NIVO + CABO over SUN across intermediate, poor and intermediate/poor IMDC risk subgroups; higher ORR and complete response rates were seen with NIVO + CABO versus SUN regardless of IMDC risk subgroup. Any-grade (grade ≥3) treatment-related adverse events occurred in 97% (67%) versus 93% (55%) of patients treated with NIVO + CABO versus SUN. CONCLUSIONS: After extended follow-up, NIVO + CABO maintained survival and response benefits; safety remained consistent with previous follow-ups. These results continue to support NIVO + CABO as a first-line treatment for aRCC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03141177.

Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group.

BACKGROUND: The treatment of testicular intraepithelial neoplasia (TIN), the progenitor of testicular germ cell tumours (GCTs), is based on little data. PATIENTS AND METHODS: Two hundred and twenty-eight GCT patients with contralateral TIN were retrospectively enrolled. Ten had surveillance, 122 radiotherapy to testis with 18-20 Gy, 30 cisplatin-based chemotherapy (two cycles), 51 chemotherapy (three cycles), and 15 carboplatin. The study end point was a malignant event (ME), defined as detection of TIN upon control biopsy or occurrence of a second GCT. The Secondary end point was hypogonadism during follow-up. RESULTS: Numbers, proportions of ME, and median event-free survival (EFS) times were: radiotherapy N = 3, 2.5%, 11.08 years; chemotherapy (two cycles) N = 15, 50%, 3.0 years; chemotherapy (three cycles) N = 12, 23.5%, 9.83 years; carboplatin N = 10, 66%, 0.9 years; surveillance N = 5, 50%, 7.08 years. EFS is significantly different among the groups. Hypogonadism rates were in radiotherapy patients 30.8%, chemotherapy (two cycles) 13%, chemotherapy (three cycles) 17.8%, carboplatin 40%, surveillance 40%. CONCLUSIONS: Local radiotherapy is highly efficacious in curing TIN. Chemotherapy is significantly less effective and the cure rates are dose-dependent. Though hypogonadism occurs in one-third of patients, radiotherapy with 20 Gy remains the standard management of TIN.

Myoglobin expression in renal cell carcinoma is regulated by hypoxia.

Myoglobin is a member of the hemoprotein superfamily, which additionally includes hemoglobin, neuroglobin and cytoglobin. Cytoplasmic localized myoglobin functions as a radical scavenger and prevents hypoxia. Besides muscle tissue MB expression could also be observed in other tissues as well as in different types of cancer. For the correlation between the expression of myoglobin, hypoxia-inducible-factor-1α, and capillary density tissue of 86 different renal cell carcinomas were immunohistochemically stained with myoglobin-specific and hypoxia-inducible-factor-1α-specific antibodies as well as with CD31 antibody. Four different renal carcinoma cell lines were cultivated under hypoxic conditions and the expression of myoglobin and hypoxia-inducible-factor-1α was evaluated by real-time PCR and Western blot. Renal cell carcinoma including clear cell, papillary, and chromophobe subtypes expressed myoglobin with an inverse relationship to capillary density being highly significant for clear cell renal cell carcinoma. For hypoxia-inducible-factor-1α a significant correlation with capillary density could also be observed in clear cell RCC. In renal cell carcinoma cell lines hypoxia induced a significant increase of myoglobin expression up to 62 fold, whereas hypoxia-inducible-factor-1α only increased up to 5 fold. The PCR results of myoglobin expression could be confirmed by Western blot. Myoglobin seems to be a sensitive marker for hypovascularized tumor entities especially during the early phase of hypoxia. Such neoplasias may benefit from an antiangiogenic therapy.

Different surgical approaches for stress urinary incontinence in women.

Stress urinary incontinence (SUI) constitutes involuntary voiding as a consequence of rising intra-abdominal pressure caused by sphincter weakness. In recent years studies were published according to surgical SUI management evaluating and comparing therapy options and outcomes. Therapy options were evaluated using a Medline search, including only publications in English between 2000-2012. Key words used were: SUI, conservative and surgical treatment, midurethral sling, colposuspension. Surgical treatment options demonstrate significantly better results than conservative treatment. MUS demonstrate better subjective and objective cure rates than colposuspension; it is less invasive and more cost-effective. First line SUI therapy such as RP MUS and TVT seem to be favored when compared to transobturator techniques. Retropubic and transobturator MUS showed equivalent objective and subjective success rates. Open colposuspension is an effective treatment possibility for recurrent SUI after failed MUS. TVT, compared with other MUS, seems to show slightly better cure rates. but perioperative complications appear to be similar. Long-term results (>10 years) of repeated SUI surgery showed that the Burch procedure had the lowest 9-year cumulative incidence of repeat SUI surgery. Mini-sling techniques may be underestimated but long-time results are pending and closer monitoring of the adverse event profile must be carried out. MUS are first choice in the treatment of SUI, of which TVT, has the best cure rate. Colpussupension continues to have its place in recurrent SUI. The new mini-MUS needs a longer follow-up for final evaluation.

Modulation of Wnt and Hedgehog signaling pathways is linked to retinoic acid-induced amelioration of chronic allograft dysfunction.

Chronic renal allograft damage (CAD) is manifested by a smoldering inflammatory process that leads to transplant glomerulopathy, diffuse interstitial fibrosis and tubular atrophy with loss of tubular structures. Using a Fischer 344 (RT1lvl) to Lewis (RT1l) rat renal allograft model, transcriptomic profiling and pathway mapping, we have previously shown that dynamic dysregulation of the Wnt signaling pathways may underlie progressive CAD. Retinoic acid, an important regulator of differentiation during vertebrate embryogenesis, can moderate the damage observed in this experimental model of CAD. We show here that subsets of the Hedgehog (Hh) and canonical Wnt signaling pathways are linked to the pathophysiology of progressive fibrosis, loss of cilia in epithelia and chronic dysfunction. Oral treatment with 13cis retinoic acid (13cRA) was found to selectively ameliorate the dysregulation of the Hh and canonical Wnt pathways associated with CAD, and lead to a general preservation of cilial structures. Interplay between these pathways helps explain the therapeutic effects of retinoic acid treatment in CAD, and suggests future targets for moderating chronic fibrosing organ damage.

Kidney-specific cadherin correlates with the ontogenetic origin of renal cell carcinoma subtypes: an indicator of a malignant potential?

INTRODUCTION AND OBJECTIVES: To evaluate retrospectively kidney-specific cadherin (Ksp-cad) expression in renal cell carcinoma (RCC) subtypes and oncocytoma in correlation with its ontogenetic origin of distal and proximal tubules and to correlate Ksp-cad expression with tumour characteristics. MATERIALS AND METHODS: Membranous and cytoplasmic expression of Ksp-cad was determined in 40 clear cell (ccRCC), 25 papillary (pRCC), 19 chromophobe carcinomas (chRCC), 27 oncocytomas (oncocytomas) (n = 111) and 32 benign kidney parenchyma specimens separated in distal tubules (DT) and proximal tubules (PT) by immunohistochemistry using tissue microarray technique. Staining intensity was quantified as a score ranging from 0 to 12. Comparison of data and correlation with tumour characteristics were done by Wilcoxon/Kruskal-Wallis tests (post hoc Tukey-Kramer analysis). RESULTS: In benign renal tissue, membranous and cytoplasmic expression of Ksp-cad in the DT was significantly higher than that in the PT (12.0 ± 0 vs. 5.2 ± 0.3 and 6.3 ± 0.5 vs. 0.0 ± 0.0, respectively; (P < 0.05)). Membranous KSP-cad expression was significantly higher in chRCC (5.2 ± 0.8) and oncocytomas (3.7 ± 0.4) than that in ccRCC (0.8 ± 0.2) and pRCC (1.4 ± 0.4; P < 0.05), while expression between oncocytomas and chRCC did not differ significantly. In RCC, Ksp-cad expression was significantly associated with higher T stage and the occurrence of synchronous metastasis (P < 0.05). Higher N stages and grading tended to correlate with a lower Ksp-cad expression. CONCLUSIONS: In this cohort, the origin of tumour subtypes-chRCC and oncocytomas develop from DT and ccRCC and pRCC from PT cells-is mirrored by the respective Ksp-cad expression. This raises the question whether DT-derived tumours have a less malignant potential than PT-derived tumours.

Akt signalling parameters are different in oncocytomas compared to renal cell carcinoma.

PURPOSE: Renal oncocytomas are assigned as benign tumours, and their detailed molecular mechanism is poorly characterised. Activation of the PKB/Akt pathway is assumed to contribute to the pathogenesis and progression of malignant disease. For oncocytomas, hardly any data are available for Akt signalling parameters. Aim of the present work was to determine the alterations of Akt parameters PTEN, phosphorylated Akt (p-Akt) and p27(Kip1) in oncocytoma to better understand the dedifferentiation of renal tumours. METHODS: By tissue microarray analysis 15 oncocytoma, 18 clear cell renal cell carcinoma (ccRCC) and the corresponding benign tissue were investigated. Significant expression differences between PTEN, p-Akt and p27(Kip1) were determined by immunohistochemistry using One-way ANOVA with all pairs Tukey-Kramer as post hoc analyses. To investigate Akt parameter interactions in the oncocytoma, linear regression analyses were performed. RESULTS: Expression of all proteins was significantly different between the groups and in all groups the lowest for oncocytoma: PTEN: 32.9 ± 13.0 versus 75.5 ± 8.0 versus 123.7 ± 8.8; p < 0.001 for oncocytoma, benign parenchyma and ccRCC and 2.7 ± 1.2 versus 40.8 ± 9.5 versus 143.6 ± 12.2; p < 0.001 for p27(Kip1). p-Akt expression was significantly different between oncocytoma and ccRCC (67.3 ± 15.7 vs. 144.0 ± 26.6; p < 0.05). CONCLUSION: All three investigated parameters were the lowest in oncocytoma when compared to ccRCC. Expression of PTEN and p27(Kip1) seems to be exceedingly associated with malignant conditions of ccRCC. These findings might contribute to the understanding of tumorous signalling of the PKB/Akt axis in renal tumours.

[BCG-induced (bacillus Calmette-Guérin) abdominal granulomatosis after occult bladder perforation]. / Intraabdominelle BCG-Granulomatose (Bacillus Calmette-Guérin) nach okkulter Blasenperforation.

We present the case of a 57-year-old man who developed an intraperitoneal bladder fistula with BCG-induced (bacillus Calmette-Guérin) abdominal granulomatosis after transurethral resection of a papillary non-muscle invasive bladder cancer and subsequent BCG-instillation therapy. The bladder fistula was eliminated surgically. The detection of Mycobacterium tuberculosis in the operative sample drawings as well as the histological detection of BCG-granuloma led to specific treatment and a report to the responsible health department.

Wnt pathway regulation in chronic renal allograft damage.

The Wnt signaling pathway, linked to development, has been proposed to be recapitulated during the progressive damage associated with chronic organ failure. Chronic allograft damage following kidney transplantation is characterized by progressive fibrosis and a smoldering inflammatory infiltrate. A modified, Fischer 344 (RT1(lvl)) to Lewis (RT1(l)) rat renal allograft model that reiterates many of the major pathophysiologic processes seen in patients with chronic allograft failure was used to study the progressive disease phenotype and specific gene product expression by immunohistochemistry and transcriptomic profiling. Central components of the Tgfb, canonical Wnt and Wnt-Ca2+ signaling pathways were significantly altered with the development of chronic damage. In the canonical Wnt pathway, Wnt3, Lef1 and Tcf1 showed differential regulation. Target genes Fn1, Cd44, Mmp7 and Nos2 were upregulated and associated with the progression of renal damage. Changes in the Wnt-Ca2+ pathway were evidenced by increased expression of Wnt6, Wnt7a, protein kinase C, Cam Kinase II and Nfat transcription factors and the target gene vimentin. No evidence for alterations in the Wnt planar cell polarity (PCP) pathway was detected. Overall results suggest cross talk between the Wnt and Tgfb signaling pathways during allograft inflammatory damage and present potential targets for therapeutic intervention.

Economic aspects of bladder cancer: what are the benefits and costs?

OBJECTIVE: Bladder cancer (BC) has the highest lifetime treatment costs per patient of all cancers. The high recurrence rate and ongoing invasive monitoring requirement are the key contributors to the economic and human toll of this disease. The purpose of this paper was to utilize the recent literature to identify opportunities for improving the benefits and costs of BC care. METHODS: A PubMed search was performed of recent publications concerning (BC) cost-effectiveness. We reviewed studies, reviews, opinion papers and cost-effectiveness analyses, focusing primarily on non-muscle-invasive bladder cancer (Ta/T1; NMIBC). RESULTS: New diagnostic tools such as urine markers may assist in more cost-effectively detecting BC at an earlier stage, however, these markers cannot replace the cystoscopy, which is the current standard of care. A photodynamic diagnostic tool (PDD) using hexylaminolevulinate (Hexvix) enhances tumor visibility and improves transurethral resection of bladder cancer (TURB) results, potentially reducing recurrence rates and lowering treatment costs. While the importance of BC research has been acknowledged, research investment has been continuously reduced during the last 5 years. CONCLUSIONS: The economic burden of BC is well-characterized in the literature. This study suggests that new technologies (i.e., urine-based tests, PDD) and therapeutic regimes (intravesical chemotherapy, adjuvant immunotherapy) have significant potential to improve the diagnosis, treatment and on-going monitoring of BC patients, with potential improvements in clinical outcomes and concurrent cost-savings. A renewed interest and investment in BC research are required to ensure future advancements.

[Surgical reconstruction of the ureter]. / Rekonstruktionsmöglichkeiten des Harnleiters.

Defects in ureteral continuity and function can originate from various etiologies such as stricture, radiotherapy, tuberculosis, tumor, trauma or perforation due to iatrogenic injury. The surgical options for the management of ureteral defects are complex and depend on the location of the defect. The aim of the surgical management of ureteral stricture is the reconstruction of an anti-refluxive and nonobstructive flow of urine to preserve kidney function. There are numerous possibilities for the reconstruction of ureteral defects ranging from ureteroneocystostomy with or without psoas-hitch- or Boari-flap to ileal ureteral replacement. Nearly all these techniques can either be done in open surgery or in a laparoscopically or robotic-assisted manner. The technique of robotic-assisted reconstruction of ureteral defects is challenging but offers a great opportunity. The aim of this article is to provide an overview of current surgical procedures in ureteric reconstruction.

[Active surveillance in prostate cancer]. / Active Surveillance beim Prostatakarzinom.

Prostate cancer remains among the most commonly diagnosed malignancies worldwide in men. In patients with low-risk prostate cancer, the risk of metastasis and mortality is very low; therefore, a tumor surveillance strategy can be used. In patients undergoing active surveillance, curative active therapy is postponed without compromising opportunities for cure until there is evidence of progression or the patient desires active therapy. The aim of active surveillance in prostate cancer patients is to minimize treatment-related toxicity without impairing patient survival. To maintain patients under active surveillance, the following criteria should be met: prostate-specific antigen (PSA) ≤10 ng/ml, Gleason score ≤6, cT1 or cT2a, ≤2 biopsy cores with <50% cancer involvement of every positive core. Follow-up in active surveillance patients is based on repeat biopsy, serial PSA measurements, and digital rectal examination.

[Influence of immunomodulators on urological imaging]. / Einfluss von Immunmodulatoren auf die urologische Bildgebung.

BACKGROUND: Immune checkpoint inhibitors (ICI) have led to great advances in the therapy of metastatic renal cell and urothelial carcinoma. Currently ICI are approved for the first-line therapy of cisplatin-unfit patients (Atezolizumab, Pembrolizumab) and second-line therapy in patients with metastasized urothelial cancer (Atezolizumab, Nivolumab, Pembrolizumab). For the therapy of metastasized RCC, Nivolumab is approved as a second-line therapy and in combination with the CTLA­4 antibody Ipilimumab as a first-line therapy. OBJECTIVES: What does the optimized radiological follow-up and therapy response assessment for ICI, which differ in their pathways from common chemotherapeutics and anti-angiogenetic drugs, look like? What strategies are needed to meet the upcoming challenges concerning interpretation of the acquired images? METHODS: A systematic literature search was carried out for urothelial and renal cell carcinoma. RESULTS: Immune-related response criteria have been introduced to better characterize the imaging changes occurring under ICI, as monitoring response to immunotherapy still relies on RECIST. CONCLUSIONS: To properly identify and predict response after treatment with ICI, additional studies with long-term follow-ups are needed. Because of the growing use of ICI, radiologists and urologist should be familiar with common imaging findings (such as pseudo progress) under immunotherapy to correctly interpret these findings in daily routine.

[Mode of action, new targets and potential biomarkers in modern immunotherapy]. / Wirkmechanismen, neue Angriffspunkte und potentielle Biomarker bei moderner Immuntherapie.

Immune checkpoint inhibitors (ICI) have significantly improved the systemic therapy of metastatic disease in genitourinary malignancies. With the European Medicines Agency (EMA) approval of the antibodies nivolumab and pembrolizumab directed against programmed cell death 1 (PD-1) as well as the PD-L1 antibody atezolizumab, three agents are available for the treatment of metastatic urothelial carcinoma and renal cell carcinoma. This article describes the underlying mode of action of PD-1/PD-L1 blockade and other ICIs to activate the immune system for effective tumor rejection. Future therapeutic strategies are focusing on the combination of ICI with targeted therapies to enhance the immune defense, especially in the local tumor microenvironment. A further clinical need exists for the establishment of biomarkers to predict a therapy response under ICI, in particular for the role of the PD-L1 status. Biomarkers for predicting primary or acquired therapy resistance are also of clinical importance to enable good patient selection for ICI therapy.