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Background Testicular germ cell tumors (GCTs) are aggressive but highly curable tumors. To avoid over/undertreatment, reliable clinical staging of retroperitoneal lymph-node metastasis is necessary. Current clinical guidelines, in their different versions, lack specific recommendations on how to measure lymph-node metastasis. Objective We aimed to assess the practice patterns of German institutions frequently treating testicular cancer for measuring retroperitoneal lymph-node size. Methods An 8‐item survey was distributed among German university hospitals and members of the German Testicular Cancer Study Group. Results In the group of urologists, 54.7% assessed retroperitoneal lymph nodes depending on their short-axis diameter (SAD) (33.3% in any plane, 21.4% in the axial plane), while 45.3% used long-axis diameter (LAD) for the assessment (42.9% in any plane, 2.4% in the axial plane). Moreover, the oncologists mainly assessed lymph-node size based on the SAD (71.4%). Specifically, 42.9% of oncologists assessed the SAD in any plane, while 28.5% measured this dimension in the axial plane. Only 28.6% of oncologists considered the LAD (14.3% in any plane, 14.3% in the axial plane). None of the oncologists and 11.9% of the urologists (n = 5) always performed an MRI for the initial assessment, while for follow-up imaging, the use increased to 36.5% of oncologists and 31% of urologists. Furthermore, only 17% of the urologists, and no oncologists, calculated lymph-node volume in their assessment (p = 0.224). Conclusion Clear and consistent measurement instructions are urgently needed to be present in all guidelines across different specialistic fields involved in testicular cancer management.

Purpose The outcome of radiotherapy (RT) for prostate cancer (PCA) depends on the delivered dose. While the evidence for dose-escalated RT up to 80 gray (Gy) is well established, there have been only few studies examining dose escalation above 80 Gy. We initiated the present study to assess the safety of dose escalation up to 84 Gy. Methods In our retrospective analysis, we included patients who received dose-escalated RT for PCA at our institution between 2016 and 2021. We evaluated acute genitourinary (GU) and gastrointestinal (GI) toxicity as well as late GU and GI toxicity. Results A total of 86 patients could be evaluated, of whom 24 patients had received 80 Gy and 62 patients 84 Gy (35 without pelvic and 27 with pelvic radiotherapy). Regarding acute toxicities, no > grade 2 adverse events occurred. Acute GU/GI toxicity of grade 2 occurred in 12.5%/12.5% of patients treated with 80 Gy, in 25.7%/14.3% of patients treated with 84 Gy to the prostate only, and in 51.9%/12.9% of patients treated with 84 Gy and the pelvis included. Late GU/GI toxicity of grade ≥ 2 occurred in 4.2%/8.3% of patients treated with 80 Gy, in 7.1%/3.6% of patients treated with 84 Gy prostate only, and in 18.2%/0% of patients treated with 84 Gy pelvis included (log-rank test p = 0.358). Conclusion We demonstrated that dose-escalated RT for PCA up to 84 Gy is feasible and safe without a significant increase in acute toxicity. Further follow-up is needed to assess late toxicity and survival.

Before postchemotherapy retroperitoneal lymph node dissection (pcRPLND), in patients with metastasized germ cell tumors (GCTs), those harboring necrosis (NEC) cannot be distinguished from those who have teratoma (TER), resulting in relevant overtreatment, whereas microRNA-371a-3p may be predictive for viable GCT. The purpose of this study was to explore messenger RNA (mRNA) and proteins to distinguish TER from NEC in pcRPLND tissue.The discovery cohort consisted in total of 48 patients, including 16 each with TER, viable GCT, and NEC. Representative areas were microdissected. A NanoString panel and proteomics were used to analyze 770 genes and5000 proteins. The most significantly and differentially expressed combination of both parameters, mRNA and its associated protein, between TER and NEC was validated using immunohistochemistry (IHC) in an independent validation cohort comprising 66 patients who were not part of the discovery cohort.The authors observed that anterior gradient protein 2 homolog (AGR2) and keratin, type I cytoskeletal 19 (KRT19) were significantly differentially expressed in TER versus NEC in mRNA and protein analyses (proteomics). The technical validation using IHC was successful in the same patients. These proteins were further validated by IHC in the independent patient cohort and exhibited significantly higher levels in TER versus NEC (p .0001; area under the curve, 1.0; sensitivity and specificity, 100% each).The current study demonstrated that KRT19 and AGR2 mRNA and protein are overexpressed in TER versus NEC in pcRPLND tissue and might serve as a future diagnostic target to detect TER, for instance, by functional imaging, to avoid overtreatment.The proteins and the corresponding genes called AGR2 and KRT19 can differentiate between teratoma and necrosis in remaining tumor masses after chemotherapy in patients who have metastasized testicular cancer. This may be a way to improve presurgical diagnostics and to reduce the current overtreatment of patients with necrosis only, who could be treated sufficiently by surveillance.

Background and Objective: The usage of permanent thermo-expandable stents and the definitive surgical treatment, like the ileal ureter replacement (IUR), both represent alternatives to repeated endourological stenting of long ureteral strictures.We aimed to assess the long-term outcomes and complications of the IUR compared to the use of Memokath® 051 for ureteral reconstruction.Material and Methods: In the last 10 years, two groups of patients with ureteral strictures (benign or malig-nant) have been followed up retrospectively. The first group presented with ureteral obstruction and was treated with an endoureteral thermo-expandable stent Memokath®, whereas the second group received an IUR as an alternative treatment method. All patients received follow-up examinations on an outpatient basis 3-4 weeks after hospital discharge, annual controls for long-term monitoring, and routine laboratory analysis and imaging of the upper urinary tract. The main outcome measure was the rate of successful upper tract decompression.Results: Mean patient age for the first group was 59 years and 55 years for the second group. In the first group (17 patients, 27 renal units), long-term upper tract decompression was successful in 6 renal units (35%); the remaining patients required auxiliary measures and further interventions. In the second group (27 patients, 32 renal units), upper tract decompression was achieved in 24 (88.8%) patients. Secondary complications occurred in 4 (14.8%) patients. Renal function remained stable in 25 of the 27 patients, and metabolic acidosis was not observed.Conclusion: The IUR is an effective reconstructive measure of the upper urinary tract with a low complication rate and decent long-term functional results. The IUR should be preferred to the Memokath, which can be seen as an alternative niche solution.

Purpose Testicular germ cell tumours (GCTs) represent the most common malignancy in young adult males with two thirds of all cases presenting with clinical stage I (CSI). Active surveillance is the management modality mostly favoured by current guidelines. This systematic review assesses the treatment results in CSI patients concerning recurrence rate and overall survival in non-seminoma (NS) and pure seminoma (SE) resulting from surveillance in comparison to adjuvant strategies. Methods/systematic review We performed a systematic literature review confining the search to most recent studies published 2010–2021 that reported direct comparisons of surveillance to adjuvant management. We searched Medline and the Cochrane Library with additional hand-searching of reference lists to identify relevant studies. Data extraction and quality assessment of included studies were performed with stratification for histology (NS vs. SE) and treatment modalities. The results were tabulated and evaluated with descriptive statistical methods. Results Thirty-four studies met the inclusion criteria. In NS patients relapse rates were 12 to 37%, 0 to 10%, and 0 to 11.8% for surveillance, chemotherapy and for retroperitoneal lymph node dissection (RPLND) while overall survival rates were 90.7−100%, 91.7−100%, and 97−99.1%, respectively. In SE CSI, relapse rates were 0−22.3%, 0−5%, and 0−12.5% for surveillance, radiotherapy, chemotherapy, while overall survival rates were 84.1−98.7%, 83.5−100%, and 92.3−100%, respectively. Conclusion In both histologic subgroups, active surveillance offers almost identical overall survival as adjuvant management strategies, however, at the expense of higher relapse rates. Each of the management strategies in CSI GCT patients have specific merits and shared-decision-making is advised to tailor treatment.

OBJECTIVE: To evaluate the relationship between pre-operative PSA value, 68Ga-prostate-specific-membrane-antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). PATIENTS AND METHODS: The study included 164 patients diagnosed with ≤2 pelvic lymph-node recurrence(s) of PCa documented on 68Ga-PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high-volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (1.5 ng/ml). Clinical recurrence (CR)-free survival after sLND was calculated using multivariable analyses and plotted over pre-operative PSA value. RESULTS: Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre-operative PSA value, with highest rates for patients with pre-operative PSA > 1.5 ng/ml (pelvic-only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre-operative PSA was associated with PSA response (p

Objective To systematically evaluate evidence on prognostic factors for tumor recurrence in clinical stage I nonseminoma patients other than lymphovascular invasion (LVI). Methods We performed a systematic literature search in the biomedical databases Medline (via Ovid) and Cochrane Central Register of Controlled Trials (search period January 2010 to February 2021) for full text publications in English and German language, reporting on retro- or prospectively assessed prognostic factors for tumor recurrence in patients with stage I nonseminomatous germ cell tumors. Results Our literature search yielded eleven studies reporting on 20 potential prognostic factors. Results are based on cohort studies of mostly moderate to low quality. Five out of eight studies found a significant association of embryonal carcinoma (EC) in the primary tumor with relapse. Among the different risk definitions of embryonal carcinoma (presence, predominance, pure), presence of EC alone seems to be sufficient for prognostification. Interesting results were found for rete testis invasion, predominant yolk sac tumor, T-stage and history of cryptorchidism, but the sparse data situation does not justify their clinical use. Conclusions No additional factors that meet the prognostic value of LVI, especially when determined by immunohistochemistry, could be identified through our systematic search. The presence of EC might serve as a second, subordinate prognostic factor for clinical use as the data situation is less abundant than the one of LVI. Further efforts are necessary to optimize the use of these two prognostic factors and to evaluate and validate further potential factors with promising preliminary data.

ZusammenfassungDas Einsatzgebiet der roboterassistierten Chirurgie in der Urologie umfasst mittlerweile ein breites Spektrum an Eingriffen. Wesentlich sind dabei neben rekonstruktiven Eingriffen insbesondere tumorchirurgische Eingriffe wie die radikale Zystektomie. Während Untersuchungen zur perioperativen Qualität der robotisch-assistierten radikalen Zystektomie einen günstigen Einfluss auf die Morbidität (und damit auch Mortalität) nahelegen, bleibt die Frage, inwieweit auch die onkologische Qualität des Eingriffs gemessen am rezidivfreien und Gesamtüberleben beeinflusst.In diesem Kontext werden in dieser Arbeit nach einer umfassenden Literaturrecherche sowohl die Daten retrospektive Kohortenvergleiche zwischen offener und robotischer Zystektomie, Registerdaten zur robotischen Zystektomie sowie die Ergebnisse prospektiv randomisierter Studien dargestellt.Zusammengefasst ist unter onkologischen Gesichtspunkten die robotische der offenen Zystektomie nicht unterlegen. Die Daten des Gesamtüberlebens, des karzinomspezifischen Überlebens und des progressionsfreien Überlebens unterscheiden sich weder in den retrospektiven Kohortestudien, im indirekten Vergleich von Registerdaten und/oder großer Serien noch in den bisherigen prospektiven Untersuchungen. Im Hinblick auf das Auftreten atypische Metastasen nach robotischer Zystektomie fehlen aktuell prospektive Daten, dies nicht das generelle onkologische Outcome zu beeinflussen.Damit ist die robotisch-assistierte Zystektomie auch aus onkologischen Gesichtspunkten eine gute Option für Patienten, bei denen eine Indikation zur radikalen Zystektomie besteht.

Purpose In this review, we summarize and discuss contemporary treatment standards and possible selection criteria for decision making after failure of adjuvant or first-line cisplatin-based chemotherapy for primarily localized or metastatic germ cell tumors. Methods This work is based on a systematic literature search conducted for the elaboration of the first German clinical practice guideline to identify prospective clinical trials and retrospective comparative studies published between Jan 2010 and Feb 2021. Study end points of interest were progression-free (PFS) and overall survival (OS), relapse rate (RR), and/or safety. Results Relapses of clinical stage I (CS I) patients irrespective of prior adjuvant treatment after orchiectomy are treated stage adapted in accordance for primary metastatic patients. Surgical approaches for sole retroperitoneal relapses are investigated in ongoing clinical trials. The appropriate salvage chemotherapy for metastatic patients progressing or relapsing after first-line cisplatin-based chemotherapy is still a matter of controversy. Conventional cisplatin-based chemotherapy is the international guideline-endorsed standard of care, but based on retrospective data high-dose chemotherapy and subsequent autologous stem cell transplantation may offer a 10–15% survival benefit for all patients. Secondary complete surgical resection of all visible residual masses irrespective of size is paramount for treatment success. Conclusions Patients relapsing after definite treatment of locoregional disease are to be treated by stage-adapted first-line standard therapy for metastatic disease. Patients with primary advanced/metastatic disease failing one line of cisplatin-based combination chemotherapy should be referred to GCT expert centers. Dose intensity is a matter of ongoing debate, but sequential high-dose chemotherapy seems to improve patients’ survival.

Background Testicular germ cell tumours (TGCTs) have a high metastasis rate. However, the mechanisms related to their invasion, progression and metastasis are unclear. Therefore, we investigated gene expression changes that might be linked to metastasis in seminomatous testicular germ cell tumour (STGCT) patients. Methods Defined areas [invasive tumour front (TF) and tumour centre (TC)] of non-metastatic (with surveillance and recurrence-free follow-up >2 years) and metastatic STGCTs were collected separately using laser capture microdissection. The expression of 760 genes related to tumour progression and metastasis was analysed using nCounter technology and validated with quantitative real-time PCR and enzyme-linked immunosorbent assay. Results Distinct gene expression patterns were observed in metastatic and non-metastatic seminomas with respect to both the TF and TC. Comprehensive pathway analysis showed enrichment of genes related to tumour functions such as inflammation, angiogenesis and metabolism at the TF compared to the TC. Remarkably, prominent inflammatory and cancer-related pathways, such as interleukin-6 (IL-6) signalling, integrin signalling and nuclear factor-κB signalling, were significantly upregulated in the TF of metastatic vs non-metastatic tumours. Conclusions IL-6 signalling was the most significantly upregulated pathway in metastatic vs non-metastatic tumours and therefore could constitute a therapeutic target for future personalised therapy. In addition, this is the first study showing intra- and inter-tumour heterogeneity in STGCT.

Accurate staging and identification of optimal candidates for local salvage therapy, such as salvage radical prostatectomy (SRP), is necessary to ensure optimal care in patients with radiorecurrent prostate cancer (PCa). We aimed to analyze performance of magnetic resonance imaging (MRI) and prostate-specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) for predicting pathologic nonorgan confined disease (pT3) and lymph node involvement (pN+) in patients treated with SRP for radiorecurrent PCa.We retrospectively reviewed the institutional database to identify patients who underwent MRI orWe identified 113 patients with radiorecurrent PCa who underwent preoperative MRI followed by SRP; 53 had preoperativeIn patients with radiorecurrent PCa, both, MRI, and

Background: Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). Methods: This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). Results: Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. Conclusions: The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. Lay Summary: Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.

The best surgical template for salvage pelvic lymph node dissection (sLND) in patients with nodal recurrence from prostate cancer (PCa) after radical prostatectomy (RP) is currently unknown. We analyzed data of 189 patients with a unilateral positive positron emission tomography (PET) scan of the pelvic lymph node areas, who were treated with bilateral pelvic sLND after RP at 11 high-volume centers. The primary endpoint was missed contralateral disease at final pathology, defined as lymph node positive for PCa in the side opposite to the positive spot(s) at the PET scan. Overall, 93 (49%) and 96 (51%) patients received a 11C-choline and a 68Ga prostate-specific membrane antigen (PSMA) PET scan, respectively, and 171 (90%) and 18 (10%) men had one and two positive spots, respectively. The rate of missed contralateral PCa was 18% (34/189), with the rates being 17% (29/171) and 28% (5/18) in men with one and two positive spots, respectively. While the rate of contralateral disease did not differ between 68Ga-PSMA and 11C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with 68Ga-PSMA versus 28% with 11C-choline in patients with a single positive spot. This finding was confirmed at multivariable logistic regression analysis predicting missed disease at final pathology after accounting for confounders (odds ratio: 0.24; p = 0.001). However, in men with a single positive spot at 68Ga-PSMA PET/computed tomography, the rate of single confirmed lymph node metastasis at final pathology was only 33%, suggesting the need for extended template even if unilateral dissection is performed. Awaiting confirmatory studies, patients diagnosed with a single positive spot at the 68Ga-PSMA PET scan might be considered for unilateral extended pelvic sLND. Patient summary We assessed the risk of missing contralateral disease in patients with a positron emission tomography (PET) scan suggestive of unilateral nodal recurrence from prostate cancer (PCa) after radical prostatectomy and who were treated with bilateral salvage lymph node dissection (sLND). Variability exists according to the number of positive spots and PET tracer, with the lowest rate of missed PCa in men diagnosed with a single positive spot at a 68Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND.

Purpose To present the current evidence and the development of studies in recent years on the management of extragonadal germ cell tumors (EGCT). Methods A systematic literature search was conducted in Medline and the Cochrane Library. Studies within the search period (January 2010 to February 2021) that addressed the classification, diagnosis, prognosis, treatment, and follow-up of extragonadal tumors were included. Risk of bias was assessed and relevant data were extracted in evidence tables. Results The systematic search identified nine studies. Germ cell tumors (GCT) arise predominantly from within the testis, but about 5% of the tumors are primarily located extragonadal. EGCT are localized primarily mediastinal or retroperitoneal in the midline of the body. EGCT patients are classified according to the IGCCCG classification. Consecutively, all mediastinal non-seminomatous EGCT patients belong to the “poor prognosis” group. In contrast mediastinal seminoma and both retroperitoneal seminoma and non-seminoma patients seem to have a similar prognosis as patients with gonadal GCTs and metastasis at theses respective sites. The standard chemotherapy regimen for patients with a EGCT consists of 3–4 cycles (good vs intermediate prognosis) of bleomycin, etoposid, cisplatin (BEP); however, due to their very poor prognosis patients with non-seminomatous mediastinal GCT should receive a dose-intensified or high-dose chemotherapy approach upfront on an individual basis and should thus be referred to expert centers Ifosfamide may be exchanged for bleomycin in cases of additional pulmonary metastasis due to subsequently planned resections. In general patients with non-seminomatous EGCT, residual tumor resection (RTR) should be performed after chemotherapy. Conclusion In general, non-seminomatous EGCT have a poorer prognosis compared to testicular GCT, while seminomatous EGGCT seem to have a similar prognosis to patients with metastatic testicular seminoma. The current insights on EGCT are limited, since all data are mainly based on case series and studies with small patient numbers and non-comparative studies. In general, systemic treatment should be performed like in testicular metastatic GCTs but upfront dose intensification of chemotherapy should be considered for mediastinal non-seminoma patients. Thus, EGCT should be referred to interdisciplinary centers with utmost experience in the treatment of germ cell tumors.

Background: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown. Objective: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. Design, setting, and participants: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. Outcome measurements and statistical analysis: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM. Results and limitations: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p 10%. Conclusions: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials. Patient summary: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

Summary Background PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. Methods KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m2] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m2] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study is completed and is no longer enrolling patients, and is registered at ClinicalTrials.gov , number NCT02853305 . Findings Between Oct 19, 2016 and June 29, 2018, 1010 patients were enrolled and allocated to receive pembrolizumab plus chemotherapy (n=351), pembrolizumab monotherapy (n=307), or chemotherapy alone (n=352). Median follow-up was 31·7 months (IQR 27·7–36·0). Pembrolizumab plus chemotherapy versus chemotherapy did not significantly improve progression-free survival, with a median progression-free survival of 8·3 months (95% CI 7·5–8·5) in the pembrolizumab plus chemotherapy group versus 7·1 months (6·4–7·9) in the chemotherapy group (hazard ratio [HR] 0·78, 95% CI 0·65–0·93; p=0·0033), or overall survival, with a median overall survival of 17·0 months (14·5–19·5) in the pembrolizumab plus chemotherapy group versus 14·3 months (12·3–16·7) in the chemotherapy group (0·86, 0·72–1·02; p=0·0407). No further formal statistical hypothesis testing was done. In analyses of overall survival with pembrolizumab versus chemotherapy (now exploratory based on hierarchical statistical testing), overall survival was similar between these treatment groups, both in the total population (15·6 months [95% CI 12·1–17·9] with pembrolizumab vs 14·3 months [12·3–16·7] with chemotherapy; HR 0·92, 95% CI 0·77–1·11) and the population with CPS of at least 10 (16·1 months [13·6–19·9] with pembrolizumab vs 15·2 months [11·6–23·3] with chemotherapy; 1·01, 0·77–1·32). The most common grade 3 or 4 adverse event attributed to study treatment was anaemia with pembrolizumab plus chemotherapy (104 [30%] of 349 patients) or chemotherapy alone (112 [33%] of 342 patients), and diarrhoea, fatigue, and hyponatraemia (each affecting four [1%] of 302 patients) with pembrolizumab alone. Six (1%) of 1010 patients died due to an adverse event attributed to study treatment; two patients in each treatment group. One each occurred due to cardiac arrest and device-related sepsis in the pembrolizumab plus chemotherapy group, one each due to cardiac failure and malignant neoplasm progression in the pembrolizumab group, and one each due to myocardial infarction and ischaemic colitis in the chemotherapy group. Interpretation The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma. Funding Merck Sharp and Dohme, a subsidiary of Merck, Kenilworth, NJ, USA.

BACKGROUND There is a trend of increasing discontent of urologic residents with educational programs. One point being mentioned is lack of time during residency for education and self-training. We analyzed the available time for education in our department depending on the used working model through the last 25 years. MATERIALS AND METHODS We calculated the absolute availability of residents during their residency for working models in 1996, 2000, 2007 and 2017. As a basis we used the working model of 1996 as no compensatory time-off for being on call was used. All days on which a delayed start is planned and no schedule in daily routine is possible had been excluded from education time. The numbers implemented in the regulation on further education in the corresponding years had been used to calculate the expenditure of time on the basis of median length of the different intervention. In addition, the patient numbers on the ward and our outpatient clinic had been documented over time. RESULTS With increasing patient numbers in the in- and outpatient clinic there is a continuous decreasing time available for education. The absolute available time in our department is calculated to be 3.1 years compared to 5 years in 1996. With the first day of training a resident has to complete 66.9 min of self-contained diagnostics or interventions per day in addition to clinical routine and administration to meet the requested numbers of the regulation on further education. CONCLUSIONS The limited time being available for the educational program is improved by the current regulation of education. To teach the complex segments of urology there is an urgent need for a well-structured curriculum, which should be used nationwide.

Introduction The outcome of radiotherapy (RT) for prostate cancer (PCA) depends on the delivered dose. While the evidence for dose-escalated RT up to 80 Gy is well established, there have been only few studies examining dose escalation above 80 Gy. We initiated the presented study to assess the safety of dose escalation up to 84 Gy. Patients and methods In our retrospective analysis, we included patients who received dose-escalated RT for PCA at our institution between 2016 and 2021. We evaluated acute genitourinary (GU) and gastrointestinal (GI) toxicity as well as late GU and GI toxicity. Results A total of 86 patients could be evaluated, of whom 24 patients had received 80 Gy and 62 patients had received 84 Gy (35 without pelvis- and 27 with pelvis-radiotherapy). Regarding acute toxicities, no adverse events > grade 2 occurred. 12.5% of patients treated with 80Gy, in 25.7% of patients treated with 84 Gy excluding pelvis, and in 51.9% of patients treated with 84Gy including pelvis suffered from Grade 2 GU acute toxicity (80 Gy versus 84 Gy: p=0.186; with pelvis versus without pelvis: p=0.032). Grade 2 GI toxicity occurred in 12.5% of patients irradiated with 80Gy, in 14.3% of patients treated with 84 Gy excluding pelvis, and in 12.9% of patients treated with 84Gy including pelvis (80 Gy versus 84 Gy: p=0.582; with pelvis versus without pelvis: p=0.510).GU late toxicity of grade ≥ 2 occurred in 4.2% of patients treated with 80 Gy, in 7.1% of patients treated with 84 Gy excluding pelvic RT, and in 18.2% of patients treated with 84 Gy including pelvic RT (logrank-test p=0.237). 8.3% of patients treated with 80 Gy, in 3.6% of patients treated with Gy excluding pelvic RT, and in 0% of patients treated with 84 Gy including pelvic RT suffered from GI late toxicity of grade ≥ 2(logrank-test p=0.358). Conclusion We were able to show that dose-escalated RT in PCA up to 84 Gy is feasible and safe without asubstantial increase in toxicity. Further follow up is needed to assess survival.

PURPOSE OF REVIEW This review aims to summarize the latest evidence of medical and surgical treatment options for patients with relapsing testicular germ cell tumors. RECENT FINDINGS Depending on International Germ Cell Cancer Classification Group risk classification 10-50% of patients with metastatic TGCT develop relapse which needs further multimodality treatment. With regard to therapy, early relapses are stratified according to their prognostic risk profile which results in a 3-year overall survival between 6% in the very high to 77% in the very low risk group. Prognostic risk score dictates systemic therapy which might be second line chemotherapy (TIP, PEI) or high dose chemotherapy. Any residual masses following salvage chemotherapy need to be completely resected due the presence of viable cancer and/or teratoma in more than 50% of cases. Targeted therapy in men with druggable mutations is for individualized cases only. Patients with late relapses developing more than 2 years after first-line chemotherapy are best managed by surgery. Desperation surgery is reserved for those patients with rising markers during or immediately after chemotherapy and good risk factors such as rising alpha-fetoprotein

427 Background: NS-RPLND represents a guideline recommended treatment option in marker negative low volume metastatic seminomas and nonseminomas (NSGCT). However, about 30% of clinical stage IIA patients demonstrate equivocal findings of uncertain dignity so that they might undergo unnecessary treatment. Elevated serum concentrations of the molecular marker miR371 have been reported to correlate with the clinical stage even in small volume metastases. It was the purpose of our pilot study to evaluate the predictive accuracy of miR371 in a cohort of patients who underwent nsRPLND for clinical stage IIA/B germ cell tumors of the testis. Methods: Between 1-9/2022, 16 patients with marker negative clinical stage IIA/B seminomas (n=10) and NSGCT (n=6) underwent primary nsRPLND with a modified template resection via an open surgical approach. Blood specimens (20ml) were drawn on the day immediately prior to surgery and processed according to the manufacturer’s protocol. miRNA is extracted and purified with the Maxwell RSC MiRNA Plasma and Serum Kits prior to its transcription into cDNA using cDNA Solution, Reverse Transcriptase and RNase Inhibitor. Subsequently, this cDNA is amplified. Using qPCR techniques, the miRNA 371a is quantified using Roche Lightcycler 480 II. Using the Lightcycler software, the median Cp (CP = crossing points) of the triplicates is calculated and converted into a RQ value (RQ= relative abundance). Results: nsRPND was performed in all patients without significant Clavien-Dindo IIIa-V complications. Mean OR time was 131 (105-195) minutes, mean blood loss was < 150ml, transfusion rate was 0%. Mean number of dissected lymph nodes was 17 (7-32), mean diameter of positive lymph nodes was 2.1 (0.8-4.1) cm. Histology revealed metastatic seminoma or nonseminoma in 12/16 (75%). In 4 patients histology revealed non-malignant disease (n=2), teratoma, and lymphoma. miR371 was positive in all 12 (100%) pts with metastases and it was negative in 3/4 (75%) pts without metastases. One patient with small volume CS IIA seminoma was false negative. Conclusions: This is the first report to demonstrate that miR371can be used as a personalized and individual biomarker to predict the presence of small volume retroperitoneal lymph node metastases in CS IIA/B seminomas and in nonseminomas. Patients with positive findings should undergo active treatment whereas negative findings should result in close follow-up. Date are currently validated in a multi-institutional trial.

421 Background: Characteristics and outcome of non-seminomatous testicular germ cell tumours (NSGCT) with teratoma-containing primaries are still under debate. Methods: We performed a retrospective analysis including 557 patients with metastatic NSGCT as a registry study within the "German Testicular Cancer Study Group". Results: Of the eligible 557 patients with NSGCT, 237 (42%) of all orchiectomy specimens had teratoma-containing primaries, while 320 (58%) were teratoma-free. Teratoma-containing primaries had a significantly higher clinical stage (p=0.002) and worse prognosis (p=0.051) compared to teratoma-free specimens. Lymph node metastasis were significantly larger before (4.5 vs 2.5cm; p

161 Background: Although still discussed controversially, cRP represents a therapeutic option for mHSPC patients in the context of a multimodality approach. It was the purpose of our study to retrospectively review the oncological and functional outcome of a single-center cohort of cRP patients. Methods: A total of 134 mHSPC patients underwent cRP with pelvic lymphadenectomy. All patients received neoadjuvant androgen deprivation therapy (ADT, n = 34), ADT + docetaxel (n=15), or ADT plus ABI/ENZA/APA (n=85) for 6 months which was continued postop. Follow-up studies were performed at 3-month intervals, new imaging studies with 68Ga-PSMA PET/CT was done at PSA-levels > 1.0 ng/ml. Perioperative complications were evaluated according to Clavien-Dindo classification. Clinical progression free survival (cPFS) and cancer specific survival (CSS) were calculated via Kaplan-Maier analysis. Multivariate regression analysis was used to assess the impact of biopsy ISUP grade, PSA at diagnosis and preop., PSA decrease, T stage, and metastatic burden on PFS and CSS. Results: 115 and 19 had low and high volume mHSPC, resp. Mean age was 64.2 (42-88) years, mean preop. PSA was 3.2 (0.1-21.6) ng/ml. The median Follow-up ist 53.7 (4 – 168) months. M1a, M1b and M1c were present in 28 (20.9%), 98 (73.1%) and 8 (6.0%) men. Pathohistology demonstrated pT0 in 3 (2.2%), pT2a-c in 21 (15.7%), pT3 and pT4 in 105 (78.3%) and 5 (3.7%). pN0 and pN+ was diagnosed in 38 (28.3%) and 96 (71.7%) pts. There was no significant difference between type of ADT and final pathohistology. Clavien-Dindo Grad 3a-b and 4 complications were observed in 13 (9.7%) and 2 (1.5%) pts. CSS was 88.1% and cPFS was 53%. None of the pts developed locally recurrent disease. Overall survival was reduced in M1 high volume (61.9% vs 92.8%, p=0.002) and pN+ (85.7% vs 96.7%, p=0.001). cT≥3b (HR=2.24, p=0.02) and M1 high volume (HR=2.35, p=0.01) were associated with reduced cPFS; M1 high volume (HR=1.49, p=0.03) and relative PSA decrease £60% (HR=1.37, p=0.03) were associated with reduced CSS. Conclusions: cRP can be performed with minimal morbidity. mHSPC patients with clinically localized high risk PCA, low metastatic burden and good response to nADT benefit most from this approach. The risk for symptomatic local relapse is low. Limitation of the study is its retrospective design.

5031 Background: The aim ofPC-RPLND for advanced nonseminomatous germ cell tumors is to resect all remaining metastatic tissue. So far, the resection of adjacent visceral or vascular organs is also commonly performed to achieve complete resection of the residual mass. To determine the possibility of more organ preservation, we aimed to analyze the pathohistology of patients with adjunctive surgery as the frequency of metastatic involvement in those organs with teratoma or vital cancer is currently unknown. Methods: We reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 as a 2-center study and identified 242 (20.1%) cases of adjunctive surgery during PC-RPLND. We analysed the pathohistological presence of germ cell tumor elements in the resected organs: viable tumor (V), teratoma (T) or necrosis / fibrosis (N). Surgery associated complications were reported according to the Clavien-Dindo classification. Outcomes of subgroups were compared by using log-rank test. Results: V, T and N were present in 54 (22%), 94 (39%) and 94 (39%) of all patients with adjunct resected organs. In 242 patients, 325 adjunct organs were resected with 66 (27.3%) of these patients receiving a resection of multiple organs. The kidney was the most often resected organ (n = 77; V: 29% T: 39% N: 32%), followed by V. Cava (n = 67; V: 25% T: 36%, N: 39%) and partial liver resections (n = 50; V: 16%, T: 30%, N: 54%). Postoperative complications occurred in 30% of which 22% were Clavien grade III-V, showing no significant differences between V, T and N; p = 0.093. 27% of all patients suffered from a relapse during a median follow-up of 22 months [0-180]. Patients with T or V in the resected specimens had a significantly reduced 5-year RFS compared to patients with only N (39%, 81%, p < 0.001). Conclusions: This study shows tremendous need for more organ preservation as 40% of all resections of adjunct organs are oncologically unnecessary due to the presence of N only in the pathological specimens. Therefore, in case of doubt, we should increase intraoperative frozen section to avoid oncologically unnecessary adjunctive surgeries, especially nephrectomies and vascular resections. Additionally, serological or image-based means for a more accurate presurgical workup are required to spare patients with N from PC-RPLND in general.

Die Behandlung von Patienten mit fortgeschrittenen, rezidivierten und chemotherapieresistenten Keimzelltumoren stellt eine besondere Herausforderung dar. Die multidisziplinare Behandlung der Patienten mit Chemotherapie und operativer Resektion von Residualtumorgewebe resultiert in insgesamt exzellenten Uberlebenschancen. In den seltenen Fallen von Keimzelltumorrezidiven, seltenen Rezidivlokalisationen, einer erworbenen oder angeborenen Chemotherapieresistenz kommt der operativen Resektion eine besondere Bedeutung zu. In diesem Ubersichtsartikel wird der Stellenwert der operativen Resektion von Residualtumorgewebe bei fortgeschrittenen Keimzelltumoren nach First-Line-Therapie sowie in der Salvage-Situation als auch im Sonderfall der „desperation surgery“ bei steigenden Tumormarkern unter oder nach Letztlinien-Chemotherapie beschrieben. Es wurde eine selektive Literaturrecherche uber PubMed durchgefuhrt. Die operative Resektion von Residualtumorgewebe von >1 cm nach Chemotherapie ist integraler Bestandteil der leitliniengerechten Therapie bei nichtseminomatosen Keimzelltumoren und senkt die Rezidivrate. Bei fortgeschrittenen Seminomen stellt die primare Residualtumorresektion eine Ausnahme dar. Nach erfolgter Salvage-Chemotherapie ist die Residualtumorresektion unabhangig von der Residualtumorgrose durchzufuhren. Mit einem Langzeituberleben von etwa 50 % stellt die „desperation surgery“ einen operativen Therapieansatz bei chemotherapieresistenten Keimzelltumoren dar. Komplette Resektabilitat ist hier jedoch zentrale Voraussetzung fur den onkologischen Erfolg.

Robot-assisted surgery in urology is now being used in a wide range of procedures. In addition to reconstructive procedures, tumour surgery such as radical cystectomy is of particular importance. While studies on the perioperative quality of robotic-assisted radical cystectomy suggest a favorable impact on morbidity (and thus mortality), the question remains as to what extent the oncological quality is influenced by this procedure in terms of recurrence-free and overall survival.In this context, following a comprehensive literature review, this paper presents data from retrospective cohort comparisons of open and robotic cystectomy, registry data and single centre series on robotic and open cystectomy, and the results of prospective randomised trials.In summary, from an oncological point of view, robotic cystectomy is not inferior to open cystectomy. Overall survival, cancer-specific survival, and progression-free survival data do not differ in retrospective cohort studies, in indirect comparisons of registry data and/or large series, or in prospective studies to date. With regard to the occurrence of atypical metastases after robotic cystectomy, prospective data are currently lacking and retrospective analysis produce conflicting data. However, general oncological outcome seems not to be affected.Thus, robotic-assisted cystectomy is also from an oncological point of view a good option for patients who have an indication for radical cystectomy.Das Einsatzgebiet der roboterassistierten Chirurgie in der Urologie umfasst mittlerweile ein breites Spektrum an Eingriffen. Wesentlich sind dabei neben rekonstruktiven Eingriffen insbesondere tumorchirurgische Eingriffe wie die radikale Zystektomie. Während Untersuchungen zur perioperativen Qualität der robotisch-assistierten radikalen Zystektomie einen günstigen Einfluss auf die Morbidität (und damit auch Mortalität) nahelegen, bleibt die Frage, inwieweit auch die onkologische Qualität des Eingriffs gemessen am rezidivfreien und Gesamtüberleben beeinflusst.In diesem Kontext werden in dieser Arbeit nach einer umfassenden Literaturrecherche sowohl die Daten retrospektive Kohortenvergleiche zwischen offener und robotischer Zystektomie, Registerdaten zur robotischen Zystektomie sowie die Ergebnisse prospektiv randomisierter Studien dargestellt.Zusammengefasst ist unter onkologischen Gesichtspunkten die robotische der offenen Zystektomie nicht unterlegen. Die Daten des Gesamtüberlebens, des karzinomspezifischen Überlebens und des progressionsfreien Überlebens unterscheiden sich weder in den retrospektiven Kohortestudien, im indirekten Vergleich von Registerdaten und/oder großer Serien noch in den bisherigen prospektiven Untersuchungen. Im Hinblick auf das Auftreten atypische Metastasen nach robotischer Zystektomie fehlen aktuell prospektive Daten, dies nicht das generelle onkologische Outcome zu beeinflussen.Damit ist die robotisch-assistierte Zystektomie auch aus onkologischen Gesichtspunkten eine gute Option für Patienten, bei denen eine Indikation zur radikalen Zystektomie besteht.

Purpose:We compared the use of 11C-choline and 68Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer.Materials and Methods:The ...