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To evaluate whether the rate of Gleason score (GS) upgrade on final pathology, the rate of positive surgical margins (PSM) and the rate of biochemical recurrence (BCR) after radical prostatectomy (RP) were different if prostate biopsy (PB) was graded by community pathologists (CP) as compared to specialized uro-pathologists (UP). A consecutive series of patients undergoing RP in our institution between 2005 and 2013 were retrospectively reviewed. Any GS higher or lower in RP specimen as compared to PB GS was defined as GS upgrade or downgrade, respectively. Additionally, stratification for the new ISUP 2014 grading system was performed. Predictors of GS upgrade and PSMs and prognostic parameters for BCR were assessed by stepwise logistic regression models and by multivariable Cox regression analyses, respectively. A total of 786 patients were available for analysis, and median follow-up was 36 months (1–101 months). A GS upgrade was found in 345 patients (43.9 %) and a GS downgrade in 91 patients (11.6 %). Discordance between PB GS and RP GS was significantly more frequent when grading had been performed by a CP (50.5 % upgrade, 9.0 % downgrade) than by a UP (33.1 % upgrade, 15.7 % downgrade, p

In 2015, an estimated number of 8430 new cases of germ cell tumour (GCT) will be diagnosed in the USA.1 Although GCTs show a high sensitivity to cisplatin-based chemotherapy, 10%–15% of patients fail first-line chemotherapy and 3%–5% of all patients with GCT will eventually die of their disease.2 Despite a response rate above 95% to cisplatin-based chemotherapy, the search for new treatment strategies remains worthwhile in accordance to reduce treatment toxicity and offer therapeutic options in non-responding patients.3–5 Various tumours have been described to express L1 cell adhesion molecule (L1-CAM) including lung carcinoma, gliomas, melanoma, renal, ovarian, endometrial and colon carcinoma.6 L1-CAM is associated with tumour cell dissemination via the regulation of prometastatic MMP-2 and MMP-9 in solid and non-solid tumours7 as well as in brain metastases.8 L1-CAM is involved in epithelial-to-mesenchymal transition.9 In various malignancies, there is evidence showing that the expression of L1-CAM is associated with a subset of highly aggressive tumours with adverse clinical outcome and might serve as a therapeutic target.10 We aimed to investigate the expression of L1-CAM in the different GCT subtypes. The construction of the tissue micro array (TMA) was described before.9 L1-CAM immunohistochemistry (IHC) was performed …

Background: Intratumoral hypoxia plays an important role with regard to tumor biology and susceptibility to radio. and chemotherapy. For further investigation of hypoxia.related changes, areas of certain hypoxia must be reliably detected within cancer tissues. Pimonidazole, a 2.nitroimindazole, accumulates in hypoxic tissue and can be easily visualized using immunohistochemistry. Materials and Methods: To improve detection of highly hypoxic versus normoxic areas in prostate cancer, immunoreactivity of pimonidazole and a combination of known hypoxia.related proteins was used to create computational oxygen supply maps of prostate cancer. Pimonidazole was intravenously administered before radical prostatectomy in n = 15 patients, using the da Vinci robot.assisted surgical system. Prostatectomy specimens were immediately transferred into buffered formaldehyde, fixed overnight, and completely embedded in paraffin. Pimonidazole accumulation and hypoxia.related protein expression were visualized by immunohistochemistry. Oxygen supply maps were created using the normalized information from pimonidazole and hypoxia.related proteins. Results: Based on pimonidazole staining and other hypoxia.related proteins (osteopontin, hypoxia.inducible factor 1.alpha, and glucose transporter member 1) oxygen supply maps in prostate cancer were created. Overall, oxygen supply maps consisting of information from all hypoxia.related proteins showed high correlation and mutual information to the golden standard of pimonidazole. Here, we describe an improved computer.based ex vivo model for an accurate detection of oxygen supply in human prostate cancer tissue. Conclusions: This platform can be used for precise colocalization of novel candidate hypoxia.related proteins in a representative number of prostate cancer cases, and improve issues of single marker correlations. Furthermore, this study provides a source for further in situ tests and biochemical investigations

A 75-year-old male with a left ventricular ejection-fraction of 20% and a Euroscore-II of 11.2% was referred for a TAVI due to severe aortic valve regurgitation and moderate–severe mitral regurgitation (AR) with NYHA class IV symptoms. The leaflets were free of calcification and with an annulus diameter of 27.7 mm, he was scheduled for the implantation of a 29 mm Direct Flow Medical valve (Direct Flow Medical Inc., Santa Rosa, CA, USA). The specific design of the prosthesis makes it an ideal choice for treatment of pure AR and …

Male germ cell tumors (GCTs) are curable cancers, yet 10-15 % of patients with metastatic disease fail cisplatin-based first-line treatments. While therapeutic options have increased for various other cancers, little progress has been made in the management of GCT in the last decades. A better understanding of the molecular alterations underlying the disease and identification of new therapeutic targets are needed. Several phase I/II studies with promising new agents are ongoing or have been completed, but most of those trials have been small and have not included translational research. Therefore, molecular profiles predictive for response or new agents have not been identified in male GCT so far. The purpose of this review is to highlight emerging targets and therapies with the potential to improve systemic treatment of metastatic male GCT and to develop strategies for future clinical trials.

Background: Many testicular germ cell cancers are curable despite metastatic disease, but about 10–15% of patients fail cisplatin-based first-line treatment. Immunotherapy is considered as additional treatment approach for these patients. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. We analysed the expression of PD-L1 in testicular germ cell tumours to evaluate its potential as target for immunotherapeutic strategies. Methods: Immunohistochemistry was performed in 479 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody (E1L3N). The tissue microarray consisted of 208 pure seminomas, 121 non-seminomas, 20 intratubular germ cell neoplasia unclassified (IGCNU) and 20 specimens of non-neoplastic testicular tissue. Results: Programmed Death Receptor Ligand-1 expression was found in 73% of all seminomas and in 64% of all non-seminomas. None of 20 IGCNU and none of 20 normal tissue specimens exhibited PD-L1 expression. PD-L1 positive stromal cells were only detected in seminomas, but not in non-seminomas. The anti PD-L1 antibody showed a pre-dominantly membranous staining pattern in testicular tumour cells, as well as expression in stromal cells. Conclusions: This frequent expression of PD-L1 in human testicular germ cell tumours suggests that patients with testicular germ cell tumours could profit from immunotherapeutic strategies using anti-PD1 and anti-PDL1 antibodies.

CD10 is a cell surface neutral endopeptidase expressed by lymphoid precursor cells, germinal centre B lymphocytes, and some myelocytes.1 Therefore, it is used as marker for the categorisation of acute leukaemia and subclassification of lymphomas.2 With focus on germ cell tumours Del Sordo et al 3 reported in a cohort of 135 germ cell tumours expression of 92% for seminomas, whereas non-seminomatous germ cell tumours were negative. The authors concluded that CD10 serves to differentiate seminoma from non-seminomatous germ cell tumours. The aim of this study was to describe CD10 expression in the so far largest germ cell tumour set and to validate the findings of previous studies. ### Tissue microarray The tissue microarray used for this study has previously been described.4 It includes 325 testicular germ cell tumours: 207 classic seminomas, 4 spermatocytic seminomas, 19 pure embryonal carcinomas, 1 pure mature teratoma and 94 mixed germ cell tumours. In mixed germ cell tumours each component was separately punched and represented on the tissue microarray. Finally, 442 different histologic tumour components were considered for evaluation. ### Immunohistochemistry CD10 was detected using the prediluted antibody from Ventana (790–4506). The staining was performed with the Ventana Benchmark automated staining system (Ventana Medical Systems, Tucson, AZ). Samples were dichotomised into positive versus negative. The intensity of immunostaining was graded as absent, weak, moderate and strong. The threshold for …

Absorption of irrigation fluid was not detected during GreenLight™ laser vaporization of the prostate using the first generation 80 W laser. However, data are lacking on intraoperative irrigation fluid absorption using the second generation 120 W high power laser. We assessed whether fluid absorption occurs during high power laser vaporization of the prostate.We performed this prospective investigation at a tertiary referral center in patients undergoing 120 W laser vaporization for prostatic bladder outlet obstruction. Normal saline containing 1% ethanol was used for intraoperative irrigation. The expired breath ethanol concentration was measured periodically during the operation using an alcometer. The volume of saline absorption was calculated from these concentrations. Intraoperative changes in hematological and biochemical blood parameters were also recorded.Of 50 investigated patients 22 (44%) had a positive breath ethanol test. Median absorption volume in the absorber group was 725 ml (range 138 to 3,452). Ten patients absorbed more than 1,000 ml. Absorbers had a smaller prostate, more capsular perforation, higher bleeding intensity and more laser energy applied during the operation. Three patients (13%) had symptoms potentially related to fluid absorption. Hemoglobin, hematocrit and serum chloride were the only blood parameters that changed significantly in the absorber group. The changes were significantly different than those in nonabsorbers.Fluid absorption occurs frequently during high power laser vaporization of the prostate. This should be considered in patients who present with cardiopulmonary or neurological symptoms during or after the procedure.

4521 Background: Residual disease is a frequent finding after chemo for metastatic seminoma. Watchful waiting is recommended for residual lesions < 3 cm or lesions ≥3 cm with negative PET. Data on the optimal management of PET positive residual lesions is lacking. Methods: A retrospective analysis within the G3 Group identified 91 patients (pts) from 9 countries with metastatic seminoma and residual PET positive lesions after chemo. Pts with elevated AFP ( > 2xULN) or non-seminomatous components at diagnosis were excluded. We analyzed the post PET management chosen and its impact on relapse and survival. Results: Median follow-up was 29 (IQR 10 – 64) months. Median age at diagnosis was 41 (range 19 – 69) years. The primary tumor was gonadal in 68 pts (76%), retroperitoneal in 12 pts (13%) and mediastinal in 10 pts (11%). Prior to chemo the median size of the largest metastasis was 10 (range 1.4 – 23) cm, 67 pts (74%) had elevated LDH and 51 pts (57%) elevated HCG. Median diameter of the largest residual mass was 4.8 (range 1.1 – 14) cm mainly located in the retroperitoneum (77%), pelvis (15%), mediastinum (16%) or lung (4%). Median time from last day of chemo to PET was 7 (IQR 4 – 10) weeks. Post PET management was repeated imaging in 46 pts (51%), resection in 32 pts (35%), biopsy in 9 pts (10%) and radiotherapy in 4 pts (4%). Histology of the resected specimen was necrosis only in 25 (78%) and vital seminoma in 7 cases (22%). No biopsy revealed vital seminoma. Relapses occurred after a median of 3.7 (IQR 2.5 – 4.9) months in 16 pts (18%): 2/9 (22%) after biopsy, 12/46 (26%) on repeated imaging and 2/32 (6%) after resection (one necrosis, one < 10% vital seminoma). Site of relapse was the area of residual disease in 14 pts (88%) and additional distant relapse (one bone, one lung) in 2 pts (12%). All relapsed pts received successful salvage chemo apart from one who died from treatment and two pts who are alive with ongoing treatment. Conclusions: PET positive post chemo residual lesions in seminoma pts are false positive in about 75%. Relapses in PET positive pts occur early and can be salvaged with chemo. Further analysis is needed to identify risk factors for relapse.

Background Patients with testicular germ cell tumors (TGCT) have an increased risk for venous thromboembolism (VTE). We identified risk factors for VTE in this patient cohort and developed a clinical risk model. Methods In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich. Results Venous thromboembolic events occurred in 34 (5.2%) patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS) and a retroperitoneal lymphadenopathy (RPLN) were the strongest predictors of VTE (p

Bipolar plasma vaporization (BPV) has been introduced as an alternative to transurethral resection of the prostate (TURP). Promising short-term results, but inferior mid-term results compared to TURP have been reported following first-generation bipolar electrovaporization. Outcome data following second-generation BPV are still scarce. The aim of this investigation was to evaluate the intra- and postoperative outcomes of contemporary BPV in a center with long-standing expertise on laser vaporization of the prostate.A consecutive series of 83 patients undergoing BPV in a tertiary referral center was prospectively evaluated. The investigated outcome parameters included the maximum flow rate (Qmax), postvoid residual volume, International Prostate Symptom Score (IPSS)/quality of life (Qol), and prostate-specific antigen (PSA) tests. Follow-up investigations took place after 6 weeks, 6 months, and 12 months. The Wilcoxon signed-rank test was used to compare pre- and post-treatment parameters.The median (range) preoperative prostate volume was 41 mL (17-111 mL). The preoperative IPSS, Qol, Qmax, and residual volume were 16 (2-35), 4 (0-6), 10.1 mL/s (3-29.3 mL/s), and 87 mL (0-1000 mL), respectively. One third of the patients were undergoing platelet aggregation inhibition (PAI). No intraoperative complications occurred. Postoperatively, 13 patients (15.7%) had to be recatheterized. Three patients (3.6%) had clot retention and 28 patients (34%) reported any grade of dysuria. After 6 weeks, all outcome parameters improved significantly and remained improved over the 12-month observation period [IPSS: 3 (0-2); Qol: 1 (0-4); Qmax: 17.2 mL/s (3.2-56 mL/s); residual volume 11 mL (0-190 mL)]. The PSA reduction was 60% at study conclusion. Three patients (3.6%) developed a urethral stricture and four patients (4.8%) bladder neck sclerosis. Re-resections were not necessary.Contemporary BPV is a safe and efficacious treatment option even for patients undergoing PAI. Early urinary retention and temporary dysuria seem to be specific side effects of the treatment. Bleeding complications are rare. Long-term follow-up is needed to confirm these promising short-term results.

To investigate if absorption of irrigation fluid occurs during bipolar plasma vaporisation (BPV) of the prostate. To examine the clinical predictors of increased risk of fluid absorption and to assess if changes in serum electrolytes, venous pH, haemoglobin or haematocrit are able to detect intra-operative fluid absorption.Over a 15-month period, 55 consecutive patients undergoing BPV of the prostate were investigated. The volume of intra-operative fluid absorption was measured using expired-breath ethanol measurements. Intra-operative irrigation was performed with isotonic saline containing 1% ethanol. The breath ethanol concentration was measured every 10 min during the operation and the volume of irrigation fluid absorption was calculated from these concentrations. Data on clinical (age, prostate volume, smoking status) and surgical variables (operation time, irrigation volume, appearance of capsular perforation) as well as intra-operative changes in serum electrolytes, venous pH, haemoglobin and haematocrit were recorded.The median (range) age of the patients was 67 (48-87) years and the median (range) prostate volume was 41 (17-111) mL. Nine patients (16%) showed a positive ethanol breath test during the procedure. The median (range) calculated fluid absorption in these patients was 346 (138-2166) mL. Three patients had a fluid absorption500 mL. One patient with absorption of2 L showed clinical symptoms (dyspnoea and agitation) during the operation under spinal anaesthesia. In the group of patients with fluid absorption, capsular perforation or injury to larger vessels was more often detectable. In the group of patients with fluid absorption, only venous pH showed a significant change during the operation (from median 7.41 to median 7.34, P = 0.02). The pH decrease was significantly greater in the fluid absorption group than in the group of patients without fluid absorption (0.09 vs. 0.02, P = 0.005).We have demonstrated that significant intra-operative fluid absorption can occur during BPV of the prostate. Care must be taken if using this procedure in patients with significant cardiovascular comorbidities. Respecting the anatomical borders of the prostate seems to play a relevant role in preventing fluid absorption during the procedure. Venous pH could be used to detect potentially dangerous fluid absorption if intra-operative monitoring with breath ethanol measurements is not available.

INTRODUCTION AND OBJECTIVES: Greenlight laser vaporisation (LV) of the prostate has been shown to be a safe procedure even for high-risk patients with lower urinary tract symptoms caused by prostate enlargement. Intra-operative fluid absorption was not detectable during LV using the first generation 80W greenlight laser. For the more powerful 120W greenlight laser, a different spectrum of adverse events, including a higher rate of capsular perforations and more bleeding complications, has been reported. The aim of the present investigation was to assess if fluid absorption occurs during LV using the more powerful 120W laser. METHODS: A total of 50 consecutive patients was investigated during 120W greenlight LV of the prostate. Intra-operative irrigation was performed using isotonic saline containing 1% ethanol. The breath ethanol concentration was measured every 10 min throughout the procedure with a conventional alcometer. The volume of fluid absorption was calculated from the results of these measurements. Intraoperative changes of haemoglobin, haematocrit, venous pH and serum electrolytes were also recorded. RESULTS: The median patients’ age was 69 y (range: 49-84) and the median prostate volume 41 mL (23-118). 25 patients (50%) were operated under thrombocyte aggregation inhibition and 8 (16 %) under anti-coagulation therapy. The median operation time was 70 min (30-170), the median irrigation volume 18 L (8-45) and the median applied laser energy 230 kJ (65-400). 22 patients (44 %) had a positive ethanol breath test. The median amount of fluid absorption in these patients was 1249 mL (138-3452). The surgeons reported intra-operative events in form of opened venous sinuses (n 2), capsular perforation (n 3) or a deep bladder neck incision (n 5) In 10 of these patients (45%). In the group of patients with a positive ethanol test, a significant decrease of the haemoglobin, haematocrit and venous pH and a significant increase of the serum chloride were detectable. CONCLUSIONS: Intra-operative fluid absorption was detectable in 44% of the patients undergoing 120W greenlight LV of the prostate. Absorption of isotonic saline does not result in a classical TUR-syndrome. However, care must be taken in cardiovascular highrisk patients because absorption of up to 3.5 liters of saline can result in serious complications in these patients. Intra-operative monitoring with venous pH or serum chloride might help to detect potentially dangerous fluid absorption if ethanol breath ethanol measurements are not performed.

Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in SPOP stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly up-regulated in CRPC. Expression of TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 gene signature predict disease-recurrence. Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR-interacting motif are essential to support proliferation. These data provide a rationale for therapeutic TRIM24 targeting in SPOP-mutant and CRPC patients. Citation Format: Anna C. Groner, Laura Cato, Jonas de Tribolet-Hardy, Tiziano Bernasocchi, Qing Zhong, Christian Fankhauser, Christine Fritz, Cédric Poyet, Ulrich Wagner, Levi A. Garraway, Peter J. Wild, Jean-Philippe Theurillat, Myles Brown. TRIM24 is an oncogenic transcriptional activator in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1806.

e16058Background: Data suggest that large RPLN significantly increase the risk of VTE in pts with mGCT receiving first line platinum based chemotherapy (chemo). This multinational G3 study aims to ...

Patient-orientated outcome questionnaires are essential to evaluate treatment success. To compare different treatments, hospitals, and surgeons, standardised questionnaires are required. The present study examined the validity and responsiveness of the Core Outcome Measurement Index for neck pain (COMI-neck), a short, multidimensional outcome instrument.Questionnaires were completed by patients with degenerative problems of the cervical spine undergoing cervical disc arthroplasty before (N = 89) and 3 months after (N = 75) surgery. The questionnaires comprised the EuroQol-Five Dimension (EQ-5D), the North American Spine Society Cervical Spine Outcome Assessment Instrument (NASS-cervical) and the COMI-neck.The COMI and NASS-cervical scores displayed no notable floor or ceiling effects at any time point whereas for the EQ-5D, the highest values [corrected] were reached in around 32.5% of patients at follow-up. With one exception (symptom-specific well-being), the individual COMI items and the COMI summary score correlated to the expected extent (R = 0.4-0.8) with the scores of the chosen reference questionnaires. The area under the curve (AUC) generated by ROC analysis was significantly higher for the COMI (0.96) than for any other instrument/subscale when self reported treatment outcome was used as the external criterion, dichotomised as "good" (operation helped a lot/helped) versus "poor" (operation helped only a little/didn't help/made things worse). The COMI had a high effect size (standardised response mean; SRM) (2.34) for the good global outcome group and a low SRM for the poor outcome group (0.34). The EQ-5D and the NASS-cervical lacked this ability to differentiate between the two groups, showing less distinct SRMs for good and poor outcome groups.This study provides evidence that the COMI-neck is a valid and responsive questionnaire in the population of patients examined. Further investigations should examine its applicability in other patient groups with less severe neck pain or undergoing other treatment modalities.

379 Background: Testicular germ-cell cancer is curable even in the presence of metastatic disease. Yet, about 10-15% of patients become cisplatin-refractory and will eventually die of their disease. Moreover, short- and long-term side effects of cisplatin make the search for less toxic treatment strategies worthwile. Programmed Death Receptor 1 (PD-1, CD279) is one member of the extended family of T cell regulators expressed on the surface of activated T cells, B cells, and macrophages. Its ligand, PD-L1 (B7-H1, CD274), is expressed on tumor cells, T cells and other tissues. The interaction of these two molecules negatively regulates immune responses. Of major interest is that inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses in vitro and mediate clinical antitumor activity . The aim of this study was to analyze the expression of PD-L1 in testicular germ-cell tumors to evaluate its potential as predictive marker for further therapeutic strategies. Methods: Immunohistochemistry was performed in 486 Formalin Fixed Paraffin Embedded (FFPE) specimens using a monoclonal rabbit antibody (E1L3N, Cell Signaling Technology, Inc. (CST) of Danvers, MA, USA). Results: PD-L1 expression was found in 171 out of 248 (69%) seminomas, 19 out of 48 (40%) yolk sac tumors, 7 out of 46 (15%) teratomas, 2 out of 10 (20%) choriocarcinomas and 53 out of 87 (61%) embryonal carcinomas. In 20 out of 20 Intratubular germ-cell neoplasia unclassified (IGCNU) and also in 20 out of 20 normal tissue specimens no single case exhibited PD-L1 expression. Conclusions: Our study describes for the first time the frequent expression of PD-L1 in a large series of human testicular germ-cell tumors, but not on normal testis tissue or IGCNU. Based on our results, checkpoint inhibition with anti-PD1 and anti-PDL1 antibodies might represent an attractive approach in germ-cell cancer, where new active agents are urgently needed.

© 2015 Springer Verlag Berlin Heidelberg This study investigates the capabilities of low tube voltage computed tomography (CT) and dual energy CT (DECT) for predicting successful shock wave lithotripsy (SWL) of urinary stones in vitro. A total of 33 urinary calculi (six different chemical compositions; mean size 6 ± 3 mm) were scanned using a dual source CT machine with single (120 kVp) and dual energy settings (80/150 100/150 Sn kVp) resulting in six different datasets. The attenuation (Hounsfield Units) of calculi was measured on single energy CT images and the dual energy indices (DEIs) were calculated from DECT acquisitions. Calculi underwent SWL and the number of shock waves for successful disintegration was recorded. The prediction of required shock waves regarding stone attenuation/DEI was calculated using regression analysis (adjusted for stone size and composition) and the correlation between CT attenuation/DEI and the number of shock waves was assessed for all datasets. The median number of shock waves for successful stone disintegration was 72 (interquartile range 30–361). CT attenuation/DEI of stones was a significant independent predictor (P < 0.01) for the number of required shock waves with the best prediction at 80 kVp (ß estimate 0.576) (P < 0.05). Correlation coefficients between attenuation/DEI and the number of required shock waves ranged between ? = 0.31 and 0.68 showing the best correlation at 80 kVp (P < 0.001). The attenuation of urinary stones at low tube voltage CT is the best predictor for successful stone disintegration being independent of stone composition and size. DECT shows no added value for predicting the success of SWL.

The online version of the original article can be found under doi:10.1007/s00586-011-1921-4. The online version of the original article can be found at http://dx.doi.org/10.1007/s00586-011-1921-4.

392 Background: The prognostic impact of LDH and HCG serum levels in marker positive metastatic seminoma patients is uncertain. This analysis evaluated the association between LDH and HCG levels with oncological outcomes in this patient population. Methods: Seminoma patients with elevated HCG levels were retrospectively analyzed. After stratification according to tumor marker levels pre- and post-orchiectomy, outcomes of subgroups were compared using log-rank test and cox-regression analysis. Study endpoints were cancer specific- (CSS) and recurrence-free survival (RFS). Results: In total, 429 HCG-positive metastatic seminoma patients (stage II n=291; stage III n=138) diagnosed between 1981 and 2018 were included. LDH + HCG levels ranged from 124 U/l to 8833 U/l (median: 619; IQR: 955) + 2 IU/l to 283,782 IU/l (median: 20; IQR: 63) pre- and from 107 U/l to 8650 U/l (median: 324; IQR: 481) + 0 IU/l to 36700 IU/l post-orchiectomy (median: 30; IQR: 121), respectively. Five-year CSS and RFS rates were 90% and 79%, respectively. Patients with LDH levels pre-orchiectomy 3 to 5 UNL (n=44) and 83% (72%) for >5 UNL (n=44) (CSS p