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Introduction and Objectives: Postchemotherapy residual tumor resection (PC-RTR) is an important part of the multimodal treatment for patients with metastatic germ cell tumors. Simultaneous retroperitoneal and thoracic metastases often require consecutive surgical procedures. This study analyzes the histologic findings after abdominal and thoracic surgery in order to tailor the sequence and intensity of surgery., Patients and Methods: From a total of 671 PC-RTRs from 2008 to 2021 we analyzed 50 patients with stage III non-seminomatous germ cell tumor (NSGCT) who had undergone both retroperitoneal and thoracic postchemotherapy residual tumor resection after first-line and salvage chemotherapy., Results: All patients included had stage III NSGCT. 39 and 11 patients received first-line and salvage chemotherapy, respectively. 45 (90%) patients received retroperitoneal resection first, followed by thoracic surgery. Three patients (6%) underwent thoracic surgery before retroperitoneal surgery and two patients (4%) underwent simultaneous surgery. Overall, the histology of retroperitoneal and thoracic specimens was discordant in 23% of cases. After first-line chemotherapy, of fourteen patients with necrosis in retroperitoneal histology, four patients had vital carcinoma in lung histology. In patients with teratoma in the retroperitoneum, the thoracic findings were concordant in most cases (78%). When teratomatous elements were also present in the orchiectomy specimen, concordance was 100%. After salvage chemotherapy, the discordance rate was 55%., Conclusion: The data presented in this study underline that retroperitoneal residual masses with necrosis cannot reliably predict histologic findings of thoracic specimens. Patients with teratoma in the retroperitoneum have a high likelihood of teratoma in the thoracic specimen., (© 2024. The Author(s).)

Purpose: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminomatous germ cell tumors (GCTs) aims to resect all remaining metastatic tissue. Resection of adjacent visceral or vascular organs is commonly performed for complete resection. Resection of organs harboring only necrosis results in relevant overtreatment. The study aimed to describe the frequency of metastatic involvement of resected organs with teratoma or viable cancer and to analyze perioperative complications and relapse-free survival., Materials and Methods: In a 2-center study, we reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 and identified 242 (20%) cases of adjunctive surgery during PC-RPLND. We analyzed the removed adjacent structures and the pathohistological presence of GCT elements in the resected organs: viable GCT, teratoma, or necrosis/fibrosis. Surgery-associated complications were reported according to the Clavien-Dindo classification., Results: Viable GCT, teratoma, and necrosis were present in 54 (22%), 94 (39%), and 94 (39%), respectively, of all patients with adjunctive resection of adjacent organs. Vascular resections or reconstructions (n = 112; viable: 23%, teratoma: 41%, necrosis: 36%) were performed most frequently, followed by nephrectomies (n = 77; viable: 29%, teratoma: 39%, necrosis: 33%). Perioperative complications of grade ≥ IIIa occurred in 6.6% of all patients, with no difference between the viable GCT and teratoma/necrosis groups ( P = .1). A total of 76 patients have been followed without a relapse for at least 36 months. Median follow-up of the whole cohort was 22 months (quartile 7 and 48). Patients with viable GCT/teratoma in the resected specimens had a significantly increased risk of recurrence by 5 years compared to patients with only necrosis (19% vs 59% vs 81%, P < .001)., Conclusions: This study shows that 33% to 40% of all resections of adjacent organs do not harbor teratoma or viable GCT. This highlights the need for better patient selection for these complex patients.

Purpose: Surveillance of clinical stage I (CSI) testicular germ cell tumors (GCT) is hampered by low sensitivity and specificity of current biomarkers for detecting relapses. This study evaluated if serum levels of microRNA371a-3p (M371 test) can: (i) Accurately detect relapses, (ii) detect relapses earlier than conventional technology, and (iii) if elevated postoperative M371 levels may predict relapse., Experimental Design: In a multicentric setting, 258 patients with testicular CSI GCT were prospectively followed by surveillance for a median time of 18 months with serial measurements of serum M371 levels, in addition to standard diagnostic techniques. Diagnostic characteristics of M371 for detecting relapses were calculated using ROC curve analysis., Results: Thirty-nine patients recurred (15.1%), all with elevated M371 levels; eight without relapse had elevations, too. The test revealed the following characteristics: area under the ROC curve of 0.993, sensitivity 100%, specificity 96.3%, positive predictive value 83%, negative predictive value 100%. Earlier relapse detection with the test was found in 28%, with non-significant median time gain to diagnosis. Postoperative M371 levels did not predict future relapse., Conclusions: The sensitivity and specificity of the M371 test for detecting relapses in CSI GCTs are much superior to those of conventional diagnostics. However, post-orchiectomy M371 levels are not predictive of relapse, and there is no significant earlier relapse detection with the test. In all, there is clear evidence for the utility of the M371 test for relapse detection suggesting it may soon be ready for implementation into routine follow-up schedules for patients with testicular GCT., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Primary retroperitoneal lymph node dissection (RPLND) for clinical stage (CS) IIA/B seminoma without adjuvant treatment is an experimental treatment to avoid radiotherapy- or chemotherapy-related toxicity from standard treatment., Objective: The PRIMETEST trial aimed to prospectively evaluate the oncological efficacy and surgical safety of primary RPLND., Design, Setting, and Participants: PRIMETEST is a single-arm, single-center prospective phase 2 trial. Patients with seminoma, unilateral retroperitoneal lymph node metastases <5 cm, and human chorionic gonadotropin levels <5 mU/ml were included. Patients with CS IIA/B seminoma at initial diagnosis, and recurrence under active surveillance or following adjuvant carboplatin for CS I disease were eligible., Outcome Measurements and Statistical Analysis: Unilateral open or robot-assisted primary RPLND was performed. The primary endpoint of the study was progression-free survival (PFS) after 36 mo. The trial was considered positive if <30% of patients experienced a recurrence., Results and Limitations: Between 2016 and 2021, 33 patients were accrued (nine with primary CS IIA/B, 19 recurrences during active surveillance, and five recurrences following adjuvant carboplatin). Thirteen and 20 patients had CS IIA and IIB, respectively. Open and robot-assisted RPLND procedures were performed in 14 (42%) and 19 (58%) patients, respectively. After a median follow-up of 32 mo (interquartile range 23-46), ten recurrences were detected (30%, 95% confidence interval: 16-49%); thus, the primary endpoint was not met. Infield recurrences occurred in three of ten patients. The current analysis of risk factors could not identify the predictors of recurrence. Three of 33 patients (9%) presented with pN0., Conclusions: The PRIMETEST trial did not meet its primary endpoint. Nevertheless, PFS of 70% after a median follow-up of 32 mo suggests this approach to be of interest for highly selected patients. Selection criteria, however, need to be defined and validated in a larger prospective cohort of patients. Until then, surgery alone for the treatment of patients with CS IIA/B seminoma cannot be recommended outside of a clinical trial setting., Patient Summary: In this study, we investigated primary surgery as an alternative to conventional treatment (chemotherapy or radiation therapy) in patients with metastatic seminoma. The primary objective of the study, to prevent at least 30% of patients from recurrence, was not met. However, certain patients may benefit from this approach and thereby avoid chemotherapy or radiation therapy. Predictive factors need to be analyzed to better select patients for this surgery-only approach., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

This is a data article from the original publication "Reasons for missing clinically significant prostate cancer by targeted magnetic resonance imaging/ultrasound fusion-guided biopsy" [1]. From January 2014 to April 2019 a sample collective of 785 patients with 3T multiparametric magnetic resonance imaging (mp-MRI) of the prostate and subsequent combined systematic biopsy (SB) and magnetic resonance imaging/ultrasound (US) fusion-guided biopsy (TB) was retrospectively analyzed. Prostate cancer (PCa) detection by TB and/or additional SB was analyzed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2022 The Authors.)

Objective: To evaluate the relationship between pre-operative PSA value, 68 Ga-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 68 Ga-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 (<0.5 ng/ml), low (0.5-0.99 ng/ml), moderate (1-1.5 ng/ml) and high (>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  < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non-linear relationship between PSA level at sLND and the 12-month CR-free survival ( p  < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml., Conclusions: In case of PET-detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short-term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68 Ga-PSMA PET in biochemical recurrent PCa., (© 2022 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Purpose: To describe the perioperative safety, functional and immediate post-operative oncological outcomes of minimally invasive RPLND (miRPLND) for testis cancer., Methods: We performed a retrospective multi-centre cohort study on testis cancer patients treated with miRPLND from 16 institutions in eight countries. We measured clinician-reported outcomes stratified by indication. We performed logistic regression to identify predictors for maintained postoperative ejaculatory function., Results: Data for 457 men undergoing miRPLND were studied. miRPLND comprised laparoscopic (n = 56) or robotic (n = 401) miRPLND. Indications included pre-chemotherapy in 305 and post-chemotherapy in 152 men. The median retroperitoneal mass size was 32 mm and operative time 270 min. Intraoperative complications occurred in 20 (4%) and postoperative complications in 26 (6%). In multivariable regression, nerve sparing, and template resection improved ejaculatory function significantly (template vs bilateral resection [odds ratio (OR) 19.4, 95% confidence interval (CI) 6.5-75.6], nerve sparing vs non-nerve sparing [OR 5.9, 95% CI 2.3-16.1]). In 91 men treated with primary RPLND, nerve sparing and template resection, normal postoperative ejaculation was reported in 96%. During a median follow-up of 33 months, relapse was detected in 39 (9%) of which one with port site (< 1%), one with peritoneal recurrence and 10 (2%) with retroperitoneum recurrences., Conclusion: The low proportion of complications or peritoneal recurrences and high proportion of men with normal postoperative ejaculatory function supports further miRPLND studies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Multiple studies have occurred to determine if a patient's blood type, Rhesus factor (Rh), and sociodemographic attributes contribute to contracting SARS-CoV-2. True association remains unknown., Methods: Inclusion criteria included in-patients who were tested for SARS-CoV-2 with blood type assessed. Study endpoints combined ABO, Rh and all-cause inpatient mortality (ACIM) with testing positivity. Pregnancy status was one of several secondary endpoints evaluated. A logistic regression analysis was used to estimate association., Results: Of the 27,662 patients who met inclusion criteria, Type A blood was associated with increased positivity [1.01 (1.0-1.21), P = .03]. Type B [1.10 (0.99-1.23), P = .08] and AB [0.98 (0.81-1.19), P = .84] showed no association. When evaluating ACIM, type A [1.18 (0.91-1.52), P = .22], B [1.13 (0.82- 1.56), P = .480], and AB [1.06 (0.62-1.81), P = .839] were not associated with increased mortality. The female subgroup was less likely to test positive [0.88 (0.82-0.986), P = .002]. Black patients demonstrated a higher likelihood of positivity when compared to White [1.96 (1.79-2.14), P < .001]. Non-pregnant women exhibited a 2.5 times greater likelihood of testing positive [2.49 (2.04-3.04), P < .001]., Conclusions: This study confirms results of previous research which showed SARS-Co-V-2 positivity related to blood type. It also confirms more recent research demonstrating inequities related to acquisition of SARS-CoV-2 for certain sociodemographic groups. Larger studies are warranted to confirm and further explore novel pregnancy findings., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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 < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >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., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Clinical stage 1 (CS1) nonseminomatous (NS) germ cell tumors involve a 30% probability of relapse upon surveillance. Adjuvant chemotherapy with one course of bleomycin, etoposide, and cisplatin (1xBEP) can reduce this risk to <5%. However, 1xBEP results are based solely on five controlled trials from high-volume centers. We analyzed the outcome in a real-life population., Patients and Methods: In a multicentric international study, 423 NS CS1 patients receiving 1xBEP were retrospectively evaluated. Median follow-up was 37 (range, 6-89) months. Primary end points were relapse-free and overall survival evaluated after 5 years. We also looked at associations of relapse with clinico-pathological factors using stratified Kaplan-Meier methods and Cox regression models. Treatment modality and outcome of recurrences were analyzed descriptively., Results: The 5-year relapse-free survival rate was 96.2%. Thirteen patients (3.1%; 95% confidence interval, 1.65-5.04%) relapsed after a median time of 13 months, of which 10 were salvaged (77%). Relapses were mostly confined to retroperitoneal nodes. Three patients succumbed, two to disease progression and one to toxicity of chemotherapy. Pathological stage >pT2 was significantly associated with relapse rate., Conclusion: The relapse rate of 3.1% found in this population of NS CS1 patients treated with 1xBEP at the routine care level was not inferior to the median rate of 2.3% reported from a meta-analysis of controlled trials. Also, the cure rate of relapses of 77% is consistent with the previously reported rate of 80%. This study clearly shows that the 1xBEP regimen represents a safe treatment for NS CS1 patients., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Purpose: The oncologic benefit of postchemotherapy (PC) residual tumor resection (RTR) in patients with germ cell tumors and elevated serum tumor markers (STMs) remains unclear. This analysis was performed to better define patients who benefit from surgery in this setting., Materials and Methods: Of 575 PC-RTR procedures (July 2008-July 2019) 153 were performed in patients with elevated STMs (human chorionic gonadotropin [HCG] >2.0 mIU/ml, alpha-fetoprotein [AFP] >7.0 µg/l), including 55 after first line and 98 after second or later line chemotherapy., Results: Viable cancer in the resected specimen was significantly more common in the salvage group than in the first line group (48.98% vs 16.36%, p=0.0001988) and was a predictor of survival in both groups. A preoperative serum level of AFP ≥30 µg/l was a significant predictor of viable cancer in the first line and salvage groups (55.56% [p=0.0157] and 66.67% [p=0.0017], respectively). The overall relapse-free survival rate (22.7% and 50%, p=0.00032) and overall survival rate (37.8% and 65%, p=0.0059) were significantly worse in the salvage group than in the first line group. A preoperative serum level of AFP ≥30 µg/l and viable cancer/teratoma found in the histological examination of the RTR specimens were significant predictors of relapse after first line chemotherapy. Serum AFP ≥30 µg/l and HCG ≥20 mIU/ml were significant factors affecting survival in the first line group., Conclusions: Patients with AFP serum levels >30 µg/l and HCG ≥20 mIU/ml after first line chemotherapy should receive salvage chemotherapy instead of surgery. After second or later line therapy, the prognosis of patients with elevated markers and surgery is poor regardless of the tumor marker levels. However, 38% of these patients are long-term survivors, which justifies PC-RTR in this setting.

Purpose: To evaluate the probability to correctly predict major vascular surgery (MVS) in patients undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for testicular cancer., Methods: From a database of 504 RPLNDs performed in 434 patients (2008-2018), 78 patients submitted to PC-RPLND for non-seminoma germ-cell cancer after cisplatin-based chemotherapy with available preoperative CT scans were identified. Second PC-PLNDs (Re-Dos), salvage RPLNDs, or RPLNDs for late-relapse were excluded as well as thoraco-abdominal approaches. Preoperative imaging was reviewed by a urologist and a radiologist blinded to operative details., Results: Of 78 patients, 16 (20.5%) underwent MVS (caval and/or aortic replacement or reconstruction). On univariable analyses, transversal diameter, sagittal diameter, tumor volume, aorta- and cava-tumor contact angle, poor IGCCCG score, clinical stage III and preoperative positive markers were predictors of MVS (all p values ≤ 0.01). At multivariable analyses aorta- (cut-off 64°) and cava-tumor contact angle (cut-off 98°) and poor IGCCCG score represented the three most important predictors of MVS (all p values ≤ 0.05). The model constructed has a PPV 100%, NPV 87% and an accuracy of 88%., Conclusions: Presence of aorta-tumor contact angle ≥ 64°, cava-tumor contact angle ≥ 98° and poor IGCCCG score identify correctly 9 out of 10 patients requiring MVS at the time of first PC-RPLND., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Late relapsing germ cell tumors (LR-GCT) are considered a rare distinct biologic entity as their clinical presentation and response to treatment is different to early recurrences. While serum tumor markers (AFP and ß-HCG) play an important role at the time of first diagnosis to correctly classify prognosis and treatment of germ cell tumors, they may not have the same significance in a late relapse situation., Patients and Methods: Thirty-seven patients with LR-GCT with elevated serum tumor markers were identified in our database. Twenty-six patients underwent primary surgical resection of the late relapsing tumor. Eleven patients received salvage chemotherapy and a post-chemotherapy residual tumor resection. Serum tumor markers, histological findings and oncological outcome were analyzed., Results: In the histopathological specimen, viable cancer was found in 20 cases (54%) and teratoma was found in 16 cases (43%). In nine cases (24%), a somatic-type malignant transformation was present. In 19 of 37 patients (51.4%), the late relapse specimen presented a histological type of GCT, which was not present in the primary histology. Twenty-two patients (59.5%) were included in follow-up analysis. Mean and median follow-up time was 62.2 and 53 months, respectively. Seventeen patients (77.3%) suffered a relapse or had progressive disease after LR therapy. Five patients (22.7%) have been relapse-free after LR therapy (mean FU 61.6 months). Ten patients died of disease during follow-up (45.5%) and had a mean time from LR to death of 66.4 months. Eleven patients were alive at last follow-up (mean FU 62.2 months). Relapse and survival rate were similar between patients who received primary resection of LR tumor and patients who received salvage chemotherapy followed by surgery., Conclusion: Patients with a late relapsing germ cell tumor and elevated markers have a poor prognosis and a high risk for another relapse independent on primary treatment. The histological type and aggressiveness of a late relapsing tumor cannot be predicted with serum tumor marker levels at the time of diagnosis of LR. In up to 54% of cases, primary histology did not coincide with LR histology. Therefore, we propose primary surgical resection of a late relapsing tumor if a complete resection is feasible in order to gain exact histology and tailor further treatment., (© 2021. The Author(s).)

Purpose: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS., Methods: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test., Results: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death., Conclusion: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach., (© 2021. The Author(s).)

Background: One cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) has shown superiority in recurrence-free survival over retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I non-seminomatous germ cell tumours (NSGCTs) of the testis in the setting of a phase III trial. We report the recurrences and late toxicities of this study after 13 years of follow-up., Methods: Questionnaires from 382 patients with CS I NSGCT treated with 1 cycle of adjuvant BEP (arm A) or RPLND + two cycles of adjuvant BEP in cases of pathological stage II disease (arm B) were evaluated regarding recurrences and late toxicity. Overall, information on recurrence status was available in 337 patients, and 170 questionnaires were evaluable for toxicity (arm A: 95; arm B: 75)., Results: With a median follow-up of 13.8 years (0-22), 3 patients (1.6%) in arm A and 16 patients (8.4%) in arm B experienced recurrence. The 15-year PFS in arm A/B was 99% (CI 96-100%)/92% (CI 89-99%) (p = 0.0049). The 15-year OS in arm A/B was 93% (CI 87-97%)/93% (CI 86-97%) (p = 0.83). Eight patients (4.2%) in arm A and four patients (2.1%) in arm B showed metachronous secondary testicular cancer (p = 0.26). Five patients (2.6%) in arm A and four patients (2.1%) in arm B developed other malignancies. Toxicities were not significantly different apart from retrograde ejaculation, which occurred more frequently after RPLND (10% versus 24%, p = 0.01)., Conclusions: With long-term observation, one cycle of BEP remains superior to RPLND in preventing recurrence and was tolerated without any clinically relevant long-term toxicities., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Thoracic growing teratoma syndrome (TGTS) is a rare disease in patients with germ cell tumors. Other than a few case reports and a limited number of case series, studies of this topic are not available., Methods: We retrospectively analyzed the data from our patients who received surgery for TGTS between 1999 and 2016. Descriptive statistical analyses were performed to analyze the characteristics of the patients, tumors, and short-term outcomes. Furthermore, the long-term outcomes and survival curves were analyzed using the Kaplan-Meier method., Results: Twenty-nine patients underwent surgery for TGTS. The median age was 32 years (range: 19-50 years). All patients received cisplatin-based chemotherapy. Many of the patients had multilocalized TGTS (n = 10). The median tumor size was 64.5 mm (range 10-210 mm). In all cases, R0 resection was achieved. The minor morbidity, major morbidity, and mortality rates were 3.4%, 6.9%, and 0%, respectively. Altogether, 28 patients were included in the long-term follow-up analysis, with a median follow-up time of 94 months (13-237 months). The 5-, 10-, and 15-year survival rates were 93%, 93%, and 84%, respectively., Conclusions: TGTS may occur in multiple localizations and grow to a large tumor size. The resection of TGTS can be performed with low morbidity and mortality rates and is associated with good overall survival after complete resection. Important are an early detection and knowledge of the systemic treatment options by the oncologist and urologist, as well as a thoracic surgeon with a large experience in extended thoracic resections., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study evaluates cases with clinically significant prostate cancer (csPCa) missed by targeted biopsy (TB) and analyzes the diagnostic impact of an additional systematic biopsy (SB) in a large patient collective., Methods: Consecutive patients with a 3 T multiparametric prostate MRI (mpMRI) and a subsequent MRI/US fusion-guided TB plus 12-core US-guided SB from 01/2014 to 04/2019 were included in this study. Primary study endpoint was the analysis of cases with a csPCa missed by TB and detected by SB. Secondary study objectives were the PCa detection and the correlation with clinical and MRI parameters., Results: In total 785 patients met the inclusion criteria. 342 patients had a csPCa (median PSAD 0.29 ng/mL/cm 3 ). In 42 patients (13 %), a csPCa was detected only by SB. In 36 of these cases, the localization of the positive SB cores matched with the cancer suspicious region described on mpMRI (mCSR). Cases with a csPCA missed by TB showed either an insufficient MRI segmentation (prostate boundary correlation) (31 %) and/or insufficient lesion registration (lesion transfer, tracking, and/or matching) (48 %), a missed small lesion (14 %), or a failed center of a large lesion (10 %). Median PSAD of patients with non-significant PCa detected by SB was 0.15 ng/mL/cm 3 ., Conclusions: Main reasons for missing a csPCa by TB were insufficient prostate segmentation or imprecise lesion registration within MRI/US fusion-guided biopsy. Consequently, verification of MRI quality, exact mCSR assessment, and advanced biopsy experience may improve accuracy. Altogether, an additional SB adds limited clinical benefit in men with PSAD ≤ 0.15 ng/mL/cm 3 ., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Among young men between the ages of 15 and 40 years, germ cell cancer is the most common solid tumor [1]. The worldwide incidence of germ cell cancer is 70 000 cases. Compared to all solid tumors of men, germ cell cancer accounts for 1% of all male tumors. Nevertheless, the mortality of this rare tumor entity is about 13% since 9507 patients died worldwide of germ cell cancer. The improvement in survival of germ cell cancer patients is due to a multimodal treatment of germ cell cancer including cisplatin-based chemotherapy and surgery leading to higher cure-rates even in advanced stages [1], whereas the increasing incidence of germ cell cancers cannot be thoroughly explained. In this article we review the current indications for surgery in metastatic germ cell cancers, highlight the strength and weaknesses of techniques and indications and raise the question how to improve surgical treatment in metastatic germ cell cancer., (© 2021 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Germ cell cancers are the most common solid tumors among men between 15 and 40 years. Non-seminomatous germ cell tumors (NSGCTs) represent a unique and exclusive cohort of germ cell tumor patients. Non-seminoma can harbor different histologic components. The most commonly found histologies are embryonal cell cancer, teratoma, yolk sack tumor and choriocarcinoma, as well as teratocarcinoma and seminoma, in combination with non-seminomatous germ cell tumors histologic types. The clinical definition of stage I non-seminoma is the absence of metastatic lesions on imaging and normal tumor markers. The cure rate for clinical stage I NSGCT is 99% and this can be achieved by three therapeutic strategies: Active surveillance with treatment at the time of relapse, retroperitoneal lymph node dissection or adjuvant chemotherapy. The balancing of these various strategies should always be based on an individual risk profile of NGSCG patient depending on the lymphovascular invasion of the tumor., Competing Interests: The authors declare no conflict of interest., (© 2021 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Objectives: To compare prostate specific membrane antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) and computed tomography (CT) alone for the detection of biochemical recurrence of prostate cancer (PCa) and effect on treatment., Methods: This retrospective study included 59 patients with recently recorded biochemical recurrence of PCa (mean PSA 1.96 ± 1.64 ng/mL) after radical prostatectomy. Patients received PET/CT with either 68 Ga-PSMA-11 (n = 36) or 18 F-PSMA-1007 (n = 23). PET/CT and CT images were evaluated separately in regard to PCa lesion count, type, and localisation by two physicians. Histopathology, follow-up imaging and PSA levels after salvage irradiation served as reference standard. A McNemar test was used to compare detection rates. Changes in therapeutic approaches based on staging differences between CT alone and PET/CT were assessed in a virtual multidisciplinary tumour board., Results: There were 142 lesions in 50 of 59 patients. PSMA PET/CT detected 141 lesions (99.3 %) in 50 patients (84.7 %), while CT detected 72 lesions (50.7 %) in 29 patients (49.2 %). A significantly higher detection rate of PSMA PET/CT was observed on a lesion-based analysis (p < 0.0001) and on a patient based analysis (p < 0.0001). Herein, both 68 Ga- and 18 F-PSMA PET/CT performed significantly better than CT alone (p < 0.0001, respectively). In 9 patients (15.3 %) no relapse was detectable by either modality. All lesions detected by CT were also detected by PSMA PET/CT. In 38 patients PSMA PET/CT detected more lesions than CT alone, altering the treatment approach in 22 of these patients., Conclusion: PSMA PET/CT is superior to CT alone in detecting biochemical recurrence in PCa patients after radical prostatectomy and offered additional therapeutic options in a substantial number of patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Robotic assisted retroperitoneal lymph node dissection in patients with testicular cancer is controversial. Lately, unusual recurrence patterns with adverse outcomes after robotic assisted retroperitoneal lymph node dissection have been published. In this report we determine the feasibility, safety and early oncologic outcome of robotic assisted retroperitoneal lymph node dissection in patients with small volume metastatic testicular cancer., Materials and Methods: We retrospectively evaluated 27 consecutive patients with small volume metastatic testicular cancer (October 2010 to November 2019) who underwent robotic assisted retroperitoneal lymph node dissection (unilateral modified template). Intraoperative and postoperative complications as well as early oncologic outcomes are reported. Surgery was performed in the primary metastatic setting in 22 (81%), post-chemotherapy in 4 (15%) and for late relapse in 1 patient (4%). Initial clinical stage was IIA for 14 (52%), IIB for 12 (43%) and III for 1 (4%) patient., Results: Median operative time, blood loss and length of hospital stay were 175 minutes, 50 ml and 4 days, respectively. Expectedly, viable tumor was found in 21/27 patients (78%) and 6 patients (22%) showed fibrosis, necrosis or no tumor. Overall 3 (11%) patients experienced intraoperative (Satava II) and 1 (4%) postoperative (Clavien-Dindo IIIb) complications, respectively. Median followup was 16.5 months (3-69), and 3 (11%) patients experienced relapse outside of the surgical field after 12, 22 and 36 months., Conclusions: In highly selected patients with low volume metastatic testicular cancer robotic assisted retroperitoneal lymph node dissection may be indicated, and appears to be technically feasible and comparable with open surgery in terms of complications and early oncologic safety. Prospective data collection in larger series is necessary to clarify the role and specific indications of this approach.

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 11 C-choline and a 68 Ga 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 68 Ga-PSMA and 11 C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with 68 Ga-PSMA versus 28% with 11 C-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 68 Ga-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 68 Ga-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 68 Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Long-term outcomes of patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer (PCa) remain unknown., Objective: To investigate long-term oncological outcomes after sLND in a large multi-institutional series., Design, Setting, and Participants: The study included 189 patients who experienced prostate-specific antigen (PSA) rise and nodal-only recurrence after radical prostatectomy (RP) and underwent sLND at 11 tertiary referral centers between 2002 and 2011. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11 C-choline or 68 Ga prostate-specific membrane antigen ligand., Outcome Measurements and Statistical Analysis: The primary outcome of the study was cancer-specific mortality (CSM). The secondary outcomes were overall mortality, clinical recurrence (CR), biochemical recurrence (BCR), and androgen deprivation therapy (ADT)-free survival after sLND. The probability of freedom from each outcome was calculated using Kaplan-Meier analyses. Cox regression analysis was used to predict the risk of prostate CSM after accounting for several parameters, including the use of additional treatments after sLND., Results and Limitations: At long term, 110 and 163 patients experienced CR and BCR, respectively, with CR-free and BCR-free survival at 10 yr of 31% and 11%, respectively. After sLND, a total of 145 patients received ADT, with a median time to ADT of 41 mo. At a median (interquartile range) follow-up for survivors of 87 (51, 104) mo, 48 patients died. Of them, 45 died from PCa. The probabilities of freedom from cancer-specific and all-cause death at 10 yr were 66% and 64%, respectively. Similar results were obtained in sensitivity analyses in patients with pelvic-only positive PET/CT scan, as well as after excluding men on ADT at PET/CT scan and patients with PSA level at sLND higher than the 75th percentile. At multivariable analyses, patients who had PSA response after sLND (hazard ratio [HR]: 0.45; p = 0.001), and those receiving ADT within 6 mo from sLND (HR: 0.51; p = 0.010) had lower risk of death from PCa., Conclusions: A third of men treated with sLND for PET-detected nodal recurrence of PCa died at long term, with PCa being the main cause of death. Salvage LND alone was associated with durable long-term outcomes in a minority of men who significantly benefited from additional treatments after surgery. Taken together, all these data argue against the use of metastasis-directed therapy alone for patients with node-only recurrent PCa. These men should instead be considered at high risk of systemic dissemination already at the time of sLND., Patient Summary: We assessed long-term outcomes of patients treated with salvage lymph node dissection (sLND) for node-recurrent prostate cancer (PCa). In contrast with prior evidence, we found that the majority of these men recurred after sLND and eventually died from PCa. A significant survival benefit associated with the administration of androgen deprivation therapy after sLND suggests that sLND should be considered part of a multimodal approach rather than an exclusive treatment strategy., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess the ability of multiparametric MRI (mp-MRI) of the prostate to exclude prostate cancer (PCa) progression during monitoring patients on active surveillance (AS)., Methods: One hundred forty-seven consecutive patients on AS with mp-MRI (T2WI, DWI, DCE-MRI) at 3T were initially enrolled. Fifty-five received follow-up mp-MRI after a minimum interval of 12 months and subsequent targeted MR/US fusion-guided biopsy (FUS-GB) plus concurrent systematic transrectal ultrasound-guided (TRUS-GB) biopsy as reference standard. Primary endpoint was the negative predictive value (NPV) of the follow-up mp-MRI to exclude histopathologic tumor progression using PRECISE recommendations. Secondary endpoints were the positive predictive value (PPV), sensitivity, specificity, Gleason score (GS) upgrades, and comparison of biopsy method., Results: Of 55 patients, 29 (53%) had a GS upgrade on re-biopsy. All 29 patients showed a tumor progression on follow-up mp-MRI. Fifteen of 55 patients (27%) displayed signs of tumor progression, but had stable GS on re-biopsy. None of the 11 patients (20%) without signs of progression on follow-up mp-MRI had a GS upgrade on re-biopsy. The NPV was 100%, PPV was 66%, sensitivity was 100%, and specificity 42%. FUS-GB resulted in GS upgrade significantly more often (n = 28; 51%) compared with TRUS-GB (n = 12; 22%; p < 0.001)., Conclusions: (Follow-up) Mp-MRI can reliably exclude PCa progression in patients on AS. Standard serial re-biopsies might be waived if follow-up mp-MRIs are stable. Over 60% of patients with signs of tumor progression on mp-MRI during AS had a GS upgrade on re-biopsy. Targeted re-biopsies should be performed if cancer progression or higher-grade PCa is suspected on mp-MRI., Key Points: • None of the patients with unsuspicious mp-MRI had a GS upgrade in re-biopsy and mp-MRI might replace serial biopsies in these cases • More than 60% of patients with mp-MRI signs of tumor progression had subsequent Gleason score (GS) upgrades • Targeted re-biopsies should be performed in case of higher GS cancer suspicion on mp-MRI.

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

The increasing knowledge of the influence of the immune system on tumour development and progression has fundamentally changed our understanding of tumour biology in recent years. While the available treatment options for patients with metastatic urothelial carcinoma of the urinary bladder have hardly improved over decades, the advent of immune checkpoint inhibitors has caused major changes in the corresponding treatment landscape.Although cisplatin-based combination therapies remain the main element, additional effective treatment options now exist with the PD-(L)-1 inhibitors atezolizumab, pembrolizumab and nivolumab, which have been approved in Europe. A remarkable long-term response is balanced by the occurrence of occasionally severe immune-mediated side effects and an overall low response rate of approximately 25 %. A large number of current clinical trials therefore address possible combinatory approaches in order to make optimal use of possible synergisms and additive effects of the substances available to date, taking into account an acceptable side effect profile. In addition, many new therapeutic approaches are also being tested in clinical trials. In this context, developments in the field of antibody-drug conjugates and FGFR inhibitors with regards to the very recent FDA approvals are particularly noteworthy.The present review provides an overview of currently available treatment options in metastatic urothelial carcinoma of the bladder and especially focuses on future therapeutic approaches based on current clinical trials., Competing Interests: GN: Vortragstätigkeiten: Pfizer Pharma GmbH (seit 2016), Roche Pharma AG (seit 2016), medac GmbH (seit 2017) Advisory Boards, Beratertätigkeit: Roche Parma AG (seit 2015), IMS Health AG (2016-2018), BMS AG (2016), Sanofi-Aventis (2018) Reisekosten- und Fortbildungsunterstützung: Roche Parma AG (seit 2015), medac GmbH (seit 2017), Pfizer Pharma GmbH (seit 2016), (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: We compared the use of 11 C-choline and 68 Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer., Materials and Methods: The study included 641 patients who experienced prostate specific antigen rise and nodal recurrence after radical prostatectomy and underwent salvage lymph node dissection. Lymph node recurrence was documented by positron emission tomography/computerized tomography using 11 C-choline (407, 63%) or 68 Ga-PSMA ligand (234, 37%). The outcome was underestimation of tumor burden (difference between number of positive nodes on final pathology and number of positive spots at positron emission tomography/computerized tomography). Multivariable analysis tested the association between positron emission tomography/computerized tomography tracer ( 11 C-choline vs 68 Ga-PSMA) and tumor burden underestimation., Results: Overall the extent of tumor burden underestimation was significantly higher in the 11 C-choline group compared to the 68 Ga-PSMA group (p <0.0001), which was confirmed on multivariable analysis (p=0.028). Repeating these analyses according to prostate specific antigen, tumor burden underestimation was lower with 68 Ga-PSMA only when prostate specific antigen was 1.5 ng/ml or less. Conversely, the underestimation of the 2 tracers became similar when prostate specific antigen was greater than 1.5 ng/ml. Furthermore, we evaluated the risk of underestimation by number of positive spots on positron emission tomography/computerized tomography. The higher the number of positive spots the higher the underestimation of tumor burden regardless of the tracer used (p=0.2)., Conclusions: Positron emission tomography/computerized tomography significantly underestimates the burden of prostate cancer recurrence, regardless of the tracer used. 68 Ga-PSMA was associated with a lower rate of underestimation in patients with a prostate specific antigen below 1.5 ng/ml and a limited nodal tumor load. In all other men there was no benefit from 68 Ga-PSMA over 11 C-choline in assessing the extent of nodal recurrence.

Objective:  To assess the impact of dynamic contrast-enhanced imaging (DCE) in mp-MRI on prostate cancer (PCa) detection in a large patient cohort assigned to PI-RADS category 4., Method:  This retrospective, single center cohort study includes 193 consecutive patients with PI-RADS assessment category 4 in mp-MRI (T2WI, DWI, DCE) at 3 T with targeted plus systematic biopsy combined as the reference standard. The detection of prostate cancer with and without the use of DCE was compared., Results:  Overall, the PCa detection rate in PI-RADS-4 patients was 62 % (119/193) with DCE and 52 % (101/193) without the inclusion of lesions upgraded on the basis of DCE. 48 % (92/193) had clinically significant PCa (csPCa; Gleason score ≥ 3 + 4 = 7) and 40 % (78/193) without use of DCE. 38 of the 193 patients (20 %) had peripheral lesions upgraded from PI-RADS category 3 to an overall PI-RADS category 4 due to focal positive DCE findings. Of these 38 patients, 18 had PCa including 14 with csPCa. Thus, 15 % (18/119) of the patients with PCa and 15 % (14/92) of the patients with csPCa were detected only based on additional DCE information., Conclusion:  DCE prevents underestimation and misclassification of a significant number of cases of peripheral csPCa and might improve detection rates in PI-RADS-4 patients. The current PI-RADS decision rules regarding upgrading PI-RADS-3 lesions to category 4 due to positive DCE imaging are useful for PCa detection., Key Points:   · Positive peripheral DCE upgraded 20 % of patients in PI-RADS category 4 from category 3.. · Clinically significant PCa was found in almost 40 % of upgraded, peripheral PIRADS-3-lesions.. · 15 % of all csPCa in PI-RADS-4-patients was detected in DCE-upgraded lesions.. · In 7 % of all PI-RADS-4-cases csPCa would had been underestimated without DCE upgrade.., Citation Format: · Ullrich T, Quentin M, Arsov C et al. Value of Dynamic Contrast-Enhanced (DCE) MR Imaging in Peripheral Lesions in PI-RADS-4 Patients. Fortschr Röntgenstr 2020; 192: 441 - 447., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: To evaluate different analgesic techniques in MRI-guided in-bore prostate biopsy (IB-GB) regarding the influence on patient procedural experience of pain., Methods: Two hundred fifty-two consecutive patients who had received an IB-GB either with intrarectal instillation of 2% lidocaine gel (n = 126, group A) or with periprostatic nerve block (PPNB) with 2% mepivacaine (n = 126, group B) were retrospectively included in this study. Pain scores were measured on a visual analog scale, the operating room time (ORT) was recorded for each biopsy and correlations between the parameters were analysed., Results: Pain scores for IB-GB were slightly lower in group B compared with group A (2.0 ± 1.9; 2.4 ± 1.7; p = 0.02). In group A, significantly more targeted biopsy cores were acquired (group B: 5.2 ± 1.1; group A: 5.6 ± 0.8; p < 0.01). ORT was comparable and not significantly different in both groups. There was only a weak correlation between pain scores and ORT in group B (r S  = 0.22; p = 0.01), but no correlation between pain scores and the number of biopsy cores or the prostate volume., Conclusions: Pain levels are generally low for MRI-guided in-bore biopsy using either PPNB or intrarectal instillation of lidocaine gel. A statistically significant, slightly lower pain score was documented for PPNB and might be preferred when the focus is analgesia. On the other hand, due to the minor difference and easier administration, intrarectal gel instillation seems to be a reasonable practice for standard analgesia for MRI-guided in-bore biopsy., Key Points: • Pain levels were low for MRI-guided in-bore biopsy using either PPNB or intrarectal instillation of lidocaine gel as analgesic method. • PPNB prior to IB-GB resulted in a slightly lower pain score but required a higher effort. • Intrarectal gel anaesthesia seems to be a reasonable practice for standard analgesia for IB-GB in an outpatient setting.

Objectives: To report pre-, postoperative and oncological outcomes in patients treated with spot-specific sLND for patients with exclusive nodal recurrence after PCa primary treatment., Materials and Methods: With regard to salvage treatment failure (sTF), 46 consecutive patients, undergoing 52 sLND for nodal recurrence detected by PET/CT scan were stratified in 3 groups (group A: post-sLND PSA nadir < 0.01 ng/ml and in follow-up reaching a value > 0.2 ng/ml, group B: post-sLND PSA nadir > 0.01 ng/ml and in follow-up reaching a value equal to pre-sLND PSA; group C: additional salvage treatment administration). Surgical outcome of patients was analyzed by descriptive statistics (Student's t test for continuous variables, Chi-square and Fisher's test for categorial ones). Time to sTF of each group was analyzed and compared by Kaplan-Meier method and correlations regarding sTF and pre-sLND PSA, time from PCa primary treatment to PET/CT scan, time from PCa primary treatment to sLND and number of positive PET/CT scan spots were assessed., Results: Median PSA at PET/CT scan was 2.9 ng/ml (IQR 1.2-6.1). Open and laparoscopic sLND were performed in 40/52 (77%) and 12/52 (23%), respectively. Median number of removed lymph nodes was 6 (IQR 4-13). Histological report was positive for PCa in 39/52 sLND (75%). Median blood loss was 50 ml (IQR 0-50, range 0-600). Median length of hospital stay was 5 days (IQR 4-6). 4 and 7 patients had low-grade (I/II) and high-grade (≥ III) Clavien-Dindo complications, respectively. Readmission rates at 30 and 90 days were 5/52 (9.6%) and 1/52 (2%), respectively. sTF was observed in 2/7 (group A), 12/12 (group B) and 22/22 patients (group C). Median time to sTF in group B and C was 3.5 (IQR 1.7-13.2) and 4 months (IQR 2.0-10), respectively., Conclusion: Even spot-specific PET/CT sLND harbors a measurable (CD > III) morbidity in 1 out of 7 patients. Only patients with positive histological report and a PSA nadir < 0.01 ng/ml after sLND seem to experience a long-term benefit. Patients with a PSA nadir > 0.01 ng/ml have a delay of systemic treatment of up to 4 months. sLND remains an experimental approach and long-term oncological benefit needs an improved selection of patients.

Growing teratoma syndrome (GTS) is a rare clinical phenomenon in patients with nonseminomatous germ cell cancer defined by growing metastatic mass during ongoing or directly after completed chemotherapy with timely decreasing tumor markers and postpubertal teratoma exclusively after resection. GTS was first described in 1982, and few reports have been published. The limited number of studies and the resulting lack of exact knowledge about development, differentiation, and treatment of GTS leaves several clinical problems regarding treatment and follow-up unsolved. This review provides an overview of clinical diagnosis and disease management and an approach to explain the molecular development of GTS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To evaluate if subgroups of patients assigned to MRI category PI-RADS 4 regarding clinical and MRI imaging aspects have distinct risks of prostate cancer (PCa) to facilitate adequate clinical management of this population, especially after negative targeted biopsy., Methods: This prospective, IRB approved single center cross-sectional study includes 931 consecutive patients after mp-MRI at 3 T for PCa detection. 193 patients with PI-RADS assessment category 4 received subsequent combined targeted MRI/US fusion-guided and systematic 12-core TRUS-guided biopsy as reference standard and were finally analyzed. The primary endpoint was PCa detection of PI-RADS 4 with MRI subgroup analyses. Secondary endpoints were analyses of clinical data, location of PCa, and detection of targeted biopsy cores., Results: PCa was detected in 119 of 193 patients (62%) including clinically significant PCa (csPCa; Gleason score ≥3 + 4 = 7) in 92 patients (48%). MRI subgroup analysis revealed 95% PCa (73% csPCa) in unambiguous PI-RADS 4 index lesions without additional, interfering signs of prostatitis in the peripheral zone or overlaying signs of severe stromal hyperplasia in the transition zone according to PI-RADS v2. Transition zone confined PI-RADS-4-lesions with overlaying signs of stromal hyperplasia showed PCa only in 11% (4% csPCa). Targeted biopsy cores missed the csPCa index lesion in 7% of the patients. PSA density (PSAD) was significantly higher in PCa patients., Conclusions: Small csPCa can reliably be detected with mp-MRI by experienced readers, but can be missed by targeted MR/US fusion biopsy alone. Targeted re-biopsy of unambiguous (peripheral) PI-RADS-4-lesions is recommended; whereas transition zone confined PI-RADS-4-lesions with overlaying signs of stromal hyperplasia might be followed-up by re-MRI primarily., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) plays a crucial role in treatment of metastatic non-seminomatous germ cell cancer. Objective: To evaluate the functional outcome regarding the preservation of ejaculatory function comparing a bilateral vs. unilateral template resection in PC-RPLND patients. In addition, oncological safety and perioperative complications of the unilateral template resection was compared to the full bilateral one. Design/Setting/Participants: Between 2003 and 2018, 504 RPLNDs have been performed in 434 patients. The database of consecutive patients was queried to identify 171 patients with PC-RPLND after 1st line chemotherapy for a non-seminoma with or without bilateral template resection. Re-Do's, late relapse, salvage patients, and thoraco-abdominal approaches were excluded. Indication for a template resection was a unilateral residual mass mainly <5 cm as published (1). Outcome, Measurement, and Statistical Analysis: Descriptive statistics were used to report preoperative features, postoperative outcomes and patterns of recurrence, on the overall population and after stratification for the type of resection (bilateral vs. unilateral). Kaplan-Meier analyses were used to describe recurrence- and cancer-specific mortality-free survival rates at different time points. Results and Limitations: Overall, 90 and 81 patients underwent unilateral and bilateral radical resection, respectively. Median size of residual mass was 7 cm for bilateral and 4 cm for unilateral template resection. Clinical stage II and III were present in 31 and 69% of patients, respectively. Median follow-up was 14.5 months (IQR 3.3-37.6). The 1- and 2-year recurrence-free survival rates were 91 and 91%, and 77 and 72% for patients treated with unilateral template and bilateral resection, respectively ( p = 0.0078). Median time to recurrence was 9.5 and 9 months in template and bilateral resection group, respectively. Adjunctive procedures were performed in 56 patients (33%) and were significantly more frequent in the bilateral resection group (43 vs. 23%, p = 0.006). The overall high-grade complication rate (Clavien-Dindo ≥ III) was 6, 3, and 9% in unilateral template and bilateral resection group, respectively ( p = 0.6). The rate of preservation of antegrade ejaculation was significantly higher in the unilateral group. Conclusions: Antegrade ejaculation in patients undergoing unilateral template resection with a residual mass <5 cm can be preserved at a much higher rate. Moreover, this surgical procedure is oncologically safe in terms of mid-term recurrence and CSM-free survival rates. This data undermines the growing evidence of limited PC-RPLND being justifiable in strictly unilateral residual mass <5 cm. This data has to be confirmed with a longer follow-up regarding in-field and retroperitoneal recurrences.

Purpose: For multiparametric magnetic resonance imaging/ultrasound fusion prostate biopsy the number of biopsy cores obtained is arbitrarily established by urologists. Moreover, a general consensus is lacking on the number of biopsy cores to be obtained from a single magnetic resonance imaging lesion. Therefore, we evaluated the feasibility of obtaining only 1 biopsy core per magnetic resonance imaging lesion., Materials and Methods: We retrospectively evaluated a total of 2,128 biopsy cores of 1,064 prostatic lesions (2 cores per lesion) in 418 patients in regard to prostate cancer detection (histology) and the Gleason score of the first biopsy core compared to the second biopsy core. Two analyses were performed, including patient level analysis based on prostate cancer detection per patient and lesion level analysis based exclusively on the histology of each lesion regardless of the overall histological outcome of the case., Results: The overall prostate cancer detection rate was 45.7% (191 of 418 patients). The first biopsy core detected 170 of all 191 prostate cancers (89%). In 17 of these 170 prostate cancers (10%) the second biopsy core revealed Gleason score upgrading. Nine of the 21 prostate cancers (43%) missed by the first biopsy core had a Gleason score of 6. Altogether 537 of the 2,128 biopsy cores were positive, including 283 first (26.6%) and 254 second (24%) biopsy cores (p ≤0.001). The concordance between the first and second biopsy cores was 89% (κ = 0.71). There was a discrepancy with Gleason score upgrading in 28 of 212 lesions (13.2%) with positive first and second biopsy cores., Conclusions: Our study shows that obtaining more than 1 biopsy core per magnetic resonance imaging lesion only slightly improves the prostate cancer detection rate and Gleason grading., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We systematically analyzed the records of patients with PI-RADS™ (Prostate Imaging Reporting and Data System) 3 lesions, which are called equivocal according to PI-RADS version 2, using prostate multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsies. Systematic transrectal ultrasound guided biopsies served as the reference standard., Materials and Methods: A total of 120 consecutive patients were retrospectively included in the study. In these patients the overall PI-RADS score was 3 after 3 Tesla T2-weighted imaging, diffusion weighted imaging and dynamic contrast enhanced multiparametric magnetic resonance imaging as well as subsequent targeted magnetic resonance imaging/ultrasound fusion guided biopsies plus systematic 12-core transrectal ultrasound guided biopsies. The study end points were the prostate cancer detection rate, the Gleason score distribution, the prostate cancer location and risk stratification by subgroup analyses., Results: Prostate cancer was detected in 13 of 118 patients for a detection rate of 11%, including 5 patients (4.2%) with a Gleason score of 3 + 4 = 7 or greater. Three of the 212 lesions (1.4%) in the transition zone and 6 of the 64 (9.4%) in the peripheral zone were positive for prostate cancer. Multiparametric magnetic resonance imaging revealed patterns of peripheral prostatitis combined with diffuse stromal hyperplasia in 54% of the patients with prostate cancer. Prostate volume was significantly lower in patients with prostate cancer (p = 0.015) but differences in prostate specific antigen levels were not statistically significant (p = 0.87). Prostate specific antigen density was higher in patients with prostate cancer (0.19 vs 0.12 ng/ml/ml)., Conclusions: Low grade prostate cancer (Gleason score 3 + 3 = 6) can develop in patients with an overall PI-RADS score of 3. Prostate cancer with a Gleason score of 3 + 4 = 7 or greater can be detected by multiparametric magnetic resonance imaging with a high degree of certainty. Gleason score 4 + 3 = 7 or greater prostate cancer is unlikely in PI-RADS 3 lesions. Therefore, these patients should primarily undergo followup multiparametric magnetic resonance imaging. In patients with a combination of multiparametric magnetic resonance imaging aspects of extensive prostatitis and diffuse stromal hyperplasia low prostate volume and/or high prostate specific antigen density biopsy might be considered., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: This study evaluates the feasibility of performing less than two core biopsies per MRI-lesion when performing targeted MR-guided in-bore prostate biopsy., Methods: Retrospectively evaluated were 1545 biopsy cores of 774 intraprostatic lesions (two cores per lesion) in 290 patients (66 ± 7.8 years; median PSA 8.2 ng/ml) regarding prostate cancer (PCa) detection, Gleason score, and tumor infiltration of the first (FBC) compared to the second biopsy core (SBC). Biopsies were acquired under in-bore MR-guidance., Results: For the biopsy cores, 491 were PCa positive, 239 of 774 (31 %) were FBC and 252 of 771 (33 %) were SBC (p = 0.4). Patient PCa detection rate based on the FBC vs. SBC were 46 % vs. 48 % (p = 0.6). For clinically significant PCa (Gleason score ≥4 + 3 = 7) the detection rate was 18 % for both, FBC and SBC (p = 0.9). Six hundred and eighty-seven SBC (89 %) showed no histologic difference. On the lesion level, 40 SBC detected PCa with negative FBC (7.5 %). Twenty SBC showed a Gleason upgrade from 3 + 3 = 6 to ≥3 + 4 = 7 (2.6 %) and 4 to ≥4 + 3 = 7 (0.5 %)., Conclusion: The benefit of a second targeted biopsy core per suspicious MRI-lesion is likely minor, especially regarding PCa detection rate and significant Gleason upgrading. Therefore, a further reduction of biopsy cores is reasonable when performing a targeted MR-guided in-bore prostate biopsy., Key Points: • Higher PI-RADS overall score (IV-V) correlated well with PCa detection rate • In more than 80 % SBC was concordant regarding overall PCa detection • In almost 90 % there was no Gleason upgrading by the SBC • Only 2/54 (3.7 %) csPCa was missed when the SBC was omitted • For IB-GB a further reduction of biopsy cores is reasonable.

Purpose: The objective of this study was to compare patient comfort between MR-guided in-bore prostate biopsy (IB-GB) and MRI/ultrasound fusion-guided prostate biopsy (FUS-GB) with additional systematic 12-core transrectal ultrasound (TRUS)-guided biopsy within a prospective randomized trial., Methods: Two hundred and ten consecutive patients were randomly assigned in a 1:1 ratio to receive either IB-GB and prior intrarectal instillation of a 2% lidocaine gel (n = 106) or FUS-GB plus additional systematic 12-core TRUS-guided biopsy and prior application of a periprostatic nerve block (PPNB) with 2% mepivacaine (n = 104). The maximal procedural pain (MPP) on a 0-10 visual analog scale and the operating room time were recorded for each biopsy session., Results: Baseline characteristics and mean number of targeted biopsy cores (5.6 ± 0.8 vs 5.4 ± 1.2 for IB-GB and FUS-GB, respectively; p = 0.278) were similar in both study arms. In relation to the IB-GB arm, the total number of biopsy cores in the FUS-GB arm, including the systematic 12-core TRUS-guided biopsy, was significantly higher (17.4 ± 1.2; p < 0.001). Patients with IB-GB had significantly higher MPP scores (2.95 ± 2.15) compared with subjects with FUS-GB (1.95 ± 1.56; p < 0.001). FUS-GB required significantly less time (28.22 ± 11.61 min) in comparison with IB-GB (42.09 ± 11.37 min; p < 0.001)., Conclusions: The PPNB can easily be administered just prior to performing FUS-GB. Thus, patients have significantly lower pain levels in comparison with IB-GB, which is usually done with intrarectal anesthetic gels. Although the addition of a systematic 12-core TRUS-guided biopsy significantly increases the number of biopsy cores, FUS-GB still requires significantly less time in comparison with IB-GB.

Purpose: Gleason grading is the strongest predictor of prostate cancer outcome and commonly used to decide for or against the different treatment options. However, Gleason upgrading between systematic transrectal ultrasound-guided prostate biopsy (TRUS-GB) and radical prostatectomy (RPE) has frequently been observed. With respect to the high accuracy of multiparametric MRI (mpMRI) for high-grade cancers and the higher percentage of cancer involvement per biopsy core in targeted MR-guided prostate biopsy (MR-GB), we hypothesized that MR-GB reduces the risk of Gleason upgrading on RPE as compared to the gold standard. The purpose of this study was to compare the rate of Gleason upgrading on RPE for MR-GB, TRUS-GB, and the combination of both biopsy modalities., Methods: Overall, 52 consecutive patients with RPE had received an mpMRI of the prostate and subsequently underwent targeted MR-GB prior to surgery. All patients underwent an additional TRUS-GB during the same biopsy session. Gleason grading was measured by two different methods: the conventional Gleason score (cGS = primary + secondary pattern) and the highest Gleason pattern (hGP)., Results: In relation to TRUS-GB, MR-GB alone showed lower rates of upgrading when comparing the cGS (40.4 vs. 50.0 %) and the hGP (21.2 vs. 32.7 %). The combination of MR-GB and TRUS-GB showed the lowest rates of upgrading (cGS: 28.8 %; hGP: 11.5 %), and compared to TRUS-GB, significantly reduced the risk of upgrading for both measurements of Gleason grading (cGS: OR 0.41, 95 % CL 0.18-0.91, p = 0.0289; hGP: OR 0.27, 95 % CL 0.10-0.75, p = 0.0123)., Conclusion: MpMRI and targeted MR-GB are useful tools to better characterize and stage the extent of disease, and therefore enable the urologist to better risk-stratify and counsel the patient. The combined use of targeted MR-GB and TRUS-GB presents the least risk of Gleason underestimation.

Background: A significant proportion of prostate cancers (PCas) are missed by conventional transrectal ultrasound-guided biopsy (TRUS-GB). It remains unclear whether the combined approach using targeted magnetic resonance imaging (MRI)-ultrasound fusion-guided biopsy (FUS-GB) and systematic TRUS-GB is superior to targeted MRI-guided in-bore biopsy (IB-GB) for PCa detection., Objective: To compare PCa detection between IB-GB alone and FUS-GB + TRUS-GB in patients with at least one negative TRUS-GB and prostate-specific antigen ≥4 ng/ml., Design, Setting, and Participants: Patients were prospectively randomized after multiparametric prostate MRI to IB-GB (arm A) or FUS-GB + TRUS-GB (arm B) from November 2011 to July 2014., Outcome Measurements and Statistical Analysis: The study was powered at 80% to demonstrate an overall PCa detection rate of ≥60% in arm B compared to 40% in arm A. Secondary endpoints were the distribution of highest Gleason scores, the rate of detection of significant PCa (Gleason ≥7), the number of biopsy cores to detect one (significant) PCa, the positivity rate for biopsy cores, and tumor involvement per biopsy core., Results and Limitations: The study was halted after interim analysis because the primary endpoint was not met. The trial enrolled 267 patients, of whom 210 were analyzed (106 randomized to arm A and 104 to arm B). PCa detection was 37% in arm A and 39% in arm B (95% confidence interval for difference, -16% to 11%; p=0.7). Detection rates for significant PCa (29% vs 32%; p=0.7) and the highest percentage tumor involvement per biopsy core (48% vs 42%; p=0.4) were similar between the arms. The mean number of cores was 5.6 versus 17 (p<0.001). A limitation is the limited number of patients because of early cessation of accrual., Conclusions: This trial failed to identify an important improvement in detection rate for the combined biopsy approach over MRI-targeted biopsy alone. A prospective comparison between MRI-targeted biopsy alone and systematic TRUS-GB is justified., Patient Summary: Our randomized study showed similar prostate cancer detection rates between targeted prostate biopsy guided by magnetic resonance imaging and the combination of targeted biopsy and systematic transrectal ultrasound-guided prostate biopsy. An important improvement in detection rates using the combined biopsy approach can be excluded., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: This study evaluates the diagnostic value of the ESUR scoring system (PI-RADS) regarding prostate cancer detection using MR-guided in-bore biopsies (IB-GB) as the reference standard., Methods: 566 lesions in 235 consecutive patients (65.7 ± 7.9 years, PSA 9.9 ± 8.5 ng/ml) with a multiparametric (mp)-MRI (T2WI, DWI, DCE) of the prostate at 3T were scored using the PI-RADS scoring system. PI-RADS single (PSsingle), summed (PSsum), and overall (PSoverall) scores were determined. All lesions were histologically verified by IB-GB., Results: Lesions with a PSsum below 9 contained no prostate cancer (PCa) with Gleason score (GS) ≥ 4+3=7. A PSsum of 13-15 (PSoverall V) resulted in 87.8% (n=108) in PCa and in 42.3% (n=52) in GS ≥ 4+3=7. Transition zone (TZ) lesions with a PSsum of 13-15 (PSoverall V) resulted in 76.3% (n=36) in PCa and in 26.3% (n=10) in GS ≥ 4+3=7, whereas for peripheral zone (PZ) lesions cancer detection rate at this score was 92.9% (n=79) and 49.4% (n=42) for GS ≥ 4+3=7. Using a threshold of PSsum ≥ 10, sensitivity was 86.0%, and negative predictive value (NPV) was 86.2%. For higher grade PCa sensitivity was 98.6%, and NPV was 99.5%., Conclusion: A PSsum below 9 excluded a higher grade PCa, whereas lesions with a PSsum ≥ 13 (PSoverall V) represented in 88% PCa, and in 42% higher grade PCa. The PSsum or PSoverall demonstrated a better diagnostic value for PZ lesions with higher detection rates for higher grade PCa compared to TZ lesions., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Magnetic resonance imaging guided biopsy is increasingly performed to diagnose prostate cancer. However, there is a lack of well controlled, prospective trials to support this treatment method. We prospectively compared magnetic resonance imaging guided in-bore biopsy with standard systematic transrectal ultrasound guided biopsy in biopsy naïve men with increased prostate specific antigen., Materials and Methods: We performed a prospective study in 132 biopsy naïve men with increased prostate specific antigen (greater than 4 ng/ml). After 3 Tesla functional multiparametric magnetic resonance imaging patients were referred for magnetic resonance imaging guided in-bore biopsy of prostate lesions (maximum 3) followed by standard systematic transrectal ultrasound guided biopsy (12 cores). We analyzed the detection rates of prostate cancer and significant prostate cancer (greater than 5 mm total cancer length or any Gleason pattern greater than 3)., Results: A total of 128 patients with a mean ± SD age of 66.1 ± 8.1 years met all study requirements. Median prostate specific antigen was 6.7 ng/ml (IQR 5.1-9.0). Transrectal ultrasound and magnetic resonance imaging guided biopsies provided the same 53.1% detection rate, including 79.4% and 85.3%, respectively, for significant prostate cancer. Magnetic resonance imaging and transrectal ultrasound guided biopsies missed 7.8% and 9.4% of clinically significant prostate cancers, respectively. Magnetic resonance imaging biopsy required significantly fewer cores and revealed a higher percent of cancer involvement per biopsy core (each p <0.01). Combining the 2 methods provided a 60.9% detection rate with an 82.1% rate for significant prostate cancer., Conclusions: Magnetic resonance imaging guided in-bore and systematic transrectal ultrasound guided biopsies achieved equally high detection rates in biopsy naïve patients with increased prostate specific antigen. Magnetic resonance imaging guided in-bore biopsies required significantly fewer cores and revealed a significantly higher percent of cancer involvement per biopsy core., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: This study evaluated the accuracy of MR sequences [T2-, diffusion-weighted, and dynamic contrast-enhanced (T2WI, DWI, and DCE) imaging] at 3T, based on the European Society of Urogenital Radiology (ESUR) scoring system [Prostate Imaging Reporting and Data System (PI-RADS)] using MR-guided in-bore prostate biopsies as reference standard., Methods: In 235 consecutive patients [aged 65.7 ± 7.9 years; median prostate-specific antigen (PSA) 8 ng/ml] with multiparametric prostate MRI (mp-MRI), 566 lesions were scored according to PI-RADS. Histology of all lesions was obtained by targeted MR-guided in-bore biopsy., Results: In 200 lesions, biopsy revealed prostate cancer (PCa). The area under the curve (AUC) for cancer detection was 0.70 (T2WI), 0.80 (DWI), and 0.74 (DCE). A combination of T2WI + DWI, T2WI + DCE, and DWI + DCE achieved an AUC of 0.81, 0.78, and 0.79. A summed PI-RADS score of T2WI + DWI + DCE achieved an AUC of 0.81. For higher grade PCa (primary Gleason pattern ≥ 4), the AUC was 0.85 for T2WI + DWI, 0.84 for T2WI + DCE, 0.86 for DWI + DCE, and 0.87 for T2WI + DWI + DCE. The AUC for T2WI + DWI + DCE for transitional-zone PCa was 0.73, and for the peripheral zone 0.88. Regarding higher-grade PCa, AUC for transitional-zone PCa was 0.88, and for peripheral zone 0.96., Conclusion: The combination of T2WI + DWI + DCE achieved the highest test accuracy, especially in patients with higher-grade PCa. The use of ≤2 MR sequences led to lower AUC in higher-grade and peripheral-zone cancers., Key Points: • T2WI + DWI + DCE achieved the highest accuracy in patients with higher grade PCa • T2WI + DWI + DCE was more accurate for peripheral- than for transitional-zone PCa • DCE increased PCa detection accuracy in the peripheral zone • DWI was the leading sequence in the transitional zone.

Purpose: To assess the feasibility of full diffusional kurtosis tensor imaging (DKI) in prostate MRI in clinical routine. Histopathological correlation was achieved by targeted biopsy., Materials and Methods: Thirty-one men were prospectively included in the study. Twenty-one were referred to our hospital with increased prostate specific antigen (PSA) values (>4ng/ml) and suspicion of prostate cancer. The other 10 men were volunteers without any history of prostate disease. DKI applying diffusion gradients in 20 different spatial directions with four b-values (0, 300, 600, 1000s/mm(2)) was performed additionally to standard functional prostate MRI. Region of interest (ROI)-based measurements were performed in all histopathologically verified lesions of every patient, as well as in the peripheral zone, and the central gland of each volunteer., Results: DKI showed a substantially better fit to the diffusion-weighted signal than the monoexponential apparent diffusion coefficient (ADC). Altogether, 29 lesions were biopsied in 14 different patients with the following results: Gleason score 3+3=6 (n=1), 3+4=7 (n=7), 4+3=7 (n=6), 4+4=8 (n=1), and 4+5=9 (n=2), and prostatitis (n=12). Values of axial (Kax) and mean kurtosis (Kmean) were significantly different in the tumor (Kax 1.78±0.39, Kmean 1.84±0.43) compared with the normal peripheral zone (Kax 1.09±0.12, Kmean 1.16±0.13; p<0.001) or the central gland (Kax 1.40±0.12, Kmean 1.44±0.17; p=0.01 respectively). There was a minor correlation between axial kurtosis (r=0.19) and the Gleason score., Conclusion: Full DKI is feasible to utilize in a routine clinical setting. Although there is some overlap some DKI parameters can significantly distinguish prostate cancer from the central gland or the normal peripheral zone. Nevertheless, the additional value of DKI compared with conventional monoexponential ADC calculation remains questionable and requires further research., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background/aim: Initial inaccurate staging is a common problem associated with active surveillance (AS) for patients detected by transrectal ultrasound-guided prostate biopsy (TRUS-GB). Subsequently, repeated biopsies are necessary to monitor such patients. Thus, in addition to the already established clinicopathological criteria, there is a considerable demand for new, objective decision criteria to more accurately select AS candidates. Recently, a novel RNA expression signature derived from 31 cell-cycle progression (CCP) genes has been shown to be a strong predictor of outcome in patients after radical prostatectomy or radiotherapy. This is a qualitative pilot study to evaluate the prognostic value of the CCP-score (CCP-S) for the first time in men managed with AS after MRI-guided prostate biopsy (MRI-GB)., Patients and Methods: Nine patients previously diagnosed with prostate cancer during an ongoing, prospective trial assessing MRI-GB with additional TRUS-GB and were subsequently managed with AS. CCP-S were retrospectively derived from biopsy specimens. The CCP-S is defined as the expression level of 31 CCP genes, normalized to 15 housekeeping genes, and is clinically validated in a range between -1.3 and 4.7. To assess the estimated 10-year mortality risk (without curative treatment), the CCP-S from each patient was combined with the individual CAPRA (Cancer of the Prostate Risk Assessment) score (CAPRA-S)., Results: Median patient age was 72 (range=58-77) years. Mean pre-biopsy PSA level was 6.33±1.94 (range 4.23-9.97) ng/ml. Eight cases had Gleason score 6 (3+3) and one cancer had Gleason score 7 (3+4). Median CCP-S was -0.9 (range=-1.5 to 0.0). Combining CCP-S with CAPRA-S [CAPRA-S: 1 (n=4), 2 (n=4), 3 (n=1)] the estimated 10-year mortality risk was not calculable for three patients because their CCP-S [CCP-S -1.4 (n=2) and -1.5 (n=1)] was outside the validated range. For the other 6 patients the estimated 10-year mortality ranged from 1.0-3.0%., Conclusion: The CCP-S confirms accurate staging of AS patients detected by MRI-based biopsy strategies and may significantly reduce inaccurate staging of AS patients and subsequent unnecessary re-biopsies. The CCP score may help to more accurately select for active surveillance candidates.

Objectives: The recent European Society of Urogenital Radiology (ESUR) guidelines for evaluation and reporting of prostate multiparametric magnetic resonance imaging (mp-MRI) include the Prostate Imaging Reporting and Data System (PI-RADS). The aim of this study was to investigate the inter-reader agreement of this scoring system., Methods: One hundred and sixty-four lesions in 67 consecutive patients with elevated prostate-specific antigen and previously negative trans-rectal ultrasound (TRUS)-guided biopsy were scored retrospectively by three blinded readers using PI-RADS. Mp-MRI was performed at 3 T using T2-weighted, diffusion-weighted and dynamic contrast-enhanced imagings (T2WI, DWI, DCE-MRI). Histology of all lesions was obtained by in-bore MRI-guided biopsy. Cohen's kappa statistics were calculated for all readers., Results: Inter-reader agreement for all lesions was good to moderate (T2WI, κ = 0.55; DWI, κ = 0.64; DCE-MRI, κ = 0.65). For tumour lesions it was good (T2WI, κ = 0.66; DWI, κ = 0.80; DCE-MRI, κ = 0.63) and for benign lesions moderate to good (T2WI, κ = 0.46; DWI, κ = 0.52; DCE-MRI, κ = 0.67). Using an overall PI-RADS score with a threshold of ≥10, we achieved a sensitivity of 85.7 %, and negative predictive value of 90.1 % for biopsied lesions., Conclusion: PI-RADS score shows good to moderate inter-reader agreement and enables standardised evaluation of prostate mp-MRI, with high sensitivity and negative predictive value., Key Points: • The European Society of Urogenital Radiology recently published guidelines for prostate MRI. • We have evaluated inter-reader agreement of ESUR scoring for multiparametric prostate MRI. • PI-RADS shows good to moderate inter-reader agreement and is clinically applicable. • PI-RADS achieves in our series high sensitivity and negative predictive value for biopsied lesions. • PI-RADS can be used as standardised scoring system in prostate cancer detection.

A 5-week-old male infant presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. Neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion (O(2)(-)) production but had normal expression and up-regulation of CD11b. Rac2, which constitutes >96% of the Rac in neutrophils, is a member of the Rho family of GTPases that regulates the actin cytoskeleton and O(2)(-) production. Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein. Addition of recombinant Rac to extracts of the patient neutrophils reconstituted O(2)(-) production in an in vitro assay system. Molecular analysis identified a point mutation in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2(D57N)). Asp57 is invariant in all defined GTP-binding proteins. Rac2(D57N) binds GDP but not GTP and inhibits oxidase activation and O(2)(-) production in vitro. These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome.