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TPS285 Background: In pts with localized high-risk PC, disease recurrence rate following RP is ̃50% (Kane et al. J Urol. 2007). Treatment (tx) with androgen blockade before RP can reduce tumor burden post RP (Taplin et al. J Clin Oncol. 2014; McKay et al. Prostate Cancer Prostatic Dis. 2018; Efstathiou et al. Eur Urol. 2019). This study examines if 12 months of perioperative APA + ADT tx before and after RP with pelvic lymph node dissection (pLND) in localized/locally advanced high-risk PC improves pathologic complete response (pCR) rate and metastasis-free survival (MFS) vs PBO + ADT. Methods: PROTEUS, an international multicenter study, is enrolling ̃2000 pts with localized/locally advanced high-risk/very high-risk PC who are candidates for RP with pLND over 3 years at > 203 sites in 18 countries. Stratification variables: Gleason score (7 vs ≥ 8), pelvic node status (N0 vs N1), international region. Randomization: 1:1 to APA (240 mg/d) + ADT or PBO + ADT. Pts receive 6-month neoadjuvant tx followed by RP and then 6 months’ adjuvant tx. Primary end points: pCR rate and MFS. In addition to MFS based on conventional imaging, MFS based on PSMA PET or conventional imaging will be assessed as a separate end point. Both pCR and MFS are assessed by blinded independent central review. Conventional imaging by CT or MRI and bone scan are done at screening, within 4 weeks after RP, at biochemical failure (BCF), and then every 6 months after BCF until distant metastasis or death. During the direct perioperative period, APA/PBO is stopped 2 weeks prior to planned RP and then resumed 4 weeks after RP if post-RP imaging has been conducted to assess for lymphocele and disease progression and resolution to grade ≤ 1 of any clinically significant adverse events considered related to RP. To reflect evolving standard of care, the following protocol amendments were added: PSMA-PET imaging at 3 months post adjuvant tx, at BCF, and every 6 months until distant metastasis or death; cardiovascular and thrombotic risk assessment at screening, prior to, and after RP; and guidance for standard thrombotic prophylaxis in the perioperative setting. An independent data monitoring committee will review trial data. Clinical trial information: NCT03767244.

Background: The phase III SPARTAN study demonstrated that apalutamide significantly improves metastasis-free survival and overall survival vs. placebo in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). However, patients receiving apalutamide experienced falls more frequently vs. those receiving placebo (15.6% vs. 9.0%). Methods: 806 patients with nmCRPC randomized to apalutamide in SPARTAN and treated with apalutamide in addition to ongoing androgen deprivation therapy (ADT) were included in this post-hoc analysis investigating clinical variables associated with a subsequent fall. Time to a fall was assessed with Cox proportional-hazards models adjusted for baseline characteristics and time-varying factors. Statistical inference was based on final multivariable models. Results: Falls were reported for 125/803 (15.6%) patients treated with apalutamide and ADT. Most falls were grade 1 or 2 and did not require hospitalization. Median time from randomization to first fall was 9.2 months (range 0.1–25.3 months). In the final multivariable model of both baseline and after-baseline covariates, baseline patient characteristics (older age, poor Eastern Cooperative Oncology Group performance status, history of neuropathy, and α-blocker use before study treatment) remained significantly associated with fall; after-baseline clinical characteristics significantly associated with time to fall were development of neuropathy, arthralgia, and weight loss before fall. Conclusions: This analysis identified risk factors for fall among nmCRPC patients treated with apalutamide. Clinical management can minimize these identified risks while enhancing patient outcomes. Preventive interventions should be considered when the identified baseline conditions and post-treatment neuropathy, arthralgia, or weight decrease are present, to reduce risk of fall. CA extern

Objective: To describe lifestyle behaviors (fruit and vegetable intake, alcohol intake, physical activity, sitting time, smoking, drug use, sleep, sexual health) and health risk factors (body mass ...

5066 Background: TITAN, a phase 3 PBO-controlled study in patients (pts) with mCSPC, showed APA + ADT improved radiographic progression-free survival and OS vs PBO + ADT. In this exploratory analysis, we report the relationships between biomarkers and OS in TITAN. Methods: Circulating tumor (ct)DNA and genomic aberrations in 17 PC-related genes, including androgen receptor (AR), were assessed at baseline (BL; 114 pts) and end of study treatment (EOST; 129 pts) using next-generation sequencing. ctDNA was assessed qualitatively; genomic aberrations were assessed within ctDNA-positive samples as inactivation (heterozygous/homozygous deletion or single nucleotide variant [SNV]) or activation (amplification or SNV). Associations of detected ctDNA/aberrations at BL or EOST with OS, and biomarkers at EOST with OS on subsequent therapies, were evaluated using univariate or multivariate analyses and Cox proportional hazards model; results were stratified by treatment arm. Results: Among pts from both treatment groups, 36% had detectable ctDNA, of which 27% had any genomic AR aberration and 24% had AR gene amplification at BL; prevalence of these biomarkers increased significantly from BL to EOST (Table). The most prevalent non-AR aberrations at BL ( TP53, homologous recombination repair [HRR] pathway, PTEN, RB1, and PIK3CA genes) increased at EOST but not significantly (Table). Among assessed aberrations, presence of ctDNA or any AR genomic aberrations at BL (HR, 1.9 or 6.7; all p < 0.05) and any AR genomic aberrations or PI3K pathway activation at EOST (1.7, p < 0.05 or 2.2, p < 0.001) was significantly associated with poor OS in multivariate analyses from both treatment groups. In univariate analyses of pts who received subsequent therapy (chemotherapy: 106; hormonal therapy: 161), worse OS was associated only with PIK3CA activation, PI3K pathway activation, or TP53 inactivation at EOST (3.7, p < 0.05; 2.4, p < 0.05; 3.0, p < 0.01, respectively) in chemo-treated pts. A small sample size in some biomarker subgroups limits interpretation. Conclusions: These hypothesis-generating data from TITAN show that presence of ctDNA or select AR and non-AR biomarkers at BL or EOST were associated with poor OS. The predictive value of these biomarkers for survival in mCSPC needs further confirmation. Clinical trial information: NCT02489318. [Table: see text]

6079 Background: Overexpression of AR is identified as a potential molecular target of SGC treatment. Combined androgen blockade (CAB) with bicalutamide has been evaluated previously, but the clinical usefulness of CAB with a next generation AR inhibitor has been unclear in SGC. We prospectively assessed the efficacy and safety of APA+GOS for pts with AR-expressing SGC. Methods: Eligible pts had fLA/RM SGC, and AR expression with at least 1% of cell nuclei immunohistochemistry staining positive. Pts were treated with APA 240 mg orally once daily and GOS 3.6 mg subcutaneously once 28 days. Primary endpoint was overall response rate (ORR) by central review according to RECIST v1.1, and a response (complete response [CR] or partial response [PR]) was confirmed by repeat assessments at least 4 weeks after the initial evaluation showing a response. Primary analysis was performed based on first 24 response evaluable (RE) pts who had been observed at least 24 weeks (Primary RE pts). The ORR was tested using exact test based on the binominal distribution, the null hypothesis for ORR of 14% was rejected when at least 8 of the 24 Primary RE pts were responders, and the efficacy was to be declared. Key secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DOR), and time to response (TTR) in the Primary RE pts, and overall survival (OS), progression free survival (PFS), and safety in the treated pts. Results: Twenty-six of the 31 pts treated with APA+GOS were regarded as RE by central review. For the 24 Primary RE pts, ORR was 25.0% (6/24), while 37.5% (9/24) including unconfirmed PR. Clinical benefit rate and DCR in the Primary RE pts were 50.0% and 70.8%, respectively. At the data cut-off (Apr 28, 2021), 5 of 6 pts with confirmed response were still on protocol treatment. Median PFS and OS in the treated pts were 7.43 months (mos) and not reached, respectively, with the median follow-up period of 8.57 mos. Grade 3 or higher treatment-related adverse events were reported in 4/31 (12.9%) pts, and the events were rash maculo-papular (n=2), anemia (n=1), and leukopenia (n=1). Conclusions: This is the first prospective trial evaluating CAB with APA for AR-expressing SGC. Although this study did not meet the predefined criteria of efficacy, clinically meaningful activity with well-tolerated safety profile of APA+GOS was shown. Clinical trial information: NCT04325828. [Table: see text]

5084 Background: Current management of HRLPC includes long-term ADT with primary RT. Despite definitive primary treatment, these pts have a high risk of metastasis and death. The phase 3 ATLAS study (NCT02531516) is investigating whether treatment intensification with the addition of APA to neoadjuvant and adjuvant treatment with gonadotropin-releasing hormone agonist (GnRHa) and external beam radiation therapy (EBRT) will improve metastasis-free survival (MFS) in high-risk pts. Here we describe (1) the distribution of baseline characteristics in this high-risk pt population and (2) the application of different RT regimens reflecting recent international guidelines and clinical practice changes for pts with HRLPC. Methods: Eligible HRLPC pts (Gleason score [GS] ≥ 8 or 7 and prostate-specific antigen [PSA] ≥ 20 ng/mL and stage ≥ cT2c), with ECOG PS 0/1 and Charlson Comorbidity Index (CCI) ≤ 3 are stratified by GS, pelvic nodal status, use of brachytherapy boost, and region; pts are randomized 1:1 to APA or PBO plus GnRHa for 30 (28-d) treatment cycles. Study treatment is applied neoadjuvant/concurrent to RT with APA 240 mg/d vs bicalutamide 50 mg/d for 4 cycles; another 26 cycles are completed adjuvantly after RT with APA 240 mg/d vs PBO. Primary end point is MFS (time from randomization to first distant metastasis on CT/MRI/bone scan by independent central review blinded to treatment or death from any cause). Imaging is conducted at baseline and q6m from biochemical failure until MFS. The protocol has been amended to include PET imaging (PSMA, fluciclovine, or choline). Results: Pts (N = 1503) were randomized at 266 sites in 24 countries in North America, Latin America, Europe, and Asia. The study is fully enrolled, but ongoing. Baseline characteristics for the total population: median age, 67 yrs; ECOG PS 0/1; 89%/11%; tumor classification at study entry: high-risk, 66%/very high–risk, 34%; median PSA, 6.3 ng/mL; cT2, 44%/cT3, 50%; cN1, 13%. In 90% of ATLAS pts, RT used was standard EBRT to prostate/pelvis over 6-8 weeks (cumulative 78-81 Gy); in 10%, recent hypofractionation schedules (per CHHiP or NRG/RTOG 0415) were applied (20x3 Gy/d or 28x2.5 Gy/d). 5.6% of pts had EBRT combined with brachytherapy (per ASCENDE-RT). Conclusions: Baseline characteristics of the ATLAS study population are reflective of pts with high- and very high–risk features and pelvic nodal involvement undergoing primary RT in clinical practice. The RT schedules applied reflect recent evidence and guideline changes for the use of hypofractionation in this pt population. ATLAS is an example of how RT can be included in phase 3 trials of HRLPC, in combination with next-generation androgen receptor inhibitors (eg, APA). Clinical trial information: NCT02531516.

89 Background: Addition of androgen receptor signaling inhibitors to ADT + DOC has been shown to improve clinical outcomes in pts with mCSPC. TITAN, a placebo-controlled phase 3 study, showed that APA + ADT improved overall survival (OS) and other clinical outcomes in mCSPC (Chi, J Clin Oncol 2021). This post hoc analysis of TITAN evaluated outcomes in pts who had received DOC prior to treatment with APA + ADT versus those who did not. Methods: In TITAN, 1052 pts were randomized 1:1 to APA (240 mg QD) or placebo added to ongoing ADT. We assessed radiographic progression-free survival (rPFS), OS, and time to prostate-specific antigen (PSA) progression in pts receiving DOC and ADT prior to adding APA vs those receiving only ADT plus APA. Outcomes by prior DOC were also assessed in pts with high- or low-volume disease at randomization (baseline [BL]) per adapted CHAARTED criteria, or those with matched BL characteristics. A Cox proportional hazards model was used to derive hazard ratios (HRs) and p values. rPFS was assessed using the first interim analysis cutoff (23 mo median follow-up); OS and time to PSA progression were assessed using the final analysis cutoff (44 mo median follow-up). Results: A total of 58/525 (11%) pts from the APA + ADT group had received DOC prior to randomization: 76% (n = 44) had high-volume disease, 62% (n = 36) had bone-only metastases, 16% (n = 9) had visceral metastases, and 59% (n = 34) had > 10 bone lesions. In the overall APA-treated population and in the subset of pts with high-volume disease, OS, rPFS, and time to PSA progression were similar in those who received prior DOC and those who did not (Table). Pts with low-volume disease also had similar results, although the number of pts was small. Clinical outcomes in pts with matched BL characteristics (including PSA and time from initial diagnosis to randomization, among others) were similar regardless of prior use of DOC (Table). The safety profile of APA was not substantially different between pts with or without prior DOC. Limitations of this analysis include lack of data on tumor volume and other disease characteristics at the initiation of prior DOC treatment; interpretation was based on small number of pts with prior DOC (only 11% of TITAN pts), most notably in the rPFS analysis. Conclusions: Prior use of DOC in pts with mCSPC did not further improve clinical benefits of APA + ADT in TITAN. Clinical trial information: NCT02489318. [Table: see text]

142 Background: In ACIS, APA + AAP improved radiographic progression-free survival in mCRPC vs AAP; difference in overall survival (OS) was not statistically significant. We report a prespecified analysis of androgen receptor (AR) or non-AR genomic/transcriptional aberrations, known to be associated with poor prognosis, and their associations with OS in patients (pts) with mCRPC. Methods: Circulating tumor (ct)DNA and aberrations in 17 PC-relevant genes were assessed using next-generation sequencing at baseline (BL; n = 197) and at end of study treatment (EOST; n = 140) (biomarker population). ctDNA was summarized qualitatively; genomic aberrations were normalized by ctDNA detection. AR splice variant version 7 (ARv7) was detected by quantitative RT-PCR. Cox proportional hazards model assessed association of OS with biomarkers in univariate/multivariate analyses overall and in pts receiving subsequent treatment (tx). Results: BL characteristics of biomarker and total study populations were similar. From BL to EOST: ctDNA detection did not differ (123/196 [63%] to 92/140 [66%], p=0.6); significant increases occurred in ARv7, AR mutations, and any AR aberration (Table). Prevalence of aberrations in PI3K and homologous recombination repair (HRR) pathways did not change from BL to EOST (40/123 [33%] to 34/92 [37%], p=0.5 and 18/123 [15%] to 14/92 [15%], p>0.9, respectively). Worse OS was associated with ctDNA detection or HRR pathway inactivation at BL (HR, 2.5 or 2.2; all p < 0.001) or presence of ctDNA, ARv7, AR amplification or inactivation of TP53, RB1, or RB1/TP35 pathway at EOST (2.2, p < 0.001; 2.1, p < 0.001; 2.6, p < 0.001; 1.5, p < 0.05; 1.7, p < 0.05; 2.1, p < 0.001, respectively) in univariate analyses. EOST ARv7, AR amplification, and inactivation of RB1, TP53, or RB1/TP53 pathway was associated with worse OS in pts receiving subsequent tx. Detection of ctDNA and RB1 inactivation at BL and RB1/TP53 pathway inactivation at EOST was strongly associated with worse OS (2.1, 3.3, 2.9, respectively, all p < 0.01) in multivariate analyses. Conclusions: In ACIS, AAP or APA + AAP tx was associated with increased AR mutations and ARv7 expression. Detection of ctDNA and select AR/non-AR aberrations may predict poor survival in mCRPC. These markers may be used to improve tx selection following confirmation of their predictive value. Clinical trial information: NCT02257736. [Table: see text]

Background. Due to increasing antibiotic resistances, relevant treatment problems are currently emerging in clinical practice. In March 2015, the German Federal Ministry of Health (BMG) published a 10-point plan designed to combat this development. Furthermore, the first German guideline on antibiotic stewardship (ABS) was implemented in 2013 and instructs physicians of different specialties about several treatment considerations. Evidence is scarce on how such concepts (10-point plan/BMG, ABS) are perceived among clinicians. Materials and methods. Within the MR2 study (Multiinstitutional Reconnaissance of practice with MultiResistant bacteria a survey focusing on German hospitals), a questionnaire including 4 + 35 items was sent to 18 German hospitals between August and October 2015, surveying internists, gyne-cologists, general surgeons, and urologists. Using multivariate logistic regression models (MLRM), the impact of medical specialty and further criteria on the endpoints (1) awareness of the 10-pointplan/BMG and (2) knowledge of ABSmeasures were assessed. Fulfillment of endpoints was predefined when average or full knowledge was reported (reference: poor to no knowledge). Results. Overall response rate was 43% (456/ 1061) for fully evaluable questionnaires. Only 63.0 and 53.6% of urologists and nonurologists (internists, gynecologists, and general surgeons), respectively, attended training courses regarding multidrugresistance or antibiotic prescribing in the 12 months prior to the study (P = 0.045). The endpoints average and full knowledge regarding 10-point plan/ BMG and ABS measures were fulfilled in only 31.4 and 32.8%, respectively. In MLRM, clinicians with at least one previous training course (reference: no training course) were 2.5-and 3.8-fold more likely to meet respective endpoint criteria (all P < 0.001). Medical specialty (urologists vs. nonurologists) did not significantly impact the endpoints in both MLRM. Conclusions. The 10-point plan/ BMG and ABS programs should be implemented into clinical practice, but awareness and knowledge of both is insufficient. Thus, it stands to reason that the actual realization of such measures is inadequate and continuous training towards rational prescription of antibiotics is necessary, regardless of medical specialty.

Evidence is scarce on subject-specific knowledge of multidrug-resistant organisms and rational use of antibiotics. We aimed at evaluating attitude, perception, and knowledge about multidrug-resistant organisms (MDRO) and antibiotic prescribing among urologists versus other medical specialties. Within the MR2-study (Multiinstitutional Reconnaissance of practice with MultiResistant bacteria), a questionnaire was conducted targeting general surgeons, internists, gynecologists, and urologists in 18 German hospitals. The influence of medical specialty on predetermined endpoints was assessed by multivariable logistic regression models. With 456 evaluable questionnaires, the response rate was 43% (456/1061). Within seven workdays prior to survey, urologists prescribed antibiotics to >5 patients more often than non-urologists (50.7 vs. 24.3%; p

BACKGROUND: Recently, antibiotic resistance rates have risen substantially and care for patients infected with multidrug-resistant organisms (MDRO) has become a common problem in most in – and outpatient settings. The objectives of the study were to compare the awareness, perception, and knowledge of MDRO and rational antibiotic use between physicians from different medical specialties in German hospitals. METHODS: A 35-item questionnaire was sent to specialists in internal medicine (internists), gynecologists, urologists, and general surgeons (non-internists) in 18 German hospitals. Likert-scales were used to evaluate awareness and perception of personal performance regarding care for patients infected with MDRO and rational use of antibiotics. Additionally, two items assessing specific knowledge in antibiotic therapy were included. The impact of medical specialty on four predetermined endpoints was assessed by multivariate logistic regression. RESULTS: 43.0% (456/1061) of recipients responded. Both internists and non-internists had low rates of training in antibiotic stewardship. 50.8% of internists and 58.6% of non-internists had attended special training in rational antibiotic use or care for patients infected with MDRO in the 12 months prior to the study. Internists deemed themselves more confidently to choose the indications for screening patients for colonization with methicillin-resistant Staphylococcus aureus (P=0.004) and to initiate adequate infection control measures (P=0.002) than other specialties. However, there was no significant difference between internists and other specialists regarding the two items assessing specific knowledge in antibiotic therapy and infection control. CONCLUSION: Among the study participants, a considerable need for advanced training in the study subjects was seen, regardless of the medical specialty.

Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common kidney tumor. If feasible, metastasectomy is preferably indicated in metastatic disease. Objective: The aim of this study was to determine the outcome of patients after pulmonary metastasectomy (PM). Methods: PM for ccRCC was performed in 35 patients in the period of January 2001–2019. Clinical characteristics, type of surgery, histopathology results, and follow-up data were recorded. Progression-free survival (PFS) after PM and overall survival (OS) were defined as outcome endpoints. Results: A total of 77 PMs were performed in 35 patients after nephrectomy for ccRCC. The mean size of pulmonary metastasis was 19.0 mm (4–90). With a median follow-up after PM of 79.2 months, the 3- and 5-year OS rates were 63.5 and 44.9%, respectively. The only statistically significant prognostic factor affecting both PFS (p = 0.019) and OS (p = 0.015) was the dimension of pulmonary metastases. Conclusions: The prognosis of metastatic ccRCC is generally poor, particularly in cases of larger size of metastasis. PM might improve the individual prognosis of patients with lung metastasis even in cases with higher number of metastases, bilaterality, synchronous metastasis, or a short progression-free interval after nephrectomy.

Aim: The aim of this study was to determine the proportion of cystic tumors according to preoperative CT (Bosniak III, IV) among surgically treated patients with histologically confirmed papillary renal cell carcinoma (pRCC) and to assess progression rates among patients with and without cystic appearance on imaging. Methods: A total of 138 patients with pRCC histology surgically treated in the period of January 2007–March 2017 were included. Clinical and radiological characteristics, type of surgery, histopathology results, and follow-up data were recorded and statistically evaluated. Results: Forty-one cases (29.7%) of cystic lesions (10× BIIF, 14× BIII, 17× BIV) were detected by CT. Patients with pRCC1 significantly more frequently presented with cystic appearance on CT (33/78; 42.3%) in comparison to other papillary types (8/60; 13.3%; p = 0.0002). During a median follow-up time of 49.4 months, only 2 patients with cystic lesions progressed after surgery. Conclusions: Cystic appearance on imaging methods is mainly a characteristic of pRCC1 (42.3%). Cystic morphology on imaging might predict a relatively indolent behavior of all pRCC types. Preoperative scoring systems including tumor growth patterns (cystic vs. solid) are needed for further classification.

Squamous cell carcinoma of the penis (SCCP) is a rare cancer type in Western industrialized nations; nevertheless, it shows an aggressive course of disease in advanced tumor stages with accordantly high recurrence and progression rates. While molecular biomarkers are not established in clinical routine for the management of SCCP patients yet, the accordant unmet need is enormous, as adequate biomarkers would be meaningful for prognostic determination, planning of modality and extent of primary therapy, indication for inguinal lymph node resection, adjuvant treatment, and as potential targets for specific systemic treatment. SCCP regularly develops from a precursor lesion. In this regard, human papillomavirus (HPV)-dependent and -independent pathways are differentiated. The potential for specific target therapy options is mainly based on the decoding of genetic and epigenetic signatures of distinct molecular pathways. In order to develop targeted and personalized treatment strategies based on molecular pathways, an increase in translational research in large multi-institutional collaborations must be promoted. This review article aims to summarize the current status of research concerning molecular changes related to SCCP under separate consideration of prognostic molecular markers, on the one hand, and biomarkers considered potential therapeutic targets, on the other hand. In addition, previous research activities of our own working group on this topic are briefly described.

Over the past few decades, some principles in the treatment of penile cancer have changed fundamentally. While 15 years ago a negative surgical margin of at least 2 cm was considered mandatory, organ-sparing surgery permitting minimal negative surgical margins has a high priority nowadays. The current treatment principle requires as much organ preservation as possible and as much radicality as necessary. The implementation of organ-sparing and reconstructive surgical techniques has improved the quality of life of surviving patients. However, oncological and functional outcomes are still unsatisfactory. Alongside with adequate local treatment of the primary tumour, a consistent management of inguinal lymph nodes is of fundamental prognostic significance. In particular, clinically inconspicuous inguinal lymph nodes staged T1b and upwards need a surgical approach. Sentinel node biopsy, minimally-invasive surgical techniques and modified inguinal lymphadenectomy have reduced morbidity compared to conventional inguinal lymph node dissection. Multimodal treatment with surgery and chemotherapy is required in all patients with lymph node-positive disease; neoadjuvant chemotherapy has been established for patients with locally advanced lymph node disease, and adjuvant treatment after radical inguinal lymphadenectomy for lymph node-positive disease. An increasing understanding of the underlying tumour biology, in particular the role of the human papilloma virus (HPV) and epidermal growth factor receptor (EGFR) status, has led to a new pathological classification and may further enhance treatment options. This review summarises current aspects in the therapeutic management of penile cancer.Einige Prinzipien der primären Therapie des Peniskarzinoms haben sich in den letzten Jahrzehnten grundlegend verändert: Galt aufgrund der Aggressivität des Tumors bei der Penisteilamputation vor 15 Jahren noch ein tumorfreier Sicherheitsabstand von 2 cm als obligat, so gilt heute, dass weitgehender Organerhalt Priorität hat und minimale tumorfreie Schnittränder ausreichend sind. Es besteht somit der Grundsatz: So viel Organerhalt wie möglich, so viel Radikalität wie nötig. Auch hat sich zunehmend die Erkenntnis durchgesetzt, dass Patienten mit begrenzter regionär-lymphogener Metastasierung heilbar sein können, allerdings nur bei Durchführung einer multimodalen Therapie bestehend aus einer radikalen inguinalen Lymphadenektomie und nachfolgenden adjuvanten Chemotherapie. Bei Patienten mit fixierten inguinalen Lymphknotenmetastasen konnte hingegen die neoadjuvante Chemotherapie etabliert werden. Trotz der verbesserten Therapieoptionen bleiben die funktionellen und onkologischen Ergebnisse bei der Behandlung des Peniskarzinoms vielfach enttäuschend. Die Möglichkeiten des Organerhalts mittels rekonstruktiver operativer Techniken verbessern zwar die Lebensqualität der Langzeitüberlebenden erheblich, doch weniger als 25 % der Patienten mit Lymphknotenmetastasierung überleben ihre Tumorerkrankung. Von großer Bedeutung ist die chirurgische Lymphknotendiagnostik bei klinisch unauffälligen Lymphknoten ab dem Tumorstadium T1b, da hier eine okkulte Mikrometastasierung in bis zu 25 % der Fälle vorliegen kann. Die minimal-invasive Sentinel-Lymphknoten-Biopsie ist ein durchaus sinnvoller Weg, diese Patienten zu diagnostizieren, ohne gleich die Morbidität einer primär radikalen Lymphadenektomie hervorzurufen. Ein zunehmendes Verständnis der zugrundeliegenden Tumorbiologie, insbesondere Erkenntnisse zum Humanen-Papillomavirus- und Epidermal-Growth-Factor-Receptor-Status, brachten zuletzt erfolgversprechende klinische Studien auf den Weg; zudem wird gegenwärtig die gezielte Immuntherapie mittels Immun-Checkpoint-Inhibitoren bei therapierefraktärem Peniskarzinom geprüft.In diesem Review werden die aktuellen Aspekte des therapeutischen Managements von Peniskarzinom-Patienten zusammengefasst.

Due to increasing antibiotic resistances, relevant treatment problems are currently emerging in clinical practice. In March 2015, the German Federal Ministry of Health (BMG) published a 10-point plan designed to combat this development. Furthermore, the first German guideline on antibiotic stewardship (ABS) was implemented in 2013 and instructs physicians of different specialties about several treatment considerations. Evidence is scarce on how such concepts (10-point plan/BMG, ABS) are perceived among clinicians.Within the MR2 study (Multiinstitutional Reconnaissance of practice with MultiResistant bacteria - a survey focusing on German hospitals), a questionnaire including 4 + 35 items was sent to 18 German hospitals between August and October 2015, surveying internists, gynecologists, general surgeons, and urologists. Using multivariate logistic regression models (MLRM), the impact of medical specialty and further criteria on the endpoints (1) awareness of the 10-point plan/BMG and (2) knowledge of ABS measures were assessed. Fulfillment of endpoints was predefined when average or full knowledge was reported (reference: poor to no knowledge).Overall response rate was 43% (456/1061) for fully evaluable questionnaires. Only 63.0 and 53.6% of urologists and nonurologists (internists, gynecologists, and general surgeons), respectively, attended training courses regarding multidrug-resistance or antibiotic prescribing in the 12 months prior to the study (P = 0.045). The endpoints average and full knowledge regarding 10-point plan/BMG and ABS measures were fulfilled in only 31.4 and 32.8%, respectively. In MLRM, clinicians with at least one previous training course (reference: no training course) were 2.5- and 3.8-fold more likely to meet respective endpoint criteria (all P 0.001). Medical specialty (urologists vs. nonurologists) did not significantly impact the endpoints in both MLRM.The 10-point plan/BMG and ABS programs should be implemented into clinical practice, but awareness and knowledge of both is insufficient. Thus, it stands to reason that the actual realization of such measures is inadequate and continuous training towards rational prescription of antibiotics is necessary, regardless of medical specialty.

Results of a retrospective single-institution study recently suggested improved prognostic outcomes in patients undergoing photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) prior to radical cystectomy (RC). We sought to validate the prognostic influence of PDD-assisted TURBT on survival after RC by relying on a multi-institutional dataset. To provide a homogeneous study population, patients with organ metastasis at the time of RC and/or after neoadjuvant chemotherapy were excluded from analysis, which resulted in overall 549 bladder cancer (BC) patients from 18 centers of the Prospective Multicenter Radical Cystectomy Series 2011 (PROMETRICS 2011). To evaluate the influence of PDD conducted during primary or final TURBT on cancer-specific mortality (CSM) and overall mortality (OM) after RC, bootstrap-corrected multivariate Cox proportional-hazards regression models were applied (median follow-up: 25 months; IQR: 19–30). Sensitivity analyses were performed for both patients with pure urothelial carcinoma and patients undergoing one single TURBT only. In 88 (16.0 %) and 100 (18.2 %) patients, PDD was used in primary and final TURBTs, respectively. In 335 (61.0 %) patients, a single TURBT was performed prior to RC; in 194 patients (35.3 %), TURBT had been performed in a different center. CSM and OM rates at 3 years were 32 and 40 %, respectively. Use of PDD during primary or final TURBT was no independent predictor of CSM or OM. These results were internally valid and were confirmed in sensitivity analyses. PDD utilization during TURBT prior to RC does not independently impact the prognosis of BC patients after RC.

A multicentre, prospective, randomized, double-blind, parallel group study was undertaken to compare the efficacy and tolerability of topical terbinafine with topical clotrimazole in the treatment of interdigital tinea pedis. Patients were randomized to receive either terbinafine 1% cream twice daily for 1 week, followed by a similar placebo cream for 5 weeks, or clotrimazole 1% cream twice daily for 4 weeks. Outcome measures were: (i) mycological cure (negative culture); (ii) effective treatment (negative culture plus a symptom score of 2 or less out of a maximum score of 18); and (iii) complete cure (negative culture and a symptom score of 0); measured at 1, 4, 8 and 12 weeks after the commencement of the study. One hundred and four of the 217 patients randomized had a culture-confirmed dermatophyte infection at baseline. In these patients, 84.6% in the terbinafine group were culture negative after 1 week, compared with only 55.8% in the clotrimazole group. Both agents were well tolerated. The study showed that terbinafine achieves mycological cure more rapidly than clotrimazole. This may result in improved compliance and better control over transmission of infection.

Treatment of interdigital tinea pedis often involves long-term therapy with topically applied preparations. Effective oral preparations, such as the allylamine terbinafine (Lamisil), taken over a shorter period, could provide a useful therapeutic alternative. A total of 269 patients from five centres with clinically diagnosed interdigital tinea pedis were entered into this double-blind, randomized, double-dummy, parallel-group study comparing oral terbinafine 250 mg once daily for 1 week with 1% clotrimazole (Canesten) cream applied twice daily for 4 weeks. Of these, 137 patients were evaluable for efficacy (confirmed dermatophyte infection by microscopy and culture): 63 terbinafine and 74 clotrimazole. At week 4, the mycological cure rates (negative culture at week 1 and negative results on microscopy and culture at week 4 onwards) were very similar (71% for clotrimazole and 72% for terbinafine). There was a faster response rate in the terbinafine group with respect to signs and symptoms at week 1. Both treatments were equally well tolerated; adverse events occurred equally in the two groups. In conclusion, oral terbinafine in a single daily dose of 250 mg for 1 week is as effective and as well tolerated as 1% clotrimazole cream applied twice daily for 4 weeks in the treatment of interdigital tinea pedis.

ContextA substantial number of patients with head and neck paragangliomas (HNPGLs) have biochemically active tumors, evidenced by increased urinary excretion of catecholamines and metabolites, including 3-methoxytyramine (3MT). It is unclear whether plasma levels of these parameters are more sensitive to detect biochemical activity in HNPGL patients than urinary excretion rates.ObjectiveTo compare plasma free levels vs urinary excretion rates of deconjugated 3MT and combined metanephrines (MNs) in patients with HNPGL.Patients and methodsWe included 124 consecutive patients with HNPGL for screening of catecholamine excess by measurement of 24-h urinary excretion rates of deconjugated (nor)metanephrine, (nor)epinephrine, dopamine, vanillylmandelic acid, 3MT, and plasma free levels of (nor)metanephrine and 3MT.ResultsPlasma free 3MT levels were increased in 35 of the 124 patients (28%), whereas 24-h urinary excretion of deconjugated 3MT was increased in 30 patients (24%) (P=0.13). Plasma free MN levels were increased in seven patients (6%) and urinary deconjugated MN levels in six patients (5%) (P=1.00). Plasma free normetanephrine (NMN) levels were increased in seven patients (6%), and five patients had increased urinary excretion of deconjugated NMN (4%) (P=0.69). Plasma free combined MN levels (NMN, MN, and 3MT) were increased in 41 patients (33%), whereas 24-h urinary excretion rates of deconjugated combined MNs were increased in 33 patients (27%, PConclusionsThe combined levels of free MNs and free 3MT in plasma indicate a higher number of biochemically active HNPGLs than the 24-h urinary excretion rates of these markers.

Objectives To assess the prognostic impact of time to recurrence (TTR) on cancer-specific survival (CSS) after recurrence in patients with renal cell carcinoma (RCC) undergoing radical nephrectomy or nephron-sparing surgery. To analyse differences in clinical and histopathological criteria between patients with early and late recurrence. Patients and Methods Of 13 107 patients with RCC from an international multicentre database, 1712 patients developed recurrence in the follow-up (FU), at a median (interquartile range) of 50.1 (25-106) months. In all, 1402 patients had recurrence at ≤5 years (Group A) and 310 patients beyond this time (Group B). Differences in clinical and histopathological variables between patients with early and late recurrence were analysed. The influence of TTR and further variables on CSS after recurrence was assessed by Cox regression analysis. Results Male gender, advanced age, tumour diameter and stage, Fuhrman grade 3-4, lymphovascular invasion (LVI), and pN + stage were significantly more frequent in patients with early recurrence, who had a significantly reduced 3-year CSS of 30% compared with patients in Group B (41%; P = 0.001). Age, gender, tumour histology, pT stage, and continuous TTR (hazard ratio 0.99, P = 0.006; monthly interval) independently predicted CSS. By inclusion of dichotomised TTR in the multivariable model, a significant influence of this variable on CSS was present until 48 months after surgery, but not beyond this time. Conclusions Advanced age, male gender, larger tumour diameters, LVI, Fuhrman grade 3-4, pN + stage, and advanced tumour stages are associated with early recurrence. Up to 4 years from surgery, a shorter TTR independently predicts a reduced CSS after recurrence. © 2013 The Authors. BJU International © 2013 BJU International.