Baseline neutrophil-to-lymphocyte ratio as a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel versus abiraterone or enzalutamide in the CARD study.

BACKGROUND: There is growing evidence that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC). In the CARD study (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and OS versus abiraterone or enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative androgen-receptor-targeted agent (ARTA). Here, we investigated NLR as a biomarker. PATIENTS AND METHODS: CARD was a multicenter, open-label study that randomized patients with mCRPC to receive cabazitaxel (25 mg/m2 every 3 weeks) versus abiraterone (1000 mg/day) or enzalutamide (160 mg/day). The relationships between baseline NLR [< versus ≥ median (3.38)] and rPFS, OS, time to prostate-specific antigen progression, and prostate-specific antigen response to cabazitaxel versus ARTA were evaluated using Kaplan-Meier estimates. Multivariable Cox regression with stepwise selection of covariates was used to investigate the prognostic association between baseline NLR and OS. RESULTS: The rPFS benefit with cabazitaxel versus ARTA was particularly marked in patients with high NLR {8.5 versus 2.8 months, respectively; hazard ratio (HR) 0.43 [95% confidence interval (CI) 0.27-0.67]; P < 0.0001}, compared with low NLR [7.5 versus 5.1 months, respectively; HR 0.69 (95% CI 0.45-1.06); P = 0.0860]. Higher NLR (continuous covariate, per 1 unit increase) independently associated with poor OS [HR 1.05 (95% CI 1.02-1.08); P = 0.0003]. For cabazitaxel, there was no OS difference between patients with high versus low NLR (15.3 versus 12.9 months, respectively; P = 0.7465). Patients receiving an ARTA with high NLR, however, had a worse OS versus those with low NLR (9.5 versus 13.3 months, respectively; P = 0.0608). CONCLUSIONS: High baseline NLR predicts poor outcomes with an ARTA in patients with mCRPC previously treated with docetaxel and the alternative ARTA. Conversely, the activity of cabazitaxel is retained irrespective of NLR.

[The "triple F" campaign of the German Society of Urology: what have we reached so far?] / Die "Triple F-Kampagne" der Deutschen Gesellschaft für Urologie: Was haben wir erreicht?

Urology is an important medical discipline for men, women and children due to the variety and frequency of urologic diseases-a fact which is unknown to the majority of the population. In 2016, the "triple F" campaign was initiated in order to inform about both the role of urology and the importance of timely urologic investigations as well as prostate-specific antigen (PSA)-based early examination. With the Roth brothers as the face of the campaign, a homepage was created with information about the main important urologic diseases. Flyers and posters for physicians and their patients were sent to 3500 urologists, a urologist search tool for patients with so far 2200 registered urologists is available on the homepage, etc. Further activities using social media are planned with the objective of increasing participation of German urologists and their patients.

[Changes in the treatment of metastatic prostate cancer-new data and open questions]. / Therapie des metastasierten Prostatakarzinoms im Wandel ­ neue Daten und offene Fragen.

The availability of taxane-based chemotherapy and androgen-receptor-targeted agents (ARTAs) have significantly broadened the therapeutic options for patients with metastatic prostate cancer and may also result in longer patient survival. The therapeutic sequence of ARTAs and taxanes may influence outcome and therefore decisions should be made on an individual basis. This article provides guidance for therapeutic decision-making in daily clinical practice by working out criteria that can be used to support individual therapeutic decisions. The focus is on metastatic castration-naive prostate cancer, oligometastatic disease as well as non-metastatic and metastatic castration-resistant prostate cancer.

[Attending physicians in urology working at university centers or non-university centers-what are the differences? : Results of a web-based cross-sectional study at German hospitals]. / Urologische Oberärztinnen und Oberärzte an universitären oder nicht-universitären Kliniken ­ welche Unterschiede gibt es? : Ergebnisse einer webbasierten Querschnittstudie an deutschen Kliniken.

BACKGROUND: Attending physicians (AP) in urology represent a very heterogeneous group covering various clinical priorities and career objectives. To date, there are no reliable data on professional, personal and position-linked aspects of AP in urology working in university centers (univ-AP) opposed to those working in non-university centers (n-univ-AP). MATERIALS AND METHODS: The objective of this study was to analyze individual professional perspectives, professional and personal settings, specific job-related activities and individual professional goals of univ-AP opposed to n­univ-AP. Thus, a web-based survey containing 55 items was designed to perform a cross-sectional study that was then forwarded using a link which was sent via a mailing list of the German Society of Urology. The survey was available for completion by AP at German urological centers from February to April 2019. Group-specific differences were evaluated using bootstrap-adjusted multivariate logistic regression models. RESULTS: Of the 192 evaluable surveys, 61 (31.8%) and 131 (68.2%) were part of the univ-AP and n­univ-AP study group, respectively. Participating n­univ-AP compared to univ-AP held the position of AP (p = 0.022) significantly longer and were on call significantly more frequently (p < 0.001). AP in urology (self)-assessed themselves as autonomously confident in performing robotic, laparoscopic, open, endo-urologic, and plastic-reconstructive surgery in 12.4%, 25%, 59.6%, 92.1%, and 25.7%, respectively, with no significant differences between the two groups among all above mentioned surgical subdomains based on multivariate analysis. AP in urology were (very) content in 92% concerning the choice of their discipline, in 73.9% concerning their actual working circumstances, and in 60.2% concerning their level of surgical expertise. Only 27.1% and 19.9% were (very) content with the amount of available time for their personal professional development and for private affairs, respectively. As opposed to n­univ-AP, univ-AP would choose a career in clinical centers once again significantly more frequently (OR 2.87; p(BS) = 0.041), but assess the position of AP as their definitive career goal significantly less frequently (OR 0.42; p(BS) = 0.40). Univ-AP state significantly more frequently that they were running for the position of head of department or full professor (OR 5.64; p(BS) = 0.001). CONCLUSION: In this first survey study world-wide on AP in urology divided according to their academic background, similarities and variances were analyzed, baring the potential to further improve identification of AP for a career in clinical centers.

[Treatment situation in metastastic Castration Naive Prostate Cancer (mCRPC) and the implications on clinical routine]. / Therapiesituation beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) und die Auswirkungen im klinischen Alltag.

There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naïve stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.

[Evaluation of the decision aid "Entscheidungshilfe Prostatakrebs" from the patients' view : Results from the first three months]. / Evaluation der Entscheidungshilfe Prostatakrebs aus Patientensicht : Ergebnisse der ersten 3 Monate.

BACKGROUND: The decision aid "Entscheidungshilfe Prostatakrebs" is available online free of charge since June 2016. It is designed to support patients with their treatment decision-making and to lighten the burden on their treating urologists. This study evaluates usage data from the first 3 months. MATERIALS AND METHODS: The ICHOM standard set was applied to allow a personalised presentation and to collect relevant data for subsequent counselling. Additionally, personal preferences and psychological burden were assessed amongst others. We collected anonymous data. A multivariate model evaluated predictors for high user satisfaction. RESULTS: From June through August 2016 a total of 319 patients used the decision aid, showing a continuous monthly increase in the number of users. There were n = 219 (68.7%) complete questionnaires. Median age was 66.1 ± 8.0 years. The oncological risk was low in 30.3%, intermediate in 43.6% and high in 26.1%. A majority of 57.5% used the decision aid together with their partner, 35.1% alone and 5.5% with their children. In all, 54.8% were "very satisfied" and 32.0% were "satisfied" with the decision aid for a total satisfaction rate of about 87%. The only predictors of total satisfaction were the usage mode and reported distress level. CONCLUSIONS: As shown by the continuously increasing number of users this decision aid is becoming well established in German urology. Patients' overall ratings are very positive. The majority of patients use the decision aid with their partner. This represents a significant advantage of a multimedia approach compared to print media.

[Decision aids for patients are widely accepted by German urologists : A survey among members of the German Society of Urology (DGU) and the Federation of German Urologists (BDU)]. / Entscheidungshilfen für Patienten finden bei deutschen Urologen breite Akzeptanz : Umfrage unter Mitgliedern von DGU und BDU.

BACKGROUND: Treatment decision making remains a complex task for localized prostate cancer. Decision aids for patients can support the medical consultation. However, it is not known if German urologists accept decision aids for patients. Comparative data exist from a current survey among american urologists and radio oncologists. MATERIALS AND METHODS: From October through November 2014 we conducted an online survey consisting of 11 multiple-choice questions and an optional free text commentary among the members of DGU and BDU. All data was processed anonymously. We received 464 complete responses for a 6.6 % return rate. For group comparison we applied the Chi2-test. RESULTS: Respondents' median age was 50 (range 26-87) years and 15 % were female. 7 % were residents, 31 % employed at a clinic, and 57 % in private practice. Due to the low response rate of younger colleagues the results were not representative for the basic population. Regardless of age (p = 0.2) and professional environment (p = 1) shared decision making was preferred by 89 %. When counseling their patients with localized prostate cancer 20 % relied exclusively on conversation. To support their conversation 63 % used print media, 49 % decision aids, 33 % contact offers to support groups, 24 % Internet resources and 13 % video material. From using decision aids 86 % expected positive effects for patients and 78 % for physicians (p = 0.017). 15 % expected a change of the treatment decision. 77 % would motivate their patients to use a decision aid. CONCLUSIONS: In comparison to the opinion of american urologists and radio oncologists the acceptance of decision aids for patients among German urologists is significantly higher.

[Open and minimally invasive partial nephrectomy. Management of complications]. / Offene und minimal-invasive partielle Nephrektomie. Komplikationsmanagement.

Current guidelines increasingly recommend organ-preserving surgical procedures in the treatment of renal tumors. Both the open surgical and minimally invasive surgical techniques are well established. In the literature, various systems for the systematic evaluation of comorbidities and complications have been reported. Already while taking the patient's history and preoperative planning prior to partial nephrectomy, it is recommended that a detailed risk assessment be carried out regarding expected complications. Essentially the two critical factors - the comorbidities of the patient and anatomic complexity level of the tumor - should be evaluated in order to achieve the best possible selection of patients for a partial nephrectomy and the determination of the surgical method.

[Secondary malignancies in urinary diversions]. / Sekundärmalignome in Harnableitungen.

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary.

[Practical information on the use of port systems]. / Praxisrelevante Informationen für den Umgang mit Portsystemen.

As a result of the dynamic developments in oncology over the last few years, multimodal therapeutic options are now available for the treatment of cancer patients in practically all diseases stages. This has led to an increase in the use of all forms of chemotherapy. Low and moderately complex chemotherapy options are being increasingly employed in outpatient and day clinic settings. For this reason, among others, the implantation of central venous port systems has progressed to become an important component in the therapeutic planning for oncological patients.

External validation of disease-free survival at 2 or 3 years as a surrogate and new primary endpoint for patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: To perform the first external validation of a recently identified association between disease-free survival at two years (DFS2) or three years (DFS3) and overall survival at five years (OS5) in patients after radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB). METHODS AND METHODS: Records of 2483 patients who underwent RC for UCB at eight European centers between 1989 and 2008 were reviewed. The cohort included 1738 patients with pT2-4a tumors and negative soft tissue surgical margins (STSM) according to the selection criteria of the previous study (study group (SG)). In addition, 745 patients with positive STSM or other tumor stages (pT0-T1, pT4b) that were excluded from the previous study (excluded patient group (EPG)) were evaluated. Kappa statistic was used to measure the agreement between DFS2 or DFS3 and OS5. RESULTS: The overall agreement between DFS2 and OS5 was 86.5% (EPG: 88.7%) and 90.1% (EPG: 92.1%) between DFS3 and OS5. The kappa values for comparison of DFS2 or DFS3 with OS5 were 0.73 (SE: 0.016) and 0.80 (SE: 0.014) respectively for the SG, and 0.67 (SE: 0.033) and 0.78 (SE: 0.027) for the EPG (all p-values <0.001). CONCLUSIONS: We externally validated a correlation between DFS2 or DFS3 and OS5 for patients with pT2-4a UCB with negative STSM that underwent RC. Furthermore, this correlation was found in patients with other tumor stages regardless of STSM status. These findings indicate DFS2 and DFS3 as valid surrogate markers for survival outcome with RC.

[Validation of pre-cystectomy nomograms for the prediction of locally advanced urothelial bladder cancer in a multicentre study: are we able to adequately predict locally advanced tumour stages before surgery?]. / Validierung von Präzystektomienomogrammen zur Vorhersage lokal fortgeschrittener Harnblasenkarzinome in einer multizentrischen Studie : Können wir lokal fortgeschrittene Tumorstadien präoperativ ausreichend sicher vorhersagen?

OBJECTIVE: Pre-cystectomy nomograms with a high predictive ability for locally advanced urothelial carcinomas of the bladder would enhance individual treatment tailoring and patient counselling. To date, there are two currently not externally validated nomograms for prediction of the tumour stages pT3-4 or lymph node involvement. MATERIALS AND METHODS: Data from a German multicentre cystectomy series comprising 2,477 patients with urothelial carcinoma of the bladder were applied for the validation of two US nomograms, which were originally based on the data of 726 patients (nomogram 1: prediction of pT3-4 tumours, nomogram 2: prediction of lymph node involvement). Multivariate regression models assessed the value of clinical parameters integrated in both nomograms, i.e. age, gender, cT stage, TURB grade and associated Tis. Discriminative abilities of both nomograms were assessed by ROC analyses; calibration facilitated a comparison of the predicted probability and the actual incidence of locally advanced tumour stages. RESULTS: Of the patients, 44.5 and 25.8% demonstrated tumour stages pT3-4 and pN+, respectively. If only one case of a previously not known locally advanced carcinoma (pT3-4 and/or pN+) is considered as a staging error, the rate of understaging was 48.9% (n=1211). The predictive accuracies of the validated nomograms were 67.5 and 54.5%, respectively. The mean probabilities of pT3-4 tumours and lymph node involvement predicted by application of these nomograms were 36.7% (actual frequency 44.5%) and 20.2% (actual frequency 25.8%), respectively. Both nomograms underestimated the real incidence of locally advanced tumours. CONCLUSIONS: The present study demonstrates that prediction of locally advanced urothelial carcinomas of the bladder by both validated nomograms is not conferrable to patients of the present German cystectomy series. Hence, there is still a need for statistical models with enhanced predictive accuracy.

[Influence of older age on survival after radical cystectomy due to urothelial carcinoma of the bladder: survival analysis of a German multi-centre study after curative treatment of urothelial carcinoma of the bladder]. / Einfluss des Alters auf das karzinomspezifische Überleben nach radikaler Zystektomie : Überlebensanalyse aus einer deutschen Multicenterstudie nach kurativer Therapie eines Urothelkarzinoms der Harnblase.

BACKGROUND: The therapeutic gold standard of muscle-invasive tumour stages is radical cystectomy (RC), but there are still conflicting reports about associated morbidity and mortality and the oncologic benefit of RC in elderly patients. The aim of the present study was the comparison of overall (OS) and cancer-specific survival (CSS) in patients <75 and >75 years of age (median follow-up was 42 months). PATIENTS AND METHODS: Clinical and histopathological data of 2,483 patients with urothelial carcinoma and consecutive RC were collated. The study group was dichotomized by the age of 75 years at RC. Statistical analyses comprising an assessment of postoperative mortality within 90 days, OS and CSS were assessed. Multivariate logistic regression and survival analyses were performed. RESULTS: The 402 patients (16.2%) with an age of ≥75 years at RC showed a significantly higher local tumour stage (pT3/4 and/or pN+) (58 vs 51%; p=0.01), higher tumour grade (73 vs 65%; p=0.003) and higher rates of upstaging in the RC specimen (55 vs 48%; p=0.032). Elderly patients received significantly less often adjuvant chemotherapy (8 vs 15%; p<0.001). The 90-day mortality was significantly higher in patients ≥75 years (6.2 vs 3.7%; p=0.026). When adjusted for different variables (gender, tumour stage, adjuvant chemotherapy, time period of RC), only in male patients and locally advanced tumour stages was an association with 90-day mortality noticed. The multivariate analysis showed that patients ≥75 years of age have a significantly worse OS (HR=1.42; p<0.001) and CSS (HR=1.27; p=0.018). CONCLUSIONS: An age of ≥75 years at RC is associated with a worse outcome. Prospective analyses including an assessment of the role of comorbidity and possibly age-dependent tumour biology are warranted.

[Patients with bladder cancer in clinical stage T2 : survival benefit of downstaging in comparison to patients with confirmed muscle invasion in cystectomy specimens]. / Harnblasenkarzinompatienten im klinischen Tumorstadium T2 : Überlebensvorteil eines Downstaging gegenüber Patienten mit bestätigter Muskelinvasion im Zystektomiepräparat.

BACKGROUND: Few and partially contradictory data are available regarding the prognostic signature of downstaging of muscle-invasive clinical tumour stages in patients treated with radical cystectomy. MATERIALS AND METHODS: Clinicopathological parameters of 1,643 patients (study group, SG) treated with radical cystectomy due to muscle-invasive urothelial bladder cancer were summarized in a multi-institutional database. Patients of the SG fulfilled the following conditions: clinical tumour stage T2 N0 M0 and no administration of neoadjuvant radiation or chemotherapy. Cancer-specific survival (CSS) rates were calculated referring to pathological tumour stages in cystectomy specimens (pT2) (mean follow-up: 51 months). Furthermore, a multivariable model integrating clinical information was developed in order to predict the probability of downstaging. RESULTS: A total of 173 patients (10.5%) of the SG presented with downstaging in pathological tumour stages (pT0: 4.8%, pTa: 0.4%, pTis: 1.3%, pT1: 4.1%); 12 of these patients had positive lymph nodes (7%, in comparison with 21% pN+ of pT2 tumours and 43% of >pT2 tumours). Patients with tumour stages pT2 had CSS rates after 5 years of 89, 69 and 46%, respectively (p<0.001). In a multivariable Cox model the presence of pathological downstaging resulted in a significant reduction of cancer-specific mortality (HR 0.30; 95% CI 0.18-0.50). By logistic regression analysis the date of TURB (benefit for more recent operations) was identified as the only independent predictor for downstaging of muscle-invasive clinical tumour stages. Age, gender, grading and associated Tis in the TURB did not reveal any significant influence. CONCLUSION: Patients with muscle-invasive clinical tumour stages and downstaging in cystectomy specimens represent a subgroup with significantly enhanced CSS rates. Further trials that integrate the parameters tumour size, stages cT2a vs cT2b and focality are required in order to define the independent prognostic signature of downstaging of tumour stages more precisely.

Update on systemic therapies of metastatic renal cell carcinoma.

PURPOSE: Recent advances in understanding the molecular biology of advanced and metastatic renal cell carcinoma (RCC) have led to the development of several targeted agents that show impressive antitumor efficacy. The integration of these drugs into clinical practice has revolutionized the therapeutic management of RCC. METHODS: We reviewed data on all approved targeted agents in the first-line and second-line setting, as well as, studies involving sequential therapy. Data from phase III trials are discussed, and an optional therapeutic algorithm is presented. RESULTS: Sunitinib should be used as the first-line treatment of choice for good- and intermediate-risk patients according to Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, whereas temsirolimus is recommended for the poor-risk group. The combination of bevacizumab and INF-alpha can be regarded as an alternative to sunitinib. After cytokine failure, patients should be recommended to sorafenib. Everolimus must be considered after first-line failure of a tyrosine kinase inhibitor (TKI); furthermore, recent evidence suggests sequential use of TKIs before administration of everolimus. CONCLUSIONS: A range of potent drugs are available to patients with metastatic RCC. Treatment decisions should be made carefully taking into consideration that all targeted agents only have a palliative effect with prolongation of life, but do not cure metastatic RCC.