Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Prognostic significance of Fuhrman grade and age for cancer-specific and overall survival in patients with papillary renal cell carcinoma: results of an international multi-institutional study on 2189 patients.

PURPOSE: Because the prognostic impact of the clinical and pathological features on cancer-specific survival (CSS) and overall survival (OS) in patients with papillary renal cell carcinoma (papRCC) is still controversial, we want to assess the impact of clinicopathological features, including Fuhrman grade and age, on survival in surgically treated papRCC patients in a large multi-institutional series. METHODS: We established a comprehensive multi-institutional database of surgically treated papRCC patients. Histopathological data collected from 2189 patients with papRCC after radical nephrectomy or nephron-sparing surgery were pooled from 18 centres in Europe and North America. OS and CSS probabilities were estimated using the Kaplan-Meier method. Multivariable competing risks analyses were used to assess the impact of Fuhrman grade (FG1-FG4) and age groups (<50 years, 50-75 years, >75 years) on cancer-specific mortality (CSM). RESULTS: CSS and OS rates for patients were 89 and 81% at 3 years, 86 and 75% at 5 years and 78 and 41% at 10 years after surgery, respectively. CSM differed significantly between FG 3 (hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.17-8.22; p < 0.001) and FG 4 (HR 8.93, 95% CI 4.25-18.79; p < 0.001) in comparison to FG 1. CSM was significantly worse in patients aged >75 (HR 2.85, 95% CI 2.06-3.95; p < 0.001) compared to <50 years. CONCLUSIONS: FG is a strong prognostic factor for CSS in papRCC patients. In addition, patients older than 75 have worse CSM than patients younger than 50 years. These findings should be considered for clinical decision making.

Perception of cure in prostate cancer: human-led and artificial intelligence-assisted landscape review and linguistic analysis of literature, social media and policy documents.

BACKGROUND: Understanding stakeholders' perception of cure in prostate cancer (PC) is essential to preparing for effective communication about emerging treatments with curative intent. This study used artificial intelligence (AI) for landscape review and linguistic analysis of definition, context and value of cure among stakeholders in PC. MATERIALS AND METHODS: Subject-matter experts (SMEs) selected cure-related key words using Elicit, a semantic literature search engine, and extracted hits containing the key words from Medline, Sermo and Overton, representing academic researchers, health care providers (HCPs) and policymakers, respectively. NetBase Quid, a social media analytics and natural language processing tool, was used to carry out key word searches in social media (representing the general public). NetBase Quid analysed linguistics of key word-specific hit sets for key word count, geolocation and sentiments. SMEs qualitatively summarised key word-specific insights. Contextual terms frequently occurring with key words were identified and quantified. RESULTS: SMEs identified seven key words applicable to PC (number of acquired hits) across four platforms: Cure (12429), Survivor (6063), Remission (1904), Survivorship (1179), Curative intent (432), No evidence of disease (381) and Complete remission (83). Most commonly used key words were Cure by the general public and HCPs (11815 and 224 hits), Survivorship by academic researchers and Survivor by policymakers (378 hits each). All stakeholders discussed Cure and cure-related key words primarily in early-stage PC and associated them with positive sentiments. All stakeholders defined cure differently but communicated about it in relation to disease measurements (e.g. prostate-specific antigen) or surgery. Stakeholders preferred different terms when discussing cure in PC: Cure (academic researchers), Cure rates (HCPs), Potential cure and Survivor/Survivorship (policymakers) and Cure and Survivor (general public). CONCLUSION: This human-led, AI-assisted large-scale qualitative language-based research revealed that cure was commonly discussed by academic researchers, HCPs, policymakers and the general public, especially in early-stage PC. Stakeholders defined and contextualised cure in their communications differently and associated it with positive value.

[Molecular characterization of penile cancer : Literature review of new prognostic markers and potential therapeutic targets]. / Die molekulare Charakterisierung des Peniskarzinoms : Literaturreview zu neuen Prognosemarkern und potentiellen Therapietargets.

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.

[Management of penile cancer patients: new aspects of a rare tumour entity]. / Das Management von Patienten mit Peniskarzinom ­ Neue Aspekte in der Therapie einer seltenen Tumorentität.

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.

[What is the perception of the 10-point plan of the German Federal Ministry of Health against multidrug-resistant pathogens and measures of antibiotic stewardship? : An interdisciplinary analysis among German clinicians and development of a decision tool for urologists]. / Wie werden der 10-Punkte-Plan des Deutschen Bundesministeriums für Gesundheit zur Bekämpfung resistenter Erreger und Maßnahmen des Antibiotic Stewardship wahrgenommen? : Eine fachübergreifende Analyse der Kenntnis deutscher Klinikärzte und Entwicklung einer urologischen Handlungsanweisung.

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, 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). 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 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. 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.

European temporal trends in the use of lymph node dissection in patients with renal cancer.

BACKGROUND: The role of lymph node dissection (LND) in renal cell carcinoma (RCC) is still under debate. We aimed to assess the utilization rates of LND over time in Europe. METHODS: A multi-institutional database of 13,581 RCC patients who underwent radical nephrectomy (RN) or nephron sparing surgery (NSS) between 1988 and 2014 was created within an European consortium. We analysed temporal trends in the frequency of LND by using Joinpoint regression. Logistic regression models were used to identify predictors of LND. RESULTS: Overall, 5114 patients (42.7%) underwent LND. Lymph node invasion was recorded in 566 cases (11% of LND patients) which represents 4.7% of the whole study cohort. A gradual decline in the use of LND started in the 1990s. After 2008 LND decreased significantly by 21.5% per year (95%CI -33.3 to -7.5, p < 0.01) until 2011 and stabilized thereafter (Annual Percentage Change 4.9%, 95%CI -3.4 to 13.8, p = 0.2). At multivariable analyses, patient age (OR 0.98, p < 0.0001), type of surgery (RN vs. NSS: OR 5.46, p < 0.0001), surgical approach (open vs. minimally invasive: OR 1.75, p < 0.0001), T stage (T2 vs. T1: OR 1.57; T3-4 vs. T1: OR 1.44, p < 0.0001), clinical tumour size (OR 1.14, p < 0.0001), and year of surgery (OR 0.95, p < 0.0001) were associated with higher probability of LND at nephrectomy. CONCLUSIONS: A trend towards lower LND was observed over time for RCC patients who underwent RN or NSS. LND is more frequently performed in younger patients, locally advanced diseases and in case of open surgery.