[Apalutamide in patients with high-risk M0CRPC: data from the pivotal SPARTAN study and initial experience from a compassionate use program]. / Apalutamid bei Patienten mit einem Hochrisiko-M0CRPC: Daten der Zulassungsstudie SPARTAN und erste Erfahrungen aus einem Härtefallprogramm.

Non-metastatic castration-resistant prostate carcinoma (M0CRPC) is associated with an increased risk of progression and mortality, especially if the prostate-specific antigen doubling time is short (PSADT ≤ 10 months). The risk of progression and mortality increases even further if the disease progresses to the metastatic stage (mCRPC). The androgen receptor inhibitors apalutamide, darolutamide and enzalutamide, each in combination with androgen deprivation therapy (ADT), are available for the treatment of patients with high-risk M0CRPC.Data from the pivotal SPARTAN study showed that apalutamide + ADT delayed metastasis-free survival (MFS) and thus also the development of mCRPC in these patients. Prior to the approval of apalutamide in the European Union, the active substance was available in Germany as part of an international compassionate use program. A total of 109 patients from 50 centres participated in Germany: 45 patients were treated for more than 3 months and 13 patients for more than 6 months. The compassionate use program continues in some countries; 556 patients have been enrolled worldwide.In our experience, this real-world population showed a good PSA response, which was also shown for this exploratory endpoint in the SPARTAN study. We were also unable to identify any significant differences from the pivotal trial with regards to the tolerability profile.Apalutamide in combination with ADT was also effective in this real-world population and led to a rapid decrease in PSA. The tolerability profile did not differ from that in the SPARTAN trial.

LHRH sparing therapy in patients with chemotherapy-naïve, mCRPC treated with abiraterone acetate plus prednisone: results of the randomized phase II SPARE trial.

BACKGROUND: Although the benefit of androgen deprivation therapy (ADT) continuation in metastatic castration-resistant prostate cancer (mCRPC) remains controversial, clinical evidence is lacking. Recent results indicated that treatment with abiraterone acetate (AA) plus prednisone (P) further suppresses serum testosterone levels over ADT alone, suggesting that continuation of ADT in the treatment of mCRPC may not be necessary. METHODS: In this exploratory phase 2 study, mCRPC patients were randomized with a 1:1 ratio to receive either continued ADT plus AA + P (Arm A) or AA + P alone (Arm B). The primary endpoint was the rate of radiographic progression-free survival (rPFS) at month 12. Secondary endpoints included PSA-response rate, objective response, time to PSA progression and safety. RESULTS: A total of 68 patients were equally randomized between the two study arms. Median testosterone-levels remained below castrate-levels throughout treatment in all patients. According to the intention-to-treat analysis the rPFS rate was 0.84 in Arm A and 0.89 in Arm B. Moderate and severe treatment-emergent adverse events were reported for 72% of the patients in Arm A and for 85% of the patients in Arm B. CONCLUSIONS: AA + P treatment without ADT may be effective in mCRPC patients and ADT may not be necessary in patients receiving AA + P.

Adherence Measures for Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate plus Prednisone: Results of a Prospective, Cluster-Randomized Trial.

Residual androgen production causes tumor progression in metastatic, castration-resistant prostate cancer (mCRPC) patients. Abiraterone acetate (AA), a prodrug of abiraterone, is an oral CYP-17 inhibitor that blocks androgen production. It was hypothesized that adherence-enhancing measures (AEM) might be beneficial for mCRPC patients receiving abiraterone acetate plus prednisone (AA + P). This multicenter, prospective, 2-arm trial allocated mCRPC patients who were progressive after docetaxel-based chemotherapy or asymptomatic/mildly symptomatic after failure of an androgen deprivation therapy to Arm A (with AEM) or Arm B (without AEM) by center-based cluster-randomization. The primary objective was to assess the influence of AEM on discontinuation rates and medication adherence in mCRPC patients treated with AA + P. A total of 360 patients were allocated to Arm A, and 315 patients to Arm B. At month 3, the rate of treatment discontinuation, not due to disease progression or the start of new cancer therapy, was low in both arms (A: 9.0% vs. B: 7.3%, OR = 1.230). Few patients had a medium/low Morisky Medication Adherence Scale (MMAS-4) score (A: 6.4% vs. B: 9.1%, OR = 0.685). The results obtained did not suggest any clear adherence difference between Arm A and Arm B. In patients with mCRPC taking AA + P medication, adherence seemed to be generally high.

Toward noninvasive follow-up of low-risk bladder cancer - Rationale and concept of the UroFollow trial.

BACKGROUND: Follow-up recommendations for patients with nonmuscle invasive bladder cancer (NMIBC) are largely based upon expert opinion. A growing body of evidence suggests that current follow-up strategies for bladder cancer patients with low and intermediate risk represent overdiagnosis and may lead to overtreatment. The goal of this study is to explore the options of a noninvasive follow-up in patients with pTa G1-2/low-grade NMIBC. METHODS: The risks and options for a urine marker-guided, noninvasive follow-up of patients with pTa G1-2/low-grade NMIBC were defined and the study design for a prospective randomized trial (UroFollow) was developed based upon the current literature. RESULTS: The investigators postulated that follow-up of patients with pTa G1-2/low-grade NMIBC requires a high sensitivity of urinary tumor markers. However, data from prospective studies with prediagnostic urine samples are scarce, even for approved markers, and cross-sectional studies with symptomatic patients overestimate the sensitivity. So far, cell-based markers (e.g., uCyt+ and UroVysion) in urine appeared to have higher sensitivities and specificities in low-grade NMIBC than urine cytology and markers analyzing soluble tumor-associated antigens. Marker panels are more sensitive than single-marker approaches at the expense of a lower specificity. Given a prospective randomized comparison with a marker sensitivity of 80% compared to usual care with cystoscopy, the sample size calculation yielded that 62 to 185 patients under study per arm are needed depending on different recurrence rates. CONCLUSIONS: Based upon these findings the UroFollow trial has been designed as a prospective randomized study comparing a noninvasive marker-based (UroVysion, NMP22, urine cytology, and ultrasound) follow-up with the current standard of care over a period of 3 years.

[Palliative care in an outpatient urological setting]. / Palliativmedizin im ambulanten urologischen Arbeitsalltag.

In their daily routine, urologists in general and uro-oncologists in particular are often confronted with non-urologic complications. To meet the need for measures of symptom control at the interface between genuine urologic and general palliative care, it is necessary for the partners from special outpatient palliative care (SAPV), general outpatient palliative care (AAPV), medical centres and other service units to cooperate. There are a significant number of urological practitioners who have completed trainings in palliative care or passed an exam as 'qualified palliative physician (QPA)'. Depending on the federal state, the local provision of health infrastructure varies greatly. The case study presented here is looking at the city of Wuppertal as an example of a medium-sized coverage area in a densely populated urban area in the western part of Germany. A viable cooperation requires timely, standardised documentation in an internet-based system as well as defined strategies for the provision of care.

The ZOTECT study: Effect of zoledronic acid on bone metabolism in patients with bone metastases from prostate or breast cancer.

PURPOSE: The ZOTECT study assesses the effect of zoledronic acid (ZOL) on bone-marker levels and potential correlations with disease outcomes in bisphosphonate-naive patients. METHODS: This prospective, single-arm, open-label study in bisphosphonate-naive (≥6 months) patients with bone metastases from prostate cancer (PC; n=301) or breast cancer (BC; n=99) enrolled at 98 German sites (May 2006 to July 2008) investigated the effect of ZOL (4 mg intravenously every 4 weeks×4 months, with a final follow-up at 12 months) on bone-marker levels. Secondary assessments: skeletal-related event (SRE) rate, pain, quality of life (QoL), and prostate-specific antigen levels. Endpoints were assessed using summary statistics by visit/tumor type and Kaplan-Meier analyses. RESULTS: ZOL treatment significantly decreased bone-marker levels (amino-terminal propeptide of type I collagen [P1NP], C-terminal cross-linking telopeptide of type I collagen [CTX]; P<0.0001), and this decrease was maintained through the final 1-year follow-up visit. Baseline P1NP and CTX levels correlated with extent of bone disease (P<0.0001, each) and on-treatment decreases in marker levels. Skeletal disease burden and bone-marker levels were similar between PC and BC patients, and ZOL did not significantly influence osteoprotegerin/receptor activator of nuclear factor-κB ligand levels. Only 13 SREs occurred in 11 patients, supporting the known ZOL-mediated reduction in SREs. On-treatment bone-marker level changes did not correlate with SRE rate, pain scores, or QoL. Generally, ZOL was well tolerated and adverse events were consistent with its known safety profile. CONCLUSIONS: This study confirms that ZOL therapy significantly reduces bone turnover (measured as P1NP and CTX levels) in patients with bone metastases from PC or BC.

Efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolic syndrome: results of a randomized, placebo-controlled trial.

INTRODUCTION: The prevalence of erectile dysfunction (ED) is increased in men with metabolic syndrome compared with the general population. AIM: The aim of this study was to evaluate the efficacy and safety of vardenafil vs. placebo in men who had ED and metabolic syndrome. METHODS: This was a 12-week, double-blind, randomized, multicenter, parallel-group, placebo-controlled prospective study in men with ED and metabolic syndrome (assessed by the International Diabetes Federation criteria). Vardenafil was administered at a starting dose of 10 mg, which could be titrated to 5 mg or 20 mg after 4 weeks, depending on efficacy and tolerability. MAIN OUTCOME MEASURES: Primary efficacy measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile (SEP) diary questions 2/3. Secondary efficacy measures included SEP1, a diary question assessing ejaculation, the percentage of men achieving "return-to-normal" erectile function, and the percentage of men who titrated to a different dose. Adverse events (AEs) were recorded throughout the study. RESULTS: The intent-to-treat population included 145 men (vardenafil, N = 75; placebo, N = 70). Baseline least squares IIEF-EF domain scores were low (vardenafil: 12.0; placebo: 12.7), indicative of moderate-to-severe ED. Vardenafil was statistically significantly superior to placebo for all primary efficacy measures (P < 0.0001) and showed nominally statistically significant superiority compared with placebo for SEP1/ejaculation success rates (P = 0.0003 and P < 0.0001, respectively) and the percentage of subjects reporting "return-to-normal" erectile function (P = 0.0004). Treatment-emergent AEs were mild-to-moderate in severity and consistent with the known AE profile of phosphodiesterase type 5 inhibitors. CONCLUSIONS: This is the first study to assess the efficacy and safety of vardenafil, taken alone, for ED therapy in a population of men who all had metabolic syndrome. Although baseline erectile function in these patients was low, vardenafil treatment was associated with significant improvements in erectile function and rates of successful intercourse, and was well tolerated.