Edwin Herrmann

Data are limited regarding routine use of everolimus after initial vascular endothelial growth factor (VEGF)–targeted therapy. The aim of this prospective, noninterventional, observational study was to assess efficacy and safety of everolimus after initial VEGF-targeted treatment in patients with metastatic renal cell carcinoma (mRCC) in routine clinical settings. Everolimus was administered per routine clinical practice. Patients with mRCC of any histology from 116 active sites in Germany were included. The main objective was to determine everolimus efficacy in time to progression (TTP). Progression-free survival (PFS), treatment duration, tumor response, adherence to everolimus regimen, treatment after everolimus, and safety were also assessed. In the total population (N = 334), median follow-up was 5.2 months (range, 0–32 months). Median treatment duration (safety population, n = 318) was 6.5 months (95% confidence interval [CI], 5–8 months). Median TTP and median PFS were similar in populations investigated. In patients who received everolimus as second-line treatment (n = 211), median (95% CI) TTP was 7.1 months (5–9 months) and median PFS was 6.9 months (5–9 months). Commonly reported adverse events (safety population, n = 318) were dyspnea (17%), anemia (15%), and fatigue (12%). Limitations of the noninterventional design should be considered. This study reflects routine clinical use of everolimus in a large sample of patients with mRCC. Favorable efficacy and safety were seen for everolimus after previous therapy with one VEGF-targeted agent. Results of this study confirm everolimus as one of the standard options in second-line therapy for patients with mRCC. Novartis study code, CRAD001LD27: VFA registry for noninterventional studies ( http://www.vfa.de/de/forschung/nisdb/ ).

To investigate whether patients with metastatic renal cell carcinoma benefit from sequential therapies with the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib.

To investigate prognostic markers in patients with metastatic renal cell carcinoma (mRCC) undergoing treatment with the tyrosine kinase inhibitors (TKIs) sorafenib (So) or sunitinib (Su).

We examined papillary renal cell carcinoma prognostic variables and validated the 2002 UICC TNM staging system in a multicenter analysis. From 10 urological institutions in Germany followup data were collected on a total of 675 patients with papillary renal cell carcinoma. Central pathological review was done to validate external histopathological diagnoses. The Kaplan-Meier method was used to derive cumulative cancer specific and overall survival, and the log rank test was used to compare the curves of 2 or more groups. For multivariate analysis of prognostic factors Cox regression analysis was done. All proportional hazard assumptions were systemically verified using the Grambsch-Therneau test. Cancer specific survival was significantly related to TNM stage and histological grading on univariate and multivariate analyses. Five-year cancer specific survival in pT1b cases was significantly shorter than in pT1a cases (90.0% vs 98.3%, p = 0.017). No significant difference was found between pT1b and pT2 tumors. Patients with pT3 or greater disease were at high risk for metastasis (50.6%) while metastatic disease associated with pT2 or less tumors occurred in 7.8% (p <0.0001). After metastatic disease was present the prognosis was poor with 7.2% 5-year cancer specific survival. Age was associated with poor prognosis in the subgroup with pT3 or greater tumors on univariate analysis (p = 0.026) but not on multivariate analysis. In its current form the 2002 UICC TNM staging system is not applicable to papillary renal cell carcinoma. Clinical and radiological followup should be offered at frequent intervals to patients with venous thrombus and/or locally advanced disease. The role of age remains unclear but should not be underestimated in risk stratification after surgery.

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. 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. 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-α 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. 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.

The endothelin axis consists of endothelin-1 (ET-1) and its two receptors, ET_A- and ET_B-receptor (ET_A-R and ET_B-R). In several tumor entities, the ET_A-R plays a significant role as a drug target. In our study, we investigated whether inhibition of ET_A-R with atrasentan leads to an antitumor effect in urinary bladder carcinoma as well. Twenty nude mice with thymic aplasia were subcutaneously administered 2 × 10⁶ KU-19-19 bladder cancer cells in the right flank. Starting on the 22nd day after the injection, ten animals were treated with atrasentan (2.5 mg/kg BW intraperitoneally), and another ten animals were treated with placebo. During treatment, absolute tumor growth and relative growth rate over time were determined. After the end of treatment, the mitosis and necrosis rates, microvessel density, and receptor density in the tumor tissue were analyzed by immunohistochemistry. In addition, the expression intensities of ET-1, ET_A-R, and ET_B-R were evaluated semiquantitatively and compared between the groups. No significant differences between the active-treatment and placebo groups were detected, either with respect to absolute tumor growth (P = 0.333) or mitosis rate (P = 0.217). In the analysis of the necrosis rate and receptor density for ET_A-R, a trend toward higher values in the active-treatment group (mean necrosis rate = 63.67%, receptor density: 1.417) than in the placebo group (mean necrosis rate = 46.25%, receptor density: 1.270) was found; however, neither difference was statistically significant (P = 0.08 and 0.219, respectively). ET_A-R blockade with atrasentan in a bladder cancer xenograft model shows no significant antitumor effect.

Our goal was to prospectively evaluate self-reported quality-of-life (QoL) during second-line therapy in 51 consecutive patients with cytokine-refractory kidney cancer treated with sorafenib or sunitinib. QoL was assessed by the EORTC QoL questionnaire QLQ-C30 at baseline and at weeks 4, 6, 10, 12 and 16. Global QoL deteriorated significantly during the first 4 weeks of treatment (P < 0.0001). Patients experienced a reduction of their role, cognitive, and social function (all P < 0.0001). In addition, fatigue (P < 0.0001), nausea/vomiting (P = 0.003), and pain (P < 0.0001) as well as dyspnoea (P < 0.0001), insomnia (P = 0.026), appetite loss (P = 0.013), and diarrhoea (P < 0.0001) increased significantly. After 16 weeks, fatigue (P < 0.0001), pain (P = 0.015), appetite loss (P = 0.002) and diarrhoea (P = 0.038) were still influenced by the therapy, while all functional scales recovered. Global QoL at baseline was predictive of overall response (P = 0.006) and progression free survival (PFS) (P < 0.0001). A better physical function at baseline, a better ECOG performance status, and a low risk profile according to MSKCC risk groups correlated with a longer PFS (all P < 0.0001). No significant differences regarding QoL were found between sorafenib and sunitinib during the study period. Second-line therapy with sorafenib or sunitinib does not adversely affect patients global QoL after 16 weeks of treatment. Evaluation of baseline QoL can help to further stratify patients into risk groups predicting overall response and PFS.

To present long-term results of a single-center series of patients undergoing bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer and to analyze the impact of pelvic lymph node metastasis and lymphovascular invasion on clinical outcome. Between 1986 and 2005 833 patients were treated with bilateral pelvic lymphadenectomy and radical cystectomy at our institution. 614 of them with valid clinical follow-up information and no neoadjuvant therapy could be evaluated. Disease-free and overall survival in the entire cohort was 56.7% and 49.5% at 5 years and 52.4% and 38.2% at 10 years, respectively. 28.1% of all patients had pelvic lymph node metastasis. We found organ-confined tumor stages (or=pT3) and positive pelvic lymph nodes had a significantly shorter overall survival than those without lymph node metastasis (P < 0.0001). In the subgroup of or=pT3) (P = 0.004) and lymphovascular invasion (P = 0.001) were independent prognostic parameters. According to the present series, survival for patients with <or=pT2 does not depend on the lymph node stage. Lymphovascular invasion is an independent parameter of impaired survival and should be determined routinely in cystectomy specimens to identify patients, who may benefit from adjuvant systemic therapy.

Einleitung: Die laparoskopische transabdominelle Entfernung von benignen Nebennierenzysten ist der heutige therapeutische Goldstandard. Der retroperitoneoskopische Zugang findet in der Literatur kaum Beachtung, obwohl er eine vergleichbare Methode darstellt. Kasuistik: Wir möchten von einer 27-jährigen Frau berichten, die sich mit epigastrischen sowie linksseitigen Flankenschmerzen vorstellte. Sonographisch und in der Computertomographie des Abdomens zeigte sich eine sehr große zystische Raumforderung im Bereich des linken Nierenoberpols. Bildgebend wurde nicht deutlich, ob sie ihren Ursprung von der Niere oder von der Nebenniere nahm. Nach retroperitoneoskopischer Exzision zeigte die histologische Aufarbeitung das Bild einer adrenalen Pseudozyste. Postoperativ erholte sich die Patientin rasch; die epigastrischen und die linksseitigen Flankenschmerzen verschwanden umgehend. Schlussfolgerung: Der retroperitoneoskopische Zugang zur Resektion von Nebennierenzysten ist eine effektive, kostengünstige und schonende Therapieoption. Introduction: Laparoscopic management of adrenal benign cysts is the method of choice today. In contrast to the transabdominal laparoscopic approach, retroperitoneoscopy is rarely performed, although it seems to be a comparable method and alternative technique for cyst resection. Case Report: A thin 27-year-old woman in good condition presented with epigastric and left flank pain as well as reflux of gastric acid. A large adrenal cystic lesion was detected on ultrasonography and computed tomography of the abdomen. The question of whether the cyst arose from the upper pole of the left kidney or from the adrenal gland could not be answered. Retroperitoneoscopic excision of the cystic lesion was performed. The histopathological work-up revealed the finding of an adrenal pseudocyst. Symptoms of epigastric and left flank pain as well as reflux of gastric acid resolved after pseudocyst removal. Conclusions: The retroperitoneoscopic approach for symptomatic adrenal cyst resection represents an effective, cost-reducing and durable treatment.