Pro- and anti-inflammatory macrophages express a sub-type specific purinergic receptor profile.

Extracellular nucleotides act as danger signals that orchestrate inflammation by purinergic receptor activation. The expression pattern of different purinergic receptors may correlate with a pro- or anti-inflammatory phenotype. Macrophages function as pro-inflammatory M1 macrophages (M1) or anti-inflammatory M2 macrophages (M2). The present study found that murine bone marrow-derived macrophages express a unique purinergic receptor profile during in vitro polarization. As assessed by real-time polymerase chain reaction (PCR), Gαs-coupled P1 receptors A2A and A2B are upregulated in M1 and M2 compared to M0, but A2A 15 times higher in M1. The ionotropic P2 receptor P2X5 is selectively upregulated in M1- and M2-polarized macrophages. P2X7 is temporarily expressed in M1 macrophages. Metabotropic P2Y receptors showed a distinct expression profile in M1 and M2-polarized macrophages: Gαq coupled P2Y1 and P2Y6 are exclusively upregulated in M2, whereas Gαi P2Y13 and P2Y14 are overexpressed in M1. This consequently leads to functional differences between M1 and M2 in response to adenosine di-phosphate stimulation (ADP): In contrast to M1, M2 showed increased cytoplasmatic calcium after ADP stimulation. In the present study we show that bone marrow-derived macrophages express a unique repertoire of purinergic receptors. We show for the first time that the repertoire of purinergic receptors is highly flexible and quickly adapts upon pro- and anti-inflammatory macrophage differentiation with functional consequences to nucleotide stimulation.

[Systemic treatment of metastatic renal cell carcinoma: change of paradigms after introduction of targeted therapy]. / Systemische Behandlung des metastasierten Nierenzellkarzinoms: Paradigmenwechsel nach Einführung der zielgerichteten Therapie.

INTRODUCTION: The goal of this work was to describe the change of treatment paradigms for metastatic renal cell carcinoma (mRCC) since 2006. PATIENTS AND METHODS: We retrospectively investigated all mRCC patients who were treated with targeted therapy between June 2006 and June 2012 at the University of Münster. RESULTS: In all, 50 of 158 (31.6 %) patients were initially treated with immunotherapy. The most often used second line treatment after immunotherapy was sorafenib (29 patients, 58.0 %). The first line treatment chosen for therapy-naïve patients was sunitinib (68 patients, 63.0 %). There was no statistically significant difference between the two groups (572 vs. 554 days, p = 0.745). A total of 77 patients had synchronous metastasis (48.8 %), 55 of whom underwent cytoreductive nephrectomy. There was a significant survival benefit in favor of surgically treated patients (510 vs. 186 days, p = 0.002). CONCLUSION: After introduction of the new agents treatment paradigms have changed substantially. Immunotherapy is used only rarely. Cytoreductive nephrectomy may continue to be regarded as standard treatment until prospective data are available.

[Complexity level simulation in the German diagnosis-related groups system: the financial effect of coding of comorbidity diagnostics in urology]. / Schweregradsimulation im G-DRG-System : Die finanziellen Auswirkungen der Nebendiagnosenkodierung in der Urologie.

BACKGROUND: Precise and complete coding of diagnoses and procedures is of value for optimizing revenues within the German diagnosis-related groups (G-DRG) system. The implementation of effective structures for coding is cost-intensive. The aim of this study was to prove whether higher costs can be refunded by complete acquisition of comorbidities and complications. METHODS: Calculations were based on DRG data of the Department of Urology, University Hospital of Münster, Germany, covering all patients treated in 2009. The data were regrouped and subjected to a process of simulation (increase and decrease of patient clinical complexity levels, PCCL) with the help of recently developed software. RESULTS: In urology a strong dependency of quantity and quality of coding of secondary diagnoses on PCCL and subsequent profits was found. Departmental budgetary procedures can be optimized when coding is effective. The new simulation tool can be a valuable aid to improve profits available for distribution. Nevertheless, calculation of time use and financial needs by this procedure are subject to specific departmental terms and conditions. CONCLUSIONS: Completeness of coding of (secondary) diagnoses must be the ultimate administrative goal of patient case documentation in urology.

[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.

High-dose chemotherapy with autologous PBSC transplantation for poor prognosis germ cell tumors: a retrospective monocenter analysis of 44 cases.

Germ cell cancer (GCC) is curable in metastatic stages. The International Germ Cell Cancer Collaborative Group (IGCCCG) reports a poor prognosis subgroup with a 5-year survival of 48%. High-dose chemotherapy with PBSC transplantation (HD-PBSCT) in these patients showed promising results in phase II, but failed to show significant advantage in randomized trials. We report our monocenter series of all poor and selected intermediate prognosis germ cell tumor patients treated with multiple-course HD-PBSCT and secondary surgery of remaining tissue. We performed a retrospective analysis of our complete series of 44 patients (40 poor prognosis and 4 intermediate prognosis) treated by HD-PBSCT as part of first-line therapy from 1999 to 2010. The CR rate after up to four cycles of HD-PBSCT and radical resection of residual manifestations was 73%. The 3-year survival rate was 79.5% (median follow-up of 51.5 months; range: 7-143 months). Disease-related death rate was 16%. HD-PBSCT-related death did not occur. One patient died postsurgery. Multiple courses of HD-PBSCT with radical secondary surgery is safe and effective in poor prognosis metastatic GCC. Despite disappointing phase III studies it is of high interest to further study this field.

Hypothyroidism correlates with a better prognosis in metastatic renal cancer patients treated with sorafenib or sunitinib.

PURPOSE: 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). PATIENTS AND METHODS: Eighty-three patients with mRCC, who were treated at our institution between 2006 and 2009, were evaluated prospectively. Clinical and laboratory parameters were investigated, as well as, treatment-related adverse events. Subclinical hypothyroidism was characterized by serum TSH above the upper limit of normal and both total triiodothyronine (T3) and thyroxine (T4) within normal limits. Clinical hypothyroidism was defined as low serum T3 and T4 together with elevated TSH. RESULTS: Thirty-one (37.3%) patients received So, and 52 (62.7%) were treated with Su. In univariate analysis, the ECOG status (P < 0.0001) as well as MSKCC criteria (P = 0.003) and response to therapy (P < 0.0001) were associated with progression-free survival (PFS). Twenty-one of 66 (31.8%) evaluable patients developed hypothyroidism during treatment. Of those patients, 8/21 (38.1%) were treated with So and 13/21 (61.9%) with Su. Response rate in this subgroup was 49.2%. Hypothyroidism was associated with a longer PFS (16.0 ± 0.8 months vs. 6.0 ± 0.8 months, P = 0.032). Most patients [16/21 (76.2%)] developed abnormal TSH values during the first 4 weeks of treatment. Hormone replacement with l-thyroxine did not have an influence on survival. In multivariate analyses, only the ECOG status (ECOG 0/1 vs. ECOG 2, P = 0.018) and hypothyroidism (P = 0.01) were independent prognostic parameters. CONCLUSIONS: The development of hypothyroidism during treatment might be useful as a predictor of PFS for mRCC patients undergoing treatment with targeted agents.

Testosterone deficiency in testicular germ-cell cancer patients is not influenced by oncological treatment.

The aim of the study was to investigate prospectively the prevalence of testosterone deficiency (TD) in patients with testicular germ-cell cancer (TGCC) using longitudinal data. A total of 376 TGCC patients were evaluated for serum testosterone levels before, during and after the following therapies: cisplatin-based polychemotherapy, carboplatin monotherapy, radiotherapy or surgery only. Complete serial hormone analyses were performed on 160 patients (age: 33.8±9.1years, mean±SD). All patients received treatment according to the guidelines of the 'German Testicular Cancer Study Group' and the 'European Germ Cell Cancer Consensus Group' or within studies performed by the 'European Organisation for Research and Treatment of Cancer' and the 'Deutsche Krebsgesellschaft'. Main outcome measurements were sexual hormone profiles over time. Statistical analysis of 1831 testosterone serum levels over time revealed a persistent TD in 23.9% of seminoma and 26.2% of non-seminoma patients. TD was associated with subnormal residual testicular volumes (<12mL). In conclusion, TD rates are high in testis cancer patients. This is present at primary diagnosis and most likely related to testicular dysgenesis or atrophy. Our longitudinal evaluation indicates that treatment modalities have minor influence and effect on the persistently high rates of TD in TGCC patients.

Long-term results of amitriptyline treatment for interstitial cystitis.

PURPOSE: We have conducted a prospective open-label study to examine the safety and efficacy of the long-term administration of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). METHODS: Patients were stratified into 2 groups: an NIDDK group including patients fulfilling the NIDDK criteria for IC and a non-NIDDK group encompassing patients who presented the characteristic IC symptoms but met at least one of the NIDDK exclusion criteria. Amitriptyline was taken strictly at bedtime following an established self-titration protocol without a limitation of the maximum daily dosage. Patients reporting improvement in a global response assessment questionnaire were defined as treatment responders. Further efficacy measures included changes of pain and urgency, functional bladder capacity and frequency. Changes in the O'Leary-Sant IC index and rating of overall satisfaction with the therapeutic outcome are reported as well. RESULTS: The mean follow-up of the study was 19.0 +/- 12.5 months. The response rate was 64% (60 patients). Overall mean dosage was 55 mg (range: 12.5-150 mg). Side effects occurred in 79 patients (84%) (dry mouth: 79%, weight gain: 59%). Patient overall satisfaction with the therapeutic result was either excellent or good in 43 patients (46%). The drop-out rate was 31% (29 patients) after a mean treatment period of 6 weeks at a mean dosage of 70 mg. Non-response to treatment was the primary reason for drop-out in all cases, side effects contributed to drop-out in 25 patients (86%). The various IC symptoms improved statistically significant compared with baseline. CONCLUSIONS: Long-term administration of amitriptyline is a feasible, safe and effective treatment for IC provided that the drug is used judiciously to minimise adverse effects. The therapeutic response to amitriptyline was uniformly observed in patients fulfilling the NIDDK criteria and in those patients with the pure clinical diagnosis of IC.

Lymphangiogenesis in kidney cancer: expression of VEGF-C, VEGF-D and VEGFR-3 in clear cell and papillary renal cell carcinoma.

The vascular endothelial growth factors VEGF-C, VEGF-D and its receptor, VEGFR-3, are overexpressed in different malignancies and associated with lymph node metastasis and poor prognosis. We analysed these factors in clear cell (ccRCC) and papillary (pRCC) renal cell carcinoma (RCC). The results were correlated with various clinicopathological parameters (CPP). We constructed a tissue microarray with tumor samples of 135 (81%) ccRCC and 31 (19%) pRCC. After immunohistochemical staining using polyclonal antibodies for VEGF-C, VEGF-D and VEGFR-3, a semiquantitative analysis was performed to determine the levels of expression. The results were compared between the two subgroups and were correlated with CPP. In the two subgroups the expression of VEGF-C was significantly correlated with that of VEGF-D (p<0.001). There was an increased expression of VEGF-C in 11% of ccRCC and 36% of pRCC (p=0.002). VEGF-D expression was positive by means of analysis in 22% of ccRCC and 42% of pRCC (p=0.039). There was no significant difference regarding the expression of VEGFR-3 between the subgroups (44% ccRCC and 61% pRCC, p=0.11). No correlation was found between the expression of the analysed parameters and CPP (TNM, grading, progression-free survival and overall survival) in either the entire group or in the two subgroups. In summary, ccRCC and pRCC show a different expression pattern of the analysed lymphangiogenic factors. Further studies are necessary to confirm these results and to determine whether the VEGF-C/VEGF-D/VEGFR-3-axis can play a role as a prognostic tool or a target for therapeutic intervention in renal cell carcinoma.

[Changes to diagnosis-related groups in urology in 2007. Urology in the G-DRG-System 2007]. / DRG-Veränderungen 2007 im Fachgebiet Urologie. Urologie G-DRGs 2007.

BACKGROUND: The German DRG (dose-related groups) system is updated each year by the institution dealing with the remuneration in hospitals (InEK). Once again, the German Spcoety for Urology has supported the adjustment process in a constructive manner. Analysis of the changes and their implications is highly significant for urology. This article describes and discusses the main changes in the system for the specialty of urology insofar as they concern the structure of the DRG system and the catalogues of diagnoses (ICD) and of procedures (OPS). RESULTS: The 2007 edition of the DRG system leads to numerous changes for urology. There are new OPS codes for partial resection of the kidney, treatment of urinary incontinence and radical resection in the pelvis minor. Additional payment for implantation of a prosthetic penis is divided with reference to the type of prosthesis. At DRG level, new DRG splits are found depending on the PCCL and patient age. Combination operations on the bladder and bowel and on the male genitalia are assigned to newly established DRGs. CONCLUSIONS: The changes described enhance the professional accuracy of the representations of urological care provision. New strategies designed to solve problems in representation have been established (e.g. multi-step interventions). Various problems persist, e.g. those of operations on the penis (DRG M03Z) and the need for more finely defined representation of laser treatment in urology. In the short term practicable solutions to the problem of improving the quality of representation are needed.

[Retroperitoneoscopic excision of an adrenal cyst]. / Die retroperitoneoskopische exzision einer nebennierenzyste.

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.

[New markers for pharmacological targeting in bladder cancer with lymph node metastasis]. / Neue Marker für das pharmakologische Targeting beim lymphogen metastasierten Harnblasenkarzinom.

PURPOSE: VECF-C, -D and their receptor Flt-4 are associated with lymph node metastasis and a poor prognosis in many tumour entities. We have analysed the expression of these factors in transitional cell carcinoma of the bladder with positive lymph nodes. MATERIALS AND METHODS: We constructed "tissue microarrays" (TMAs) from bladder cancer specimens (BC-array) and corresponding lymph node metastases (LN-array) of 73 patients, who all underwent radical cystectomy and bilateral lymphadenectomy. After immunohistochemical staining, semiquantitative analysis was performed using polyclonal antibodies for VEGF-C, -D and Flt-4. The results were correlated with various histopathological and clinical variables. RESULTS: VEGF-C (p = 0.007) and Flt-4 (p = 0.019) were significantly higher expressed in the LN-array compared to the BC-array. In the LN-array VEGF-D correlated with T-(p = 0.013) and N-stage (p = 0.030) Flt-4 correlated with N-stage (p = 0.011) and distant metastasis (p = 0.011) in the BC-array, as well as with T-(p = 0.004) and N-stage (p = 0.014) in the LN-array. Accordingly, in the LN-array VEGF-D positive patients showed both a shorter disease-free survival (p = 0.028) and a poorer overall survival (p = 0.014). Similarly, Flt-4 positive patients had a shorter overall survival (p = 0.033). CONCLUSIONS: Patients with transitional bladder cancer and lymph node metastasis have a poorer prognosis when they overexpress VEGF-D and Flt-4 in their lymph nodes. Pharmacological targeting of these factors could improve their overall survival.

Implementation of a map in radical prostatectomy specimen allows visual estimation of tumor volume.

INTRODUCTION: Tumor volume is one of the best documented prognostic factors for prostate cancer. There are several methods to gain this important parameter but unfortunately most of the clinicians in the world do not get this information in their routine practice from the pathologist. We developed a standardized method to handle radical prostatectomy specimens including a special form of mapping in order to document relevant morphological data. The aim of this study was to investigate if our model of mapping prostate cancer, which we use in routine practice, may serve for visual estimation of tumor volume. METHODS: We estimated the tumor volume of prostate cancer by visual estimation of 350 maps of radical prostatectomy specimens and correlated these data with established prognostic parameters and clinical outcome. RESULTS: Significant correlations between tumor volumes, as obtained from our mapping, and known prognostic parameters such as preoperative serum levels of prostatic specific antigen, loss of differentiation, histological grade, lymph node metastasis, and margins were found. In a multivariate analysis, only Gleason score and tumor stage were shown to be independent prognostic parameters. DISCUSSION: We demonstrate that mapping of prostate cancer is more than a simple method of documentation but may serve as a method for visual estimation of tumor volume of prostate cancer after radical prostatectomy. This method can further be used for a visual documentation of the tumor stage independent of changes in the TNM classification. The method is inexpensive and practicable and can therefore be applied in routine surgical pathology.

Reconstruction of ureteral necrosis in kidney transplantation using an ileum interposition.

PURPOSE: Ureteral necrosis is a serious problem in kidney transplantation. Sometimes re-ureterocystostomy is possible, while other cases require an elaborate reconstruction to maintain kidney function. We report our experience with ileum interposition for ureteral reconstruction. METHODS: After 9 years of dialysis treatment a 58-year-old patient was grafted using the left kidney of a 59-year-old donor with a cold ischemic time of 9.5 hours. The early postoperative course was uneventful apart from delayed graft function. Immunosuppression consisted of an IL-2-receptor antibody, calcineurin inhibitor, mycophenolate mofetil, and corticosteroids. Discharge serum creatinine was 2.3 mg/dL. In month 4 the patient showed a pararenal urinoma; cystoscopy revealed necrosis of the distal ureter. Operative revision showed urine leakage from the renal pelvis through the urinoma into the bladder. As the whole ureter was necrotic, a re-ureterocystostomy was not possible. The patient's own ureter had been extirpated, and the bladder was too small to do a direct anastomosis between it and the kidney. Consequently, an ileum interposition was performed. RESULTS: The postoperative course was uneventful. Kidney function was stable with a nadir creatinine concentration of 2.0 mg/dL 18 months' posttransplantation, and 14 months' post ileal interposition the kidney function was still satisfactory, with a creatinine level of 2.0 mg/dL. CONCLUSION: Ureteral necrosis is a serious complication following kidney transplantation. Whenever a re-ureterocystostomy or an uretero-ureterostomy is not possible, the interposition of the ileal segment represented a safe procedure to deal with this problem.

[Bilateral renal angiomyolipomas with a thrombus in the inferior caval vein. Rare growth pattern of a benign tumor]. / Bilaterale renale Angiomyolipome mit Thrombus in der Vena cava inferior. Seltenes Wachstumsverhalten eines benignen Tumors.

Renal angiomyolipomas are mesenchymal tumors that are composed of fat tissue, smooth muscle cells and vessels. These are benign tumors, but in rare cases they show a more aggressive growth pattern with invasion into the venous system but without revealing any signs of malignancy. We report a new case of bilateral renal angiomyolipomas with a caval thrombus in a 36 year old female patient with tuberous sclerosis, and give a brief review of the related literature.

[Expression of Her2/neu in locally advanced bladder cancer: implication for a molecular targeted therapy]. / Die Her2/neu-Expression beim lokal fortgeschrittenen Harnblasenkarzinom: Ansatz für eine molekulare Therapie?

PURPOSE: The Her2/neu oncoprotein, belonging to the erbB-receptor family, is known to contribute to physiological mechanisms of cell proliferation by intrinsic tyrosine-kinase-activity. Overexpression has been shown for several tumors and is known to influence malignant cell proliferation, metastasis and angiogenesis. The clinical use of Her2-targeting agents has emerged in clinical research. In our study, we analyzed Her2/neu expression in urothelial tumors. MATERIALS AND METHODS: Her2/neu expression was evaluated immunohistochemically (IHC) in 127 patients undergoing radical cystectomy (DAKO- Herceptest). Additionally, fluorescent-in-situ-hybridisation (FISH) was carried out in all immunohistochemically "2+" cases (n = 41) to assess gene amplification. After grading the Her2/neu-overall status, Her2/neu expression was correlated with clinicopathological parameters and survival data. RESULTS: An immunohistochemical Her2/neu expression was found in 95 of 127 cases (74.8 %). Of all 41 cases with "2+" staining (32.2 %), 11 cases (26.8 %) showed positive amplification by FISH. Therefore, including the IHC 3+ cases, a Her2/neu overall status of 22 positive (17.3 %) tumors was assessed. Correlation with clinical data showed a relation to lymph node metastasis (P = 0.06), lymph vessel invasion (P = 0.07) and metastasis (P = 0.002). No further associations with other parameters nor with overall survival (P = 0.73) or disease-free survival (P = 0.63) were found. CONCLUSIONS: Her2/neu upregulation is found in invasive bladder cancer with significant differences in protein expression and gene amplification. The association with lymphogenic and distant metastases implicates a late event in carcinogenesis. Moreover, there was no further association with clinicopathological parameters and survival. The possible role of a molecular targeted therapy of advanced bladder cancer with Her2/neu targeting agents should be assessed in further clinical trials.

[Obstructive uropathy in childhood]. / Obstruktive Uropathien im Kindesalter.

"Obstructive uropathy" is a generic term which combines different diseases in infants and childhood. Both the upper and lower urinary tract may be affected. Diseases of the urinary tract can cause an intrinsic obstruction. Sometimes tumours may cause a compression and as secondary effect an obstruction (extrinsic). Ultrasound is the key diagnostic tool and shows dilatation of the obstructed urinary tract. But for the functional exploration of babies and toddlers, renal scanning and X-ray examinations are necessary. These examinations lead to an exposure to radiation which necessitates careful indication. Some of the congenital diseases (for example ureteropelvic junction obstruction, megaureter) show a maturation without any intervention. So one has to decide whether to wait and see or to operate. A percutaneous nephrostomy or a DJ-catheter is not often used in the treatment of obstruction in general. These forms of drainage are more often used in the treatment of stones or of extrinsic obstruction. A pyelocutaneostomy or ureterocutaneostomy is a special surgical procedure in pediatric urology for transient drainage of the upper urinary tract (megaureter). The operation of a seriously ill new-born should be done in a centre for pediatric urology and pediatric nephrology. When the upper urinary tract is dilated, patients may need an antibiotic prophylaxis, because the dilatation of the upper urinary tract increases the risk of urinary tract infections (UTI). The indication for antibiotic prophylaxis should by guided by the criteria of the APN-Consensus Paper. Long-term follow-up is necessary and should comprise ultrasound, physical examination, controlling the blood pressure, urine analysis and blood tests. The aims of diagnostics, treatment and long-term follow-up are the preservation of renal function and to protect the children from UTI. This goal must be reached under conditions that are appropriate for children and their parents.

[Therapy of hormone refractory prostate cancer: new standards, new trends]. / Die Behandlung des hormonrefraktären Prostatakarzinoms -- neue Standards, neue Trends.

Hormone-refractory prostate cancer is diagnosed with increasing incidence and has become a growing challenge for urologists. The improved understanding of the tumor biological mechanisms of the hormone-refractory state has led to innovative therapeutic developments in the field of hormonal and cytotoxic therapies. Recently, two large randomized Phase III trials with docetaxel-based chemotherapy were able to show prolonged survival and a positive influence on pain and quality of life, establishing a new standard of care for these patients. Moreover, bisphosphonates seem to have positive influence on selected patients. In the growing field of molecular targeted therapy, first trials with compounds, such as tyrosine kinase inhibitors, anti-sense oligonucleotides, angiogenesis inhibitors and endothelin receptor antagonists, show promising results in the treatment of patients with hormone-refractory prostate cancer.