[Precision oncology : How can high-quality healthcare remain affordable for all in the face of diagnostic and therapeutic costs?] / Präzisionsonkologie : Wie bleibt hochwertige Versorgung für alle angesichts steigender Diagnostik und Therapiekosten bezahlbar?

Medicine is becoming increasingly precise. This is particularly evident in the field of pharmaceuticals and especially in oncology. Driven by the steadily growing understanding of biomedical interrelationships and the resulting increase in precision, we are currently experiencing a paradigm shift from a one-drug-fits-all model towards an individualized biomarker-driven approach. This essentially enables the transition from efficacy to effectiveness. In order to ensure that the promise of high-quality, affordable precision medicine for all remains valid in the future, the step from efficacy in clinical studies to effectiveness in the practice of care is crucial in the next decade. This will be achieved with end-to-end precision from diagnostics to real-world evidence.

[Network medicine and health services research in urology]. / Urologische Netzwerkmedizin und Versorgungsforschung.

It is the aim of the Medical Informatics Funding Scheme and other national and local projects for digital networking in healthcare to facilitate the exchange and use of patient data between institutions in compliance with data protection regulations. This requires the integration of data from various sources-such as digital workplace systems, laboratory systems, picture archiving and communication (PAC) systems or tumor boards-into a data warehouse or research databases. Digital networking of service providers and research institutions will open access to high-performance and precision medicine (e.g., virtual molecular tumor boards) for even more patients, thereby providing data for basic and care research. Network medicine will establish the translational link between basic research (e.g., genome research) and patient care. Digitally integrated "real world" patient data will also facilitate a detailed analysis of health care and the quality of treatments.

Adherence of the indication to European Association of Urology guideline recommended pelvic lymph node dissection at a high-volume center: Differences between open and robot-assisted radical prostatectomy.

PURPOSE: Contemporary adherence of the indication to European Association of Urology (EAU) guideline recommendation for pelvic lymph node dissection (PLND) at either open (ORP) or robot-assisted radical prostatectomy (RARP) at a high-volume center is unknown. To assess guideline recommended and observed PLND rates in a high-volume center cohort. METHODS: We relied on the Martini-Clinic database and focused on patients treated with either ORP or RARP, between 2010 and 2013. Actual performed PLND was compared to European Association of Urology (EAU) guideline recommendation defined by nomogram predicted risk of lymph node invasion >5%. Categorical and multivariable logistic regression analyses targeted two endpoints: 1) probability of guideline recommended PLND and 2) probability of no PLND, when not recommended by EAU guideline. RESULTS: Within 7868 PCa patients, adherence to EAU PLND guideline recommendation was 97.1% at ORP and 96.8% at RARP (p = 0.7). When PLND was not recommended, it was more frequently performed at RARP (71.6%) than at ORP (66.2%) (p = 0.002). Gleason score, PSA and number of positive biopsy cores were independent predictors for both either PLND when recommended, or no PLND when not recommended (all p < 0.05). Clinical tumor stage, age and surgical approach were also independent predictors for no PLND when not recommended (all p < 0.05). CONCLUSIONS: Adherence of the indication to EAU guideline recommended PLND is high at this high-volume center. Neither ORP nor RARP represent a barrier for PLND, when recommended. However, a high number of patients underwent PLND despite absence of guideline recommendation. Possible staging advantages and PLND related complications needs to be individually considered, especially, when LNI risk is low.

UAP1 is overexpressed in prostate cancer and is protective against inhibitors of N-linked glycosylation.

Prostate cancer is the second most common cause of cancer-associated deaths in men, and signaling via a transcription factor called androgen receptor (AR) is an important driver of the disease. Consequently, AR target genes are prominent candidates to be specific for prostate cancer and also important for the survival of the cancer cells. Here we assess the levels of all hexosamine biosynthetic pathway (HBP) enzymes in 15 separate clinical gene expression data sets and identify the last enzyme in the pathway, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), to be highly overexpressed in prostate cancer. We analyzed 3261 prostate cancers on a tissue microarray and found that UAP1 staining correlates negatively with Gleason score (P=0.0039) and positively with high AR expression (P<0.0001). Cells with high UAP1 expression have 10-fold increased levels of the HBP end-product, UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is essential for N-linked glycosylation occurring in the endoplasmic reticulum (ER) and high UAP1 expression associates with resistance against inhibitors of N-linked glycosylation (tunicamycin and 2-deoxyglucose) but not with a general ER stress-inducing agent, the calcium ionophore A23187. Knockdown of UAP1 expression re-sensitized cells towards inhibitors of N-linked glycosylation, as measured by proliferation and activation of ER stress markers. Taken together, we have identified an enzyme, UAP1, which is highly overexpressed in prostate cancer and protects cancer cells from ER stress conferring a growth advantage.

No impact of blood transfusion on oncological outcome after radical prostatectomy in patients with prostate cancer.

PURPOSE: To assess the association between blood loss, blood transfusion (BT) and biochemical recurrence (BCR)-free, metastasis-free and overall survival after radical prostatectomy (RP) in a large single-center cohort of patients. Perioperative BT at oncologic surgery has been reported to be a potential risk factor for cancer recurrence and survival in several cancer entities. Current studies addressing the relationship between BT, blood loss and BCR-free survival in prostate cancer patients are controversial and include only series with fairly small patient cohorts. MATERIALS AND METHODS: The data of 11,723 patients who underwent RP between 01/1992 and 08/2011 were analyzed. Cox regression analysis, including preoperative PSA level, pT stage, lymph node status, Gleason score, margin status, blood loss, transfusion rate (allogeneic or autologous), tested the relationship between blood loss, transfusion and BCR-free, metastasis-free and overall survival. Additionally, propensity score-matching analysis was performed to adjust differences in tumor characteristics. RESULTS: There was no statistically significant relationship between blood loss or BT and BCR-free, metastasis-free or overall survival. In multivariate analysis PSA level, pT stage, Gleason score, margin status and lymph node status were independent factors for a BCR (p < 0.0001). These results were identical after propensity score matching analysis, comparing patients with and without BT. CONCLUSIONS: This large-scale analysis revealed no correlation between blood loss, blood transfusion and oncological outcome in prostate cancer patients treated with RP. Therefore, the association between higher blood loss or transfusion rate and cancer recurrence as described in other surgical treated tumor entities seems to be irrelevant in prostate cancer patients.

[Prognostic and predictive molecular markers for urologic cancers]. / Prognostische und prädiktive molekulare Marker urologischer Tumoren.

Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.

Oncological long-term outcome of 4772 patients with prostate cancer undergoing radical prostatectomy: does the anaesthetic technique matter?

INTRODUCTION: Recent data suggest that using additional neuroaxial anaesthesia during oncological surgery is associated with favourable recurrence-free survival, when compared with general anaesthesia alone. We assessed the impact of adjunctive perioperative spinal anaesthesia and dose of opioids on the oncological long-term outcome of patients following radical prostatectomy. METHODS: We selected patients from our institutional review board-approved database who consecutively underwent radical prostatectomy between 2002 and 2007. Patients were stratified by type of anaesthesia, administered as general anaesthesia alone, or spinal anaesthesia in addition to general anaesthesia. Biochemical recurrence-free survival, metastasis-free survival and overall survival were analysed by a multivariate Cox regression model and by Kaplan-Meier analysis in propensity-score based matched cohorts, adjusted for standard clinico-pathological variables and year of surgery. RESULTS: Overall, 4772 patients were analysed. Regarding the type of anaesthesia no significant difference for biochemical recurrence-free survival, metastasis-free survival and overall survival was analysed by a multivariate Cox regression model (p = 0.5, 0.8 and 0.7). The Kaplan-Meier analyses after propensity-score matched based comparisons revealed no significant difference depending on type of anaesthesia for biochemical recurrence-free survival, metastasis-free survival and overall survival (p = 0.6, 0.1 and 0.4). The same accounted for a propensity-score matched model adjusted for the year of surgery on biochemical recurrence-free survival (p = 0.7). CONCLUSIONS: The oncological outcome after radical prostatectomy was not affected by the adjunctive use of spinal anaesthesia.

[Current results on PSA-based prostate cancer detection]. / Aktuelle Ergebnisse zur PSA-basierten Früherkennung des Prostatakarzinoms.

Prostate cancer is the most common cancer and the third leading cause of cancer-specific death in men in Western industrialized countries. Implementation of the prostate-specific antigen (PSA) blood test as an early detection tool has led to a significant reduction of prostate cancer mortality in the USA. Apart from an earlier detection of clinically relevant tumors, regular PSA testing increases the risk of over-detection and over-treatment of clinically indolent tumors. In our view, a reliable stratification of indolent tumors in active surveillance programs is the key in avoiding or reducing overtreatment of early diagnosed prostate cancers. Along with better risk stratification, the expansion of PSA screening should be discussed in order to reduce the still high numbers of palliative treatments, metastases, and prostate cancer-related deaths.

High Nr-CAM expression is associated with favorable phenotype and late PSA recurrence in prostate cancer treated by prostatectomy.

BACKGROUND: Neuron-glia-related cell-adhesion molecule (Nr-CAM) is another potential membrane-bound target molecule for specific prostate cancer therapy. The role of Nr-CAM in normal and neoplastic prostate tissue has not been extensively studied. The aim of our study is to evaluate the prevalence of Nr-CAM expression in prostate cancer and to explore its association with phenotype and clinical disease course. METHODS: A preexisting tissue microarray including more than 3000 prostate cancers that underwent prostatectomy at our center with clinical follow-up data was used. The tissue microarray (TMA) was immunhistochemically stained for Nr-CAM. RESULTS: A total of 2883 (88.4%) of tumor samples were interpretable in our TMA analysis. Membranous Nr-CAM staining was seen in 1418 (49.2%) of 2883 analyzable cases. According to predefined criteria, staining was considered weak in 778 (27.0%), moderate in 412 (14.3%) and strong in 228 (7.9%) cancers. Significant associations were found with pathological tumor stage (P=0.0015), Gleason grade (P=0.0003), nodal stage (P=0.0061), preoperative PSA (P=0.0138) and prolonged PSA recurrence-free survival (P<0.0001). CONCLUSIONS: Nr-CAM expression is frequent in prostate cancer. High level of Nr-CAM expression is associated with favorable tumor phenotype and reduced risk of PSA recurrence. The abundant presence of Nr-CAM in prostate cancer epithelium makes Nr-CAM a potential target of therapy.

Influence of low-molecular-weight heparin dosage on red blood cell transfusion, lymphocele rate and drainage duration after open radical prostatectomy.

BACKGROUND: To assess the rates of red blood cell (RBC) transfusions, pelvic lymphoceles, and prolonged drainage duration in patients after radical prostatectomy (RP) receiving perioperative bridging with low-molecular-weight heparin (LMWH). PATIENTS AND METHODS: Between 2006 and 2009, 114 RP patients receiving bridging therapy with 60 mg (n = 63) or ≥80 mg (n = 51) Enoxaparin/d were compared to 1327 consecutive RP patients receiving 40 mg Enoxaparin/d. Logistic regression models were used to test the effect of LMWH dosage on all three outcomes. Covariables included age, body mass index (BMI), Charlson comorbidity index (CCI), prostate volume, pelvic lymph node dissection, and pathological stage. RESULTS: The RBC transfusion rates in patients treated with 40, 60 and ≥80 mg were 4.9, 9.5 and 19.6%, respectively (p < 0.001). The respective lymphocele rates were 6.4, 3.2 and 2.0% (p = 0.26). The respective rates of drainage duration of ≥4 days were 6.7, 4.8 and 16.7% (p = 0.088). After adjusting for confounding factors, patients receiving ≥80 mg were 4.1-fold more likely to be transfused than patients receiving prophylactic LMWH (p = 0.02). Similarly, patients receiving ≥80 mg were 3.2-fold more likely to have a drainage duration of ≥4 days than patients receiving prophylactic LMWH (p = 0.03). CONCLUSIONS: Patients with a perioperative bridging with LMWH in RP are more likely to receive a RBC transfusion and to have prolonged drainage duration. Conversely, bridging therapy was not associated with an increased risk of lymphocele formation.

[Upper tract urothelial carcinoma. An update on clinical and pathological prognostic factors]. / Das Urothelkarzinom des oberen Harntraktes. Ein Update über klinische und pathologische prognostische Faktoren.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon but potentially lethal disease. Accurate risk stratification remains a challenge owing to the difficulty of clinical staging. Identification of risk factors may lead to individualized treatment and patient counselling and holds the potential to improve outcome. A non-systematic PubMed/Medline literature research was performed to identify and summarize clinical and pathological risk factors and urine-based markers which are associated with clinical outcome. Although knowledge of potential prognostic factors has improved over the last 5 years the overall evidence on UTUC risk factors remains limited and prospective, randomized trials are still missing. Radical nephroureterectomy is currently standard treatment for high-grade and muscle invasive UTUC. Several clinical and pathological factors (e.g. stage, grade, age, hydronephrosis, lymphovascular invasion, tumor necrosis and architecture, delay between diagnosis and surgery) were identified to be associated with outcome. Urinary cytology and fluorescence in-situ hybridization are the most commonly used urinary markers. Prospective randomized controlled trials are urgently needed to identify new risk factors and assess the efficacy. The incorporation of such prognosticators into multivariable prediction models may help to guide decision-making with regard to type of treatment, performance of lymphadenectomy and consideration of neoadjuvant or adjuvant systemic therapy.

Predicting the risk of lymph node invasion during radical prostatectomy using the European Association of Urology guideline nomogram: a validation study.

BACKGROUND: The 2011 European Association of Urology (EAU) guidelines for prostate cancer recommend a pelvic lymph node dissection (PLND) at radical prostatectomy (RP) in all individuals with a nomogram predicted lymph node invasion (LNI) risk of >7%. METHODS: To test the performing characteristics for several thresholds (1-14%) and to examine the overall accuracy and calibration plot of the EAU nomogram at our institution. The study population consisted of 3081 patients treated with RP and PLND limited to the obturator fossa and the external iliac vein between 2008 and 2010 at a single European institution from Germany. More extensive PLNDs were performed at the surgeon's discretion. RESULTS: Overall, 260 patients (9.2%) had LNI. The 7% threshold would have avoided 30% of PLNDs, at the cost of missing 8% of patients with LNI. The use of 8% and 9% threshold would have allowed the avoidance of respectively 39% and 48% of PLNDs, at the cost of missing respectively 12% and 14% of patients with LNI. The accuracy of the LNI nomogram was 78%, and the unadjusted departure from ideal calibration was 5.3%. CONCLUSIONS: We confirmed adequate accuracy and calibration of the LNI nomogram. The 7% cut-off may be overly conservative. Better trade-offs between avoided PLNDs and missed LNI cases may be achieved with a limit of 8 or even 9%.

Prognostic relevance of Bcl-2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene.

BACKGROUND: Overexpression of anti-apoptotic Bcl-2 plays a role in prostate cancer progression, particularly in transformation to androgen-independent disease. Androgen-independent prostate cancers have been shown to harbor Bcl-2 gene copy number gains frequently suggesting that this genetic alteration might play a role in Bcl-2 overexpression. The relation of Bcl-2 overexpression and copy number gains or translocation of the BCL-2 gene in prostate cancer under hormone-naïve conditions is unknown. METHODS: Prostate cancers of 3,261 hormone-naïve patients undergoing radical prostatectomy were arrayed in a TMA with one tissue core (diameter 0.6 mm) per tumor. Bcl-2 immunohistochemistry, analyzed for Bcl-2 expression level (negative, low, and high), was correlated with clinical, histopathological and molecular (Ki67, p53) tumor features, and biochemical failure. Cancers with high-level Bcl-2 expression were evaluated for genetic aberrations by fluorescence in situ hybridization (FISH). RESULTS: Bcl-2 expression was significantly up-regulated in tumors with aggressive phenotype as indicated by high Gleason score (P < 0.0001), advanced stage (P < 0.0001), and high proliferation index (P = 0.0114). The different Bcl-2 expression levels translated into significantly different survival curves showing better outcome for patients with lower Bcl-2 levels. The prognostic information obtained from the anti-apoptotic Bcl-2 was independent from the proliferation index (Ki67) of the cancer. FISH analysis detected no copy number gains or translocation of the Bcl-2 gene. CONCLUSION: Bcl-2 overexpression in prostate cancers under hormone-naïve conditions is not associated with increased copy numbers of the gene. This suggests that these frequently detected genetic alterations in androgen-independent tumors occur late in prostate cancer progression.

Transcription alterations of members of the ubiquitin-proteasome network in prostate carcinoma.

The purpose of this work was to investigate the role of the ubiquitin-proteasome network (UPN) in prostate cancer (PCA) and to elicit potential markers for this disease. The UPN represents a key factor in the maintenance of cellular homoeostasis as a result of its fundamental function in the regulation of intracellular protein degradation. Members of this network have a role in the biology of haematological and solid tumours. Tumour cells and normal epithelial cells from 22 prostatectomy specimens were isolated by laser microdissection. Prostate biopsy samples from healthy individuals served for technical calibration and as controls. Transcript levels of eight selected genes with E3 ubiquitin ligase activity (labelling target proteins for proteasome degradation) and two genes belonging to the proteasome-multienzyme complex itself were analysed by quantitative real-time RT-PCR. The proteasome genes PSMC4 and PSMB5 and the E3 ubiquitin ligase NEDD4L were significantly and coherently upregulated in PCA cells compared with the corresponding adjacent normal prostate tissue. Transcription of the E3 ubiquitin ligase SMURF2 was significantly higher in organ-confined tumours (pT2) compared with non-organ-confined cancers (pT3). The results indicate a role for PSMC4 and PSMB5 and the E3 ubiquitin ligase NEDD4L in prostate tumourigenesis, whereas SMURF2 downregulation could be associated with clinical progression. NEDD4L and SMURF2 both target transforming growth factor (TGF)-ß for degradation. This reflects the pleiotropic role of the TGF-ß signalling pathway acting as a tumour suppressor in normal and pre-cancerous cells, but having oncogenic properties in progressing cancer. Further studies have to elucidate whether these alterations could represent clinically relevant PCA-diagnostic and progression markers.

Activating BRAF gene mutations are uncommon in hormone refractory prostate cancer in Caucasian patients.

Activating mutations in the cytosolic serine/threonine kinase, BRAF, have been reported in a variety of neoplasms. BRAF activation may contribute to tumor growth via activation of the MAP/ERK kinase pathway, and BRAF represents a possible therapeutic target. Activating BRAF mutations were recently reported in approximately 10% of prostate cancer cases in Asian patients. In the present study, 43 hormone refractory prostate cancers were analyzed for BRAF mutations in order to determine whether anti-BRAF therapy is a suitable approach for advanced prostate cancer patients. In all of the studied tumors, BRAF exons 11 and 15 were PCR-amplified and sequenced, including the backward and forward sequences. BRAF mutations were noted only in the positive control tissues, but were not found in any of the 43 analyzed prostate cancers. We conclude that BRAF mutations occur only rarely in prostate cancers in Caucasian patients and are not associated with tumor progression. The application of anti-BRAF therapies may therefore not be beneficial for prostate cancer.

[F(18)]-fluoroethylcholine combined in-line PET-CT scan for detection of lymph-node metastasis in high risk prostate cancer patients prior to radical prostatectomy: Preliminary results from a prospective histology-based study.

PURPOSE: To evaluate the diagnostic potential of PET/CT using ([F(18)]fluorethylcholine (FEC) for lymph node (LN) staging in high risk prostate cancer (PCa) patients prior to radical prostatectomy (RP). PATIENTS AND METHODS: Twenty patients with localised PCa and > or =20% LN risk according to a published nomogram were prospectively enrolled. FEC PET/CT was done minimum 14 d after prostate biopsy. Afterwards, open RP and extended pelvic LN dissection (ePLND) were performed. Clinical stage, Prostate Specific Antigen (PSA) and biopsy Gleason Grading were assessed and histopathological evaluation of the RP-specimens and dissected LN has been performed. The results from PET/CT were compared with LN metastasis according to their anatomical site. RESULTS: Overall, 285 LN have been removed with a mean number of 15 nodes per patient (7-26). Of the 20 patients, 9 men were LN positive (45%), which corresponds to 31 positive LN with a mean size of 7 mm (0.8-12 mm). Dissection of the obturator fossa, external iliac artery/vein and internal iliac artery/vein revealed 36%, 48% and 16% of positive LN, respectively. FEC PET/CT did not detect one single positive LN, thus was false-negative in 31 metastasis and true negative in 254 LN. CONCLUSION: Based on our results which confirmed experience from the previous studies, FEC PET/CT scan did not prove to be useful for LN staging in localised PCa prior to treatment and should thus not be applied if clinically occult metastatic disease is suspected.

[Identification and validation of clinically relevant molecular alterations in prostate cancer]. / Identifizierung und Validierung klinisch relevanter molekularer Veränderungen im Prostatakarzinom.

Significant cellular alterations required for the development and progression of cancers are detectable at the molecular level and represent potential targets for gene-specific therapies. Modern chip techniques allow the parallel analysis of virtually all known human genes and proteins in a single experiment. Using modern high-throughput techniques, numerous potential new biomarkers for the diagnosis and prediction of prostate cancer have been identified. However, so far none of these markers has improved clinical practice. One of the most important challenges in the coming years is the extensive clinical validation of molecular data using clinically relevant end points. For this venture the pivotal prerequisite is the availability of large, comprehensively annotated and standardized high-quality bioresources.

Partin Tables cannot accurately predict the pathological stage at radical prostatectomy.

PURPOSE: The Partin Tables represent the most commonly used staging tool for radical prostatectomy (RP) candidates. The Partin Tables' predictions are used to guide the type (nerve preserving RP) and/or the extent (RP with wide resection) of RP. We examined the ability of the Partin Tables' predictions incorrectly assigning the stage at RP. METHODS: The testing of the Partin Tables (external validation) was based on 3105 patients treated with RP at a single European institution. Standard validation metrics were used (area under the receiver operating characteristics curve, AUC) to test the three endpoints predicted by the Partin Tables, namely the presence of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node invasion (LNI). RESULTS: Ideal predictions are denoted with 100% accuracy vs. 50% for entirely random predictions. For the 2001 version of the Tables the accuracy defined by the AUC was 79.7, 77.8, and 73.0 for ECE, SVI, and LNI, respectively. For the 2007 version of the Tables the corresponding accuracy estimates were 79.8, 80.5, and 76.2. The relationship between predicted probabilities and observed rates was poor. CONCLUSION: The Partin Tables are meant to guide clinicians about the safety of nerve bundle preservation at RP, about the need for seminal vesicle resection or for lymphadenectomy. Therefore, the use of the Partin Tables predictions may significantly affect the type and/or the extent of RP. In their present format the Partin Tables are not accurate enough to influence the pre-operative decision making regarding the type or extent of RP.

[Role of lymph node dissection in prostate cancer]. / Stellenwert der Lymphadenektomie beim Prostatakarzinom.

We present a comprehensive literature review and critical discussion of the diagnostic and therapeutic value of lymph node dissection in prostate cancer. Lymph node dissection is currently the most reliable staging procedure for detecting lymph node metastases in prostate cancer. Accuracy increases with the extent of the procedure. Overall, in patients with positive lymph nodes after radical prostatectomy and lymph node dissection, a favorable long-time cancer-specific survival can be observed. These data seem to be independent of the extent of the lymph node dissection and also independent of the administration of adjuvant therapy. It can be suspected that patients with lymph node metastases present different prognostic groups based on the extent of lymph node involvement. However, these risk groups might reflect only a lead-time bias, so the therapeutic value of lymph node dissection remains unclear. In conclusion, the therapeutic value of lymph node dissection in prostate cancer must be sufficiently evaluated in prospective clinical trials. Each patient should be individually counseled regarding his individual tumor features and the use of statistical prognostic tools such as nomograms.

[Identification and validation of clinically relevant molecular alterations in prostate cancer]. / Identifizierung und Validierung klinisch relevanter molekularer Veränderungen im Prostatakarzinom.

Significant cellular alterations required for the development and progression of cancers are detectable at the molecular level and represent potential targets for gene-specific therapies. Modern chip techniques allow the parallel analysis of virtually all known human genes and proteins in a single experiment. Using modern high-throughput techniques, numerous potential new biomarkers for the diagnosis and prediction of prostate cancer have been identified. However, so far none of these markers has improved clinical practice. One of the most important challenges in the coming years is the extensive clinical validation of molecular data using clinically relevant end points. For this venture the pivotal prerequisite is the availability of large, comprehensively annotated and standardized high-quality bioresources.