Michael Fröhner

High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients

BackgroundThe Wnt inhibitor Dickkopf-1 (DKK-1) has been linked to the progression of malignant bone disease by impairing osteoblast activity. In addition, there is increasing data to suggest direct tumor promoting effects of DKK-1. The prognostic role of DKK-1 expression in prostate cancer remains unclear.MethodsA prostate cancer tissue microarray (n = 400) was stained for DKK-1 and DKK-1 serum levels were measured in 80 patients with prostate cancer. The independent prognostic value of DKK-1 expression was assessed using multivariate analyses.ResultsDKK-1 tissue expression was significantly increased in prostate cancer compared to benign disease, but was not correlated with survival. However, high DKK-1 serum levels at the time of the diagnosis were associated with a significantly shorter overall and disease-specific survival. Multivariate analyses defined high serum levels of DKK-1 as an independent prognostic marker in prostate cancer (HR 3.73; 95%CI 1.44-9.66, p = 0.007).ConclusionHigh DKK-1 serum levels are associated with a poor survival in patients with prostate cancer. In light of current clinical trials evaluating the efficacy of anti-DKK-1 antibody therapies in multiple myeloma and solid malignancies, the measurement of DKK-1 in prostate cancer may gain clinical relevance.

Advances in renal cell carcinoma treatment.

The treatment of advanced renal cell carcinoma has been completely changed by the development of new therapeutic modalities during the past 3 years. In this time period six targeted agents have been approved for the treatment of advanced or metastatic disease. Phase 3 data support the use of sunitinib, bevacizumab plus interferon-α and pazopanib for patients with low and intermediate risk of clear-cell renal cell carcinoma. In the pivotal study of temsirolimus a significant longer overall survival compared with interferon-α in high-risk disease including non-clear-cell histology was observed. Patients pretreated with cytokines will benefit from sorafenib and pazopanib while everolimus has been shown to increase significantly progression-free survival after previous anti-angiogenesis therapy. In addition to these phase 3 data-based recommendations, several other factors have to be considered for treatment selection, for example, side effect profile and patients’ comorbidities. Currently, the sequential use of the available targeted drugs and adjuvant treatment are the subject of ongoing clinical trials. However, medical treatment of renal cell carcinoma remains palliative and surgery remains the only curative approach in patients with localized, locally advanced and limited metastatic disease.

Treatment of Locally Advanced Prostate Cancer – The Case for Radical Prostatectomy

The treatment of clinically locally advanced prostate carcinoma (stage cT3) remains controversial. One of the main reasons for this controversy results from the substantial staging error attached to the clinical diagnosis cT3 with overstaged T2 tumors and understaged node-positive cases. Treatment options in this situation include radical prostatectomy, external beam radiotherapy, immediate or delayed androgen deprivation treatment and the so-called ‘watchful waiting’. Acceptable and often surprisingly good tumor-specific survival rates have been reported for radical prostatectomy in pT3 series – based on good clinical case selection – approaching those of pT2 series. In lymph node-positive pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does not in lymph node-negative pT3 disease. A benefit of adjuvant external beam radiotherapy after radical prostatectomy for pT3 cases in prolonging overall survival has not been shown, despite the fact that it can prevent or delay biochemical and local recurrence. External beam radiotherapy as the only treatment for cT3 disease results in unfavorable tumor-specific survival rates, which can be significantly improved with adjuvant hormonal treatment with LHRH agonists. If, in case of advanced age and/or significant comorbidity, primary hormonal treatment is chosen, early hormonal deprivation therapy seems to offer marginal benefits in survival compared to delayed treatment.

Implementierung der S3-Leitlinie Prostatakarzinom im klinischen Alltag

BACKGROUND Beside the quality of a guideline, the implementation in daily practice is of particular concern. The aim of this study was to determine the degree of implementation of the interdisciplinary S3 guideline on diagnostics and treatment of prostate cancer. METHODS A questionnaire containing questions regarding the implementation of the S3 guideline was sent to 119 private practice urologists and 37 urologists working in hospitals. Comparisons were made with the χ(2) test. RESULTS The response rate was 63%. Of the responding urologists, 93% reported that they used the guideline in the daily practice, while 95% considered the strong recommendations of the guideline as treatment standard. Urologists working in a hospital recommended the guideline less frequently to their patients as source of information (30 versus 58%, p = 0.0283), but more frequently to other physicians (95 versus 72%, p = 0.0294), than private practice urologists did. CONCLUSION The interdisciplinary S3 guideline on diagnostics and treatment of prostate cancer is used by the vast majority of urologists in their daily practice. The strong guideline recommendations are considered as treatment standard. A more compact presentation and a propagation of the guideline outside the urologic community might improve implementation of the guideline.

Association of tissue mRNA and serum antigen levels of members of the urokinase-type plasminogen activator system with clinical and prognostic parameters in prostate cancer.

The objective was to determine the mRNA expression and protein levels of uPA system components in tissue specimens and serum samples, respectively, from prostate cancer (PCa) patients and to assess their association with clinicopathological parameters and overall survival (OS). The mRNA expression levels of uPA, its receptor (uPAR), and its inhibitor type 1 (PAI-1) were analyzed in corresponding malignant and adjacent nonmalignant tissue specimens from 132 PCa patients by quantitative PCR. Preoperative serum samples from 81 PCa patients were analyzed for antigen levels of uPA system members by ELISA. RNA levels of uPA system components displayed significant correlations with each other in the tumor tissues. A significantly decreased uPA mRNA expression in PCa compared to the corresponding nonmalignant tissue was detected. High uPA mRNA level was significantly associated with a high Gleason score. Elevated concentration of soluble uPAR (suPAR) in serum was significantly associated with a poor OS of PCa patients (P = 0.022). PCa patients with high suPAR levels have a significantly higher risk of death (multivariate Coxs regression analysis; HR = 7.12, P = 0.027). The association of high suPAR levels with poor survival of PCa patients suggests a prognostic impact of suPAR levels in serum of cancer patients.

[Implementation of the S3 prostate cancer guideline in daily clinical practice: results of a survey among urologists].

BACKGROUND Beside the quality of a guideline, the implementation in daily practice is of particular concern. The aim of this study was to determine the degree of implementation of the interdisciplinary S3 guideline on diagnostics and treatment of prostate cancer. METHODS A questionnaire containing questions regarding the implementation of the S3 guideline was sent to 119 private practice urologists and 37 urologists working in hospitals. Comparisons were made with the χ(2) test. RESULTS The response rate was 63%. Of the responding urologists, 93% reported that they used the guideline in the daily practice, while 95% considered the strong recommendations of the guideline as treatment standard. Urologists working in a hospital recommended the guideline less frequently to their patients as source of information (30 versus 58%, p = 0.0283), but more frequently to other physicians (95 versus 72%, p = 0.0294), than private practice urologists did. CONCLUSION The interdisciplinary S3 guideline on diagnostics and treatment of prostate cancer is used by the vast majority of urologists in their daily practice. The strong guideline recommendations are considered as treatment standard. A more compact presentation and a propagation of the guideline outside the urologic community might improve implementation of the guideline.

Prostataspezifisches Antigen zur Therapiesteuerung

Today, most incident prostate cancer cases are diagnosed in early and thus potentially curable stages because of the determination of prostate-specific antigen (PSA). Treatment monitoring is another important aspect of the tumor marker PSA. In this article, contemporary recommendations for the use of PSA in treatment monitoring are discussed in the settings of active surveillance, radical prostatectomy and radiotherapy.ZusammenfassungDurch die Messung des prostataspezifischen Antigens (PSA) werden Prostatakarzinome heute überwiegend in einem frühen und somit potentiell heilbaren Stadium diagnostiziert. Eine weitere wichtige Bedeutung des Tumormarkers PSA liegt in der Therapiesteuerung. Die vorliegende Arbeit diskutiert aktuelle Empfehlungen zur PSA-Bestimmung im Therapiemonitoring bei aktiver Überwachung sowie nach radikaler Prostatektomie und Strahlentherapie.AbstractToday, most incident prostate cancer cases are diagnosed in early and thus potentially curable stages because of the determination of prostate-specific antigen (PSA). Treatment monitoring is another important aspect of the tumor marker PSA. In this article, contemporary recommendations for the use of PSA in treatment monitoring are discussed in the settings of active surveillance, radical prostatectomy and radiotherapy.

Superglue in the Urethra: Surgical Treatment

We describe a case of superglue application into the male urethra with successful surgical treatment of the glue particles by external urethrotomy.

Alter und Komorbidität beim frühen Prostatakarzinom

With increasing age the risk-benefit balance of immediate curative treatment of early prostate cancer worsens. While the advantage of immediate intervention becomes increasingly uncertain the probability of unfavourable functional outcomes increases with an adverse impact on the quality of life. Therefore, a careful selection is particularly important in elderly patients with prostate cancer. For this purpose comorbidity classifications may be used; however up to now, there is no consensus on the instruments to be preferred and on the way of application. When different patient populations or clinical settings are considered the survival probabilities may differ significantly between patients with apparently identical levels of comorbidity. Therefore, when comorbidity classifications are intended to be used during treatment decision-making, it should be checked whether and how they are applicable in the individual clinical situation.ZusammenfassungMit zunehmendem Alter verschlechtert sich die Balance zwischen Risiko und Nutzen einer sofortigen kurativen Intervention beim frühen Prostatakarzinom. Während der Vorteil einer sofortigen Intervention im hohen Alter zunehmend unsicherer wird, steigt die Wahrscheinlichkeit, durch ungünstige funktionelle Resultate eine Einschränkung der Lebensqualität zu erleiden. Eine sorgfältige Selektion ist darum beim älteren Prostatakarzinompatienten besonders wichtig. Hierfür können Komorbiditätsklassifikationen herangezogen werden. Bisher gibt es jedoch keinen Konsens über die vorzugsweise zu nutzenden Instrumente und die Art ihrer Anwendung. Bei Betrachtung unterschiedlicher Populationen oder klinischer Konstellationen können Patienten mit scheinbar identischer Komorbidität sehr unterschiedliche Überlebenswahrscheinlichkeiten aufweisen. Daher sollte bei Einbeziehung von Komorbiditätsklassifikationen in die Therapieentscheidungsfindung immer geprüft werden, ob und wie diese in der konkreten Situation angewandt werden können.AbstractWith increasing age the risk-benefit balance of immediate curative treatment of early prostate cancer worsens. While the advantage of immediate intervention becomes increasingly uncertain the probability of unfavourable functional outcomes increases with an adverse impact on the quality of life. Therefore, a careful selection is particularly important in elderly patients with prostate cancer. For this purpose comorbidity classifications may be used; however up to now, there is no consensus on the instruments to be preferred and on the way of application. When different patient populations or clinical settings are considered the survival probabilities may differ significantly between patients with apparently identical levels of comorbidity. Therefore, when comorbidity classifications are intended to be used during treatment decision-making, it should be checked whether and how they are applicable in the individual clinical situation.

MP02-03 NEXT-GENERATION SEQUENCING REVEALS TRANSCRIPT CLUSTERS WITH PROGNOSTIC POTENTIAL FOR PROSTATE CANCER

measured using RT-qPCR. Results from cohort A were used to develop a model with (combinations of) the four genes based on the comparative CT method, and the model was validated in the independent cohort B. RESULTS: The HOXC6-DLX1 score model resulted in the highest area-under-the-curve (AUC) of 0.75 (95% confidence interval: 0.70-0.80) for the diagnosis of high-grade PCa upon prostate biopsy, with a specificity of 36% and 91% sensitivity. The HOXC6-DLX1 score outperformed PCA3 in both cohorts (cohort A: AUC 0.75 vs. 0.65; cohort B: 0.73 vs. 0.62). Furthermore, the HOXC6-DLX1 score was significantly correlated with the Gleason score upon biopsy. Subgroup analysis confirmed the added value of this urine test for the prediction of high-grade PCa in patients with low serum PSA values (<10 ng/ml) (Figure 1). Figure 1 Predictive accuracy (AUC) of the HOXC6-DLX1 score and sPSA for the detection of high-grade PCa at low sPSA subgroups for cohort A (A) and cohort B (B). CONCLUSIONS: The HOXC6-DLX1 score urine test predicts the risk of high-grade PCa upon prostate biopsy. Using the HOXC6DLX1 score could reduce the amount of unnecessary prostate biopsies and potential overtreatment, particularly in patients with low serum PSA levels.