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1.
Trials ; 24(1): 167, 2023 Mar 06.
Article in English | MEDLINE | ID: mdl-36879271

ABSTRACT

BACKGROUND: The primary objective is to determine the proportion of men with suspected prostate cancer (PCA) in whom the management plans are changed by additive gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) guided prostate biopsy (PET-TB) in combination with standard of care (SOC) using systematic (SB) and multiparametric magnetic resonance imaging-guided biopsy (MR-TB) compared with SOC alone. The major secondary objectives are to determine the additive value of the combined approach of SB + MR-TB + PET-TB (PET/MR-TB) for detecting clinically significant PCA (csPCA) compared to SOC; to determine sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of imaging techniques, respective imaging classification systems, and each biopsy method; and to compare preoperatively defined tumor burden and biomarker expression and pathological tumor extent in prostate specimens. METHODS: The DEPROMP study is a prospective, open-label, interventional investigator-initiated trial. Risk stratification and management plans after PET/MR-TB are conducted randomized and blinded by different evaluation teams of experienced urologists based on histopathological analysis and imaging information: one including all results of the PET/MR-TB and one excluding the additional information gained by PSMA-PET/CT guided biopsy. The power calculation was centered on pilot data, and we will recruit up to 230 biopsy-naïve men who will undergo PET/MR-TB for suspected PCA. Conduct and reporting of MRI and PSMA-PET/CT will be performed in a blinded fashion. DISCUSSION: The DEPROMP Trial will be the first to evaluate the clinically relevant effects of the use of PSMA-PET/CT in patients with suspected PCA compared to current SOC. The study will provide prospective data to determine the diagnostic yields of additional PET-TB in men with suspected PCA and the impact on treatment plans in terms of intra- and intermodal changes. The results will allow a comparative analysis of risk stratification by each biopsy method, including a performance analysis of the corresponding rating systems. This will reveal potential intermethod and pre- and postoperative discordances of tumor stage and grading, providing the opportunity to critically assess the need for multiple biopsies. TRIAL REGISTRATION: German Clinical Study Register DRKS 00024134. Registered on 26 January 2021.


Subject(s)
Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Image-Guided Biopsy , Positron-Emission Tomography , Prospective Studies , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Randomized Controlled Trials as Topic
3.
EPMA J ; 13(1): 1-7, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35251382

ABSTRACT

According to GLOBOCAN, about 1.41 million new prostate cancer (PCa) cases were registered in the year 2020 globally. The corresponding socio-economic burden is enormous. Anti-cancer mRNA-based therapy is a promising approach, the principle of which is currently applied for anti-COVID-19 vaccination, undergoing a detailed investigation in populations considering its short- and long-term effectiveness and potential side effects. Pragmatically considered, it will take years or even decades to make mRNA therapy working for any type of cancers, and if possible, for individual malignancy sub-types which are many specifically for the PCa. Actually, the costs of treating PCa are increasing more rapidly than those of any other cancer. The trend has to be reversed now, not in a couple of years. In general, two main components are making currently applied reactive (management of clinically manifested disease) PCa treatment particularly expensive. On one hand, it is rapidly increasing incidence of the disease and metastatic PCa as its subtype. To this end, rapidly increasing PCa incidence rates in young and middle-aged male sub-populations should be taken into account as a long-term contributor to the metastatic disease potentially developed later on in life. On the other hand, patient stratification to differentiate between non-metastatic PCa (no need for an extensive and costly treatment) and particularly aggressive cancer subtypes requiring personalised treatment algorithms is challenging. Considering current statistics, it becomes obvious that reactive medicine got at its limit in PCa management. Multi-professional expertise is unavoidable to create and implement anti-PCa programmes in the population. In our strategic paper, we exemplify challenging PCa management by providing detailed expert recommendations for primary (health risk assessment), secondary (prediction and prevention of metastatic disease in PCa) and tertiary (making palliative care to the management of chronic disease) care in the framework of predictive, preventive and personalised medicine.

4.
Clin Transl Oncol ; 22(9): 1524-1531, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31965534

ABSTRACT

PURPOSE: Long non-coding RNAs (lncRNA) are involved in oncogenesis and tumor progression in various tumor entities. At present, little is known about the role in tumor biology of the lncRNA Fer-1 like family member 4 (Fer1L4) in clear-cell renal-cell carcinoma (ccRCC). The aim of this study is to evaluate the expression of Fer1L4 in patients with ccRCC, its association with clinicopathological parameters, and value as prognostic biomarker. MATERIAL AND METHODS: The expression of Fer1L4 was analyzed in the TCGA ccRCC cohort (n = 603; ccRCC n = 522, normal n = 81) and subsequently validated by quantitative real-time PCR in an independent cohort (n = 103, ccRCC n = 69, normal n = 34). Expression profiles were statistically correlated with clinicopathological and survival data. RESULTS: Fer1L4 lncRNA is overexpressed in ccRCC compared to adjacent normal tissues. Increased expression significantly correlates with tumor aggressiveness: high expression levels of Fer1L4 RNA were found in higher grade, higher stage, and metastatic tumors. Furthermore, Fer1L4 overexpression is an independent prognostic factor for overall, cancer-specific, and progression-free survival of patients with ccRCC. CONCLUSION: Fer1L4 expression significantly correlates with aspects of tumor aggressiveness. Based on this impact on tumor progression and its influence as an independent prognostic factor, Fer1L4 appears to exert properties as an oncogene in ccRCC. As a prognostic tissue biomarker, further functional investigations are warranted to investigate Fer1L4 as a potential therapeutic target.


Subject(s)
Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , RNA, Long Noncoding/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Computational Biology/methods , Databases, Genetic , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Prognosis , Survival Rate
5.
Urologe A ; 56(7): 933-944, 2017 Jul.
Article in German | MEDLINE | ID: mdl-28573413

ABSTRACT

In the era of personalized medicine and precision oncology, innovative genetic biomarkers are of emerging interest to close the diagnostic and prognostic gap that is left by current clinicopathologic risk classifiers. The current review article summarizes evidence regarding prognostic and predictive genetic biomarkers that are currently in widespread clinical use at initial diagnosis as well as following definitive treatment of prostate cancer. We give a brief summary about basic principles of biomarker research studies and present current data for the Progensa PC3 test, TMPRSS2:ERG gene fusion, ConfirmMDx, Prolaris gene panel, OncotypeDX Genomic Prostate score, and Decipher classifier. Evidence regarding those genetic biomarkers has heavily increased recently. However, there is still a lack of large, multicentric and prospective clinical validation studies. Furthermore, comparative studies that investigate the prognostic value of various genetic biomarkers are needed.


Subject(s)
Genetic Markers/genetics , Prostatic Neoplasms/genetics , Humans , Male , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/genetics , Precision Medicine , Predictive Value of Tests , Prognosis , Prostatic Neoplasms/diagnosis
6.
Urologe A ; 56(5): 564-569, 2017 May.
Article in German | MEDLINE | ID: mdl-28314967

ABSTRACT

Cisplatin-based polychemotherapy is still the standard therapy for metastatic urothelial carcinoma, although disease progression is often noted at an early time point even in patients with response. In recent years, cytoreductive surgery has been gaining increasing interest in many tumor entities in the setting of metastatic disease to improve patients outcome, but urothelial carcinoma is not regarded as a candidate for such a multimodal therapy approach. However, several retrospective studies suggest a survival benefit of radical cystectomy and/or metastasectomy for well-selected patients with metastatic urothelial carcinoma. Prognostically relevant parameters for consolidative cystectomy/metastasectomy after chemotherapy seem to be a distinct response to inductive chemotherapy and limited metastatic spread (regional lymph node, single lung metastasis).


Subject(s)
Carcinoma, Transitional Cell/secondary , Carcinoma, Transitional Cell/surgery , Cystectomy/statistics & numerical data , Neoplasm Recurrence, Local/mortality , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/surgery , Carcinoma, Transitional Cell/epidemiology , Cystectomy/mortality , Evidence-Based Medicine , Female , Humans , Lymphatic Metastasis , Male , Neoplasm Recurrence, Local/prevention & control , Prevalence , Survival Rate , Treatment Outcome , Urinary Bladder Neoplasms/pathology
7.
Urologe A ; 54(6): 819-25, 2015 Jun.
Article in German | MEDLINE | ID: mdl-25312755

ABSTRACT

BACKGROUND: The analysis of circulating RNA molecules is of increasing interest since tumor-specific RNA expression patterns could be a useful cancer biomarker. A new entity of RNA molecules, the so-called long non-coding RNAs (lncRNA), are of particular interest because of its high tissue- and tumor-specificity. The importance of analytical factors in the quantification of lncRNAs is largely unclear and should therefore be investigated in the present study. PATIENTS AND METHODS: Serum RNA was isolated from patients with bladder, prostate and kidney cancer as well as patients with non-malignant disease. Analytical variables like different RNA isolation procedures, cDNA synthesis and preamplification were studied with respect to quantification of MALAT1 and ACTB via real-time PCR. RESULTS: The quantification of cell-free serum RNA is feasible although the levels of ACTB and MALAT1 were often only slightly above the detection limit. RNA isolation with a combined phenol-based column purification (Ambion mirVana PARIS miRNA Isolation Kit; Qiagen miRNeasy Serum/Plasma Kit) was most effective. The elimination of DNA contamination was most successful during cDNA synthesis with (Takara-Bio PrimeScript RT Reagent Kit with gDNA Eraser). Preamplification with the Applied Biosystems TaqMan PreAmp Master Mix Kit improved sensitivity. Serum ACTB and MALAT1 levels were not significantly increased in patients with urological tumors compared to patients with non-malignant diseases. CONCLUSION: An optimized protocol for the analysis of circulating lncRNAs is described in the present study.


Subject(s)
Biomarkers, Tumor/blood , Neoplasms/blood , Neoplasms/genetics , RNA, Untranslated/blood , RNA, Untranslated/genetics , Real-Time Polymerase Chain Reaction/methods , Adult , Aged , Aged, 80 and over , Blood Chemical Analysis/methods , Cell-Free System , Female , Humans , Male , Middle Aged , Neoplasms/diagnosis , RNA, Long Noncoding/blood , RNA, Long Noncoding/genetics , Reproducibility of Results , Sensitivity and Specificity
8.
World J Urol ; 32(2): 365-71, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23736527

ABSTRACT

PURPOSE: Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. METHODS: In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. RESULTS: cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. CONCLUSIONS: In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.


Subject(s)
Carcinoma, Transitional Cell/pathology , Lymph Node Excision/methods , Lymph Nodes/pathology , Urinary Bladder Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/therapy , Chemotherapy, Adjuvant , Cohort Studies , Cystectomy , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Staging , Pelvis , Proportional Hazards Models , Retrospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/therapy
9.
Eur J Surg Oncol ; 39(4): 372-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23465180

ABSTRACT

AIM: The outcome of patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) shows remarkable variability. We evaluated the ability of artificial neural networks (ANN) to perform risk stratification in UCB patients based on common parameters available at the time of RC. METHODS: Data from 2111 UCB patients that underwent RC in eight centers were analysed; the median follow-up was 30 months (IQR: 12-60). Age, gender, tumour stage and grade (TURB/RC), carcinoma in situ (TURB/RC), lymph node status, and lymphovascular invasion were used as input data for the ANN. Endpoints were tumour recurrence, cancer-specific mortality (CSM) and all-cause death (ACD). Additionally, the predictive accuracies (PA) of the ANNs were compared with the PA of Cox proportional hazards regression models. RESULTS: The recurrence-, CSM-, and ACD- rates after 5 years were 36%, 33%, and 46%, respectively. The best ANN had 74%, 76% and 69% accuracy for tumour recurrence, CSM and ACD, respectively. Lymph node status was one of the most important factors for the network's decision. The PA of the ANNs for recurrence, CSM and ACD were improved by 1.6% (p = 0.247), 4.7% (p < 0.001) and 3.5% (p = 0.007), respectively, in comparison to the Cox models. CONCLUSIONS: ANN predicted tumour recurrence, CSM, and ACD in UCB patients after RC with reasonable accuracy. In this study, ANN significantly outperformed the Cox models regarding prediction of CSM and ACD using the same patients and variables. ANNs are a promising approach for individual risk stratification and may optimize individual treatment planning.


Subject(s)
Carcinoma, Transitional Cell/pathology , Cystectomy , Diagnosis, Computer-Assisted , Neural Networks, Computer , Urinary Bladder Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/surgery , Disease-Free Survival , Female , Germany , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , Risk Assessment , Sensitivity and Specificity , Survival Analysis , Urinary Bladder Neoplasms/surgery
10.
Eur J Surg Oncol ; 38(7): 637-42, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22459902

ABSTRACT

PURPOSE: To perform the first external validation of a recently identified association between disease-free survival at two years (DFS2) or three years (DFS3) and overall survival at five years (OS5) in patients after radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB). METHODS AND METHODS: Records of 2483 patients who underwent RC for UCB at eight European centers between 1989 and 2008 were reviewed. The cohort included 1738 patients with pT2-4a tumors and negative soft tissue surgical margins (STSM) according to the selection criteria of the previous study (study group (SG)). In addition, 745 patients with positive STSM or other tumor stages (pT0-T1, pT4b) that were excluded from the previous study (excluded patient group (EPG)) were evaluated. Kappa statistic was used to measure the agreement between DFS2 or DFS3 and OS5. RESULTS: The overall agreement between DFS2 and OS5 was 86.5% (EPG: 88.7%) and 90.1% (EPG: 92.1%) between DFS3 and OS5. The kappa values for comparison of DFS2 or DFS3 with OS5 were 0.73 (SE: 0.016) and 0.80 (SE: 0.014) respectively for the SG, and 0.67 (SE: 0.033) and 0.78 (SE: 0.027) for the EPG (all p-values <0.001). CONCLUSIONS: We externally validated a correlation between DFS2 or DFS3 and OS5 for patients with pT2-4a UCB with negative STSM that underwent RC. Furthermore, this correlation was found in patients with other tumor stages regardless of STSM status. These findings indicate DFS2 and DFS3 as valid surrogate markers for survival outcome with RC.


Subject(s)
Carcinoma/mortality , Carcinoma/surgery , Cystectomy , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/surgery , Urothelium , Adult , Aged , Carcinoma/secondary , Cohort Studies , Cystectomy/methods , Disease-Free Survival , Endpoint Determination , Europe , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Prognosis , Reproducibility of Results , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/pathology , Urothelium/pathology , Urothelium/surgery
11.
Urologe A ; 50(6): 706-13, 2011 Jun.
Article in German | MEDLINE | ID: mdl-21340594

ABSTRACT

OBJECTIVE: Pre-cystectomy nomograms with a high predictive ability for locally advanced urothelial carcinomas of the bladder would enhance individual treatment tailoring and patient counselling. To date, there are two currently not externally validated nomograms for prediction of the tumour stages pT3-4 or lymph node involvement. MATERIALS AND METHODS: Data from a German multicentre cystectomy series comprising 2,477 patients with urothelial carcinoma of the bladder were applied for the validation of two US nomograms, which were originally based on the data of 726 patients (nomogram 1: prediction of pT3-4 tumours, nomogram 2: prediction of lymph node involvement). Multivariate regression models assessed the value of clinical parameters integrated in both nomograms, i.e. age, gender, cT stage, TURB grade and associated Tis. Discriminative abilities of both nomograms were assessed by ROC analyses; calibration facilitated a comparison of the predicted probability and the actual incidence of locally advanced tumour stages. RESULTS: Of the patients, 44.5 and 25.8% demonstrated tumour stages pT3-4 and pN+, respectively. If only one case of a previously not known locally advanced carcinoma (pT3-4 and/or pN+) is considered as a staging error, the rate of understaging was 48.9% (n=1211). The predictive accuracies of the validated nomograms were 67.5 and 54.5%, respectively. The mean probabilities of pT3-4 tumours and lymph node involvement predicted by application of these nomograms were 36.7% (actual frequency 44.5%) and 20.2% (actual frequency 25.8%), respectively. Both nomograms underestimated the real incidence of locally advanced tumours. CONCLUSIONS: The present study demonstrates that prediction of locally advanced urothelial carcinomas of the bladder by both validated nomograms is not conferrable to patients of the present German cystectomy series. Hence, there is still a need for statistical models with enhanced predictive accuracy.


Subject(s)
Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/surgery , Cystectomy , Nomograms , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphatic Metastasis/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Neoplasm Staging , Predictive Value of Tests , ROC Curve , Urinary Bladder/pathology
12.
Urologe A ; 50(7): 821-9, 2011 Jul.
Article in German | MEDLINE | ID: mdl-21340593

ABSTRACT

BACKGROUND: The therapeutic gold standard of muscle-invasive tumour stages is radical cystectomy (RC), but there are still conflicting reports about associated morbidity and mortality and the oncologic benefit of RC in elderly patients. The aim of the present study was the comparison of overall (OS) and cancer-specific survival (CSS) in patients <75 and >75 years of age (median follow-up was 42 months). PATIENTS AND METHODS: Clinical and histopathological data of 2,483 patients with urothelial carcinoma and consecutive RC were collated. The study group was dichotomized by the age of 75 years at RC. Statistical analyses comprising an assessment of postoperative mortality within 90 days, OS and CSS were assessed. Multivariate logistic regression and survival analyses were performed. RESULTS: The 402 patients (16.2%) with an age of ≥75 years at RC showed a significantly higher local tumour stage (pT3/4 and/or pN+) (58 vs 51%; p=0.01), higher tumour grade (73 vs 65%; p=0.003) and higher rates of upstaging in the RC specimen (55 vs 48%; p=0.032). Elderly patients received significantly less often adjuvant chemotherapy (8 vs 15%; p<0.001). The 90-day mortality was significantly higher in patients ≥75 years (6.2 vs 3.7%; p=0.026). When adjusted for different variables (gender, tumour stage, adjuvant chemotherapy, time period of RC), only in male patients and locally advanced tumour stages was an association with 90-day mortality noticed. The multivariate analysis showed that patients ≥75 years of age have a significantly worse OS (HR=1.42; p<0.001) and CSS (HR=1.27; p=0.018). CONCLUSIONS: An age of ≥75 years at RC is associated with a worse outcome. Prospective analyses including an assessment of the role of comorbidity and possibly age-dependent tumour biology are warranted.


Subject(s)
Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/surgery , Cystectomy/mortality , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/surgery , Adult , Age Factors , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/pathology , Female , Follow-Up Studies , Germany , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Neoplasm Staging , Sex Factors , Survival Analysis , Urinary Bladder Neoplasms/pathology
13.
Urologe A ; 49(11): 1356-64, 2010 Nov.
Article in German | MEDLINE | ID: mdl-20945059

ABSTRACT

Changes in the methylation pattern in particular gene promoters as well as genetic sequence mutations play an important role in carcinogenesis. Molecular methods like pyrosequencing provide the specific analysis of these epigenetic and genetic modifications. In this review the relevance of these alterations for prostate cancer and the function of pyrosequencing will be described and explained on the basis of a search of the PubMed literature database. At present, in uro-oncology only a few studies outlining methylation in prostate cancer and pyrosequencing have been published. Nevertheless, it becomes evident that epigenetic mechanisms as well as specific gene sequence alterations have an impact on the carcinogenesis of prostate cancer and knowledge of these factors might open perspectives in diagnostic approaches of the future.


Subject(s)
Biomarkers, Tumor/genetics , DNA Mutational Analysis/trends , Genetic Markers/genetics , Genetic Testing/trends , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Sequence Analysis, DNA/trends , Genetic Predisposition to Disease/genetics , Humans , Male , Medical Oncology/trends , Urology/trends
14.
Urologe A ; 49(12): 1508-15, 2010 Dec.
Article in German | MEDLINE | ID: mdl-20922515

ABSTRACT

BACKGROUND: Few and partially contradictory data are available regarding the prognostic signature of downstaging of muscle-invasive clinical tumour stages in patients treated with radical cystectomy. MATERIALS AND METHODS: Clinicopathological parameters of 1,643 patients (study group, SG) treated with radical cystectomy due to muscle-invasive urothelial bladder cancer were summarized in a multi-institutional database. Patients of the SG fulfilled the following conditions: clinical tumour stage T2 N0 M0 and no administration of neoadjuvant radiation or chemotherapy. Cancer-specific survival (CSS) rates were calculated referring to pathological tumour stages in cystectomy specimens (pT2) (mean follow-up: 51 months). Furthermore, a multivariable model integrating clinical information was developed in order to predict the probability of downstaging. RESULTS: A total of 173 patients (10.5%) of the SG presented with downstaging in pathological tumour stages (pT0: 4.8%, pTa: 0.4%, pTis: 1.3%, pT1: 4.1%); 12 of these patients had positive lymph nodes (7%, in comparison with 21% pN+ of pT2 tumours and 43% of >pT2 tumours). Patients with tumour stages pT2 had CSS rates after 5 years of 89, 69 and 46%, respectively (p<0.001). In a multivariable Cox model the presence of pathological downstaging resulted in a significant reduction of cancer-specific mortality (HR 0.30; 95% CI 0.18-0.50). By logistic regression analysis the date of TURB (benefit for more recent operations) was identified as the only independent predictor for downstaging of muscle-invasive clinical tumour stages. Age, gender, grading and associated Tis in the TURB did not reveal any significant influence. CONCLUSION: Patients with muscle-invasive clinical tumour stages and downstaging in cystectomy specimens represent a subgroup with significantly enhanced CSS rates. Further trials that integrate the parameters tumour size, stages cT2a vs cT2b and focality are required in order to define the independent prognostic signature of downstaging of tumour stages more precisely.


Subject(s)
Cystectomy/mortality , Muscle Neoplasms/mortality , Muscle Neoplasms/surgery , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/surgery , Aged , Female , Germany/epidemiology , Humans , Male , Muscle Neoplasms/pathology , Neoplasm Staging , Prevalence , Risk Assessment , Risk Factors , Survival Analysis , Survival Rate , Treatment Outcome , Urinary Bladder Neoplasms/pathology
15.
Urologe A ; 49(9): 1131-2, 1134, 2010 Sep.
Article in German | MEDLINE | ID: mdl-20628864

ABSTRACT

The presence of circulating cell-free DNA was demonstrated already in the 1940s. Improved detection methods have led to increased knowledge on cell-free DNA, and recent studies showed that most cancer patients have increased levels of cell-free DNA. Measurement of cell-free DNA allowed sensitive and specific discrimination between cancer patients and those with non-malignant diseases.


Subject(s)
Biomarkers, Tumor/blood , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , Diagnostic Techniques, Urological , Urologic Neoplasms/diagnosis , Urologic Neoplasms/genetics , Cell-Free System , Humans
16.
Urologe A ; 49(6): 727-30, 2010 Jun.
Article in German | MEDLINE | ID: mdl-20503034

ABSTRACT

There is no technique which can be used in all types and localizations of urethral strictures. Urethral strictures occur in the majority of cases in the bulbar urethra. The success rate of urethroplasty is above 80% and results are much better compared to DVIU. Dorsal onlay shows a significantly better success rate than ventral onlay. If the graft bed has poor vascularization a flap should be used or a staged approach should be considered.


Subject(s)
Urethral Stricture/surgery , Anastomosis, Surgical , Humans , Male , Microsurgery/methods , Postoperative Complications/diagnostic imaging , Risk Factors , Surgical Flaps/blood supply , Surgical Mesh , Tissue and Organ Harvesting/methods , Urethra/surgery , Urethral Stricture/diagnostic imaging , Urethral Stricture/etiology , Urography
17.
Aktuelle Urol ; 40(1): 37-43, 2009 Jan.
Article in German | MEDLINE | ID: mdl-19177320

ABSTRACT

Tomatoes are discussed to have an important role in the prevention of and therapy for prostate cancer (PCA). Whether or not they are also useful in the primary and secondary prevention of benign prostate hyperplasia (BPH) is not clear. This review summarises the results of original contributions with a focus on interventional studies. Whereas epidemiological studies on BPH prevention provide no evidence for a preventive potential of tomatoes and tomato products, the majority of interventional trials points to an increased DNA resistance against oxidative-induced damage. Even though their effect on a surrogate marker of the IGF pathway cannot be evaluated so far due to insufficient data, the consumption of tomatoes and tomato products may probably protect from PCA--at least when considering low-grade PCA. Thus, regular consumption of these foods can be recommended for the prevention of PCA. Tomato products might also be useful in the therapy for BPH and PCA. The intake of isolated lycopene does not protect from the development of PCA. However, in the doses achieved by consumption of tomato products, lycopene ingestion might also be effective in PCA therapy.


Subject(s)
Anticarcinogenic Agents/administration & dosage , Carotenoids/administration & dosage , Prostatic Hyperplasia/prevention & control , Prostatic Neoplasms/prevention & control , Solanum lycopersicum , Clinical Trials as Topic , Cohort Studies , DNA Damage/genetics , Evidence-Based Medicine , Humans , Lycopene , Male , Middle Aged , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/therapy , Randomized Controlled Trials as Topic , Risk Reduction Behavior , Time Factors , beta Carotene/administration & dosage
18.
Urologe A ; 48(3): 270-1, 274-83, 2009 Mar.
Article in German | MEDLINE | ID: mdl-19153707

ABSTRACT

Prostate cancer patients increasingly use complementary and alternative medicines to support the body's immune system in addition to conventional treatment to minimize morbidity associated with conventional treatment, to enhance the quality of life, and ultimately in the hope to cure cancer when conventional treatment fails. As there is a large variety of phytomedicines promoted as potential treatment for prostate cancer, the aim of this review was to differentiate between preventive and therapeutic approaches and evaluate which phytochemicals might be suited for therapy of prostate cancer. Therefore, preclinical in vitro and in vivo data as well as clinical trials with phytosubstances such as genistein, lycopene, epigallocatechin gallate, resveratrol, and mistletoe were assessed. The presented data show that at present there is no clinical evidence that phytochemicals might have a therapeutic use in prostate cancer in relation to reduction of tumor progression or improved survival. The question about an improved immune function or quality of life remains open. Potentially the use of phytochemicals could play a role in a preventive setting.


Subject(s)
Evidence-Based Medicine , Phytotherapy/methods , Phytotherapy/trends , Plant Extracts/administration & dosage , Prostatic Neoplasms/drug therapy , Clinical Trials as Topic , Humans , Male , Treatment Outcome
19.
Urologe A ; 47(9): 1205-7, 2008 Sep.
Article in German | MEDLINE | ID: mdl-18651120

ABSTRACT

The exact classification of clinically significant versus insignificant prostate cancer displays one of major problems in current urological practice. Using novel molecular biomarkers, we are trying to decrease overdiagnosis of insignificant cancer. CpG island hypermethylation as a common epigenetic event is a well-recognized phenomenon during carcinogenesis. We have shown that hypermethylation at several gene loci distinguishes between benign and malignant forms of prostatic disorders. Furthermore using tests in cancer tissue and serum samples, one can draw prognostic conclusions and predict biochemical failure following radical prostatectomy with curative intent.


Subject(s)
CpG Islands/genetics , DNA Methylation/genetics , Epigenesis, Genetic/genetics , Genetic Markers/genetics , Prostatic Neoplasms/genetics , Cell Transformation, Neoplastic/genetics , Diagnosis, Differential , Gene Expression Regulation, Neoplastic/genetics , Genetic Testing , Glutathione S-Transferase pi/genetics , Humans , Male , Predictive Value of Tests , Prostatic Neoplasms/diagnosis , Risk Factors
20.
Urologe A ; 47(9): 1190-2, 2008 Sep.
Article in German | MEDLINE | ID: mdl-18651121

ABSTRACT

A better understanding of signal transduction and gene regulation during prostate carcinogenesis will allow the development of novel diagnostic and prognostic biomarkers and a better prediction of the individual course of prostate cancer disease. It will also enhance the design and development of specific small molecular components aiming for specific therapies. The research groups in Bonn succeeded in the competition for an endowed professorship supported by the Rudolf Becker Stiftung (German Science Endowment Fund) settled in the"Centrum für integrierte Onkologie" funded by the German Cancer Aid. This should be the perfect breeding ground for future research in the field of prostate cancer.


Subject(s)
Biomarkers, Tumor/genetics , Prostatic Neoplasms/genetics , Apoptosis/genetics , Cell Line, Tumor , CpG Islands/genetics , DNA Methylation/genetics , Gene Expression Regulation, Neoplastic/genetics , Genetic Research , Humans , Male , Prognosis , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Receptors, Androgen/genetics , Signal Transduction/genetics , Transcription, Genetic/genetics
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