Kidney transplantation in prostate cancer patients after local therapy with curative intent: a systematic review.

PURPOSE: It is still unclear whether kidney transplantation can be safely performed in patients with prostate cancer after local therapy with curative intent. METHODS: The protocol was registered in PROSPERO. We systematically searched Google, MEDLINE, the Cochrane Library, and the ICTRP for studies, official standards, clinical practice guidelines and organ transplant laws. Two review authors independently examined the full-text reports and identified relevant studies and one review author extracted the data. We assessed the overall certainty of the evidence for each outcome according to the GRADE approach. RESULTS: We identified 1346 references through electronic database searching and finally included 6 references for official standards, clinical practice guidelines, and organ transplant laws, and 6 references for retrospective studies with very low certainty of evidence. We identified no prospective or ongoing studies and reported all results narratively. CONCLUSION: We recommend that decisions on kidney transplantation in patients with prostate cancer after local therapy with curative intent should be made on a case-by-case basis. It is indispensable to consult with health care professionals or specialists at transplant centers to obtain individualized information regarding the waiting time requirements for renal transplantation in prostate cancer patients after local therapy with curative intent. No recommendation can be made regarding the waiting times after prostate cancer therapy with curative intent.

Timing of androgen deprivation monotherapy and combined treatments in castration-sensitive and castration-resistant prostate cancer: a narrative review.

PURPOSE: Standard androgen deprivation therapy (ADT) can be initiated early at the time of diagnosis in asymptomatic castration-sensitive advanced prostate cancer. This definition has recently been expanded to also include an early combined treatment with standard ADT and new antihormonal drugs. We aimed to present the best available evidence for the timing of initiation of ADT monotherapy and combined treatments in castration-sensitive/-resistant prostate cancer. METHODS: For this narrative review, we searched Cochrane reviews in the Cochrane Library, systematic reviews and randomized controlled trials in MEDLINE, phase III and ongoing trials in ClinicalTrials.gov and screened the reference lists to extract articles of interest. One author screened the references which were finally included after assessing their relevance through discussion with other experts in the field. RESULTS: The identified references were grouped by medication (standard ADT, androgen biosynthesis inhibitor, androgen receptor antagonists or combined therapies) and tumor stage (castration sensitive or resistant). The evidence was narratively summarized and discussed in the context of the current therapeutic landscape. CONCLUSIONS: Early standard ADT can reduce symptoms of disease progression and may extend progression-free and overall survival. The patient should be well informed about the higher rates of treatment-related side effects. Deferring standard ADT might be indicated only for well-informed or unfit patients. Early standard ADT is increasingly combined with new antihormonal drugs in castration-sensitive metastatic prostate cancer to gain additional survival and quality of life benefits. Combined treatment at the time of development of castration-resistant disease is well established.

Prognostic models for predicting overall survival in metastatic castration-resistant prostate cancer: a systematic review.

PURPOSE: Prognostic models are developed to estimate the probability of the occurrence of future outcomes incorporating multiple variables. We aimed to identify and summarize existing multivariable prognostic models developed for predicting overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: The protocol was prospectively registered (CRD42017064448). We systematically searched Medline and reference lists up to May 2018 and included experimental and observational studies, which developed and/or internally validated prognostic models for mCRPC patients and were further externally validated or updated. The outcome of interest was overall survival. Two authors independently performed literature screening and quality assessment. RESULTS: We included 12 studies that developed models including 8750 patients aged 42-95 years. Models included 4-11 predictor variables, mostly hemoglobin, baseline PSA, alkaline phosphatase, performance status, and lactate dehydrogenase. Very few incorporated Gleason score. Two models included predictors related to docetaxel and mitoxantrone treatments. Model performance after internal validation showed similar discrimination power ranging from 0.62 to 0.73. Overall survival models were mainly constructed as nomograms or risk groups/score. Two models obtained an overall judgment of low risk of bias. CONCLUSIONS: Most models were not suitable for clinical use due to methodological shortcomings and lack of external validation. Further external validation and/or model updating is required to increase prognostic accuracy and clinical applicability prior to their incorporation in clinical practice as a useful tool in patient management.

[Vertebral metastases of urogenital carcinomas: Diagnosis and conservative therapy]. / Wirbelsäulenmetastasen urologischer Tumoren : Diagnostik und konservative Therapie.

The high incidence of bone metastases of urologic neoplasms and their morbidity, especially of vertebral metastases, requires exact diagnosis and consequent therapy. Conventional radiography plays an important role in the diagnosis of symptomatic bone lesions. Computed tomography can evaluate the stability of metastatic lesions and is indispensable for therapy planning. MRI and PET-CT have the highest diagnostic accuracy for the detection of bone metastases and MRI can evaluate their intra- and extraosseus components. PET-CT, PET-MRI, or SPECT-CT in combination with specific tracers - due to their high specificity and sensitivity - have the potential to replace conventional methods in the future. Conservative treatment basically consists of analgesic therapy, the administration of calcium and vitamin D3 and bisphosphonates or inhibitors of RANKL (denosumab). Moreover radium-223-dichloride can improve overall survival and the time to the first symptomatic skeletal event in castration-resistant prostate cancer patients with bone metastases.

[Operative therapy of spinal metastases from urological tumors]. / Operative Therapie von Wirbelsäulenmetastasen urologischer Tumoren.

The treatment of bone metastases from urological tumors represents a palliative form of therapy, apart from the resection of solitary metastases from renal cell carcinomas. Due to the high incidence of spinal metastases this can result in clinically significant symptoms and possible complications for patients, such as pain, spinal instability and compression of the spinal canal with corresponding neurological deficits. By the use of targeted diagnostics and induction of radiotherapeutic and/or surgical treatment, for the majority of patients an immediate reduction in pain as well as early mobilization and sometimes even regression of existing neurological deficits and therefore an improved quality of life can be achieved.

Neuropilin-2 and its ligand VEGF-C predict treatment response after transurethral resection and radiochemotherapy in bladder cancer patients.

The standard treatment for invasive bladder cancer is radical cystectomy. In selected patients, bladder-sparing therapy can be performed by transurethral resection (TURBT) and radio-chemotherapy (RCT) or radiotherapy (RT). Our published in vitro data suggest that the Neuropilin-2 (NRP2)/VEGF-C axis plays a role in therapy resistance. Therefore, we studied the prognostic impact of NRP2 and VEGF-C in 247 bladder cancer patients (cN0M0) treated with TURBT and RCT (n = 198) or RT (n = 49) and a follow-up time up to 15 years. A tissue microarray was analyzed by immunohistochemistry. NRP2 expression emerged as a prognostic factor in overall survival (OS; HR: 3.42; 95% CI: 1.48 - 7.86; p = 0.004) and was associated with a 3.85-fold increased risk of an early cancer specific death (95% CI: 0.91 - 16.24; p = 0.066) in multivariate analyses. Cancer specific survival (CSS) dropped from 166 months to 85 months when NRP2 was highly expressed (p = 0.037). Patients with high VEGF-C expression have a 2.29-fold increased risk of shorter CSS (95% CI: 1.03-5.35; p = 0.043) in univariate analysis. CSS dropped from 170 months to 88 months in the case of high VEGF-C expression (p = 0.041). Additionally, NRP2 and VEGF-C coexpression is a prognostic marker for OS in multivariate models (HR: 7.54; 95% CI: 1.57-36.23; p = 0.012). Stratification for muscle invasiveness (T1 vs. T2-T4) confirmed the prognostic role of NRP2 and NRP2/VEGF-C co-expression in patients with T2-T4 but also with high risk T1 disease. In conclusion, immunohistochemistry for NRP2 and VEGF-C has been determined to predict therapy outcome in bladder cancer patients prior to TURBT and RCT.

[Trial registration for the improvement of transparency in scientific research. The German Association of Urology now enables registration in the register network of the WHO]. / Studienregistrierung zur Verbesserung der Transparenz in der klinischen Forschung. Die DGU ermöglicht jetzt eine einfache WHO-konforme Registrierung klinischer Studien.

Transparency is essential for the efficient transfer of scientific knowledge from research into practice but is often impaired by non-publication of whole studies or by inappropriate publication of trial results. Prospective trial registration has the potential to increase transparency in scientific research because it allows the evaluation of trial methodology and the appraisal of potential publication bias. Trial registration is a scientific, ethical and moral obligation which needs self-commitment of researchers and sponsors to prospective trial registration. The urological trial register of the German Society of Urology is now affiliated with the German Register of Clinical Studies, a national primary register, which enables easy registration in the register network of the WHO.

[Evidence-based anesthesiology: knowledge transfer from research into clinical practice]. / Evidenzbasierte Anästhesiologie : Wissenstransfer aus der Forschung in die klinische Praxis.

In the interest of patients evidence-based healthcare should be provided and is increasingly being demanded worldwide. In the daily medical practice however, healthcare based on proven scientific findings has not yet become firmly established. There are several causes for this. Problems occur at the level of knowledge generation, knowledge transfer from research into practice and also at the individual level of the treating healthcare professional. Nowadays, with a rapidly growing amount of knowledge it is almost impossible for the individual to quickly filter out the relevant facts. This article aims to shed light on the various aspects of the process of knowledge transfer from a clinical trial to evidence-based guidelines. It will make the reader aware of potential problems during this process and show some feasible approaches to solving them. Wherever possible, the field of anesthesiology will be used as the reference point. Evidence-based information sources will be presented and advice on how to use them will be given.

[The work of the Cochrane Collaboration in urology]. / Die Arbeit der "Cochrane Collaboration" in der Urologie.

The Cochrane Collaboration collects medical information from clinical trials and presents the results as systematic reviews. The aim of these evidence-based publications is to enable medical decisions which are based on the best available evidence and to improve knowledge transfer in healthcare decisions. Accurately developed systematic reviews identify relevant clinical trials, evaluate their quality, abstract the results and are being published in an increasing frequency in professional urological journals. The Cochrane Library provides, with diverse databases, a quick overview of the best available evidence in urology. The quality of systematic reviews depends on the quality of the included studies. A checklist provided by the PRISMA statement could help authors and thereby readers to improve methodology and recommendations in evidence-based urology.

[The urological trial registry of the German Society of Urology]. / Das urologische Studienregister der DGU.

Germany is an important hub for urological research and clinical trials are therefore very important for evidence-based medicine. In September 2010, the German Society of Urology commissioned a subject-specific clinical trial registry. The broad overview of ongoing and completed clinical trials in urology should help to increase transparency in research and to deploy resources in health care more efficiently. The urological trial registry aims to negotiate cooperation with a national primary registry to allow an automatic inclusion in the WHO Registry Network and to enable an ICMJE-compliant registry.