Erdafitinib in BCG-treated high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. PATIENTS AND METHODS: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. RESULTS: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. CONCLUSIONS: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy.

Systemic therapy in metastatic renal cell carcinoma (mRCC): an evidence-based recommendation of the German interdisciplinary RCC guidelines group.

PURPOSE: The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated current medical treatments and gave recommendations. METHODS: A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate. RESULTS: Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated. CONCLUSION: ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.

Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

Advances in targeted alpha therapy for prostate cancer.

Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment.

Patterns of failure after radical prostatectomy in prostate cancer - implications for radiation therapy planning after 68Ga-PSMA-PET imaging.

BACKGROUND: Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). 68Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases. OBJECTIVE: In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not. METHODS AND MATERIALS: Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from 68Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, 68Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a "blind" radiation therapy after RPE and LAE. RESULTS: Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by 68Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of 68Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of 68Ga-PSMA-PET imaging. CONCLUSION: Compared to conventional CT or MRI staging, 68Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

Education in sexual medicine - a nationwide study among German urologists/andrologists and urology residents.

Although sexual-related problems are very prevalent, inadequate training for physicians has been reported. The aim was to investigate the educational situation in sexual medicine, including sexual dysfunctions, gender dysphoria and paraphilia, among German physicians in urology and andrology. Additional, barriers when addressing sexual health issues and confidence in taking care of patients with sexual-related problems were evaluated. A questionnaire was sent to 5955 urologists, urology residents and andrologists throughout Germany. The results of this study emphasise the need for continuing education and training in sexual medicine including sexual dysfunctions (83.9%), gender dysphoria (58.2%) and paraphilia (56.6%). Physicians, especially when working in urology, need basic skills in order to feel confident (89.0% in taking care of patients with sexual dysfunctions, 25.8% with gender dysphoria and 22.9% with paraphilia) and be able to reduce several barriers when addressing sexual health issues. The main reported barriers were lack of time (61.0%), inadequate financial compensation (42.5%), lack of necessity (29.9%) and the assumption of patients feeling uncomfortable (20.9%). It is within the competence of urologists and andrologists to correctly assess the situation and to refer patients to multidisciplinary support, such as psychologists, psychosomatics or couple therapists.

The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer.

BACKGROUND: Intratumoural lymphocytic infiltration is strongly associated with the outcome of many human epithelial cancers. The current paper investigated whether subpopulations of tumour-infiltrating T lymphocytes are associated with certain clinicopathological parameters and the prognosis of patients with invasive bladder cancer (BCa). PATIENTS AND METHODS: The infiltration densities of the adaptive immune markers CD3 (the whole T cell population), FOXP3 (regulatory T cells; Tregs), CD8 (T effector cells) and CD45R0 (T effector memory cells) were analysed by immunohistochemistry and image analysis with tissue microarrays of tumour tissues from 149 patients with invasive BCa treated with radical cystectomy. The findings were correlated with certain clinicopathological parameters. RESULTS: Higher FOXP3/CD3 [OS: p = 0.016, HR 1.29, 95% confidence intervals (95% CIs 1.05-1.59)] and FOXP3/CD8 (OS: p = 0.013, HR 1.32, 95% CIs 1.06-1.65) ratios were significantly associated with briefer overall survival and time to cancer-specific death; the latter ratio represented an independent prognostic factor according to a multivariate analysis adjusted for pathological T and N stages (HR 1.32, 95% CIs 1.05-1.67, p = 0.018). The infiltration densities of individual markers (CD3, CD8, FOXP3 and CD45R0) were not significantly associated with clinicopathological parameters or survival; however, a trend towards a better outcome was observed for higher log-transformed CD8 (p = 0.070, HR 0.80, 95% CIs 0.63-1.02) and CD3 (p = 0.113, HR 0.84, 95% CIs 0.68-1.04) infiltration values. CONCLUSIONS: A high fraction of Tregs amongst CD3- and CD8-positive lymphocytes indicated a poor prognosis, thereby emphasising the important role that Tregs play in the suppression of the anti-tumour immune response. No single lymphocytic marker was significantly correlated with clinical outcomes, but high CD3 and CD8 infiltration showed trends towards better prognosis.

Mutant PIK3CA controls DUSP1-dependent ERK 1/2 activity to confer response to AKT target therapy.

BACKGROUND: Alterations in the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway are frequent in urothelial bladder cancer (BLCA) and thus provide a potential target for novel therapeutic strategies. We investigated the efficacy of the AKT inhibitor MK-2206 in BLCA and the molecular determinants that predict therapy response. METHODS: Biochemical and functional effects of the AKT inhibitor MK-2206 were analysed on a panel of 11 BLCA cell lines possessing different genetic alterations. Cell viability (CellTiter-Blue, cell counts), apoptosis (caspase 3/7 activity) and cell cycle progression (EdU incorporation) were analysed to determine effects on cell growth and proliferation. cDNA or siRNA transfections were used to manipulate the expression of specific proteins such as wild-type or mutant PIK3CA, DUSP1 or CREB. For in vivo analysis, the chicken chorioallantoic membrane model was utilised and tumours were characterised by weight and biochemically for the expression of Ki-67 and AKT phosphorylation. RESULTS: Treatment with MK-2206 suppressed AKT and S6K1 but not 4E-BP1 phosphorylation in all cell lines. Functionally, only cell lines bearing mutations in the hotspot helical domain of PIK3CA were sensitive to the drug, independent of other genetic alterations in the PI3K or MAPK signalling pathway. Following MK-2206 treatment, the presence of mutant PIK3CA resulted in an increase in DUSP1 expression that induced a decrease in ERK 1/2 phosphorylation. Manipulating the expression of mutant or wild-type PIK3CA or DUSP1 confirmed that this mechanism is responsible for the induction of apoptosis and the inhibition of tumour proliferation in vitro and in vivo, to sensitise cells to AKT target therapy.Conclusion or interpretation:PIK3CA mutations confer sensitivity to AKT target therapy in BLCA by regulating DUSP1 expression and subsequent ERK1/2 dephosphorylation and can potentially serve as a stratifying biomarker for treatment.

[Value of immunotherapy in the perioperative treatment of localized muscle invasive bladder cancer]. / Stellenwert der Immuntherapie in der perioperativen Behandlung des lokalisierten muskelinvasiven Harnblasenkarzinoms.

Immune checkpoint inhibitors are standard of care in the treatment of metastatic and locally advanced urothelial cancer. Their use in perioperative treatment is currently under investigation as monotherapy as well as in combination with chemotherapy or radiation regimens. This article provides an overview of recent trials, current data as well as an outlook on future developments in the perioperative management of urothelial cancer.

[Quality assurance for the treatment of muscle-invasive and metastasized bladder carcinoma in Germany : An initiative of the Working Groups Urological Oncology (AUO) and Internal Oncology (AIO) in the German Cancer Society (DKG)]. / Qualitätssicherung zur Therapie des muskelinvasiven und metastasierten Harnblasenkarzinoms in Deutschland : Eine Initiative der Arbeitsgemeinschaften Urologische Onkologie (AUO) und Internistische Onkologie (AIO) in der Deutschen Krebsgesellschaft (DKG).

BACKGROUND: The S3-guideline on bladder cancer recommends radical cystectomy and cisplatin-based perioperative chemotherapy (POC) for muscle-invasive bladder cancer (MIBC). Recommendation for metastatic urothelial cancer (mUC) is cisplatin-based or immuno-oncological (IO) treatment in platinum-ineligible patients (pts) or as 2nd-line therapy. OBJECTIVES: Aim of the study was to obtain representative data on clinical routine treatment of MIBC and mUC in Germany. MATERIALS AND METHODS: A nationwide survey was performed to obtain data on stage-related patient volume in hospitals and office-based physicians. Based on these results, a representative sample of treatment data was collected retrospectively from pts with MIBC and mUC. RESULTS: Data from 956 pts (MIBC 576; mUC: 380) were collected. Of the MIBC pts, 49.8% received a systemic therapy (80.4% of them received cisplatin/gemcitabine) and 50.2% were treated with a cystectomy without POC. Significant factors for cystectomy without POC were higher age > 75 years (odds ratio [OR] 4.91, 95% confidence interval [CI] 3.01-8.11, p < 0.001) and platinum-ineligible pts (OR 2.15, 95% CI 1.30-3.59; p = 0.003). Treatment decision without interdisciplinary tumor board was also correlated with no POC (OR 2.43, 95% CI 1.65-3.61, p < 0.001). In mUC platinum-pretreated pts generally receive IO therapy (OR 12.07, 95% CI 6.94-21.82, p < 0.001). Other significant factors are positive PD-L1 status (OR 3.72, 95% CI 1.30-5.71, p < 0.001), higher age > 75 years (OR 2.83, 95% CI 1.43-5.73, p = 0.003) and platinum-ineligible pts (OR 2.57, 95% CI 1.30-5.71, p = 0.007). CONCLUSIONS: The "gold standard" cisplatin/gemcitabine is established in Germany if pts are treated with POC. Nonetheless half of the MIBC pts did not receive a POC, especially if the treatment decision is not discussed in a tumor board. In mUC IO therapy is established as 2nd-line therapy after a platinum-based treatment. Although the guideline recommendations are largely implemented, there is potential for optimization, especially in the establishment of interdisciplinary tumor boards.

[EMMPRIN (CD147). A prognostic and potentially therapeutic marker in urothelial cancer]. / EMMPRIN (CD147). Ein prognostischer und potenzieller therapeutischer Marker im Urothelkarzinom.

In 50% of all cases, bladder cancer patients develop tumor progression despite modern surgical methods such as radical cystectomy. A solution to the problem might be the identification and understanding of molecular biomarkers which could result in the development of advanced methods with better preventive, diagnostic, and therapeutic potential. One suitable approach is the identification of a bladder cancer-specific molecular marker in order to enhance patients' outcome. We and others have identified EMMPRIN as a prognostic biomarker in a variety of tumor diseases. EMMPRIN (CD147, extracellular matrix metalloproteinase inducer) is a cell surface protein that is expressed among other cell types, in particular in tumor cells. Since its first description in 1982 it is established that overexpression of EMMPRIN correlates with tumor progression and patient outcome. EMMPRIN expression levels can be used as an independent prognostic factor for survival. Recently, EMMPRIN has been defined as a potential target for tumor therapy in preclinical studies.

CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models.

BACKGROUND: CD147 (basigin, EMMPRIN) is a multifunctional, highly conserved glycoprotein enriched in pancreatic ductal adenocarcinomas (PDACs) which is associated with poor prognosis in many malignancies. The role of CD147 in pancreatic cancer, however, remains elusive. METHODS AND RESULTS: Silencing of CD147 by RNA interference (RNAi) reduced the proliferation rate of MiaPaCa2 and Panc1 cells. CD147 is required for the function and expression of the monocarboxylate transporters MCT1 and MCT4 that are expressed in human PDAC cells as demonstrated by real-time reverse transcription-PCR (RT-PCR) as well as immunohistology. MCT1 and MCT4 are the natural transporters of lactate, and MiaPaCa2 cells exhibited a high rate of lactate production, which is characteristic for the Warburg effect, an early hallmark of cancer that confers a significant growth advantage. Further induction of lactate production by sodium azide in MiaPaCa2 cells increased MCT1 as well as MCT4 expression. CD147 silencing inhibited the expression and function of MCT1 and MCT4 and resulted in an increased intracellular lactate concentration. Addition of exogenous lactate inhibited cancer cell growth in a dose-dependent fashion. In vivo, knock-down of CD147 in MiaPaCa2 cells by inducible short hairpin RNA (shRNA)-mediated CD147 silencing reduced invasiveness through the chorioallantoic membrane of chick embryos (CAM assay) and inhibited tumourigenicity in a xenograft model in nude mice. CONCLUSION: The function of CD147 as an ancillary protein that is required to sustain the expression and function of MCT1 and MCT4 is involved in the association of CD147 expression with the malignant potential of pancreatic cancer cells exhibiting the Warburg effect.

Multimodal tumor therapy in a 31-year-old pregnant woman with Wilms tumor.

Wilms tumor, or nephroblastoma, is the most common malignant tumor of the urinary tract in children, but is rarely found in adults. Here, we report the first case of a female patient with a Wilms tumor, diagnosed during pregnancy, who underwent radical nephrectomy and adjuvant chemotherapy before and after delivering a healthy child. Generally, treatment should follow the guidelines established for the pediatric setting.

[Internet use after prostate cancer : Search for information and trust in disease-related information in long-term survivors]. / Internetnutzung nach Prostatakrebs : Informationssuche und Vertrauen in erkrankungsrelevante Informationen bei Langzeitüberlebenden.

BACKGROUND AND OBJECTIVE: The internet provides numerous sources of information about prostate cancer (PCa). The present study investigated internet use among long-term PCa survivors, trust in online PCa-related information, and associated factors. MATERIALS AND METHODS: Based on the German national research project Familial Prostate Cancer long-term PCa survivors were asked about their internet use in 2017. Associations with sociodemographic (age at survey, children, intimate relationship, education) and disease-related parameters (time since diagnosis, PCa family history, progress) were analyzed using multivariable logistic regression. RESULTS: In all, 4636 long-term PCa survivors were included in the analysis (mean age 76.9 years; standard deviation 6.6 years). Mean follow-up was 14.0 years. Of long-term PCa survivors, 62.1% were using the internet. Among non-users 23.5% expressed strong concerns, among users only 2.8%. Furthermore, 47.2% of internet users sought information about PCa, 18.0% of them indicated difficulties while searching for information. More than half of the users found the online information inappropriate. Lower age, shorter time since diagnosis, progress, and a more frequent internet use were associated with search for information. Only one-third fully trusted online information. Trust in online information was associated with high age, higher educational level, and frequent search for online information. Many survivors stressed that they were primarily trusting their treating urologist. CONCLUSIONS: Two-thirds of long-term PCa survivors are using the internet. A significant proportion expressed difficulties finding proper and reliable information. Urologists should be familiar with online resources on PCa in order to offer advice to patients and to recommend adequate information on the internet.

[Active immunotherapy of urologic malignancies and tumor-mediated immunosuppression]. / Aktive Immuntherapie urologischer Tumoren und tumorbedingte Immunsuppression.

The absence of curative treatment strategies for metastatic prostate cancer requires further development of novel, more effective treatment regimens. Because of recent advances in immunologic and translational research, therapeutic vaccines are becoming important as promising treatment modalities against prostate cancer. Immunizing patients who have hormone-refractory prostate cancer with an allogenic IL-2 and IFN-gamma secreting tumor cell vaccine is safe and feasible with no dose-limiting toxicity; it has been shown to reduce the progression of prostate-specific antigen in treated subjects and to induce vaccine-specific immune responses. Despite these results, current vaccine strategies have shown only limited success in clinical settings. There is ample evidence that multiple immunosuppressive mechanisms, such as regulatory T cells and myeloid suppressor cells, exist that considerably dampen antitumor responses and weaken the activity of current immunotherapeutic regimens. Recent insights into the characteristics of the regulatory elements of the immune system have provided new opportunities to enhance vaccine-mediated antitumor immunity by reversing tumor-mediated immunosuppression before immunotherapies can be used successfully for cancer patients.

[Value of cystoprostatectomy in locally advanced prostate carcinoma]. / Stellenwert der Zystoprostatektomie beim lokal fortgeschrittenen Prostatakarzinom.

Patients suffering from locally advanced prostate carcinoma are often stressed by debilitating local symptoms limiting their quality of life. At the same time life expectancy often exceeds several years, whereas urologists and oncologists tend to underestimate their patients' life expectancy. Cystoprostatectomy for locally advanced prostate carcinoma is a reasonable therapeutic option concerning frequency and kind of imminent complications and possibly alleviates or completely eliminates local symptoms in 80% or more. According to the literature cancer-specific 10-year survival rates are 38% or median cancer-specific survival lies between 24 and 31 months. The role of neoadjuvant or adjuvant hormonal therapy, chemotherapy, or radiotherapy has not yet been defined. Mostly after cystoprostatectomy due to locally advanced prostate carcinoma an ileal conduit is formed for urinary diversion, but also orthotopic neobladders or continent pouches are used. Incontinence rates for orthotopic neobladders may reach 50% and more. In synopsis cystoprostatectomy may be a viable therapeutic option for patients suffering from locally advanced prostate carcinoma. It surely is important that the indication for surgery is based on an individual decision.

[EMMPRIN (CD147). A new key protein during tumor progression in bladder cancer]. / EMMPRIN (CD147). Ein neues Schlüsselprotein in der Tumorprogression des Harnblasenkarzinoms.

EMMPRIN (CD147) is a cell surface protein that is highly expressed on tumor cells. Elevated EMMPRIN levels have been detected in a variety of malignant tumors and have been associated with tumor progression in experimental and clinical conditions. Recent studies have shown that EMMPRIN is an independent prognostic factor for overall survival in bladder cancer patients. In a multicenter phase II trial, antibodies against EMMPRIN were shown to be successful in hepatocellular cancer therapy. We are characterizing the functional importance of EMMPRIN in bladder cancer in order to evaluate this protein as a new target molecule for therapy.

[Muscle-invasive urothelial carcinoma of the bladder. Detection and topography of micrometastases in lymph nodes]. / Muskelinvasives Urothelkarzinom der Harnblase. Detektion und Topographie von Mikrometastasen in Lymphknoten.

Detection of metastases in lymph nodes is an important prognostic factor for progression-free survival in bladder cancer patients. Patients undergoing radical cystectomy with pelvic lymphadenectomy are randomized in the LEA study (AUO AB 25/02) into two groups receiving standard (obturator and external nodes) or extended lymphadenectomy (complete pelvic nodes up to the inferior mesenteric artery).The aim of this study is the detection of lymph node metastases that are not identified with classic pathological methods using RT-PCR as a highly sensitive and specific method. For detection of occult disseminated tumor cells we analyze the expression of the tumor markers cytokeratin 20 (CK-20), uroplakin II (UP II), mucin 2 (MUC2), and mucin 7 (MUC7).We examined 315 lymph nodes from 19 cystectomy patients for the expression of CK-20. In 93 lymph nodes CK-20 expression was detected whereas only 18 lymph nodes were histopathologically positive. More than one third of CK-20-positive lymph node metastases were located outside the standard lymphadenectomy field. We did not detect any skip lesions. Follow-up data will validate if there is a correlation between detection of occult disseminated tumor cells and progression-free survival.

[Photodynamic diagnostics in the urinary tract. Consensus paper of the Working Group for Oncology of the German Society for Urology]. / Photodynamische Diagnostik im Harntrakt. Konsensusempfehlungen des Arbeitskreises Onkologie der Deutschen Gesellschaft für Urologie.

Because of the frequency of occurrence and the long protracted course, bladder carcinoma is the most expensive solid tumor in terms of costs, from diagnosis to death of the patient. The most important cost factor within the total cost is the treatment of recurrent, non-muscle invasive bladder carcinoma. Photodynamic diagnosis (PDD) improves the early detection rate of non-muscle invasive bladder cancer, especially the detection of carcinoma in situ and severe dysplasia. PDD also reduces the number of residual tumors after TUR-B compared to white-light guided TUR-B and also the early recurrence rate although long-term outcome with hexylaminolaevulinic acid with regards to the general course of bladder cancer is still lacking. PDD has been used mainly for detection of bladder cancer and specifically carcinoma in situ in conjunction with diagnostic and therapeutic transurethral resection of the bladder. In 2006 hexylaminolaevulinic acid (HAL) was approved in the EU (EMEA) as a photosensitizer for the use in photodynamic diagnosis of the bladder. Several guidelines have incorporated PDD as optional form of diagnosis during endoscopy in proven or suspected bladder cancer, but no specific recommendations regarding indication and application of PDD exist. The German group of urologic oncology (AKO) invited urologists and biologists involved in the development of hexylaminolaevulinic acid as well its clinical use to participate in evaluating the data for HAL and its predecessor delta-aminolaevulinic acid (5-ALA). A consensus with regards to the indications, contraindications, technique, pre-clinical data, comparison of HAL and 5-ALA, current results, costs and follow-up was reached and are presented in this paper.

[Efficacy of a ketogenic diet in urological cancers patients : A systematic review]. / Wirksamkeit der ketogenen Diät bei urologischen Tumorerkrankungen : Ein systematischer Review.

BACKGROUND: Beside the classical anticancer treatment tumor patients try to find proactive alternative therapies to fight their disease. Lifestyle changes such as introducing a ketogenic diet is one of the most popular among them. The German Association of Urological Oncology (AUO, Arbeitsgemeinschaft Urologische Onkologie) presents a systematic review investigating the evidence of ketogenic diet in cancer patients. MATERIALS AND METHODS: A systematic literature research was conducted in the databases Medline, Livivo, and the Cochrane Library. Only clinical studies of tumor patients receiving chemotherapy while on a ketogenic diet were included. The assessment of the results was performed according to the predefined primary endpoints overall survival and progression-free survival and secondary endpoints quality of life and reduction of adverse effects induced by cytostatics. RESULTS: Nine studies met the inclusion criteria: eight prospective and one retrospective study case series respectively cohort-studies, with a total of 107 patients. Currently there is no evidence of a therapeutic effect of a ketogenic diet in patients with malignant tumors regarding the clinical outcome or quality of life. CONCLUSION: Based on the current data, a ketogenic diet can not be recommended to cancer patients because prospective, randomized trials are missing.