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BACKGROUND: Neoadjuvant cisplatin-based chemotherapy is standard care prior to radical cystectomy in patients with muscle-invasive bladder cancer (MIBC). OBJECTIVE: To assess efficacy and safety of two commonly used neoadjuvant schedules with different total doses and dose-intensities of gemcitabine and cisplatin (GC). METHODS: Data were collected retrospectively from all patients treated between 2010 and 2018 with neoadjuvant chemotherapy according to clinical routine at seven centres in Sweden and Denmark. Patients in Sweden received three cycles of a 4-week schedule (GC-4w: cisplatin 70 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1, 8, 15, q 28 days) and in Denmark four cycles of a 3-week schedule (GC-3w: cisplatin 70 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1, 8, q 21 days). Primary endpoint was pathological response at cystectomy (pT0N0 and

Objective This study aims to provide an overview of current treatment guidelines within the context of metastatic bladder cancer illustrated by a case report. Data Sources International guidelines from The American Society of Clinical Oncology (ASCO), The European Society of Medical Oncology (ESMO), and scientific references supporting these clinical guidelines. To illustrate the implementation of current evidence-based guidelines a patient case report was presented. Conclusion Historically, there have been limited treatment options available for metastatic bladder cancer for three decades. However, with the introduction of immunotherapy and emergent targeted therapies for metastatic bladder cancer increasing survival rates are expected. Implications for Nursing Practice To achieve improved treatment outcome in people affected by metastatic bladder cancer it is important that both doctors and nurses are aware of contemporary evidence-based treatment options in keeping with ESMO and ASCO international clinical guidelines. Nurses play an important role in educating patients about the potential side effects of therapy and in offering timely, tailored, and supported self-management.

The aim of the present study was to emphasize the critical importance of the clinician's awareness of signet-ring cell carcinoma (SRCC) of the urinary bladder, a rare and aggressive disease entity.A review of the current literature was conducted and a classic case of advanced SRCC of the urinary bladder is reported, clearly demonstrating the severity of this disease and the imperative need for standardized recommendations for the diagnostic work-up and management of urinary bladder SRCC.The prognosis for patients with SRCC of the urinary bladder is poor, attributed to presentation at advanced stages following asymptomatic progression, inefficacy of multimodality therapy and possibly an aggressive underlying biological phenotype. Treatment options are limited and not well studied.Given the rarity of SRCC, multi-institutional clinical trials and international cooperation are mandatory to improve survival for patients with primary SRCC of the bladder.

BACKGROUND: The role of the neurokinin-1 (NK-1) receptor antagonists in the prevention of radiation-induced nausea and vomiting has not been established. The purpose of the GAND-emesis study was to investigate the efficacy and safety of fosaprepitant in combination with palonosetron and dexamethasone in the prevention of nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly cisplatin in patients with cervical cancer.METHODS: This investigator initiated, multinational, randomised, double-blind, placebo-controlled phase 3 trial, included women with cervical cancer scheduled to receive fractionated radiotherapy and weekly cisplatin 40 mg/m2 for 5 weeks. Patients had to be naive to chemotherapy and radiotherapy. Patients were randomly assigned to receive either single doses of fosaprepitant 150 mg intravenously or placebo (saline) in combination with palonosetron 0·25 mg intravenously and dexamethasone 16 mg orally before cisplatin administration. Randomisation was done by the unmasked pharmacist, who used a list of six numbers (a block) provided in a sealed envelope. A web-based randomisation number generator was used to generate the full list of randomisation numbers that was split up in blocks of six numbers. All patients received oral dexamethasone 8 mg twice a day on day 2, 4 mg twice a day on day 3, and 4 mg once on day 4. The treatment was repeated for 5 weeks. The primary endpoint was the proportion of patients with sustained no emesis after 5 weeks of treatment. The modified intention-to-treat population (all patients who received study medication) was used for the statistical analyses. The study was registered with ClinicalTrials.gov, number NCT01074697.FINDINGS: Between June 15, 2010, and March 8, 2015, 246 patients from four countries consented to the study and were randomly assigned. Of these, 234 patients were eligible, having received study medication (118 received fosaprepitant, 116 received placebo). The proportion of patients with sustained no emesis at 5 weeks (competing risk analysis) was 48·7% (95% CI 25·2-72·2) for the placebo group compared with 65·7% (42·2-89·2) of patients for the fosaprepitant group. There was a significantly lower cumulative risk of emesis in the fosaprepitant group compared with the placebo group (subhazard ratio 0·58 [95% CI 0·39-0·87]; p=0·008). Treatments were generally well tolerated with few grade 3 adverse events none of which were related to the study treatment; the most common grade 3 adverse event during the 5 weeks of treatment was diarrhoea (11 [9%] of 118 patients in the fosaprepitant group vs six [5%] of 116 patients in the placebo group). There was only one report of a grade 4 adverse event (neutropenia), in the fosaprepitant group. No deaths were recorded in either group.INTERPRETATION: To our knowledge, this is the first study to investigate safety and efficacy of a NK-1 receptor antagonist during 5 weeks of radiotherapy and concomitant weekly cisplatin. Patients receiving fosaprepitant in addition to palonosetron and dexamethasone were less likely to experience emesis and nausea compared with those receiving palonosetron and dexamethasone alone. Both treatments were safe and well tolerated. Further investigations in other radiotherapy settings are warranted.FUNDING: Private and hospital or university funding, unrestricted grants from Biovitrum and Helsinn Healthcare SA. BACKGROUND: The role of the neurokinin-1 (NK-1) receptor antagonists in the prevention of radiation-induced nausea and vomiting has not been established. The purpose of the GAND-emesis study was to investigate the efficacy and safety of fosaprepitant in combination with palonosetron and dexamethasone in the prevention of nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly cisplatin in patients with cervical cancer.METHODS: This investigator initiated, multinational, randomised, double-blind, placebo-controlled phase 3 trial, included women with cervical cancer scheduled to receive fractionated radiotherapy and weekly cisplatin 40 mg/m(2) for 5 weeks. Patients had to be naive to chemotherapy and radiotherapy. Patients were randomly assigned to receive either single doses of fosaprepitant 150 mg intravenously or placebo (saline) in combination with palonosetron 0·25 mg intravenously and dexamethasone 16 mg orally before cisplatin administration. Randomisation was done by the unmasked pharmacist, who used a list of six numbers (a block) provided in a sealed envelope. A web-based randomisation number generator was used to generate the full list of randomisation numbers that was split up in blocks of six numbers. All patients received oral dexamethasone 8 mg twice a day on day 2, 4 mg twice a day on day 3, and 4 mg once on day 4. The treatment was repeated for 5 weeks. The primary endpoint was the proportion of patients with sustained no emesis after 5 weeks of treatment. The modified intention-to-treat population (all patients who received study medication) was used for the statistical analyses. The study was registered with ClinicalTrials.gov, number NCT01074697.FINDINGS: Between June 15, 2010, and March 8, 2015, 246 patients from four countries consented to the study and were randomly assigned. Of these, 234 patients were eligible, having received study medication (118 received fosaprepitant, 116 received placebo). The proportion of patients with sustained no emesis at 5 weeks (competing risk analysis) was 48·7% (95% CI 25·2-72·2) for the placebo group compared with 65·7% (42·2-89·2) of patients for the fosaprepitant group. There was a significantly lower cumulative risk of emesis in the fosaprepitant group compared with the placebo group (subhazard ratio 0·58 [95% CI 0·39-0·87]; p=0·008). Treatments were generally well tolerated with few grade 3 adverse events none of which were related to the study treatment; the most common grade 3 adverse event during the 5 weeks of treatment was diarrhoea (11 [9%] of 118 patients in the fosaprepitant group vs six [5%] of 116 patients in the placebo group). There was only one report of a grade 4 adverse event (neutropenia), in the fosaprepitant group. No deaths were recorded in either group.INTERPRETATION: To our knowledge, this is the first study to investigate safety and efficacy of a NK-1 receptor antagonist during 5 weeks of radiotherapy and concomitant weekly cisplatin. Patients receiving fosaprepitant in addition to palonosetron and dexamethasone were less likely to experience emesis and nausea compared with those receiving palonosetron and dexamethasone alone. Both treatments were safe and well tolerated. Further investigations in other radiotherapy settings are warranted.FUNDING: Private and hospital or university funding, unrestricted grants from Biovitrum and Helsinn Healthcare SA.

Introduction and objectives: More than 90% of bladder tumors are urothelial neoplasias, characterised as heterogeneous cell populations consisting of tumor cells, macrophages and stromal cells. At time of diagnosis, most neoplasias are non-invasive (stage Ta) or with invasion of lamina propria (stage T1). Despite advances in surgical techniques and intra-vesical therapy, patients with stage Ta and T1 have high recurrence and progression rates. Pathologic stage and grade, have limited ability to predict the invasive and metastatic potential, probably due to tumors of similar stage and grade having a significantly different biology. Biomarkers discriminating the microenvironment in non-invasive from invasive neoplasia are needed in order to improve curability. For this reason we have investigated one of the key players in proteolytic activity of invasive neoplasias, the plasminogen activation system. Components of this system: urokinase plasminogen activator (uPA), its cellular receptor (uPAR) and inhibitor (PAI-1), have prognostic, diagnostic and/or predictive value in several human cancers, but are poorly investigated in urothelial cancer. Materials and methods: Retrospectively collected, formalin fixed and paraffin embedded tissue samples (Haukeland University Hospital, Bergen) from 107 patients who underwent cystectomy for urothelial neoplasias in the period 1988-2005 were investigated. The material consists of 10 Ta, 24 T1, 73 T2-4 tumors, including 39 low-grade (LG) and 68 high-grade (HG) tumors. uPAR expression was investigated by immunohistochemistry using a polyclonal antibody against uPAR. uPAR expression was evaluated as either negative or positive. All cases were re-diagnosed by the same pathologist. Cancer cells were identified by staining for cytokeratin (CK-pan and CK7 combined), macrophages by CD68 and tumour associated myofibroblasts by α-smooth muscle actin (α-SMA). Results: 7/10 (70%) of the non-invasive neoplasias (stage Ta) showed no uPAR-immunoreactivity. The uPAR positive cells were only found in the surrounding stroma and not in cancer cells. In the neoplasias showing stromal- (stage T1) or muscular invasion (stage T2-T4), uPAR-positivity was found in 14/24 (58%) and 63/73 (86%) respectively. uPAR-positivity was found in 58/68 (85%) of HG tumors and in 17/39 (44%) LG tumors (p There was a significant trend between uPAR-positivity and T-stage for cancer cells, macrophages and myofibroblasts (p0.57). Conclusions: This study demonstrated that uPAR-positivity in the complex microenvironment of human urothelial neoplasia of the bladder significantly increases with T-stage and grade. Myofibroblasts and macrophage expression of uPAR may be an early marker for invasive potential in urothelial neoplasia of the bladder. This may help in the identification of T1 neoplasias with high invasive potential. The expression of uPAR, as well as PAI-1 and uPA, will be investigated in a larger material and correlated with survival/clinical data. Our aim is to establish predictive and prognostic tools for use in clinical setting based on semi-quantitative immunohistochemical methodology. Citation Format: Line Hammer Dohn, Martin Illemann, Gunilla Høyer-Hansen, Hans von der Maase, Ib Jarle Christensen, Jorunn Litlekalsoey, Jens G. Hoestmark, Helle Pappot, Ole Didrik Laerum. uPAR expression in the microenvironment of human urothelial neoplasia of the bladder is associated with invasive behavior and increases significantly with T-stage and grade. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B14.