Listening to Music during Outpatient Cystoscopy Reduces Pain and Anxiety and Increases Satisfaction: Results from a Prospective Randomized Study.

BACKGROUND: This study investigates the effect of classical music, music of patients' own choice, or no music on pain reduction during elective cystoscopy. OBJECTIVES: The aim of the study was to describe the effect of listening to classical music, music of patients' own choice, or no music on patient's pain and satisfaction rates when carrying out an elective cystoscopy and the effect on the assessment capability of the performing urologist. DESIGN, SETTING, AND PARTICIPANTS: This randomized trial included 127 patients undergoing elective cystoscopy at the Urological Department of the University Clinic of Munich between June 2019 and March 2020. Outcome Measurements and Statistical Analysis: Patients were assigned randomly to 3 groups: group I: listening to standardized classical music (n = 35), group II: listening to music according to the patients' choice (n = 34), and control group III: no music (n = 44). Prior to cystoscopy, anxiety levels were assessed by the Beck Anxiety Inventory (BAI). The Visual Analog Scale (VAS, range 1-100) was used for a self-assessment of pain, discomfort, and satisfaction. Statistical analysis was done with Spearman's rank correlation and t-tests. RESULTS AND LIMITATIONS: The median age was 63 (range 27-91) years. The duration of cystoscopy was 5.7 (1-30) min. Patients had undergone a median of 2.3 cystoscopies in the past. Between giving informed consent and cystoscopy, patients had to wait for a median of 64 (0-260) min. The median VAS pain score was significantly lower in group I at 1.7 and group II at 2.3 versus 5.2 in the control group III (p < 0.001). The control group III had significantly worse pain and patient satisfaction rates compared with groups I and II. Group I had a significant lower VAS pain score than groups II and III (p < 0.001). Classical music also increased the assessment capability of the preforming urologist. CONCLUSIONS: Listening to music during elective cystoscopy significantly reduces pain and distress and leads to higher patient and surgeon satisfaction. We recommend listening to classical music or music chosen by the patients during outpatient flexible/rigid cystoscopy in daily clinical routine. Patient Summary: In this study, we found that patients who listened to classical music or music of their own choice while undergoing a cystoscopy showed significant reduction of pain and distress.

A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma.

CONTEXT: While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown. OBJECTIVE: To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC. EVIDENCE ACQUISITION: Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken. EVIDENCE SYNTHESIS: The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03-1.92 and 1.41, 95% CI: 0.88-2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67-2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9-2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91-1.86). Sunitinib was associated with more Grade 3-4 adverse events than everolimus, although this was not statistically significant. CONCLUSIONS: This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed. PATIENT SUMMARY: We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need.

SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer.

BACKGROUND: Understanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit. OBJECTIVES: To prospectively evaluate sequential use of the multikinase inhibitors sorafenib followed by sunitinib (So-Su) versus sunitinib followed by sorafenib (Su-So) in patients with mRCC. DESIGN, SETTING, AND PARTICIPANTS: The multicentre, randomised, open-label, phase 3 SWITCH study assessed So-Su versus Su-So in patients with mRCC without prior systemic therapy, and stratified by Memorial Sloan Kettering Cancer Center risk score (favourable or intermediate). INTERVENTION: Patients were randomised to sorafenib 400mg twice daily followed, on progression or intolerable toxicity, by sunitinib 50mg once daily (4 wk on, 2 wk off) (So-Su), or vice versa (Su-So). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was improvement in progression-free survival (PFS) with So-Su versus Su-So, assessed from randomisation to progression or death during second-line therapy. Secondary endpoints included overall survival (OS) and safety. RESULTS AND LIMITATIONS: In total, 365 patients were randomised (So-Su, n=182; Su-So, n=183). There was no significant difference in total PFS between So-Su and Su-So (median 12.5 vs 14.9 mo; hazard ratio [HR] 1.01; 90% confidence interval [CI] 0.81-1.27; p=0.5 for superiority). OS was similar for So-Su and Su-So (median 31.5 and 30.2 mo; HR 1.00, 90% CI 0.77-1.30; p=0.5 for superiority). More So-Su patients than Su-So patients reached protocol-defined second-line therapy (57% vs 42%). Overall, adverse event rates were generally similar between the treatment arms. The most frequent any-grade treatment-emergent first-line adverse events were diarrhoea (54%) and hand-foot skin reaction (39%) for sorafenib; and diarrhoea (40%) and fatigue (40%) for sunitinib. CONCLUSIONS: Total PFS was not superior with So-Su versus Su-So. These results demonstrate that sorafenib followed by sunitinib and vice versa provide similar clinical benefit in mRCC. PATIENT SUMMARY: We investigated if total progression-free survival (PFS) is improved in patients with advanced/metastatic kidney cancer who are treated with sorafenib and then with sunitinib (So-Su), compared with sunitinib and then sorafenib (Su-So). We found that total PFS was not improved with So-Su compared with Su-So, but both treatment options were similarly effective in patients with advanced/metastatic kidney cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00732914, www.clinicaltrials.gov.

Course of size and density of metastatic renal cell carcinoma lesions in the early follow-up of molecular targeted therapy.

OBJECTIVE: Imaging-based monitoring of molecular therapies in oncology remains a challenge. Molecular therapies might have more pronounced effects on lesion density than on lesion size. We analyzed changes in lesion diameter and density in patients with metastasized renal cell cancer (mRCC) in the early follow-up of targeted therapy and compared size-based measurements according to Response Evaluation Criteria in Solid Tumors (RECIST) with size- and density-based response evaluations according to the Choi criteria. PATIENTS AND METHODS: A total of 22 patients treated with sorafenib (800 mg/d) were retrospectively analyzed. Relative changes (in %) in the greatest diameter and density of defined neoplastic "target lesions" were determined 8 weeks and 1 year after start of therapy in relation to a pretherapeutic baseline investigation. Data were analyzed according to RECIST (ver. 1.0), and results were compared with the response assessment based on Choi. Median survival was determined for all subgroups according to Choi or RECIST at the 8-week and 1-year follow-up. RESULTS: Applying RECIST, 18 patients (82%) demonstrated stable disease (SD) 8 weeks after the start of targeted therapy, 3 patients (14%) partial response (PR), and 1 patient (4%) progressive disease (PD). Partial responders at 8 weeks had a median survival of 48 months. After 1 year, 59% of all patients still showed SD. Applying Choi, 15 patients (68%) showed PR 8 weeks after the start of therapy, 5 patients (23%) SD, and 2 patients (9%) PD. After 1 year, PR was still the predominant response group (64% of the patients). Partial responders after 8 weeks had a median survival of 18 months. CONCLUSION: Choi defined more patients as partial responders at early stages of therapy than RECIST, but this was not an effective selection for patients with prolonged median survival. Evaluation of a larger patient cohort will further clarify the role of combined size- and density-based follow-up strategies in targeted therapy of mRCC.

Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell carcinoma: a prospective evaluation.

BACKGROUND: Sarcomatoid renal cell cancer (RCC) is a distinct histological variant of RCC that is associated with rapid progression and a poor prognosis. The optimal treatment for patients with sarcomatoid RCC remains to be defined. Gemcitabine plus doxorubicine (GD) has shown some efficacy, however durability of response is limited. We carried out a prospective, open-label study to investigate the efficacy and safety of sorafenib in patients after GD failure in sarcomatoid RCC. METHODS: Fifteen patients with pure sarcomatoid RCC and objective progressive disease were treated with GD (gemcitabine 1500 mg/m², doxorubicine 50 mg/m² administered by weekly intravenous infusion) until progression of disease. Subsequently 9 patients were switched to sorafenib (400 mg twice daily). Tumor response was measured by physical examination and computerized tomography scans and evaluated according to Response Evaluation Criteria in Solid Tumors criteria. RESULTS: Median time to progression (TTP) under GD was 6.6 months (range 0.8 - 8 months). During GD treatment there were no remissions and 6 patients died from progressive disease. Median TTP for the 9 patients switched to sorafenib was 10.9 months (range 0.6 - 25.5 months). During sorafenib therapy one patient had a partial remission lasting for 3 months and 4 patients experienced stable disease with a duration of 3 to 9 months. Four patients immediately progressed on sorafenib treatment but had a slower dynamic of tumor progression than under GD. Dosing in both treatment phases was generally well tolerated with manageable toxicities and no requirement for dose reduction. CONCLUSIONS: Chemotherapy with GD was ineffective in our patients with pure sarcomatoid RCC. Subsequent anti-angiogenic treatment using the multi-tyrosine kinase inhibitor sorafenib resulted in additional progression-free survival in 5 of 9 patients. Further evaluation of targeted anti-angiogenic agents for the treatment of sarcomatoid RCC is warranted.

Complete remission achieved with angiogenic therapy in metastatic renal cell carcinoma including surgical intervention.

BACKGROUND: Former systemic therapy for metastatic renal cell cancer (mRCC) based on immunomodulation could achieve complete remissions (CR) in only some patients. Angiogenic therapy with sunitinib, sorafenib, and temsirolimus changed the paradigm of treating mRCC based on a doubled progression-free survival (PFS) and 10% to 30% of patients achieving partial remission (PR). Unfortunately, CR is rarely seen. Within our patients we could achieve some CR, which we are presenting in this study. PATIENTS AND METHODS: We assessed 194 consecutive patients of an institutional database that were treated for mRCC with either sorafenib or sunitinib between 05/2006 and 12/2007. Restaging with repeated high-resolution computed tomography (CT) of thorax and abdomen was performed in an 8 to 10 weeks interval. Five patients who achieved CR in repeated CT under therapy are included in this analysis. RESULTS: Of the patients in whom we achieved CR, two were female and three were male. Median age was 63.2 years (range 52-70). All patients had clear cell histology. In three of the five patients, CR was achieved by surgery after partial remission, and in two patients it was achieved by sole medical therapy. All patients remained in CR until now with a median duration of CR of 24 months (range 24-29 months). One patient still is on therapy, while four patients do not receive any systemic treatment. CONCLUSIONS: We proof long-term confirmed CR in mRCC achieved by anti-angiogenic therapy alone or in combination with surgery. Combining surgery and anti-angiogenic therapy based on sorafenib and sunitinib could render patients free of disease even after repeated cycles of systemic treatment.

Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial.

PURPOSE: Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in patients with renal cell carcinoma (RCC) are reported. PATIENTS AND METHODS: Nine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated. RESULTS: The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio [HR] = 0.88; P = .146); however, when post-cross-over placebo survival data were censored, the difference became significant (17.8 v 14.3 months, respectively; HR = 0.78; P = .029). Adverse events at 16 months after cross over were similar to those previously reported. Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status (P < .0001), Memorial Sloan-Kettering Cancer Center score (P < .0001), and PFS and OS in univariate (PFS, P = .0013; OS, P = .0009) and multivariate (PFS, P = .0231; OS, P = .0416) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib (P = .0145). Both high-VEGF (P < .01) and low-VEGF (P < .01) groups benefited from sorafenib. CONCLUSION: Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC.

Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma.

PURPOSE: An open-label, phase II study to evaluate progression-free survival (PFS), overall best response, adverse events (AEs), and patient-reported outcomes with sorafenib versus interferon alfa-2a (IFN-alpha-2a) in patients with untreated, advanced renal cancer. PATIENTS AND METHODS: A total of 189 patients were randomly assigned to oral sorafenib 400 mg twice daily or to subcutaneous IFN-alpha-2a 9 million U three times weekly (period 1). Sorafenib patients who progressed were dose-escalated to 600 mg twice daily; IFN-alpha-2a patients who progressed were switched to sorafenib 400 mg twice daily (period 2). RESULTS: In period 1 PFS was similar for sorafenib-treated (n = 97; 5.7 months) and IFN-alpha-2a-treated patients (n = 92; 5.6 months); more sorafenib-treated patients had tumor shrinkage (68.2% v 39.0%). Common drug-related AEs (Grades > or = 3) for sorafenib were hand-foot skin reaction (11.3%), diarrhea (6.2%), and rash/desquamation (6.2%); for IFN-alpha-2a, these were fatigue (10.0%), nausea (3.3%), flu-like syndrome (2.2%), and anorexia (2.2%). Sorafenib-treated patients reported fewer symptoms, better quality of life (QOL), and greater treatment satisfaction. In period 2, 41.9% of patients who received sorafenib 600 mg twice daily (n = 43) experienced tumor reduction (median PFS, 3.6 months). After the switch to sorafenib 400 mg twice daily, tumors were reduced in 76.2% of 50 patients (median PFS, 5.3 months). AEs were mostly grade 1 to 2; no increase in AEs of grades > or = 3 occurred after sorafenib dose escalation. CONCLUSION: In this study, sorafenib resulted in similar PFS as IFN-alpha-2a in patients with untreated RCC. However, sorafenib-treated patients experienced greater rates of tumor size reduction, better QOL, and improved tolerability. Both dose escalation of sorafenib after progression and a switch to sorafenib after progression on IFN-alpha-2a resulted in clinical benefit.

Resolution of macular oedema in occult choroidal neovascularization under oral Sorafenib treatment.

PURPOSE: To report on the effect of oral nexavar (Sorafenib) treatment in one patient with neovascular age-related macular degeneration (AMD) and advanced renal cell cancer (RCC). METHODS: After two intravitreal injections of bevacizumab (1.25 mg) for occult choroidal neovascularization (CNV) in AMD, the patient was started on oral Sorafenib (400 mg twice daily) treatment for RCC. RESULTS: Visual acuity (VA) was 20/80 in the left eye and optical coherence tomography (OCT) demonstrated persistent central thickening to 251 microm after bevacizumab. After 6 weeks of oral Sorafenib treatment, VA had increased to 20/70 and a significant decrease in retinal thickness to 208 microm was observed on OCT. The patient remained stable during a further 3 months of follow-up. CONCLUSIONS: Resolution of macular oedema and stabilization of VA under oral treatment with the multikinase inhibitor Sorafenib was observed. This observation warrants further investigation.