Muscle mass and physical function in patients with bladder cancer-Data from a prematurely terminated prospective cohort study.

Background: Patients with bladder cancer (BC) have a high prevalence of comorbidity and low adherence to systemic anticancer treatment but it is unknown whether this is associated with sarcopenia. Objective: We aimed to investigate if the sarcopenia-defining parameters (muscle strength, muscle mass and physical performance) were associated with reduced adherence to systemic anticancer treatment in patients with BC, and if these muscle domains changed during treatment. Methods: Patients >18 years of age with BC referred for chemotherapy or immunotherapy at Department of Oncology, Rigshospitalet, Denmark were eligible for study inclusion. Measurements were performed before treatment initiation and within one week after treatment termination, and consisted of assessments of muscle strength, muscle mass, and physical performance. Data was compared with thresholds outlined by the European Working Group on Sarcopenia in Older Patient's (EWGSOP2) guidelines and a healthy, age-matched Danish cohort. Results: Over a period of 29 months, we included 14 patients of whom two completed follow-up measurements. The recruitment rate was <50% of planned due to logistics and Covid-19 related limitations. Consequently, a decision to prematurely terminate the study was made. No patients fulfilled EWGSOP2 criteria for sarcopenia, but the majority had reduction in one or more muscle domains compared to healthy, age-matched individuals. The majority of patients had poor treatment tolerance, leading to dose reductions and postponed treatments. Conclusions: In this prematurely terminated study, no patients fulfilled EWGSOP2 criteria for sarcopenia, yet, most patients were affected in one or more muscle domains and the majority had compromised treatment adherence.

PD-L1 expression and FGFR-mutations among Danish patients diagnosed with metastatic urothelial carcinoma: A retrospective and descriptive study.

Checkpoint inhibitors have changed the treatment landscape of advanced urothelial carcinoma (mUC), and recently, a fibroblast-growth-factor-receptor (FGFR) inhibitor has been introduced. This study aimed at estimating programmed death-ligand 1 (PD-L1) expression in primary tumors (PTs) and the PD-L1 expression concordance between PTs and paired metastases in 100 patients with UC managed in the real-world setting. Further, the aim was to investigate FGFR1-3 aberrations and the correlation between FGFR1-3 aberrations and PD-L1 expression. PD-L1 immunohistochemistry was performed on 100 formalin-fixed paraffin-embedded archival primary UC samples and 55 matched metastases using the 22C3 PD-L1 assay. PD-L1 expression was determined by the combined positive score, considered positive at ≥10. Targeted next-generation sequencing on the S5+/Prime System with the Oncomine Comprehensive Assay version 3 was used to detect FGFR1-3 aberrations in PTs. We found that 29 of 100 PTs had positive PD-L1 expression. The PD-L1 concordance rate was 71%. FGFR1-3 aberrations were observed in 18% of PTs, most frequently FGFR3 amplifications or mutations. We found no association between FGFR1-3 aberrations and PT PD-L1 expression (p = 0.379). Our data emphasize the need for further studies in predictive biomarkers.

Implications for Efficacy and Safety of Total Dose and Dose-Intensity of Neoadjuvant Gemcitabine-Cisplatin in Muscle-Invasive Bladder Cancer: Three-Week Versus Four-Week Regimen.

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 < pT2N0). RESULTS: A total of 251 patients were treated with GC-4w and 455 with GC-3w. pT0N0 was significantly higher for patients treated with GC-3w compared to GC-4w, 46% versus 32% (adjusted odds ratio [aOR] 1.80; 95% confidence interval [CI] 1.16-2.80; P = 0.009); and for < pT2N0 60% versus 47% (aOR 1.08; 95% CI 0.70-1.66; P = 0.743). There were no significant differences between GC-4w and GC-3w regarding survival parameters. GC-3w patients discontinued treatment more frequently and showed a higher degree of neutropenia. CONCLUSIONS: A significantly higher complete response-rate was observed in the patient group treated with the more cisplatin-dose-intense 3-week schedule. The side-effect profile was in favor of the 4-week approach while relapse-free and overall survival were similar.

Status of Metastatic Bladder Cancer Treatment Illustrated by a Case.

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.

Development of Sarcopenia in Patients With Bladder Cancer: A Systematic Review.

OBJECTIVE: Sarcopenia is known to influence cancer-related complications and overall survival. However, the effect of cancer treatment on the development or progression of sarcopenia is relatively unknown. The primary aim of this systematic review was to determine the prevalence and development of sarcopenia among people with bladder cancer. DATA SOURCES: A systematic search was performed in PubMed, Web of Science, and EMBASE. Studies with ≥2 assessments of sarcopenia were eligible for inclusion. Five retrospective cohorts were included with a total of 438 participants. The baseline prevalence of sarcopenia across studies varied from 25% to 69% and post-treatment prevalence from 50% to 81%. The average loss of muscle mass was 2.2% to 10% during a time course of 3 to 12 months. CONCLUSION: The prevalence of sarcopenia markedly increased during cancer treatment in patients with bladder cancer. Further research into the effect of different treatment regimens on the development of sarcopenia, and how these changes might affect functional capacity and survival is needed. IMPLICATIONS FOR NURSING PRACTICE: The development of sarcopenia is important to understand because of its negative affect on quality of life, complications, and mortality. Further, understanding how sarcopenia develops during treatment could potentially strengthen nurses' future care plans for patients with bladder cancer.

Real-World Study of Treatment with Pembrolizumab Among Patients with Advanced Urothelial Tract Cancer in Denmark.

BACKGROUND: Investigating the effect of newly approved oncological drugs in the real-world is warranted. With emerging novel treatments rapidly being approved for urothelial tract cancers, we aimed to assess real-world data, regarding effect and safety, during the first year after approval of pembrolizumab in Denmark for patients with locally advanced and unresectable or metastatic urothelial tract cancer (mUTC) in the first- and second-line setting. MATERIALS AND METHOD: At the six oncological departments treating mUTC in Denmark, we identified all mUTC patients receiving pembrolizumab during the first year after approval, between March 1, 2018 and February 28, 2019. A retrospective data collection was conducted from January to June 2020. Patient characteristics matching that of the relevant clinical trials for pembrolizumab in first- and second-line treatment-setting, overall survival (OS), progression-free survival (PFS), toxicity and tumor response were assessed. RESULTS: 139 patients were identified, 53 in first-line treatment, 77 in second-line, and 9 receiving third or later lines of treatment. The population was characterized by a majority of males (70%), most patients had ECOG PS 0-1 (60.4%) and primary tumor in the bladder was predominant (90.6%). The overall response rate (ORR) in first-line was 30.2%, PFS was 3,5 months (95%CI 2,3-7,9 months) and OS 9,2 months (95%CI 7,0-20.9 months). For second-line treatment the ORR was 27,3%, PFS 2,9 months (95%CI 2,5-5,3) and OS 9.1 months (95%CI 5,4-12,8 months). Toxicity was comparable to clinical trials without any new toxicities registered. CONCLUSION: Real-world data on response rates, OS, PFS and toxicity for patients with mUTC receiving pembrolizumab in first- and second-line, shows comparable results to clinical trials. This study further establishes immunotherapy as an effective and tolerable treatment for mUTC.

Electronic reporting of patient-reported outcomes in a fragile and comorbid population during cancer therapy - a feasibility study.

BACKGROUND: Electronic collection of patient-reported outcomes (ePROs) is becoming widespread in health care, but the implementation into routine cancer care during therapy remains to be seen. Especially, little is known of the use and success of electronic reporting during active cancer treatment in fragile and comorbid patients. The aim of this study was to test the feasibility of ePRO and its incorporation into routine cancer care, measured by physician compliance, for a fragile and comorbid bladder cancer (BC) population receiving chemo- or immunotherapy. METHODS: All BC patients initiating treatment for locally advanced or metastatic bladder cancer at Rigshospitalet or Herlev Hospital, Denmark, were approached during an 8 month period. Exclusion criteria were patients not speaking Danish or not being signed up for electronic communication with health authorities. Enrolled patients were prompted to complete weekly ePROs from home. Patients completed the European Organisation for Research and Treatment of Cancer's general quality of life questionnaire, QLQ-C30, and the module for muscle-invasive bladder cancer QLQ-BLM30, the Hospital Anxiety and Depression Scale, HADS, and selected items from the Patient Reported-Outcomes version of the Common Terminology Criteria of Adverse Events (PRO-CTCAE), in total 158 questions weekly. If failing to report when prompted, patients were sent two e-mail reminders. Patients were informed that the physician would have an overview of the reported ePROs at their following clinical visits. Physicians were at all clinical visits informed to look at the ePROs in a software solution separate from the medical records. Physicians were logged to check their compliance to the task. No continuous surveillance of ePROs was established. RESULTS: Of 91 patients screened for enrolment, 19 patients (21%) were not found eligible for standard treatment, eight patients (9%) were not signed up for electronic communication with the health authorities and nine patients (10%) declined participation. Another six patients did not meet other inclusion criteria. In total 49 BC patients were enrolled, 29 initiating chemotherapy and 20 initiating immunotherapy. A total of 466 electronic questionnaires were completed. The overall adherence of the patients to complete ePROs was at an expected level for an elderly cancer population (75%) and remained above 70% until the 6th cycle of treatment. The physician' compliance was in contrast low (0-52%) throughout the course of treatment. CONCLUSIONS: Electronic reporting of PROs is feasible in a fragile and comorbid population of patients during routine active cancer treatment. Despite clear implementation strategies the physician compliance remained low throughout the study proving the need for further implementation strategies.