EffectiveNess of a multimodal preHAbilitation program in patieNts with bladder canCEr undergoing radical cystectomy: protocol of the ENHANCE multicentre randomised controlled trial.

INTRODUCTION: Radical cystectomy (RC) is the standard treatment for patients with non-metastatic muscle-invasive bladder cancer, as well as for patients with therapy refractory high-risk non-muscle invasive bladder cancer. However, 50-65% of patients undergoing RC experience perioperative complications. The risk, severity and impact of these complications is associated with a patient's preoperative cardiorespiratory fitness, nutritional and smoking status and presence of anxiety and depression. There is emerging evidence supporting multimodal prehabilitation as a strategy to reduce the risk of complications and improve functional recovery after major cancer surgery. However, for bladder cancer the evidence is still limited. The aim of this study is to investigate the superiority of a multimodal prehabilitation programme versus standard-of-care in terms of reducing perioperative complications in patients with bladder cancer undergoing RC. METHODS AND ANALYSIS: This multicentre, open label, prospective, randomised controlled trial, will include 154 patients with bladder cancer undergoing RC. Patients are recruited from eight hospitals in The Netherlands and will be randomly (1:1) allocated to the intervention group receiving a structured multimodal prehabilitation programme of approximately 3-6 weeks, or to the control group receiving standard-of-care. The primary outcome is the proportion of patients who develop one or more grade ≥2 complications (according to the Clavien-Dindo classification) within 90 days of surgery. Secondary outcomes include cardiorespiratory fitness, length of hospital stay, health-related quality of life, tumour tissue biomarkers of hypoxia, immune cell infiltration and cost-effectiveness. Data collection will take place at baseline, before surgery and 4 and 12 weeks after surgery. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Medical Ethics Committee NedMec (Amsterdam, The Netherlands) under reference number 22-595/NL78792.031.22. Results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05480735.

Dutch Economic Value of Radium-223 in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: The treatment of metastatic castration-resistant prostate cancer has changed with the introduction of radium-223, cabazitaxel, abiraterone and enzalutamide. To assess value for money, their cost effectiveness in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel from the Dutch societal perspective was investigated. METHODS: A cost-effectiveness analysis was conducted using efficacy, symptomatic skeletal-related event and safety data obtained from indirect treatment comparisons. Missing skeletal-related event data for cabazitaxel were conservatively assumed to be identical to radium-223. A Markov model combined these clinical inputs with Dutch-specific resource use and costs for metastatic castration-resistant prostate cancer treatment from a societal perspective. Total quality-adjusted life-years and costs in 2017 euros were calculated over a 5-year (lifetime) time horizon. RESULTS: Radium-223 resulted in €6092 and €4465 lower costs and 0.02 and 0.01 higher quality-adjusted life-years compared with abiraterone and cabazitaxel, respectively, demonstrating dominance of radium-223. Sensitivity analyses reveal a 64% (54%) chance of radium-223 being cost effective compared with abiraterone (cabazitaxel) at the informal €80,000 willingness-to-pay threshold. Compared with enzalutamide, radium-223 resulted in slightly lower quality-adjusted life-years (-0.06) and €7390 lower costs, revealing a 61% chance of radium-223 being cost effective compared with enzalutamide. The lower costs of radium-223 compared with abiraterone and enzalutamide are driven by lower drug costs and prevention of expensive skeletal-related events. Compared with cabazitaxel, the lower costs of radium-223 are driven by lower costs of the drug, administration and adverse events. CONCLUSION: Radium-223 may be a less costly treatment strategy offering similar gains in health benefits compared with abiraterone, cabazitaxel and enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel from the Dutch societal perspective.

Correction to: Dutch Economic Value of Radium-223 in Metastatic Castration-Resistant Prostate Cancer.

The article Dutch Economic Value of Radium-223 in Metastatic Castration-Resistant Prostate Cancer, written by Michel L. Peters, Claudine de Meijer, Dirk Wyndaele, Walter Noordzij, Annemarie M. Leliveld-Kors, Joan van den Bosch, Pieter H. van den Berg, Agni Baka, Jennifer G. Gaultney was originally published electronically on the publisher's internet portal (currently SpringerLink) on 2nd September, 2017 without open access.

89Zr-Bevacizumab PET: Potential Early Indicator of Everolimus Efficacy in Patients with Metastatic Renal Cell Carcinoma.

Currently, biomarkers that predict the efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans on mRCC patients with 89Zr-bevacizumab, a VEGF-A-binding antibody tracer. The aims were to determine a change in tumor tracer uptake after the start of everolimus and to explore whether 89Zr-bevacizumab PET can identify patients with early disease progression. Methods:89Zr-bevacizumab PET was done before and 2 and 6 wk after the start of everolimus, 10 mg/d, in mRCC patients. Routine CT scans were performed at baseline and every 3 mo thereafter. Tumor tracer uptake was quantified using SUVmax The endpoints were a change in tumor tracer uptake and treatment response on CT after 3 mo. Results: Thirteen patients participated. The median SUVmax of 94 tumor lesions was 7.3 (range, 1.6-59.5). Between patients, median tumor SUVmax varied up to 8-fold. After 2 wk, median SUVmax was 6.3 (1.7-62.3), corresponding to a mean decrease of 9.1% (P < 0.0001). Three patients discontinued everolimus early. At 6 wk, a mean decrease in SUVmax of 23.4% compared with baseline was found in 70 evaluable lesions of 10 patients, with a median SUVmax of 5.4 (1.1-49.4, P < 0.0001). All 10 patients who continued treatment had stable disease at 3 mo. Conclusion: Everolimus decreases 89Zr-bevacizumab tumor uptake. Further studies are warranted to evaluate the predictive value of 89Zr-bevacizumab PET for everolimus antitumor efficacy.