Introduction: Recent health technology assessments (HTAs) of robot-assisted radical prostatectomy (RARP) in Ontario and Alberta, Canada, resulted in opposite recommendations, calling into question whether benefits of RARP offset the upfront investment. Therefore, the study objectives were to conduct a cost-utility analysis from a Canadian public payer perspective to determine the cost-effectiveness of RARP. Methods: Using a 10-year time horizon, a five-state Markov model was developed to compare RARP to open radical prostatectomy (ORP). Clinical parameters were derived from Canadian observational studies and a recently published systematic review. Costs, resource utilization, and utility values from recent Canadian sources were used to populate the model. Results were presented in terms of increment costs per quality-adjusted life years (QALYs) gained. A probabilistic analysis was conducted, and uncertainty was represented using cost-effectiveness acceptability curves (CEACs). One-way sensitivity analyses were also conducted. Future costs and QALYs were discounted at 1.5%. Results: Total cost of RARP and ORP were $47 033 and $45 332, respectively. Total estimated QALYs were 7.2047 and 7.1385 for RARP and ORP, respectively. The estimated incremental cost-utility ratio (ICUR) was $25 704 in the base-case analysis. At a willingness-to-pay threshold of $50 000 and $100 000 per QALY gained, the probability of RARP being cost-effective was 0.65 and 0.85, respectively. The model was most sensitive to the time horizon. Conclusions: The results of this analysis suggest that RARP is likely to be cost-effective in this Canadian patient population. The results are consistent with Alberta’s HTA recommendation and other economic evaluations, but challenges Ontario’s reimbursement decision.
Introduction: Placement of a ureteral stent at the time of renal transplantation can reduce complications when compared to non-stented anastomoses. Removal by flexible cystoscopy can be associated with discomfort, risk for infection, and high costs. New magnetic stents offer a means of bypassing cystoscopy by use of a magnetic retrieval device. Our objective was to compare clinical and cost-related outcomes of conventional and magnetic stents in patients undergoing deceased donor renal transplantation. Methods: Patients were randomized to receive either a conventional or a Black-Star® magnetic stent. Clinical, procedural, and cost outcomes were assessed, and the Ureteral Stent Symptom Questionnaire (USSQ) was administered with the stent in situ and after stent removal. All variables were compared between groups. Results: Forty-one patients were randomized to conventional (n=19) or Black-Star (n=22) stent. The total time for stent removal under cystoscopy was significantly longer compared to Black-Star removal (6.67±2.47 and 4.80±2.21 minutes, respectively; p=0.019). No differences were found in the USSQ domains between groups. Rates of urinary tract infections and surgical complications between groups were similar. Stent removal was well-tolerated in both groups. Black-Star stent use resulted in a cost savings of $304.02 Canadian dollars (CAD) per case. Conclusions: USSQ scores suggest that stent removal with the Black-Star magnetic stent is as equally well-tolerated as flexible cystoscopy by renal transplant patients. Black-Star stent removal was significantly faster than conventional stents. No differences in discomfort, infection rate, or complication rate were found. Use of the Black-Star stent resulted in an estimated annual savings of $27 360 CAD at our centre.
Tumor cells display on their surface several molecular chaperones that normally reside in the endoplasmic reticulum. Because this display is unique to cancer cells, these chaperones are attractive targets for drug development. Previous epitope-mapping of autoantibodies (AutoAbs) from prostate cancer patients identified the 78-kDa glucose-regulated protein (GRP78) as one such target. Although we previously showed that anti-GRP78 AutoAbs increase tissue factor (TF) procoagulant activity on the surface of tumor cells, the direct effect of TF activation on tumor growth was not examined. In this study, we explore the interplay between the AutoAbs against cell surface-associated GRP78, TF expression/activity, and prostate cancer progression. First, we show that tumor GRP78 expression correlates with disease stage and that anti-GRP78 AutoAb levels parallel prostate-specific antigen concentrations in patient-derived serum samples. Second, we demonstrate that these anti-GRP78 AutoAbs target cell-surface GRP78, activating the unfolded protein response and inducing tumor cell proliferation through a TF-dependent mechanism, a specific effect reversed by neutralization or immunodepletion of the AutoAb pool. Finally, these AutoAbs enhance tumor growth in mice bearing human prostate cancer xenografts, and heparin derivatives specifically abrogate this effect by blocking AutoAb binding to cell-surface GRP78 and decreasing TF expression/activity. Together, these results establish a molecular mechanism in which AutoAbs against cell-surface GRP78 drive TF-mediated tumor progression in an experimental model of prostate cancer. Heparin derivatives counteract this mechanism and, as such, represent potentially appealing compounds to be evaluated in well-designed translational clinical trials.
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