Cost-effectiveness analysis of 7 treatments in metastatic hormone-sensitive prostate cancer: a public-payer perspective.

BACKGROUND: Recently, several new treatment regimens have been approved for treating metastatic hormone-sensitive prostate cancer, building on androgen deprivation therapy alone. These include docetaxel androgen deprivation therapy, abiraterone acetate-prednisone androgen deprivation therapy, apalutamide androgen deprivation therapy, enzalutamide androgen deprivation therapy, darolutamide-docetaxel androgen deprivation therapy, and abiraterone-prednisone androgen deprivation therapy with docetaxel. There are no validated predictive biomarkers for choosing a specific regimen. The goal of this study was to conduct a health economic outcome evaluation to determine the optimal treatment from the US public sector (Veterans Affairs). METHODS: We developed a partitioned survival model in which metastatic hormone-sensitive prostate cancer patients transitioned between 3 health states (progression free, progressive disease to castrate resistance state, and death) at monthly intervals based on Weibull survival model estimated from published Kaplan-Meier curves using a Bayesian network meta-analysis of 7 clinical trials (7208 patients). The effectiveness outcome in our model was quality-adjusted life-years (QALYs). Cost input parameters included initial and subsequent treatment costs and costs for terminal care and for managing grade 3 or higher drug-related adverse events and were obtained from the Federal Supply Schedule and published literature. RESULTS: Average 10-year costs ranged from $34 349 (androgen deprivation therapy) to $658 928 (darolutamide-docetaxel androgen deprivation therapy) and mean QALYs ranged from 3.25 (androgen deprivation therapy) to 4.57 (enzalutamide androgen deprivation therapy). Treatment strategies docetaxel androgen deprivation therapy, enzalutamide androgen deprivation therapy docetaxel, apalutamide androgen deprivation therapy, and darolutamide-docetaxel androgen deprivation therapy were eliminated because of dominance (ie, they were more costly and less effective than other strategies). Of the remaining strategies, abiraterone acetate-prednisone androgen deprivation therapy was the most cost-effective strategy at a willingness-to-pay threshold of $100 000/QALY (incremental cost-effectiveness ratios = $21 247/QALY). CONCLUSIONS: Our simulation model found abiraterone acetate-prednisone androgen deprivation therapy to be an optimal first-line treatment for metastatic hormone-sensitive prostate cancer from a public (Veterans Affairs) payer perspective.

Progression of symptomatic bilateral rotator cuff disease.

Background: Prior studies have demonstrated that conservatively treated rotator cuff tears and rotator cuff tendinopathy may continue to progress. It is unclear whether that rate of progression differs between sides in patients with bilateral disease. This study evaluated the likelihood of progression of rotator cuff disease as confirmed via magnetic resonance imaging (MRI) in individuals with symptomatic bilateral pathology, treated conservatively for a minimum of 1 year. Methods: We identified patients with bilateral rotator cuff disease confirmed via MRI within the Veteran's Health Administration electronic database. A retrospective chart review via the Veteran's Affairs electronic medical record was performed. Progression was determined using 2 separate MRIs with a minimum of 1 year apart. We defined progression as (1) a progression from tendinopathy to tearing, (2) an increase from partial-thickness to full-thickness tearing, or (3) an increase in tear retraction or tear width of at least 5 mm. Results: Four hundred eighty MRI studies from 120 Veteran's Affair patients with bilateral, conservatively treated rotator cuff disease were evaluated. Overall, 42% (100/240) of rotator cuff disease had progressed. No significant difference was found between progression of right vs. left rotator cuff pathology, with right shoulder pathology progressing at a rate of 39% (47/120), while left shoulder disease progressed at a rate of 44% (53/120). The likelihood of disease progression was associated with less initial tendon retraction (P value = .016) and older age (P value = .025). Conclusions: Rotator cuff tears are no more likely to progress on the right, as compared to the left side. Older age and less initial tendon retraction were found to be predictors of disease progression. These suggest that higher activity level may not associate with greater progression of rotator cuff disease. Future prospective studies evaluating progression rates between dominant vs. nondominant shoulders are warranted.

Recovery Curve for Patients With Pilon Fractures Using Patient-Reported Outcome Measurement Information System.

BACKGROUND: The time frame in which patients can expect functional improvement after open reduction internal fixation (ORIF) of pilon fractures is unclear. The purpose of this study was to determine the trajectory and rate at which patients' physical function improves up to 2 years postinjury. METHODS: The patients studied sustained a unilateral, isolated pilon fractures (AO/OTA 43B/C) and followed at a level 1 trauma center over a 5-year period (2015-2020). Patient-Reported Outcomes Measurement Information Systems (PROMIS) Physical Function (PF) scores from these patients at defined follow-up times of immediately, 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery defined the cohorts and were retrospectively studied. RESULTS: There were 160 patients with PROMIS scores immediately postoperatively, 143 patients at 6 weeks, 146 patients at 12 weeks, 97 at 24 weeks, 84 at 1 year, and 45 at 2 years postoperatively. The average PROMIS PF score was 28 immediately postoperatively, 30 at 6 weeks, 36 at 3 months, 40 at 6 months, 41 at 1 year, and 39 at 2 years. There was a significant difference between PROMIS PF scores between 6 weeks and 3 months (P < .001), and between 3 and 6 months (P < .001). Otherwise, no significant differences were detected between consecutive time points. CONCLUSION: Patients with isolated pilon fractures demonstrate the majority of their improvement in terms of physical function between 6 weeks and 6 months postoperatively. No significant difference was detected in PF scores after 6 months postoperatively up to 2 years. Furthermore, the mean PROMIS PF score of patients 2 years after recovery was approximately 1 SD below the population average. This information is helpful in counseling patients and setting expectations for recovery after pilon fractures. LEVEL OF EVIDENCE: Level III, prognostic.

Cost-Effectiveness Analysis of Six Immunotherapy-Based Regimens and Sunitinib in Metastatic Renal Cell Carcinoma: A Public Payer Perspective.

PURPOSE: Several new treatment combinations have been approved in metastatic renal cell carcinoma (mRCC). To determine the optimal therapy on the basis of cost and health outcomes, we performed a cost-effectiveness analysis of approved immunotherapy-tyrosine kinase inhibitor/immunotherapy drug combinations and sunitinib using public payer acquisition costs in the United States. METHODS: We constructed a decision model with a 10-year time horizon. The seven treatment drug strategies included atezolizumab + bevacizumab, avelumab + axitinib, pembrolizumab + axitinib, nivolumab + ipilimumab (NI), nivolumab + cabozantinib, lenvatinib + pembrolizumab, and sunitinib. The effectiveness outcome in our model was quality-adjusted life-years (QALYs) with utility values on the basis of the published literature. Costs included drug acquisition costs and costs for management of grade 3-4 drug-related adverse events. We used a partitioned survival model in which patients with mRCC transitioned between three health states (progression-free, progressive disease, and death) at monthly intervals on the basis of parametric survival function estimated from published survival curves. To determine cost-effectiveness, we constructed incremental cost-effectiveness ratios (ICERs) by dividing the difference in cost by the difference in effectiveness between nondominated treatments. RESULTS: The least expensive treatment was sunitinib ($357,948 US dollars [USD]-$656,100 USD), whereas the most expensive was either lenvatinib + pembrolizumab or pembrolizumab + axitinib ($959,302 USD-$1,403,671 USD). NI yielded the most QALYs (3.6), whereas avelumab + axitinib yielded the least (2.5). NI had an incremental ICER of $297,465 USD-$348,516 USD compared with sunitinib. In sensitivity analyses, this ICER fell below $150,000 USD/QALY if the initial 4-month cost of NI decreased by 22%-38%. CONCLUSION: NI was the most effective combination for mRCC, but at a willingness-to-pay threshold of $150,000 USD/QALY, sunitinib was the most cost-effective approach.

High ligation in adolescents: Is it enough?

BACKGROUND: In adults, the gold standard for surgical repair of an inguinal hernia is a mesh repair, whereas, in children, the standard is high ligation of the hernia sac. However, adolescents represent a "gray zone" between children and adults, and there is no consensus on the most appropriate operation for inguinal hernias in these patients. We aimed to describe the outcomes in adolescents undergoing high ligation for inguinal hernia repair and determine what factors may portend an increased risk of recurrence in this population. METHODS: A retrospective cohort study was performed of all children that underwent open high ligation for an inguinal hernia at our tertiary children's hospital from January 2000 to January 2018, who were 12 to 18 years old at the time of surgery. We compared the patient demographic data, medical history, and repair characteristics for the cohort of hernias that developed a recurrence to the cohort that did not. RESULTS: During our study period, 256 adolescent patients underwent repair with 11 of those patients having both sides repaired for a total of 267 hernias repaired. The median age at surgery was 14.7 years, and 83.9% of the hernias were in male patients. There was a 6.0% recurrence rate, and all patients that developed recurrence underwent a reoperation. The median time from surgery to reoperation for recurrence was 3.1 years. Patients with recurrence were more likely to have cardiac (25.0% vs. 5.8%, p = 0.02) and gastrointestinal comorbidities (25% vs. 7.1%, p = 0.01). There were no other significant differences between the two cohorts. CONCLUSION: High ligation of the hernia sac in adolescents is effective and has an acceptable risk of recurrence while avoiding any additional morbidity that may come from the use of mesh. Patients with cardiac and gastrointestinal comorbidities should be counseled on the higher risk of recurrence.