Risk Prediction And Multicenter Health Economics Evaluation Of Re-intervention After Focused Ultrasound Ablation Surgery For Uterine Fibroids

In recent years,great breakthroughs have been made in the new technology of uterine fibroid treatments,especially the rapid development of minimally invasive and noninvasive treatments such as laparoscope,hysteroscopy,uterine artery embolisation?UAE?and high intensity focused ultrasound?HIFU?,which have become the trend of medical development,and have been sought and chosen as the primary treatment by more and more female patients.However,the previous experience of UAE and laparoscope has confirmed that there were chances of recurrence and re-intervention for fibroids after uterus-preserving treatment.HIFU,or focused ultrasound ablation surgery?FUAS?,as a rapidly developing noninvasive treatment technique in recent years,has the similar clinical problem.Therefore,it is urgent to obtain evidence of re-intervention after focused ultrasound ablation for uterine fibroids,find relevant risk factors,predict the risk of re-intervention,guide and standardize clinical practice.Moreover,it is in demand to evaluate the health economic impact of re-intervention,so as to provide evidence-based guidance for health economic decision-making for treatment for patients with uterine fibroids.Objective?1?To explore the long-term result of re-intervention of HIFU for uterine fibroids;?2?To analyze factors associated with the re-intervention after HIFU for uterine fibroids and find out the relevant characteristics,to construct a risk prediction model and predict the re-intervention risk;?3?To evaluate the re-intervention of uterine fibroids after HIFU by multicenter health economic analysis.Materials and methods?1?According to the inclusion and exclusion criteria,eligible patients in two clinical centers were enrolled in the study,and the baseline clinical features and fibroids characteristics of these patients were recorded.The characteristics and ablation results of fibroids were evaluated by contrast-enhanced magnetic resonance imaging?MRI?before and after the procedure,the long-term symptoms and quality of life of uterine fibroids patients were evaluated by the UFS-QoL scale,and the results of re-intervention,including the time of re-intervention,were also followed up.The way and reason of re-intervention,and the Kaplan-Meier survival rate were analyzed.?2?The patients with uterine fibroids included in the above were enrolled in the study.The Kaplan-Meier survival rate by the clinical characteristics and the characteristics of fibroids was analyzed.Setting the re-intervention events as dependent variables,selecting age,BMI,gravidity,parity,smoking history,drinking history,fibroids family history,previous abdominal operation history,symptom score,fibroids number,fibroids size,fibroids position,fibroids type,T2 signal and enhancement type as covariables,CoX univariate and multivariate analysis were performed to construct multivariate CoX proportional risk regression model to explore the influence of covariables on re-intervention.?3?Multicenter study of cost,and measurement of effectiveness and utility for patients who underwent focused ultrasound surgery,myomectomy or hysterectomy were performed.Baseline analysis,cost-effectiveness and cost-utility analysis were performed to evaluate the cost-effectiveness and cost-utility of HIFU in patients with uterine fibroids under re-intervention,and the sensitivity analysis was made to compare with that of traditional surgery.Results?1?A total of 412 eligible uterine fibroid patients who received HIFU were enrolled in the study.Long-term follow-up of symptom score was 4.8�7.3?95%Confidence Interval[CI],4.0-5.6?and quality of life score was 92.3�8.0?95%CI,91.4-93.2?after focused ultrasound ablation surgery of uterine fibroids,both score showed continuous significant improvement?P=0.000?compared with that of before.The symptom relived rate at 72 months follow-up was 91.6%.The cumulative estimated re-intervention rates were 3.3%,11.3%and 14.6%at 2,5 and 8 years after HIFU.?2?Results of Kaplan-Meier survival stratification of re-intervention after HIFU showed that there were significant differences in age,BMI,number of pregnancy,number of birth,symptom score,T2signal of fibroids,enhancement type,residual small submucous fibroids and Non-perfused volume ratio?NPVR??P<0.05?.Based on the univariate and multivariate Cox analysis,four covariables were identified as the risk factors for re-intervention after focused ultrasound surgery for uterine fibroids,which were as follows:residual small submucous fibroids[HR,5.243,95CI%,2.538-10.831,P=0.000],age[HR,4.791,95CI%,2.789-8.231,P=0.000],enhancement type[HR,2.440,95%CI,1.311-4.540,P=0.005],and T2 signal[HR,1.632,95CI%,1.062-2.506,P=0.025].After statistical verification,the multivariate CoX proportional risk model is:h?t,X?=h₀?t?exp?1.657X₁+1.567X₂+0.892X₃+0.490X₄?.The covariate X₁ indicates residual small submucous fibroids,X₂indicates age and X₃ enhancement type?significant enhancement and mild enhancement?,and X₄ indicates T2 signal?divided into three categories:isointense and hypointense,slightly homogenous hyperintense,non-homogenous hyperintense?.?3?Multicenter health economics evaluation included 2411patients for measurement of cost,effectiveness and utility,showing that the total cost of HIFU was 11910.6?95%CI,11793.7-12027.5?CNY,which was significantly lower than that of hysterectomy 15388.8?95%CI,15008.9-15768.7?CNY and myomectomy 13082.5?95%CI,12714.4-13450.7?CNY.The short-term multicenter health economic evaluation of focused ultrasound surgery for uterine fibroid showed that the cost-effectiveness ratio of symptoms improvement of focused ultrasound surgery and myomectomy was 979.0 CNY/UFS and 1347.8CNY/UFS respectively;the cost-effectiveness ratio of quality of life improvement of focused ultrasound surgery,myomectomy and hysterectomy was 1317.6 CNY/QOL,1754.2 CNY/QOL and 1913.9CNY/QOL for patients in the multicenter cohort study.Under the long-term re-intervention,according to the baseline analysis of multicenter health economic evaluation of focused ultrasound surgery for uterine fibroid,the cost utility ratio of focused ultrasound surgery,myomectomy and hysterectomy was 18206.0 CNY/QALY,21974.2CNY/QALY and 21468.6 CNY/QALY respectively,and the incremental cost utility ratio of myomectomy and hysterectomy was-1869.5CNY/QALY and-14978.6 CNY/QALY respectively.Sensitivity analyses revealed that the results of long-term health economic evaluation based on the model were sensitive to multiple parameters.One-way sensitivity analysis revealed that the re-intervention rate after focused ultrasound ablation,the re-intervention rate after myomectomy,the utility improved after focused ultrasound surgery,and the utility improved after myomectomy and hysterectomy were factors associated with baseline analysis result.According to the results of probabilistic sensitivity analysis?PSA?,compared with myomectomy,incremental cost utility ratio?ICUR?analysis showed that when willness to pay?WTP?was 1 or 3times of GDP per capita,FUAS was not significantly changed as the preferred treatment strategy.Compared with hysterectomy,ICUR analysis showed that when WTP was between 1 and 3 times of GDP per capita,the probability of treatment strategy preferred by focused ultrasound was 62.6%-69.5%.Conclusions?1?The symptoms and quality of life of uterine fibroids treated by HIFU have been sustainably improved,and as a noninvasive uterus-preserving treatment,the level of long-term re-intervention for HIFU is acceptable.?2?The CoX proportional risk regression model indentified the residual small submucous fibroids,age,enhancement type and T2signal as covariables,which could predict the risk of re-intervention for focused ultrasound surgery for uterine fibroids,and provide evidence for clinical treatment decision-making.?3?Multicenter health economics evaluation indicated that the total cost of focused ultrasound ablation surgery was lower than that of myomectomy and hysterectomy.According to the short-term health economics evaluation analysis,the cost-effectiveness of focused ultrasound surgery is better than that of myomectomy and hysterectomy;Under the long-term re-intervention,the baseline analysis showed that focused ultrasound surgery is cost-effective among the three kinds of procedures for women with uterine fibroid within their childbearing period,and it is the preferred treatment strategy.But probilisitic sensitivity analysis showed that there was no significant change between focused ultrasound and myomectomy that focused ultrasound is the preferred treatment strategy.Compared with hysterectomy,the probability of focused ultrasound as the preferred treatment strategy was62.6%-69.5%.