| Objective:Robot-assisted thoracoscopic surgery(RATS)has become one of the choices for radical surgery in non-small cell lung cancer(NSCLC).However,the debate about RATS in radical thoracotomy of NSCLC,especially the comparison between RATS and video-assisted thoracoscopic surgery(VATS),is still the focus of minimally invasive surgery in thoracic surgery.Moreover,the long-term follow-up results of RATS are not sufficient,especially the high cost,which make a large number of patients and medical workers shrink from it.Based on the clinical data of our large sample size,this study will comprehensively explore the differences between RATS,VATS and Open thoracotomy(OT)in terms of perioperative effect,postoperative complications,pathological outcomes and mid-term survival,so as to explore the best indications for RATS.Methods and Materials:This study consists of five chapters.Chapters 1 and 2 discuss the clinical effects of RATS versus VATS and OT,respectively,including short-term and medium-term follow-up results.Due to the gradual decrease of planned thoracotomy in our center,we compared RATS with VATS and OT respectively instead of simultaneously analyzing the three procedures.We continuously selected the patients who were treated and operated in the Department of Thoracic Surgery of our hospital from January 2016 to December 2018.Patients meeting the inclusion/exclusion criteria were selected.Due to the retrospective characteristics of this study,the propensity score matching method was introduced to minimize the bias of confounding factors on the results.Follow-up data were obtained mainly through telephone contact with patients or their family members,and could be supplemented through the hospital’s outpatient electronic medical record system.The follow-up deadline was January 31,2021.On the basis of the previous two chapters,the third chapter further discusses the differences between conversion to OT and Minimally invasive surgery(MIS)/planned OT in terms of demographic indicators,perioperative effects,postoperative complications and long-term prognosis.Propensity score matching method was introduced to remove the interference of confounding factors.In addition,we compared the differences in the causes of RATS and VATS converting to OT,and further explore the risk factors for conversion from minimally invasive surgery to thoracotomy.Chapter four is the cost-effectiveness analysis comparing RATS to OT/VATS.Markov model was built by Tree AGE Pro 2011 software to simulate the disease progress of stage I-III NSCLC from surgery to 5 years postoperatively.By introducing cost variables and combining with clinical efficacy,this model discusses the cost-effectiveness of RATS compared with OT and VATS.The willingness-to-pay(WTP)threshold was regard as three times of 2019 GDP per capital of China($30,000/quality-adjusted life year(QALY)).As the perioperative data used by OT group in this chapter are from Chapter 1,RATS and VATS in this chapter do not include the cases with thoracotomy,and the corresponding model data comparing RATS to VATS needs to be re-analyzed and obtained.Chapter 5 focuses on subgroup analyses of the cost-effectiveness between RATS and VATS.Firstly,the patients were divided into lobectomy group and extensive lobectomy group according to the resection,and then the lobectomy group was further subgroup analyzed based on demographic indicators.We aimed to explore under what circumstances RATS has a higher probability of cost-effectiveness.Based on this quantitative analysis,we explored the best indication of RATS in the treatment of NSCLC compared with VATS.The above propensity score matching and the drawing of long-term survival curves were completed by R software,and the remaining statistical analysis was performed by SPSS software.Results:Chapter 1:The final number of cases included in OT group and RATS group was 265 and 437,respectively.After propensity score matching,a cohort containing 128 pairs of cases was finally generated.In terms of perioperative results,the RATS group was significantly shorter than the OT group in terms of operative time(135.7 min vs.193.8 min,P<0.001)and postoperative hospital stay(8.9 d vs.11.5 d,P<0.001).Compared with RATS,OT surgery had more intraoperative blood loss(274.3 ml vs.82.5 ml,P<0.001).In terms of total hospitalization costs,RATS was significantly higher than OT($18754.6 vs.$15456.3,P<0.001).Survival analysis showed that there was no significant difference in PFS(Hazard ratio,HR)=1.09,95%confidence interval(CI)0.71-1.68,P=0.69)and OS(HR=0.68,95%CI 0.36-1.29,P=0.24)between the two groups.Chapter 2:A total of 1174 cases were included,including 447(38.1%)in the RATS group and 727(61.9%)in the VATS group.A total of 396 pairs of cases were matched by propensity adjustment,and the baseline factors of the two pairs were even after matching.RATS significantly outperformed VATS on several perioperative measures,including operative time(124.2 min vs.166.1 min,P<0.001),intraoperative blood loss(80.2 ml vs.130.4 ml,P<0.001),and postoperative hospital stay(8.5d vs.10.0d,P<0.001).After adjustment,the intraoperative conversion rate of RATS was also significantly lower than that of VATS(2.3%vs.16.2%,P<0.001).In addition,VATS significantly outperformed RATS in terms of hospitalization costs($17,955.9 vs.$14,154.4,P<0.001).After matching baseline characteristics,RATS was still significantly superior to VATS in terms of major complications(3.5%vs.7.6%,P=0.013),while the difference on other outcomes was not statistically significant.In terms of lymph node dissection,RATS were significantly superior to VATS in lymph node dissection(11.8 vs.8.8,P<0.001),nodal station(5.2 vs.4.1,P<0.001),N1nodal station(2.5 vs.1.6,P<0.001)and N2 nodal station(2.7 vs.2.4,P=0.016).Survival analysis indicated that there was no statistically difference in PFS(HR=1.16,95%CI0.90-1.48,P=0.24)and OS(HR=1.33,95%CI 0.93-1.90,P=0.12)between the two groups before propensity adjustment.When the propensity method balanced baseline factors,there was still no statistical difference in PFS and OS between RATS and VATS.Chapter 3:A total of 1177 surgeries were eventually included,including 912 in the MIS group(404 RATS and 508 VATS),180 in the conversion group,and 85 in the OT group.The overall conversion rate was 16.5%.The conversion rate of RATS was significantly lower than that of VATS(2.4%vs.25.1%).The main causes of VATS transit were lymph nodes with difficult situations(38.2%),large thoracic vessel involvement(28.8%),and dense thoracic adhesion(14.7%).Multivariate logistic regression analysis suggested that the following demographic characteristics may be independent predictors of unplanned conversion to OT:RATS(vs.VATS,OR=0.037,95%CI 0.016-0.087,P<0.001),tumor diameter<5cm(OR=0.274,95%CI 0.152-0.493,P<0.001),preoperative asymptomatic(OR=0.311,95%CI0.178-0.545,P<0.001),BMI<25kg/m~2(OR=0.537,95%CI 0.343-0.842,P=0.007)and lobectomy(vs.Pneumonectomy,OR=0.079,95%CI 0.017-0.370,P=0.001).After propensity score matching,the outcomes for post-operative complications and long-term survival of conversion group were similar to those for MIS and OT.Chapter 4:Data on perioperative and state transition probabilities of the model were obtained through propensity matching cohort analysis and individual case data meta-analysis.The cost-effectiveness analysis showed that OT patients had a total medical cost of$21246.31with a gain of 3.06 QALYs during the five-year period.In comparison,the additional medical cost of RATS is$3104.82,and the additional gain is 0.28 QALYs.Compared with OT,the ICER of RATS is$10967.41/QALY.In this model,patients who underwent VATS paid$18891.88 in medical expenses over a 5-year period and obtained 3.58 QALYs.However,if the RATS spend$4006.86 more,their QALYs increase by 0.05 and ICER is$80.324.98/QALY.Probability sensitivity analysis indicated that when WTP threshold was$30,000/QALY,compared with OT and VATS,RATS had a probability of 0.64 and 0.21 for cost-effectiveness,respectively.Chapter 5:In the lobectomy group,patients receiving VATS had a cost of$19,166.00 and a gain of 3.55 QALYs.In comparison,the additional medical cost of RATS is$3744.62 and0.07 QALYs are gained.At this point,the ICER of RATS compared with VATS was$55937.49/QALY.In the extended lobectomy group,RATS at an additional cost of$3398.36increased QALYs by 0.22 and achieved ICER of$15333.96/QALY.Probability sensitivity analysis showed that in the above two groups,the probability of RATS achieving cost-effectiveness is 0.58 and 0.36,respectively.Further subgroup analysis revealed that the four subgroups with RATS obtained the ICERs that were the first four closest to the WTP threshold($30,000/QALY)compared with VATS,including pathological stage≥IIb($31785.3/QALY),tumor diameter≥3cm($37928.1/QALY),non-adenocarcinoma($38048.3/QALY),and BMI≥25kg/m~2($38848.0/QALY).The 4 subgroups with the highest probability of cost-effectiveness in RATS were pathological stage≥IIB(0.463),non-adenocarcinoma(0.449),tumor diameter≥3cm(0.462),and BMI≥25kg/m2(0.430).Conclusions:1.RATS has a significant advantage over OT in the perioperative effect;The effects of the two on postoperative complications were comparable.More importantly,RATS is comparable to OT in terms of survival.2.It was found in this study that RATS had a slight advantage over VATS in terms of perioperative outcomes and postoperative complications.Compared with VATS,RATS performs better in lymph node dissection,which means it is easier to meet oncology requirements.The survival results of RATS are similar to those of VATS.The only drawback of RATS is the high cost of hospitalization.3.Compared with MIS and OT,intraoperative conversion to thoracotomy did not increase the incidence of postoperative complications and had no significant effect on the prognosis.In addition,we identified seven independent demographic predictors of conversion to thoracotomy.For patients with preoperative indications of a high risk of conversion to thoracotomy,RATS is more recommended than VATS when conditions are available.4.From the perspective of medical payment in China,RATS has obvious cost-effectiveness compared with OT at the WTP threshold of$30,000/QALY.In contrast,RATS is not cost-effective compared to VATS in the absence of intraoperative conversion to thoracotomy.5.Furthermore,RATS is more cost-effective than VATS in extended lobectomy for NSCLC.Subgroup analysis suggested that RATS were more likely to achieve cost-effectiveness in conventional lobotomy for NSCLC in patients with IIb-III stage disease,non-adenocarcinoma,tumor diameter≥3cm,and BMI≥25kg/m~2.Therefore,the above conditions may be recognized as the best indications for RATS. |
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