| Cervical cancer is the most common malignant tumor of the female reproductive tract.It is the fourth most common malignant tumor in women,and the fourth leading cause of cancer death in women worldwide.The International Federation of Gynecology and Obstetrics(FIGO)launched a new cervical cancer staging in 2018 and corrected it in 2019.The stage IB of the original FIGO 2009 were divided into three stages:FIGO 2018 stage ⅠB1 with tumor diameter<2cm,stage ⅠB2 with tumor diameter>2cm and tumor diameter<4cm,stage ⅠB3 with tumor diameter>4cm.In addition,the original FIGO 2009 stage ⅠAl(LVSI+)-ⅡA2 was all classified into the new ⅢC stage as long as there was lymph node metastasis.Lymph node metastasis is an important factor affecting the prognosis of cervical cancer.FIGO 2018 new stageⅠA1(LVSI+)-ⅡA2 cervical cancer after excluding lymph node metastasis factor and stage IB according to the diameter of the tumor for more detailed staging,the treatment strategies recommended by major guidelines still adopted experimental evidence under the old stage.At present,there is no multicenter large sample clinical evidence on the most suitable treatment strategy for cervical cancer in FIGO 2018 new stage ⅠAl(LVSI+)-ⅡA2.Therefore,through the clinical diagnosis and treatment for cervical cancer in China(Four C)database,this study retrospectively analyzed the treatment strategies for FIGO 2018 stage ⅠA1(LVSI+)-ⅡA2 cervical cancer from the oncological outcomes of different treatment methods,surgical approaches and surgical resection scope.Part Ⅰ Investigation on the treatment of FIGO 2018 stage ⅠA1(LVSI+)-ⅡA2 cervical cancerObjective:To retrospectively analyze the different treatment methods,surgical approaches and surgical resection scope of stage ⅠA1(LVSI+)-ⅡA2 cervical cancer through Four C database,and the trend in the past 15 years.Methods:Based on the large database of 63926 cervical cancer cases collected from 47 tertiary hospitals in China from 2004 to 2018,the clinical staging of all cases was revised according to the principle of FIGO 2018 staging(based on the updated version in 2019),and the FIGO 2018 stage ⅠA1(LVSI+)-ⅡA2 was selected.The proportions of total and different stages,the proportions of surgical treatment and radio-chemotherapy,the proportions of laparotomy and laparoscopy,the proportions of type QM-B and QM-C,and the proportions changing with years were analyzed.Results:(1)A total of 7993 cases of FIGO 2018 ⅠA1(LVSI+)-ⅡA2 cervical cancer were selected according to the entry and exclusion criteria,including 6741 cases in the direct surgery group(open surgery:4282 cases,laparoscopic surgery:2459 cases)and 833 cases in the neoadjuvant chemotherapy followed by surgery group(NACT group)(open surgery:542 cases,laparoscopic surgery:291 cases)and radical chemoradiotherapy(n=419).(2)Stage ⅠA1(LVSI+)-ⅡA2 cervical cancer has the highest proportion of stageⅠB1 and stage IB2,and the proportion of cervical cancer from 2013 to 2016 is the largest.(3)The main treatment methods were direct surgery.The proportion of surgery and radical chemoradiotherapy after ⅠB3 and ⅡA2 NACT was about 39.66%,but direct surgery was still the main method.(4)Laparotomy is the main surgical approach,and laparoscopic surgery is also an important surgical approach.Before 2016,laparotomy was the main method,while laparoscopic surgery was the main method from 2016 to 2018.(5)The surgical scope was mainly type QM-B and QM-C2,but the laparoscopic surgery was mainly type QM-C2.Before 2013,type QM-B surgery was the main type,while type QM-C2 surgery gradually increased.From 2013 to 2015,type QM-B and QM-C2 surgery accounted for the similar proportion,and type QM-C2 surgery was the main type in 2016 and later.Stage ⅠA1(LVSI+)-ⅠA2 is also dominated by QM-C2 surgery in 2016 and later.Conclusions:FIGO 2018 ⅠA1(LVSI+)-ⅡA2 stage cervical cancer was mainly treated by direct surgery.Laparotomy was the main surgical approach,laparoscopic surgery also accounted for an important proportion,but with the passage of time,laparoscopic surgery was the main;Hysterectomy type QM-B accounted for an important proportion,but over time,hysterectomy type QM-C2 dominated.Part Ⅱ Comparison of oncological outcomes between open surgery and radical chemoradiotherapy for FIGO 2018 stage ⅠAl(LVSI+)-ⅡA2 cervical cancerObjective:To retrospectively analyze the differences in oncological outcomes of abdominal radical hysterectomy(ARH group),neoadjuvant chemotherapy followed by surgery(NACT group)and radio-chemotherapy(R-CT group),and explore the most appropriate treatment for FIGO 2018 stage ⅠA1(LVSI+)-ⅡA2 cervical cancer.Methods:The data screening process was the same as the first part,a total of 5243 cases were included,including ARH group(n=4282),NACT group(n=542)and R-CT group(n=419).The overall and different stage oncological outcomes of the three groups were compared,and the propensity score matching(PSM)was used to reduce the possible selection bias and confounding factors.Results:(1)Overall and stage ⅠB3,ⅡA1 and ⅠA2 oncological outcomes in the ARH and R-CT groups:the 5-year OS and DFS in the ARH group were better than those in the R-CT group(OS 95.2%vs 77.6%,P<0.001;DFS 91.3%vs 72.7%,P<0.001).Cox multivariate analysis suggested that R-CT was an independent risk factor for 5-year OS and DFS compared with ARH(OS HR=3.997;95%CI,2.857 to 5.593;P<0.001;DFS HR=3.067;95%CI,2.328 to 4.040;P<0.001).After PSM matching,the 5-year OS and DFS of the ARH group were better than those in the R-CT group(OS 92.6%vs.77.7%,P<0.001;DFS 89.2%vs 74.8%,P<0.001).Cox multivariate analysis suggested that R-CT was an independent risk factor for 5-year OS and DFS compared with ARH(OS HR=3.490;95%CI,2.402 to 5.072;P<0.001;DFS HR=2.781;95%CI,2.033 to 3.804;P<0.001).The results before and after matching of stage ⅠB3,ⅡA1 and ⅡA2 suggested that the oncological outcomes of ARH group was better than that of R-CT group.(2)Overall and stage ⅠB3,ⅡA1,and ⅡA2 oncological outcomes in the NACT and R-CT groups:the 5-year OS and DFS in the NACT group were better than those in the R-CT group before overall matching(OS 93.5%vs.77.6%,P<0.001;DFS 88.1%vs 72.7%,P<0.001).Cox multivariate analysis suggested that R-CT was an independent risk factor for 5-year OS and DFS compared with NACT followed by surgery(OS HR=3.338;95%CI,2.048 to 5.442;P<0.001;DFS HR=2.546;95%CI,1.728 to 3.751;P<0.001).After PSM matching,the 5-year OS and DFS of the NACT group were better than those in the R-CT group(OS 92.3%vs.78.0%,P<0.001;DFS 85.9%vs 72.8%,P<0.001).Cox multivariate analysis suggested that R-CT was an independent risk factor for 5-year OS and DFS compared with open surgery after NACT(OS HR=3.143;95%CI,1.789 to 5.521;P<0.001;DFS HR=2.311;95%CI,1.491 to 3.582;P<0.001).The results before and after matching of stage ⅠB3,ⅡA1 and IIA2 suggested that the oncological outcomes of NACT group was better than that of R-CT group.(3)Overall and stage ⅠB2,ⅠB3,ⅡA1 and ⅡA2 oncological outcomes in the ARH and NACT groups:the 5-year OS and DFS in the ARH group were better than those in the NACT group(OS 95.2%vs 93.5%,P=0.020;DFS 91.3%vs 88.1%,P=0.003).However,Cox multivariate analysis suggested that NACT was not an independent risk factor for 5-year OS and DFS compared with ARH(OS HR=1.243;95%Cl,0.817 to 1.891;P=0.309;DFS HR=1.348;95%CI,0.986 to 1.843;P=0.061).There was no significant difference in oncological outcomes between the two groups after PSM matching(OS 93.1%vs 93.6%,P=0.993;DFS 90.7%vs 89.5%,P=0.443).Cox multivariate analysis suggested that NACT was not an independent risk factor for OS and DFS at 5 years compared with ARH(OS HR=1.206;95%CI,0.790 to 1.841;P=0.385;DFS HR=1.324;95%CI,0.966 to 1.815;P=0.081).Results before and after matching of stage ⅠB2,ⅠB3 and ⅡA1 indicated no statistically significant difference in oncological outcomes between the two groups,while results before and after matching of stage ⅡA2 suggested that the oncological outcomes of NACT group were worse than those of ARH group.Conclusions:In FIGO 2018 ⅠA1(LVSI+)-ⅡA2 stage cervical cancer patients,the oncological outcomes of ARH group and NACT group are similar,and both of them are better than those of R-CT group.ARH is recommended and NACT should be carefully chosen.ARH is recommended for patients with stage ⅡA2 whose oncological outcomes is better than that after NACT.Part Ⅲ Comparison of oncological outcomes between abdominal and laparoscopic surgery for FIGO 2018 stage ⅠA1(LVSI+)-ⅡA2 cervical cancerObjective:To retrospectively analyze the optimal surgical approach of FIGO 2018 stage ⅠA1(LVSI+)-ⅡA2 cervical cancer by comparing the oncological outcomes of abdominal radical hysterectomy(ARH group)and laparoscopic radical hysterectomy(LRH group).Methods:The screening data flow was the same as the first part,including 6741 cases,including 4282 cases in ARH group and 2459 cases in LRH group.The overall and different stage oncological outcomes of the two groups were compared,and propensity score matching(PSM)was used to reduce possible selection bias and confounding factors.Results:(1)Overall oncological outcomes:before matching,K-M univariate analysis showed that 5-year DFS in LRH group was significantly worse than that in ARH group(88.7%vs 91.3%,P=0.004),and there was no significant difference in 5-year OS between LRH group and ARH group(94.0%vs 95.2%,P=0.911).Cox multivariate analysis suggested that compared with ARH group,LRH was an independent risk factor for 5-year DFS(HR=1.425;95%CI,1.143 to 1.777;P=0.002),but was not an independent risk factor for 5-year OS(HR=1.126;95%CI,0.805 to 1.754;P=0.489).After PSM matching,K-M univariate analysis showed that 5-year DFS in LRH group was still significantly worse than that in ARH group(88.6%vs 91.2%,P=0.023),and there was no significant difference in 5-year OS between LRH group and ARH group(93.9%vs 95.5%,P=0.451).Cox multivariate analysis suggested that LRH was an independent risk factor for 5-year DFS compared with ARH(HR-1.348;95%CI,1.054 to 1.723;P=0.017),but was not an independent risk factor for 5-year OS(HR=1.166;95%CI,0.801 to 1.698;P=0.423).(2)Oncological outcomes of stage ⅠA1(LVSI+)-ⅠA2,ⅠB1,ⅠB2,ⅠB3,ⅡA1 and IIA2:the 5-year DFS in ARH group was significantly better than that in LRH group before matching of stage ⅠB3 and ⅡA2(stage IB3 90.3%vs 83.9%,P=0.039;stage IIA2 91.3%vs 83.2%,P=0.023),but there was no significant difference in Cox before matching,K-M univariate analysis and Cox multivariate analysis after matching.The results before and after matching stage ⅠAl(LVSI+)-ⅠA2,ⅠB1,ⅠB2 and ⅡA1 indicated that there was no significant difference in oncological outcomes between the two groups.However,the 5-year DFS in ARH group of stage ⅠB2,ⅠB3,ⅡA1 and ⅡA2 had a tendency to be better than that of LRH group.(3)Oncological outcomes of FIGO 2018 stage ⅠA1(LVSI+)-ⅠB1:1403 cases were included in ARH group and 969 cases in LRH group.There was no significant difference in oncological outcomes between the two groups in K-M univariate analysis before matching(OS 98.4%vs 98.0%,P=0.850;DFS 94.7%vs 94.2%,P=0.192).Cox multivariate analysis suggested that LRH was not an independent risk factor for 5-year OS and DFS compared with ARH(OS HR=1.311;95%CI,0.536 to 3.205;P=0.553;DFS HR=1.373;95%CI,0.858 to 2.198;P=0.186).There was no significant difference in oncological outcomes between the two groups after PSM matching(OS 98.1%vs 97.4%,P=0.839;DFS 93.8%vs.93.7%,P=0.464),Cox multivariate analysis suggested that LRH was not an independent risk factor for OS and DFS at 5 years compared with ARH(OS HR=1.078;95%CI,0.418 to 2.783;P=0.876;DFS HR=1.202;95%CI,0.725 to 1.994;P=0.476).(4)Oncological outcomes of FIGO 2018 stage IB2-IIA2:there were 2879 cases in ARH group and 1490 cases in LRH group.Before matching,the 5-year DFS of ARH group was significantly better than that of LRH group(89.6%vs 84.8%,P=0.001).There was no significant difference in 5-year OS between the LRH group and the ARH group(93.6%vs 91.1%,P=0.558).Cox multivariate analysis suggested that LRH was an independent risk factor for 5-year DFS compared with ARH(HR=1.444;95%Cl,1.125 to 1.855;P=0.004),but not an independent risk factor for 5-year OS(HR=1.099;95%Cl,0.767 to 1.576;P=0.606).After PSM matching,5-year DFS of ARH group was still significantly better than that of LRH group(89.4%vs 84.6%,P=0.029),and there was no significant difference in 5-year OS between LRH group and ARH group(93.8%vs 91.8%,P=0.581).Cox multivariate analysis suggested that LRH was an independent risk factor for 5-year DFS compared with ARH(HR=1.372;95%CI,1.033 to 1.822;P=0.029),but was not an independent risk factor for 5-year OS(HR=1.102;95%CI,0.720 to 1.686;P=0.654).Conclusion:Since the overall oncological outcome of FIGO 2018 stageⅠAl(LVSI+)-ⅡA2 cervical cancer in ARH group is better than that of LRH group,ARH is recommended.For specific different stages of ⅠA1(LVSI+)-ⅠA2 and ⅠB1,ARH or LRH can be selected,while ARH is recommended in stage ⅠB2,ⅠB3,ⅡA1 and ⅡA2,and LRH should be carefully selected.Part Ⅳ Comparison of oncological outcomes between type QM-B and QM-C2 hysterectomy for FIGO 2018 stage ⅠAl(LVSI+)-ⅡA2 cervical cancerObjective:To retrospectively analyze the optimal surgical range of FIGO 2018 stage ⅠA1(LVSI)-ⅡA2 cervical cancer by comparing the oncological outcomes of hysterectomy type QM-B and QM-C2.Methods:A total of 4125 patients were enrolled in the same data screening process as the first part,including the type QM-B group(n=2894)and type QM-C2 group(n=1231).The overall and different stages of oncological outcomes of the two groups were compared,and propensity score matching(PSM)was used to reduce possible selection bias and confounding factors.Results:(1)Overall oncological outcomes:there was no significant difference in oncological outcomes between the two groups before matching(OS 95.3%vs 94.8%,P=0.789;DFS 91.3%vs 90.8%,P=0.548).Cox multivariate analysis suggested that type QM-C2 was not an independent factor affecting 5-year OS and DFS compared with type QM-B(OS HR=1.180;95%CI,0.826 to 1.685;P=0.362;DFS HR=1.165;95%CI,0.899 to 1.508;P=0.248).After PSM matching,there was no significant difference in oncological outcomes between the two groups(OS 95.9%vs 94.7%,P=0.256;DFS 91.4%vs 90.9%,P=0.438).Cox multivariate analysis suggested that type QM-C2 was not an independent factor influencing 5-year OS and DFS compared with type QM-B(OS HR=1.369;95%CI,0.889 to 2.107;P=0.154;DFS HR=1.154;95%CI,0.850 to 1.566;P=0.358).(2)Oncological outcomes of different stages of ⅠA1(LVSI+)-ⅠA2,ⅠB1,ⅠB2,ⅠB3,ⅡA1 and ⅡA2:there was no statistically significant difference in oncological outcomes between the two groups before and after matching.Conclusions:Retrospective analysis suggested that the total or different stages of type QM-B and QM-C2 hysterectomy of FIGO 2018 stage ⅠAl(LVSI+)-ⅡA2 cervical cancer had similar oncological outcomes.Type QM-B hysterectomy with smaller range of parametrial resection could be selected. |
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