| ObjectiveAdnexal metastasis of cervical cancer is rare in clinic.The purpose of this study is to investigate and analyze the incidence of adnexal metastasis of cervical cancer,its related factors,metastasis pathway and its impact on oncological prognosis in the context of big medical data and real world study,and to provide new evidence for further exploring the clinical significance of adnexal metastasis of cervical cancer.MethodsIn the original big database of cervical cancer in China,the original medical records were selected as positive cases of ovarian or fallopian tube metastasis,which were classified as adnexal metastasis cases,and the negative cases were duplicated according to 1:2 matching.Real world study was used to analyze the related factors,overall survival（OS）,disease-free survival（DFS）,hazard ratio（HR）of cervical cancer with or without adnexal metastasis,and to explore the ways of metastasis and treatment of cervical cancer with adnexal metastasis.ResultFour databases have been established,which are:（1）the China cervical cancer original big database,which included 38098 data;（2）the adnexa excision database,which included 17532 data;（3）the reviewed slides database,which included 245 data;（4）the adnexal metastasis database,which included 182 data.Part I Detection Rate and Composition of Ovarian/Fallopian Tube Metastasis in Cervical CancerThe adnexa excision database and adnexal metastasis database were selected for analysis.1.The primary metastasis rate of ovarian metastasis was 0.53%（68/12951）and that of fallopian tube metastasis was 0.33%（47/14442）.Then 245 cases of pathological duplication were reviewed,including 102 cases of positive metastasis and 140 cases of negative metastasis.The coincidence rate of ovarian metastasis and fallopian tube metastasis was 98.7%（77/78）,94.0%（47/50）and 100%（140/140）respectively.The corrected metastasis rate of ovarian metastasis was 0.53%（68/12951）and that of fallopian tube metastasis was 0.31%（45/14442）.2.The positive cases of metastasis were further divided into four groups:single ovarian metastasis group,single fallopian tube metastasis group,ovarian-fallopian tube simultaneous metastasis group and adnexal metastasis group.The original metastasis rate,corrected metastasis rate and coincidence rate of compound film were 0.39%（50/12951）,0.39%（50/12951）,98.1%（54/55）in the single ovarian metastasis group,0.20%（29/14442）,0.19%（27/14442）in the single fallopian tube metastasis group,.86.2%（25/29）,0.14%（18/12951）,0.14%（18/12951）,100.0%（22/22）in the ovarian-fallopian tube simultaneous metastasis group,0.67%（97/14442）,0.66%（95/14442）and 96.2%（102/106）in the adnexal metastasis group,respectively.3.Select the adnexa excision database and analyze the rate of adnexal metastasis in different histological types and clinical stages.The metastasis rates of Ⅰa,Ⅰb1,Ⅰb2,Ⅰb,Ⅱa1,Ⅱa2,Ⅱa,Ⅱb and above were 0.2%（2/1028）,0.3%（16/5124）,0.8%（13/1537）,0.7%（4/579）,0.9%（17/1809）,0.9%（7/823）,1.1%（8/733）,2.0%（28/1411）,respectively.Squamous cell carcinoma 0.4%（43/12178）,adenocarcinoma 2.8%（40/1404）,adenosquamous cell carcinoma 0.4%（1/246）.5.Multivariate analysis,histologic type（p<0.001）,tumor size（p=0.027）,depth of stromal invasion（p<0.001）,parametrial invasion（p<0.001）,involvement of the body of the uterus（p<0.001）,pelvic lymph node metastasis（p=0.012）are independent risk factors for ovarian metastasis.Part Ⅱ:Analysis of the correlation between ovarian/fallopian tube metastasis and other clinicopathological factors in cervical cancerSelect the adnexa excision database for related factors analysis.According to the inclusion criteria and exclusion criteria of the second part,16217 cases were selected from the adnexa excision database as the whole data group.Next,13373 cases were screened out from the previous data based on the criteria of non-preoperative radiotherapy and chemotherapy as direct operation group.1.Single factor analysisIn whole data group,there were differences in histological type,parametrial invasion,depth of stromal invasion,involvement of the body of the uterus between single ovarian metastasis group,single fallopian tube metastasis group,ovarian-fallopian tube simultaneous metastasis group and adnexal metastasis group（p<0.05）.In direct operation group,there were differences in histological type,parametrial invasion,involvement of the body of the uterus,pelvic lymph node metastasis between the o single ovarian metastasis group,single fallopian tube metastasis group,ovarian-fallopian tube simultaneous metastasis group and adnexal metastasis group.2.Multivariate analysisIn whole data group,binary logistic regression analysis showed that histological type of adenocarcinoma was an independent risk factor in all four groups.Histological types of adenocarcinoma was 7.008 times（95%CI 3.564-13.779,P<0.001）,4.707 times（95%CI 1.915-11.565,P=0.001）,9.671 times（95%CI 3.292-28.411,P<0.001）,6.759 times（95%CI 4.146-11.02）in the non-metastasis group,respectively.（p<0.001）.In direct operation group,binary logistic regression analysis showed that the histological type of adenocarcinoma and positive parametrial invasion were the common independent risk factors in all four groups.Histological types of adenocarcinoma was 8.817 times（95%CI 3.735-20.816,P<0.001）,4.787 times（95%CI 1.585-14.458,P=0.005）,10.406 times（95%CI 2.888-37.489,P<0.001）,7.336 times（95%CI 4.146-11.02,P<0.02）as compared with non-metastasis group,respectively.The risk of positive parametrial invasion was 4.094 times（95%CI 1.053-15.918,P=0.042）,8.875 times（95%CI 1.937-40.668,P=0.005）,13.403 times（95%CI 3.185-56.395,P<0.001）,6.053 times（95%CI 2.453-14.941,P<0.001）in non-metastasis group,respectively.Part Ⅲ Oncological prognosis analysis of ovarian/fallopian tube metastases in cervical cancerThe China cervical cancer original big database and the reviewed slides database were selected.According to the inclusion criteria and exclusion criteria of the third part,15146 cases and 143 cases were selected for Oncological prognosis analysing by the Real World Study（RWS）.1.Original Big DatabaseOS:There were differences in OS between single ovarian metastasis group,single fallopian tube metastasis group,ovarian-fallopian tube simultaneous metastasis group and adnexal metastasis group.The risk of death was the highest in the single fallopian tube metastasis group（HR=3.466,95%CI 1.722-6.977,P<0.001）and the single ovarian metastasis group（HR=1.995,95%CI 1.247-3.191,P=0.004）.DFS:There were differences in DFS between single ovarian metastasis group,single fallopian tube metastasis group,ovarian-fallopian tube simultaneous metastasis group and adnexal metastasis group.The recurrence risk was the highest in the single fallopian tube metastasis group（HR=2.762,95%CI 1.479-5.156,p=0.001）and the single ovarian metastasis group（HR=1.661,95%CI 1.107-2.491,p=0.014）.2.Reviewed slides databaseOS:There were differences in OS between single ovarian metastasis group,ovarian-fallopian tube simultaneous metastasis group and adnexal metastasis group..The risk of death was the highest in the single fallopian tube metastasis group（HR=6.072,95%CI 2.053-17.962,p=0.001）and the single ovarian metastasis group（HR=2.411,95%CI 1.124-5.174,p=0.024）.DFS:There were differences in DFS between single ovarian metastasis group,ovarian-fallopian tube simultaneous metastasis group and adnexal metastasis group.The recurrence risk was the highest in the single fallopian tube metastasis group（HR=6.039,95%CI 2.152-16.943,p=0.001）and the single ovarian metastasis group（HR=2.418,95%CI 1.24-4.717,p=0.010）.Part Ⅳ HR for ovarian/fallopian tube metastasis in cervical cancerThe data are the same as the third part.1.Original Big DatabaseThe HR for cervical cancer mortality were 1.995,3.466,2.727,2.375 in single ovarian metastasis group,single fallopian tube metastasis group,ovarian-fallopian tube simultaneous metastasis group and adnexal metastasis group,and 1.661,2.762,1.982,1.904 in recurrence of cervical cancer.2.Reviewed slides databaseThe HR for cervical cancer mortality were 2.411,6.072,2.525 in single ovarian metastasis group,single fallopian tube metastasis group and adnexal metastasis group,and 2.418,6.039,2.555 in recurrence of cervical cancer.Part Ⅴ Metastasis Pathway of Ovarian/Fallopian Tube Metastasis in Cervical CancerAccording to the inclusion criteria and exclusion criteria of the fifth part,a total of 13266 low-risk cases were selected from the China cervical cancer original big database.In the low-risk group,the risk of involvement of the body of the uterus in the four groups was 14.641 times（95%CI 5.962-35.957,P<0.001）,5.99 times（95%CI 1.666-21.528,P=0.006）,59.024 times（95%CI 9.957-349.903,P<0.001）,13.177 times（95%C<0.006）,respectively.Part Ⅵ Investigation on the Treatment of Ovarian/Fallopian Tube Metastasis of Cervical CancerAccording to the inclusion criteria and exclusion criteria of the sixth part,182 cases of adnexal metastasis were selected from the adnexal metastasis database to enter the study.The 5-year OS（86.2%vs 61.8%）and 5-year DFS（75.9%vs 52.9%）of the low-risk group were higher than those of the high-risk group.The effect of adjuvant therapy on the oncological prognosis of the low-risk group with adnexal metastasis of cervical cancer could not be statistically analyzed.ConclusionsThis study is the largest statistical analysis of cervical cancer adnexal metastasis data so far.In the database,the actual metastasis rate of ovarian and fallopian tube metastasis of cervical cancer was low,only 0.53%and 0.31%,the coincidence rate of positive cases was about 95%,and the accuracy rate of negative cases was 100%.Ovarian metastasis and fallopian tube metastasis of cervical cancer are correlated with histological types,parametrial invasion,involvement of the body of the uterus,pelvic lymph node metastasis and other high-risk pathological and clinical factors.In addition,the 5 year-OS and 5 year-DFS of single ovarian metastasis group,single fallopian tube metastasis group,ovarian-fallopian tube simultaneous metastasis group and adnexal metastasis group are lower than the non-metastasis group.Cervical cancer adnexal metastasis is an independent risk factor for the death and recurrence of cervical cancer,and its HR of cervical cancer oncology prognosis is comparable to known high-risk factors.However,it is not yet possible to analyze whether additional adjuvant therapy after operation is beneficial to the prognosis of cervical cancer with adnexal metastasis.Therefore,clinicians should pay attention to the diagnosis and treatment of adnexal metastasis of cervical cancer. |
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