| Objective: To analyze the clinical characteristics,treatment modalities,prognosis and influencing factors,and treatment-related complications of our patients with stage IB2 and IIA2 cervical cancer,to provide more clinical data on the treatment and prognosis of patients with locally advanced cervical cancer,and to provide reference significance for the formulation of reasonable treatment plans for such patients.Method:Clinical and pathological data were collected from January 2013 to December 2017 from patients diagnosed with cervical adenocarcinoma,adenosquamous carcinoma,and squamous carcinoma at the Third Affiliated Hospital of Kunming Medical University(Yunnan Provincial Cancer Hospital)with stage IB2 and IIA2(2009 version of FIGO stage).The patients were divided into surgical treatment group and radiotherapy group according to the main treatment modality,and stratified analysis according to the adjuvant treatment.Patients were followed up for current survival status,time to last review or treatment,5-year OS,DFS,and comparison of 5-year OS,DFS,related complications and prognosis between the groups.Statistical analysis of the data was performed using IBM SPSS version 26.0 software.Results:1.Basic clinical characteristics1.1 The surgical group included 253 patients,199 cases(78.7%)in stage IB2 and 54 cases(21.3%)in stage IIA2;193 cases with tumor diameter of 4-5.9 cm(76.3%)and 60 cases ≥6 cm(23.7%);53 cases(20.9%)with imaging suggestive of lymph node metastasis and 200 cases(79.1%)with imaging not suggestive of lymph node metastasis;postoperative Pathological squamous carcinoma in 199 cases(75.5%),adenocarcinoma and adenosquamous carcinoma in 54 cases(24.5%);pathology showed lymph node metastasis in 68 cases(26.9%)and no lymph node metastasis in 185 cases(73.1%);lymphatic vascular positive in 32 cases(12.6%);lymphatic vascular negative in 221 cases(87.4%);muscle layer infiltration depth ≥1/2 in 117 cases(46.2%),136(53.8%);2 cases(0.8%)with positive parametrial margins;0 cases(0%)with positive vaginal margins;127 cases(50.2%)with neoadjuvant chemotherapy and 126 cases(49.8%)without neoadjuvant chemotherapy;174 cases(69.2%)with postoperative adjuvant radiotherapy(chemotherapy),32 cases(13%)with adjuvant chemotherapy,and 47 cases(17.8%)without adjuvant therapy.1.2 Radiotherapy group: 38 cases(53.5%)in stage IB2,33 cases(46.5%)in stage IIA2;34 cases with tumor diameter 4cm-5.9cm(47.9%),37 cases with tumor diameter ≥6cm(52.1%);30 cases with imaging suggestive of lymph node metastasis(42.3%),41 cases without lymph node metastasis(57.1%);52 cases with histological pathology squamous carcinoma(73.2%),adenocarcinoma and adenosquamous carcinoma 19 cases(26.8%);28 cases with imaging suggestive of vaginal invasion(39.4%),43 cases without imaging suggestive of vaginal invasion(60.6%);17 cases with imaging suggestive of parametrial invasion(23.9%),54 cases without imaging suggestive of parametrial invasion(76.1%);49 cases with neoadjuvant chemotherapy(69%),22 cases without neoadjuvant chemotherapy(31%);24 cases(33.8%)had supplemental chemotherapy after radiotherapy and 47 cases(66.2%)had no supplemental chemotherapy.2.Analysis of prognostic factors in the surgery group and radiotherapy group2.1 Analysis of prognostic factors of DFS and OS in the surgery group2.1.1 The median follow-up time of the surgical group was 85 months,and the analysis of prognostic factors of DFS,univariate analysis showed histological type of glandular and adenosquamous carcinoma(P<0.001),tumor stage IIA2(P=0.007),tumor diameter ≥6 cm(P<0.001),imaging showed lymph node metastasis(P=0.019),pathology showed pelvic lymph node metastasis(P<0.001),lymphatic vascular infiltration(P=0.009),and deep muscular infiltration(P=0.001),which were statistically significant;multifactorial analysis showed that:pathological type adenocarcinoma,adenosquamous carcinoma(P=0.001),tumor diameter ≥6 cm(P<0.001),pathology showing pelvic lymph node metastasis(P<0.001),and deep muscular infiltration(P=0.001)were statistically significant.2.1.2 Analysis of prognostic factors for OS in the surgical group showed univariate analysis: histopathological adenocarcinoma,adenosquamous carcinoma(P<0.001),tumor stage IIA2(P<0.001),tumor diameter ≥6 cm(P<0.001),pathology showing pelvic lymph node metastasis(P<0.001),lymphatic vascular infiltration(P=0.007),deep muscular infiltration(P= 0.011),and imaging suggestive of lymph node metastasis(P=0.006)were statistically significant;multifactorial analysis showed that pathological type adenocarcinoma,adenosquamous carcinoma(P=0.003),tumor diameter ≥6 cm(P<0.001),pathological pelvic lymph node metastasis(P=0.006),and imaging suggestive of lymph node metastasis(P=0.041)were statistically significant.2.2 Analysis of prognostic factors of DFS and OS in radiotherapy group2.2.1 The median follow-up time of the radiotherapy group was 73 months,and the analysis of the prognostic factors of DFS showed that the univariate analysis showed that the pathological types of adenocarcinoma and adenosquamous carcinoma(P=0.017)and tumor diameter ≥6 cm(P=0.01)were statistically significant;the multivariate analysis showed that the tumor stage IIA2(P=0.012)and tumor diameter ≥6 cm(P=0.009)were statistically significance.2.2.2 For the analysis of prognostic factors of OS in the radiotherapy group,the univariate analysis showed that: histopathological adenocarcinoma,adenosquamous carcinoma(P=0.048),tumor stage IIA2(P=0.027),tumor diameter ≥6 cm(P=0.035),and imaging showing lymph node metastasis(0.038)were statistically significant,and the multivariate analysis showed that: tumor stage IIA2(P= 0.011),imaging showing lymph node metastasis(P=0.024)were statistically significant.3 Survival prognosis by treatment modality3.1 Survival prognosis of different treatment modalities in the surgical group3.1.1 The 5-year DFS was 79.8% in the overall surgery group;79.4% in the postoperative supplemental radiotherapy;in the postoperative patients without highrisk factors: 91% in the postoperative supplemental chemotherapy DFS and 73% in the postoperative unsupplemented treatment group;in the group with imaging suggestive of lymph node negativity: stage IB2 and IIA2(stage IB3 and IIA2 in the 2018 version of FIGO staging)DFS: 88.1%,respectively 67%;imaging suggestive of lymph node metastasis group(2018 version of FIGO staging as stage IIIC1r)DFS: 64.2%.3.1.2 OS in the overall surgery group: 82.6%;OS in the postoperative supplemental radiotherapy group: 83.4%;no postoperative high-risk factors: 90.9% in the supplemental chemotherapy group,OS without supplemental treatment: 73.3%;imaging suggestive of lymph node negative group: stage IB2 0S:90%,stage IIA2 OS: 70%;OS in the imaging suggestive of lymph node positive group: 70%3.2 Survival prognosis of different treatment modes in radiotherapy group3.2.1 5-year DFS in the overall radiotherapy group was 77.5%;supplemental chemotherapy after radiotherapy(chemotherapy)was 66.7%;no supplemental chemotherapy after radiotherapy(chemotherapy)was 83%;imaging showed lymph node non-metastasis group(2018 version of FIGO staging as stage IB3 and IIA2): stage IB2 DFS:68.4%,stage IIA2 DFS:82%;imaging suggested lymph node metastasis group(2018 version of FIGO staging as stage IIIC1r): DFS:66.7%.3.2.2 OS was 70.4% in the overall radiotherapy group;66.7% in the supplemental chemotherapy group;72% in the unsupplemented chemotherapy;imaging showed no lymph node metastasis group: stage IB2 0S:74%,stage IIA2 OS:68%;imaging suggested lymph node metastasis group: OS:56.7%.3.3 Prognostic analysis of different treatment modalities3.3.1 Prognostic analysis of DFS showed that there was no significant difference in DFS between the overall surgery group and the overall radiotherapy group(P=0.662);further comparing the surgery+radiotherapy(chemotherapy)group with the overall radiotherapy group,no significant difference in DFS was also seen(P=0.732).No significant difference was seen in DFS between surgery + chemotherapy and surgery alone(no postoperative high-risk factors)(P=0.152).Adjuvant chemotherapy in the radiotherapy group also did not improve patient DFS(P=0.12).For patients with imaging suggestive of positive lymph nodes(2018 version of FIGO stage IIIC1r),there was no significant difference in DFS between surgery and radiotherapy(P=0.817);for patients with imaging suggestive of negative lymph nodes(2018 version of FIGO stage IB3 and IIA2),surgery improved patient DFS compared to radiotherapy in patients with stage IB3(P=0.019),and in patients with stage IIA2 In stage IIA2 patients,surgery and radiotherapy showed similar DFS(P=0.227).3.3.2 Prognostic analysis of OS: The overall surgery group showed better OS than the overall radiotherapy group(P=0.023).Postoperative radiotherapy(chemotherapy)significantly improved OS compared to radiotherapy(P=0.022).Surgery + chemotherapy versus surgery alone(no postoperative high-risk factors): no significant difference in OS was seen(P=0.08).Adjuvant chemotherapy failed to improve patient OS in the radiotherapy group(P=0.62).For patients with imaging suggestive of positive lymph nodes(2018 version of FIGO stage IIIC1r),there was no significant difference in OS between surgery and radiotherapy(P=0.228);for patients with imaging negative lymph nodes(2018 version of FIGO stage IB3 and IIA2),surgery improved patient OS compared to radiotherapy in patients with stage IB3(P=0.005),and in patients with stage IIA2 Surgery showed similar OS to radiotherapy in stage IIA2 patients(P=0.882).3.4 Neoadjuvant chemotherapy in the surgery group did not improve prognostic DFS(P=0.9)and OS(P=0.977)in the surgery group.Although it reduced the incidence of postoperative intermediate risk factors such as positive lymphatic vasculature(P=0.008)and deep muscle infiltration(P<0.001),it failed to reduce the rate of lymph node metastasis(P=0.545).Neoadjuvant chemotherapy in the radiotherapy group also failed to improve patient DFS(P=0.522)and OS(P=0.397).4 Recurrence: between the surgery group and the radiotherapy group,there was no significant difference in the overall recurrence rate(P=0.662),but surgery reduced the occurrence of local recurrence(P=0.038).5 Complications: there was no significant difference in the incidence of complications between the surgery + radiotherapy group and the overall radiotherapy group(P=0.687),and supplemental chemotherapy after radiotherapy increased the incidence of acute complications(P=0.045).Conclusion(s):1 Although surgery did not improve the overall DFS of patients with locally advanced cervical cancer,it reduced the local recurrence rate and improved OS;therefore,surgery may also be an option.2 Neoadjuvant chemotherapy did not improve DFS and OS in either the surgery or radiotherapy groups.preoperative neoadjuvant chemotherapy reduced the rate of positive intermediate risk factors in the postoperative period,but failed to reduce the rate of lymph node metastasis and the rate of postoperative adjuvant therapy.3 According to the 2018 version of the FIGO staging system,for patients with stage IB3,surgery had better OS and DFS compared with radiotherapy,and treatment of stage IB3 cervical cancer was preferred to surgery;for patients with stage IIA2 or IIIC1 r surgery and radiotherapy did not show differences in DFS and OS.Therefore,more studies are necessary to evaluate better treatment modalities for patients with stage IB3,stage IIA2 or stage IIIC1 r cervical cancer under the new staging system. |
