Chunlin Chen

Comparison of the clinical outcomes of patients with stage IA–IIA2 cervical adenocarcinoma and squamous cell carcinoma after radical hysterectomy: A propensity score‐matched real‐world analysis

AbstractObjectiveTo compare the pathological findings and survival outcomes of patients with 2009 FIGO stage IA–IIA2 cervical cancer between groups with adenocarcinoma (ADC) and squamous cell carcinoma (SCC) using the Chinese Cervical Cancer Clinical (FOUR‐C) study database.MethodsPatients from 2004 to 2018 with cervical ADC and SCC who underwent radical hysterectomy were identified through the FOUR‐C database. Propensity score matching (PSM) was conducted to balance baseline clinicopathological characteristics. The Kaplan–Meier method and Cox regression analysis were used to evaluate the prognostic effect of ADC on the 5‐year overall survival (OS).ResultsWe identified 1611 (9.8%) patients with ADC and 14 894 (90.2%) patients with SCC. Compared with SCC, ADC was significantly associated with an increased risk of death (odds ratio [OR] 1.40, 95% CI 1.12–1.74) and disease progression (OR 1.34, 95% CI 1.14–1.57). ADC had a greater propensity for lymph node metastasis, uterine corpus invasion, perineural invasion, and ovarian metastases than SCC (P < 0.05). After 1:2 PSM, significant differences were still observed between these two histology subtypes (OS: OR 1.43, 95% CI 1.10–1.86; DFS: OR 1.45, 95% CI 1.19–1.76). The subgroup analysis further showed a worse prognosis for patients with ADC than for patients with SCC among patients with any of the high‐ or intermediate‐ risk factors (OR 1.60, 95% CI 1.21–2.12), but no significant differences were observed for the patients with no risk factors (OR 0.71, 95% CI 0.32–1.58).ConclusionADC is an independent prognostic factor for shorter survival in surgically treated patients with cervical cancer presenting intermediate‐ or high‐risk factors but does not affect survival outcomes in patients without any risk factors.

Comparison of oncological outcomes between radical hysterectomy and radiochemotherapy for International Federation of Gynecology and Obstetrics 2018 stage IIIC1 cervical adenocarcinoma: A retrospective multicenter cohort study

AbstractBackgroundTo compare oncological outcomes of radical hysterectomy (RH) and radiochemotherapy (R‐CT) for stage IIIC1 (FIGO 2018) cervical adenocarcinoma patients.MethodsBased on the Chinese Cervical Cancer Clinical Diagnosis and Treatment Project Database, we retrospectively reviewed 236 cases of FIGO stage IIIC1 cervical adenocarcinoma diagnosed between 2005 and 2019. The 5‐year overall survival (OS) and 5‐year disease‐free survival (DFS) rates were compared between the two treatment groups using multivariate Cox regression models and the log‐rank test, both in the overall study population and after propensity score matching (PSM).ResultsFrom 63 926 patients, we selected 236 cases, including 203 in the RH group and 33 in the R‐CT group. In the overall study population, R‐CT was associated with significantly worse 5‐year OS (51.8% vs. 67.2%, p < 0.05) and 5‐year DFS (43.1% vs. 60.1%, p < 0.05) compared to RH. Multivariate analysis revealed that R‐CT was an independent risk factor for 5‐year DFS (hazard ratio [HR] = 2.226, 95% confidence interval [CI] 1.141–4.343, p < 0.05) but not for 5‐year OS (HR = 1.834, 95% CI: 0.829–4.061, p > 0.05) in FIGO stage IIIC1 cervical adenocarcinoma. After matching (n = 26 in R‐CT group vs. 73 in RH group), the R‐CT group showed significantly lower 5‐year OS (50.3% vs. 77.4%, p < 0.05) and DFS (38.2% vs. 65.0%, p < 0.05) compared to the RH group. In the matched cohort, R‐CT remained an independent risk factor for 5‐year DFS (HR = 2.299, 95% CI: 1.113–4.750, p < 0.05) but not for 5‐year OS (HR = 1.926, 95% CI: 0.792–4.682, p > 0.05).ConclusionAmong patients with stage FIGO 2018 IIIC1 cervical cancer adenocarcinoma, R‐CT was not associated with better oncological outcomes than RH. Radiotherapy should not be the only recommended treatment.

Galectin-1-targeted theranostic nanoprobe for multimodal imaging and photothermal therapy in cervical cancer lymph node metastases

Accurately evaluating lymph node (LN) status is essential for cervical cancer staging and making treatment decisions. However, the current preoperative imaging modalities for diagnosing LN metastasis in patients with cervical cancer are suboptimal, and the existing radiochemotherapy methods lack specificity, which leads to increased toxicity and side effects. To overcome these limitations, we aimed to develop a theranostic strategy for LN metastases with a galectin-1-targeted nanoprobe for dual-modal magnetic resonance imaging (MRI)/near-infrared (NIR) imaging and photothermal therapy (PTT). The PEG@MnPb-IR820 nanoparticles were synthesized through an integrated approach combining microemulsion, thin-film hydration, and esterification coupling methods. The nanoparticles were synthesized and characterized for their physicochemical properties and biosafety. After extensive in vitro and in vivo experiments, the TDG@PMI NPs demonstrated low biological toxicity, excellent stability, and a diameter of 74 nm, which is suitable for LN accumulation. With effective MRI and NIR imaging guidance, this nanoprobe displayed outstanding anticancer activity in tumors and metastatic sentinel LNs upon single NIR laser irradiation by inducing mitochondrial apoptosis in tumor cells.

Predictive value of number of metastatic lymph nodes and lymph node ratio for prognosis of patients with FIGO 2018 stage IIICp cervical cancer: a multi-center retrospective study

To identify the cut-off values for the number of metastatic lymph nodes (nMLN) and lymph node ratio (LNR) that can predict outcomes in patients with FIGO 2018 IIICp cervical cancer (CC). Patients with CC who underwent radical hysterectomy with pelvic lymphadenectomy were identified for a propensity score-matched (PSM) cohort study. A receiver operating characteristic (ROC) curve analysis was performed to determine the critical nMLN and LNR values. Five-year overall survival (OS) and disease-free survival (DFS) rates were compared using Kaplan-Meier and Cox proportional hazard regression analyses. This study included 3,135 CC patients with stage FIGO 2018 IIICp from 47 Chinese hospitals between 2004 and 2018. Based on ROC curve analysis, the cut-off values for nMLN and LNR were 3.5 and 0.11, respectively. The final cohort consisted of nMLN ≤ 3 (n = 2,378) and nMLN > 3 (n = 757) groups and LNR ≤ 0.11 (n = 1,748) and LNR > 0.11 (n = 1,387) groups. Significant differences were found in survival between the nMLN ≤ 3 vs the nMLN > 3 (post-PSM, OS: 76.8% vs 67.9%, P = 0.003; hazard ratio [HR]: 1.411, 95% confidence interval [CI]: 1.108-1.798, P = 0.005; DFS: 65.5% vs 55.3%, P  0.11 (post-PSM, OS: 82.5% vs 76.9%, P = 0.010; HR: 1.407, 95% CI: 1.103-1.794, P = 0.006; DFS: 72.8% vs 65.1%, P = 0.002; HR: 1.347, 95% CI: 1.110-1.633, P = 0.002) groups. This study found that nMLN > 3 and LNR > 0.11 were associated with poor prognosis in CC patients.

Perineural invasion in cervical cancer: A multicenter retrospective study

The study aimed to evaluate the accuracy of perineural invasion (PNI) diagnosis in cervical cancer, and to analyze the impact of PNI on the prognosis and postoperative adjuvant treatment decisions for cervical cancer. A retrospective pathological review of PNI in cervical cancer was conducted from 2004 to 2016 in 15 hospitals. This study included a total of 1208 cases, comprising 273 cases with PNI and 935 cases without. The false positive rate and false negative rate of PNI diagnosis were 5.35% (50/935) and 33.33% (91/273), respectively. Adenocarcinoma, deep stromal invasion, lymphovascular space invasion (LVSI) (+), and margin involvement were independent risk factors for PNI. Both 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) of PNI group were worse than non-PNI group. PNI was an independent risk factor for 5-year OS and 5-year DFS. In cases receiving standard postoperative adjuvant treatment, among those with two intermediate-risk factors, both 5-year OS and DFS were worse in the PNI group. Among cases with three intermediate-risk factors or at least one high-risk factor, there was no difference in 5-year OS between the two groups, but 5-year DFS was worse in the PNI group. The diagnosis of PNI in cervical cancer was not accurate. Adenocarcinoma, deep stromal invasion, LVSI, and margin involvement were independent risk factors for PNI. PNI was an independent risk factor for 5-year OS and DFS. PNI has the potential to serve as a new high-risk factor, thus providing guidance for postoperative adjuvant therapy.

Impact of histological subtypes on clinical outcome of endocervical adenocarcinoma

This multicenter study aimed to investigate the disparity in clinical features and prognosis among different histopathologic subtypes of endocervical adenocarcinoma (EA) based on the 2014 World Health Organization (WHO) classification. We retrieved and analyzed data from the Chinese Four C Database between 2004 and 2018. 672EA patients with radical hysterectomies from 32 institutions were retrospectively reviewed. Clinicopathologic characteristics, five-year overall survival (OS), and disease-free survival (DFS) were compared based on histological subtypes. The 5-year DFS and OS rates for usual, endometrioid, mucinous, gastric, villoglandular, clear cell/serous/mesonephric EAs were as follows: 81.3 %, 89.1 %, 63.0 %, 35.6 %, 88.6 %, 79.9 %, respectively (P < 0.0001); 87.4 %, 96.6 %, 74.7 %, 34.0 %, 96.7 %, 86.3 %, respectively (P < 0.0001). Gastric- and mucinous-type exhibited a higher frequency of lymph node metastasis, deep stromal invasion, uterine corpus invasion, and recurrence than the usual -type (recurrence rate:50.00 % vs 29.90 % vs 15.50 %, P < 0.0001). Multivariate analysis revealed gastric-type was significantly associated with inferior DFS (HR,3.018; 95 % CI, 1.688-5.397; P < 0.0001) and OS(HR, 4.114; 95 % CI, 2.002-8.453; P < 0.0001). Furthermore, compared to the usual -type, mucinous-type demonstrated significantly worse DFS (HR, 1.773; 95 % CI,1.123-2.8; P = 0.014) and OS (HR, 2.168; 95 % CI,1.214-3.873; P = 0.009) whereas endometrioid-type was an identified as independent factor for better DFS (HR, 0.365; 95 % CI,0.143-0.928; P = 0.034). Villoglandular subtype displayed similar features and favorable prognosis as the usual type. Relevant clinical features and prognosis varied significantly among histological subtypes of EA, thus offering valuable guidance for the development of subtype-specific treatment strategies to optimize EA management.

Comparison between laparoscopic and abdominal radical hysterectomy for low-risk cervical cancer: a multicentre retrospective study

To compare oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for low-risk cervical cancer. We retrospectively compared the 3-year overall survival (OS) and 3-year disease-free survival (DFS) of 1269 low-risk cervical cancer patients with FIGO 2009 stage IA2, IB1 and IIA1 with a tumour size < 2 cm, no lymphovascular space invasion (LVSI), superficial stromal invasion and no lymph node involvement on imaging, and who received LRH (n = 672) and ARH (n = 597) between 2009 and 2018 at 47 hospitals. In the total study population, LRH and ARH showed similar 3-year OS (98.6% vs. 98.9%, P = 0.850) and DFS rates (95.7% vs. 96.4%, P = 0.285). LRH was not associated with worse 3-year OS (HR 0.897, 95% CI 0.287-2.808, P = 0.852) or DFS (HR 0.692, 95% CI 0.379-1.263, P = 0.230) as determined by multivariable analysis. After propensity score matching in 1269 patients, LRH (n = 551) and ARH (n = 551) still showed similar 3-year OS (98.4% vs. 98.8%, P = 0.704) and DFS rates (95.5% vs. 96.3%, P = 0.249). LRH was still not associated with worse 3-year OS (HR 0.816, 95% CI 0.262-2.541, P = 0.725) or DFS (HR 0.694, 95% CI 0.371-1.296, P = 0.251). Among patients with low-risk cervical cancers < 2 cm, no LVSI, superficial stromal invasion, and no lymph node involvement on imaging, no significant differences were observed in 3-year OS or DFS rates between LRH and ARH.

Comparison between laparoscopic and abdominal radical hysterectomy for stage IB1 and tumor size &lt;2 cm cervical cancer with visible or invisible tumors: a multicentre retrospective study

To compare 5-year disease-free survival (DFS) and overall survival (OS) rates of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IB1 and tumor size <2 cm with visible or invisible tumors. We retrospectively compared the oncological outcomes of 1,484 cervical cancer patients with IB1 and tumor size <2 cm on final pathology, who received ARH (n=899) or LRH (n=585) between January 2004 and December 2016. Patients were divided into visible tumor subgroup (ARH: n=668, LRH: n=444) and invisible tumor subgroup (ARH: n=231, LRH: n=141) according to tumor type. LRH and ARH showed similar 5-year DFS and OS rates (93.3% vs. 93.1%, p=0.997; 96.2% vs. 97.5%, p=0.351) in total study population. LRH was not associated with worse 5-year DFS rate (hazard ratio [HR]=0.96; 95% confidence interval [CI]=0.58-1.58; p=0.871) or OS rate (HR=1.37; 95% CI=0.65-2.89; p=0.409) by multivariable analysis. In the visible tumor subgroups, LRH and ARH showed similar 5-year DFS and OS rates (91.9% vs. 91.9%, p=0.933; 95.0% vs. 96.9%, p=0.276), and LRH was not associated with worse 5-year DFS or OS rate (p=0.804, p=0.324). In the invisible tumor subgroups, LRH and ARH also showed similar 5-year DFS and OS rates (97.3% vs. 97.1%, p=0.815; 100% vs. 99.5%, p=0.449), and LRH was not associated with worse 5-year DFS rate (p=0.723). Among patients with stage IB1 and tumor size <2 cm, whether the tumor is visible or not, the oncological outcomes of LRH and ARH among cervical cancer patients are comparable. This suggests that LRH may be suitable for stage IB1 and tumor size <2 cm with visible or invisible tumors. International Clinical Trials Registry Platform Identifier: CHiCTR180017778.

Impact of neoadjuvant chemotherapy on the postoperative pathology of locally advanced cervical squamous cell carcinomas: 1:1 propensity score matching analysis

To assess the impact of neoadjuvant chemotherapy on postoperative pathology for stage IB2 and IIA2 cervical squamous cell carcinoma. Postoperative pathology was compared between patients who received neoadjuvant chemotherapy followed by radical hysterectomy (NACT group) and patients who received upfront radical hysterectomy (URH group). Then, patients in the NACT group were divided into a chemotherapy-sensitive group and a chemotherapy-insensitive group according to their response to chemotherapy. After 1:1 propensity score matching (PSM), the positive rates of lymphovascular space invasion (LVSI) (7.9% vs 17.7%, P = 0.001) and cervical deep stromal invasion (60.4% vs 76.2%, P < 0.001) in the NACT group were significantly lower than those in the URH group, while the positive rates of parametrial invasion, lymph node metastasis, and vaginal margin invasion were not significantly different between the two groups. The rate of positive lymph node metastasis in the chemotherapy-sensitive group was significantly lower than that in the URH group (18.1% vs 26.5%, P = 0.037). Among patients with stage IB2 and IIA2 cervical squamous cell carcinomas, NACT can reduce the positive rate of intermediate-risk factors, such as deep cervical stromal invasion and LVSI, but cannot reduce the positive rate of high-risk factors. For patients who are chemotherapy sensitive, NACT can reduce the positive rate of lymph node metastasis.

Comparison of survival outcomes between radio-chemotherapy and radical hysterectomy with postoperative standard therapy in patients with stage IB1 to IIA2 cervical cancer: long-term oncological outcome analysis in 37 Chinese hospitals

Abstract Background This study aimed to compare the survival outcomes of radio-chemotherapy (R-CT) and radical hysterectomy with postoperative standard therapy (RH) in stage IB1-IIA2 cervical cancer patients. Methods Based on the large amount of diagnostic and treatment cervical cancer data in China, a real-world study and 1:1 case-control matching were used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients. Results In this real-world study, the 5-year OS and DFS in the R-CT group (n = 8949) were lower than those in the RH group (n = 18,152). After applying the inclusion criteria, the OS and DFS in the R-CT group (n = 582) were lower than those in the RH group (n = 4308). After 1:1 case-control matching, the 5-year OS and DFS in the R-CT group (n = 535) were lower than those in the RH group (n = 535) (OS: 76.1% vs. 84.6%, p &lt; 0.001, HR = 1.819; DFS: 75.1% vs. 81.5%, p &lt; 0.001, HR = 1.462, respectively). Further stratification showed that for stage IB1 and IIA1 patients, the 5-year OS and DFS in the R-CT group (n = 300) were lower than those in the RH group (n = 300) (OS: 78.9% vs. 87.0%, p &lt; 0.001, HR = 2.160; DFS: 77.0% vs. 84.9%, p &lt; 0.001, HR = 2.053, respectively). In stage IB2 and IIA2 patients, the 5-year OS in the R-CT group (n = 235) was lower than that in the RH group (n = 235) (72.5% vs. 81.5%, p = 0.039; HR = 1.550), but no difference in the 5-year DFS was found between the two groups (72.6% vs. 76.9%, p = 0.151). Conclusions Our study found that for stage IB1-IIA2 cervical cancer patients, RH offers better overall survival and disease-free survival outcomes than R-CT, however, due to the inherent biases of retrospective study, it needs to be confirmed by randomized trials. In addition, we need to further understand the quality of life of the two treatments. Trial registration registration number: CHiCTR1800017778; International Clinical Trials Registry Platform Search Port, http://apps.who.int/trialsearch/. registration date: August 14, 2018.

Comparison between robot-assisted radical hysterectomy and abdominal radical hysterectomy for cervical cancer: A multicentre retrospective study

To compare 3-year overall survival (OS) and disease-free survival (DFS) rates of robot-assisted radical hysterectomy (RRH) and abdominal radical hysterectomy (ARH) for cervical cancer. We retrospectively compared the oncological outcomes of 10,314 cervical cancer patients who received RRH (n = 1048) or ARH (n = 9266) and whose stages were IA1 with lymphovascular space invasion (LVSI)-IIA2. Kaplan-Meier survival analysis and log-rank tests were used to compare the 3-year OS and DFS rates between the RRH and ARH groups. Cox proportional hazards model and propensity score matching was used to estimate the surgical approach-specific survival. RRH and ARH showed similar 3-year OS and DFS rates (93.5% vs. 94.1%, p = 0.486; 90.0% vs. 90.4%, p = 0.302). RRH was not associated with a lower 3-year OS rate by the multivariable analysis (HR 1.23, 95% CI 0.89-1.70, p = 0.206), but it was associated with a lower 3-year DFS rate (HR 1.20, 95% CI 1.09-1.52, p = 0.035). After propensity score matching, patients who underwent RRH had decreased 3-year OS and DFS rates compared to those who underwent ARH (94.4% vs. 97.8%, p = 0.002; 91.1% vs. 95.4%, p = 0.001), and RRH was associated with lower 3-year OS and DFS rates. Among patients with stage IB1 and tumor size <2 cm, RRH was not associated with decreased 3-year OS and DFS rates (HR1.688, 95% CI 0.423-6.734, p = 0.458; HR1.267, 95%CI 0.518-3.098, p = 0.604). Overall, RRH was associated with worse 3-year oncological outcomes than ARH in patients with FIGO stage IA1 with LVSI- IIA2 cervical cancer. However, RRH showed similar 3-year oncological outcomes with ARH among those with stage IB1 and tumor size <2 cm.

Laparoscopic versus abdominal radical hysterectomy for stage IB1 cervical cancer patients with tumor size ≤ 2 cm: a case-matched control study

To investigate the survival outcomes of stage IB1 cervical cancer patients with tumor size ≤ 2 cm who underwent laparoscopic or abdominal radical hysterectomy. We retrospectively analyzed stage IB1 cervical cancer patients with a tumor size ≤ 2 cm who underwent laparoscopic or abdominal radical hysterectomy in China between 2004 and 2016. A real-world study (RWS) and 1:1 matching was used in the study. After 1:1 matching, laparoscopic (n = 926) and abdominal radical hysterectomy (n = 926) had similar 5-year overall survival and disease-free survival rates in stage IB1 cervical cancer with a tumor size ≤ 2 cm. Subsequently, in cervical squamous carcinoma with tumor size ≤ 2 cm, the laparoscopic and abdominal groups (724 cases, respectively) showed comparable 5-year overall survival and disease-free survival rates. Finally, in cervical adenocarcinoma or adenosquamous carcinoma with tumor size ≤ 2 cm, the laparoscopic group (n = 174) had a similar 5-year overall survival rate but a lower disease-free survival rate compared to those of the abdominal group (disease-free survival: 89.9% vs. 98.0%, respectively, P = 0.006; hazard ratio (HR), 5.094; 95% confidence interval (CI), 1.400-18.535; P = 0.013; n = 174). The RWS results were similar to the 1:1 matching results. Patients with squamous cell carcinoma in stage IB1 cervical cancer with tumor size ≤ 2 cm might be suitable for laparoscopic surgery, while patients with adenocarcinoma or adenosquamous carcinoma with tumor size ≤ 2 cm are not candidates for laparoscopic surgery.

Effects of preoperative radiotherapy or chemoradiotherapy on postoperative pathological outcome of cervical cancer——from the large database of 46,313 cases of cervical cancer in China

To investigate the effect of preoperative radiotherapy or chemoradiotherapy combined with radical surgery on pathological outcomes in cervical cancer patients. Based on a large Chinese cervical cancer database of clinical diagnosis and treatment (C4 Project), the postoperative pathological outcomes of patients who received preoperative radiotherapy or chemoradiotherapy followed by open surgery (PR group) or surgery alone (SD group) were compared. Among the strictly selected patients, the incidence of lymph node metastasis in the PR group (n = 574) was higher than that in the SD group (231 VS 9; P < 0.001), while the incidence of vascular space invasion was lower than that in the SD group (72 VS 2041; P < 0.001). The logistic regression analysis showed that preoperative radiotherapy was a protective factor for parametrial involvement, positive surgical margins, deep cervical stromal invasion, and vascular space invasion (P < 0.05). The median number of resected lymph nodes in both groups was 18. After 1:1 case matching, the incidence of deep cervical stromal invasion and vascular space invasion was reduced by preoperative radiotherapy (292 vs 376, P < 0.001; 60 vs 106, P < 0.001). Logistic regression analysis indicated that preoperative radiotherapy was a protective factor for deep cervical stromal invasion and vascular space invasion (P < 0.05). The median numbers of resected lymph nodes in the two groups were 18 and 19, separately. Preoperative radiotherapy can reduce both the incidence of deep cervical stromal invasion and vascular space invasion, but it cannot reduce lymph node positivity, parametrial involvement and positive surgical margins.

Reconstruction of three-dimensional vascular models for lymphadenectomy before surgery

Uterine corpus invasion in cervical cancer: a multicenter retrospective case–control study

To determine the accuracy of uterine corpus invasion (UCI) diagnosis in patients with cervical cancer and identity risk factors for UCI and depth of invasion. Clinical data of patients with cervical cancer who underwent hysterectomy between 2004 and 2016 were retrospectively reviewed. UCI was assessed on uterine pathology. Independent risk factors for UCI and depth of invasion were identified using binary and ordinal logistic regression models, respectively. A total of 2,212 patients with cervical cancer from 11 medical institutions in China were included in this study. Of these, 497 patients had cervical cancer and UCI, and 1,715 patients had cervical cancer and no UCI, according to the original pathology reports. Retrospective review of the original pathology reports revealed a missed diagnosis of UCI in 54 (10.5%) patients and a misdiagnosis in 36 (2.1%) patients. Therefore, 515 patients with cervical cancer and UCI (160 patients with endometrial invasion, 176 patients with myometrial invasion < 50%, and 179 patients with myometrial invasion ≥ 50%), and 1697 patients with cervical cancer without UCI were included in the analysis. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI. These risk factors, except resection margin involvement, were independently associated with depth of UCI. UCI may be missed or misdiagnosed in patients with cervical cancer on postoperative pathological examination. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI and depth of UCI, with the exception of resection margin involvement.

Comparison of survival outcomes of abdominal radical hysterectomy and radiochemotherapy IIA2 (FIGO2018) cervical cancer: a retrospective study from a large database of 63,926 cases of cervical cancer in China

This study aimed to compare the 5-year overall survival (OS) and 5-year DFS disease-free survival (DFS) of abdominal radical hysterectomy (ARH) and radiochemotherapy (R-CT) for stage IIA2 (FIGO 2018) cervical cancer patients. Based on this multicenter, retrospective cohort study based on data from the clinical diagnosis and treatment of cervical cancer in China (Four C) database, 609 cases with 2018 FIGO stage IIA2 cervical cancer from 2004 to 2018 were reviewed. The 5-year OS and 5-year DFS of patients with either of the two treatment methods were compared by means of a multivariate Cox regression model and the log-rank method in the total study population and after propensity score matching (PSM). We selected 609 of 63,926 patients and found that R-CT was associated with a significantly worse 5-year OS (71.8% vs. 95.3%, P < 0.001; hazard ratio (HR) = 6.596, 95% CI 3.524-12.346) and 5-year DFS (69.4% vs. 91.4%, P < 0.001; HR = 4.132, 95% CI 2.570-6.642, P < 0.001) than ARH in the total study population. After matching (n = 230/230), among FIGO 2018 IIA2 patients, the 5-year OS and DFS were lower in the R-CT group than in the ARH group (OS: 73.9% vs. 94.7%, P < 0.001; HR = 5.633, 95% CI 2.826-11.231, P < 0.001; DFS: 69.2% vs. 91.1%, P < 0.001; HR = 3.978, 95% CI 2.336-6.773, P < 0.001, respectively). In patients with stage FIGO 2018 IIA2 cervical cancer, ARH offers better 5-year OS and DFS outcomes than R-CT; however, due to the inherent biases of retrospective studies, this needs to be confirmed by randomized trials.

Comparison of survival outcomes with or without Para-aortic lymphadenectomy in surgical patients with stage IB1-IIA2 cervical cancer in China from 2004 to 2016

Abstract Background Current opinions on whether surgical patients with cervical cancer should undergo para-aortic lymphadenectomy at the same time are inconsistent. The present study examined differences in survival outcomes with or without para-aortic lymphadenectomy in surgical patients with stage IB1-IIA2 cervical cancer. Methods We retrospectively compared the survival outcomes of 8802 stage IB1-IIA2 cervical cancer patients (FIGO 2009) who underwent abdominal radical hysterectomy + pelvic lymphadenectomy (n = 8445) or abdominal radical hysterectomy + pelvic lymphadenectomy + para-aortic lymphadenectomy (n = 357) from 37 hospitals in mainland China. Results Among the 8802 patients with stage IB1-IIA2 cervical cancer, 1618 (18.38%) patients had postoperative pelvic lymph node metastases, and 37 (10.36%) patients had para-aortic lymph node metastasis. When pelvic lymph nodes had metastases, the para-aortic lymph node simultaneous metastasis rate was 30.00% (36/120). The risk of isolated para-aortic lymph node metastasis was 0.42% (1/237). There were no significant differences in the survival outcomes between the para-aortic lymph node unresected and resected groups. No differences in the survival outcomes were found before or after matching between the two groups regardless of pelvic lymph node negativity/positivity. Conclusion Para-aortic lymphadenectomy did not improve 5-year survival outcomes in surgical patients with stage IB1-IIA2 cervical cancer. Therefore, when pelvic lymph node metastasis is negative, the risk of isolated para-aortic lymph node metastasis is very low, and para-aortic lymphadenectomy is not recommended. When pelvic lymph node metastasis is positive, para-aortic lymphadenectomy should be carefully selected because of the high risk of this procedure.

Effect of pre‐operative radiotherapy on long‐term outcomes among women with Stage IB1 to IIB cervical squamous cell carcinoma

AbstractObjectiveTo compare long‐term outcomes between pre‐operative radiotherapy followed by open surgery and direct open surgery among women with Stage IB1–IIB cervical squamous cell carcinoma.MethodsA multicenter retrospective cohort study among women with Stage IB1–IIB cervical squamous cell carcinoma who underwent open surgery either directly (SD group) or with pre‐operative radiotherapy (PR group) in China 2004–2016. Five‐year overall survival (OS) and disease‐free survival (DFS) between the two groups were compared by Kaplan–Meier methods and multivariate Cox regression.ResultsOverall, 8385 women with Stage IB1–IIB were included (PR group, n = 447; SD group, n = 7938). Five‐year OS and DFS was significantly lower in the PR than in the SD group (OS: 81.7% vs 91.6%, P &lt; 0.001; DFS: 76.3% vs 86.7%, P &lt; 0.001). As compared with direct surgery, pre‐operative radiotherapy was an independent risk factor for 5‐year OS (adjusted hazard raio [aHR], 1.75; 95% confidence interval [CI], 1.34–2.30) and DFS (aHR, 1.37; 95% CI, 1.09–1.73) by multivariate Cox regression. Sensitivity analyses confirmed the findings.ConclusionAmong women with Stage IB1–IIB cervical squamous cell carcinoma, outcomes were found to be worse for those undergoing pre‐operative radiotherapy followed by open surgery than for those undergoing direct open surgery.

Risk factors for and delayed recognition of genitourinary fistula following radical hysterectomy for cervical cancer: a population-based analysis

This study aimed to identify the risk factors for genitourinary fistulas and delayed fistula recognition after radical hysterectomy for cervical cancer. This study was a retrospective analysis of data collected in the Major Surgical complications of Cervical Cancer in China (MSCCCC) database from 2004-2016. Data on sociodemographic characteristics, clinical characteristics, and hospital characteristics were extracted. Differences in the odds of genitourinary fistula development were investigated with multivariate logistic regression analyses, and differences in the time to recognition of genitourinary fistula were assessed by Kruskal-Wallis test. In this study, 23,404 patients met the inclusion criteria. Surgery in a cancer center, a women's and children's hospital, a facility in a first-tier city, or southwest region, stage IIA, type C1 hysterectomy, laparoscopic surgery and ureteral injury were associated with a higher risk of ureterovaginal fistula (UVF) (p<0.050). Surgery in southwest region, bladder injury and laparoscopic surgery were associated with greater odds of vesicovaginal fistula (VVF) (p<0.050). Surgery at cancer centers and high-volume hospitals was associated with an increase in the median time to UVF recognition (p=0.016; p=0.005). International Federation of Gynecology and Obstetrics (FIGO) stage IIA1-IIB was associated with delayed recognition of VVF (p=0.040). Intraoperative urinary tract injury and surgical approach were associated with differences in the development of UVFs and VVFs. Patients who underwent surgery in cancer centers and high-volume hospitals were more likely to experience delayed recognition of UVF. Patients with FIGO stage IIA1-IIB disease were more likely to experience delayed recognition of VVF.

Tumor lesion detection in patients with cervical cancer by indocyanine green near-infrared imaging

To investigate the feasibility and accuracy of near-infrared fluorescence (NIRF) imaging for detecting the extent of tumor invasion in cervical cancer using indocyanine green (ICG). We enrolled 51 patients who were diagnosed with cervical cancer with FIGO stage IB1-IIA2 disease. Patients were administered indocyanine green (ICG) at a dose of 5 mg/kg 24 h prior to surgery. A customized near-infrared fluorescence (NIRF) imaging system was used to identify the extent of tumor invasion when radical hysterectomy specimens were harvested. The relationship between tumor fluorescence intensity and clinicopathological characteristics was analyzed. Of the 51 enrolled patients, 3 patients did not have residual tumors after cervical conization, and tumor lesions were identified by NIRF imaging in all the remaining 48 patients. The results of NIRF imaging were in agreement with the postoperative pathological findings in 95.8% of the patients with stromal invasion, 100% of those with surgical margin invasion, 100% of those with parametrial tumor involvement, and 100% of patients with uterine corpus invasion. The mean signal-to-background ratio (SBR) of the cervical tumors was 2.91 ± 1.64, and the SBR was independent of clinicopathological characteristics. Fluorescence microscopy confirmed that ICG fluorescence was present in the tumor nests. NIRF imaging enables objective, accurate, and safe identification of tumor invasion during cervical cancer surgery. ClinicalTrials.gov NCT04224467.

The long-term outcomes of clinical responders to neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer

To compare the long-term oncological outcome of neoadjuvant chemotherapy before radical surgery (NCRS) and definitive chemoradiotherapy (DR) for stage IB2 and IIA2 cervical squamous cell carcinoma. The clinical outcome of 480 patients with stage IB2 and IIA2 cervical cancer (308 clinical responders, 111 clinical non-responders, 61 unclear) who underwent NCRS (and subgroup assessments) were compared with those of 233 patients who underwent DR. The clinical response rate was 73.5% in the NCRS group. Multivariate COX regression analyses revealed that NCRS was not correlated with the 5-year overall survival (OS) rate (p = 0.067) or disease-free survival (DFS) rate (p = 0.249). In a subgroup of NCRS, the clinical response group was also shown to be a protective independent factor of 5 year OS rate compared to the DR group (aHR, 0.403; 95% CI, 0.209-0.777), but had no correlation with the 5 year DFS rate (p = 0.089). On the other hand, the clinical non-response group had no correlation with the 5 year OS rate (p = 0.780) or DFS rate (p = 0.669). Clinical responders who underwent NCRS exhibited a better oncological outcome compared to those who underwent DR. International Clinical Trials Registry Platform Search Port, http://apps.who.int/trialsearch/ ; CHiCTR1800017778.

Development of a deep learning‐based nomogram for predicting lymph node metastasis in cervical cancer: A multicenter study

The pathological risk score: A new deep learning‐based signature for predicting survival in cervical cancer

AbstractPurposeTo develop and validate a deep learning‐based pathological risk score (RS) with an aim of predicting patients' prognosis to investigate the potential association between the information within the whole slide image (WSI) and cervical cancer prognosis.MethodsA total of 251 patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IA1–IIA2 cervical cancer who underwent surgery without any preoperative treatment were enrolled in this study. Both the clinical characteristics and WSI of each patient were collected. To construct a prognosis‐associate RS, high‐dimensional pathological features were extracted using a convolutional neural network with an autoencoder. With the score threshold selected by X‐tile, Kaplan–Meier survival analysis was applied to verify the prediction performance of RS in overall survival (OS) and disease‐free survival (DFS) in both the training and testing datasets, as well as different clinical subgroups.ResultsFor the OS and DFS prediction in the testing cohort, RS showed a Harrell's concordance index of higher than 0.700, while the areas under the curve (AUC) achieved up to 0.800 in the same cohort. Furthermore, Kaplan–Meier survival analysis demonstrated that RS was a potential prognostic factor, even in different datasets or subgroups. It could further distinguish the survival differences after clinicopathological risk stratification.ConclusionIn the present study, we developed an effective signature in cervical cancer for prognosis prediction and patients' stratification in OS and DFS.

Initial treatment for FIGO 2018 stage IIIC cervical cancer based on histological type: A 14‐year multicenter study

AbstractBackgroundTo compare the oncological outcomes of radical chemotherapy (R‐CT), abdominal radical hysterectomy (ARH), and neoadjuvant chemotherapy and radical surgery (NACT) for International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC cervical cancer, according to histological types: squamous cell carcinoma (SCC) and adenocarcinoma (AC)/adenosquamous cell carcinoma (ASC).MethodsA comparison of 5‐year overall survival (OS) and disease‐free survival (DFS) was performed for the SCC and AC/ASC subgroups for the three initial treatments, assessed using Kaplan–Meier and Cox proportional hazards regression analysis and validated using propensity score matching (PSM).ResultsThe study included 4086 patients: R‐CT, n = 1913; ARH, n = 1529; and NACT, n = 644. AC/ASC had a lower survival rate (63.7%) than SCC (73.6%) and a higher recurrence and mortality rate (36.3% and 26.4%, respectively). The 5‐year OS and DFS rates were different in the SCC group for R‐CT, ARH, and NACT (OS: 69.8% vs. 80.8% vs. 73.0%, p &lt; 0.001; DFS: 66.7% vs. 70.7% vs. 56.4%, p &lt; 0.001), also in the AC/ASC group (OS: 46.1% vs. 70.6% vs. 55.6%, p &lt; 0.001; DFS: 42.7% vs. 64.6% vs. 40.8%, p &lt; 0.001). As for initial treatment, survival outcomes were worse for AC/ASC treated with R‐CT and ARH than for SCC (both p &lt; 0.05), with no group differences between the two treated with NACT.ConclusionInitial treatment influences oncological prognosis for patients with FIGO 2018 stage IIIC cervical cancer. ARH is an alternative treatment for stage IIIC cervical SCC and AC/ASC, and NACT needs to be chosen with caution, moreover, R‐CT for AC/ASC requires careful selection.

Laparoscopic versus open radical hysterectomy in FIGO 2018 early‐stage cervical adenocarcinoma: Long‐term survival outcomes after propensity score matching

AbstractObjectiveTo compare the long‐term survival outcomes of laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in International Federation of Gynecology and Obstetrics (FIGO) 2018 early‐stage cervical adenocarcinoma.MethodsBased on the clinical diagnosis and treatment for cervical cancer in mainland China (Four C) database, the medical records of 1098 patients with FIGO 2018 early‐stage cervical adenocarcinoma were retrospectively reviewed. Long‐term and short‐term survival outcomes of the two groups were compared using a multivariate Cox regression model and the log‐rank method in the whole study population and after propensity score matching.ResultsThere was no difference in disease‐free survival (hazard ratio [HR] 0.921, 95% confidence interval [CI]: 0.532–1.595, p = 0.770) and overall survival (HR 1.168, 95% CI: 0.526–2.592, p = 0.702) between LRH (n = 468) and ORH (n = 468) in the risk‐adjusted analysis. LRH resulted in significantly lower estimated blood loss (342.7 vs. 157.5 mL, p &lt; 0.001) and shorter postoperative anal exhaust time (2.8 vs. 2.5 days, p &lt; 0.001) in risk‐adjusted analysis. The overall rates of intraoperative complications (2.4% vs. 4.3%, p = 0.100) and postoperative complications (7.5% vs. 6.2%, p = 0.437) showed no significant difference between the two groups. However, the LRH group had a significantly higher incidence of ureter injury (0.4% vs. 2.4%, p = 0.012) and great vessel injury (0.0% vs. 0.9%, p = 0.045) compared to the other group. No statistical variation in the site of recurrence was observed between the two groups (p = 0.613).ConclusionsLRH has comparable survival outcomes with ORH and was associated with earlier recovery in FIGO 2018 early‐stage adenocarcinoma of the uterine cervix. However, the LRH group had higher risk of ureter injury and great vessel injury.

Rationality of FIGO 2018 IIIC restaging of cervical cancer according to local tumor size: A cohort study

AbstractIntroductionFIGO 2018 IIIC remains controversial for the heterogeneity of its prognoses. To ensure a better management of cervical cancer patients in Stage IIIC, a revision of the FIGO IIIC version classification is required according to local tumor size.Material and methodsWe retrospectively enrolled cervical cancer patients of FIGO 2018 Stages I–IIIC who had undergone radical surgery or chemoradiotherapy. Based on the tumor factors from the Tumor Node Metastasis staging system, IIIC cases were divided into IIIC‐T1, IIIC‐T2a, IIIC‐T2b, and IIIC‐(T3a+T3b). Oncologcial outcomes of all stages were compared.ResultsA total of 63 926 cervical cancer cases were identified, among which 9452 fulfilled the inclusion criteria and were included in this study. Kaplan–Meier pairwise analysis showed that: the oncology outcomes of I and IIA were significantly better than of IIB, IIIA+IIIB, and IIIC; the oncology outcome of IIIC‐(T1‐T2b) was significantly better than of IIIA+IIIB and IIIC‐(T3a+T3b); no significant difference was noted between IIB and IIIC‐(T1‐T2b), or IIIC‐(T3a+T3b) and IIIA+IIIB. Multivariate analysis indicated that, compared with IIIC‐T1, Stages T2a, T2b, IIIA+IIIB and IIIC‐(T3a+T3b) were associated with a higher risk of death and recurrence/death. There was no significant difference in the risk of death or recurrence/death between patients with IIIC‐(T1‐T2b) and IIB. Also, compared with IIB, IIIC‐(T3a+T3b) was associated with a higher risk of death and recurrence/death. No significant differences in the risk of death and recurrence/death were noted between IIIC‐(T3a+T3b) and IIIA+IIIB.ConclusionsIn terms of oncology outcomes of the study, FIGO 2018 Stage IIIC of cervical cancer is unreasonable. Stages IIIC‐T1, T2a, and T2b may be integrated as IIC, and it might be unnecessary for T3a/T3b cases to be subdivided by lymph node status.

Postoperative management of FIGO 2018 stage IIA1 cervical squamous cell carcinoma with only one intermediate‐risk factor: Is radiotherapy needed?

AbstractObjectiveTo investigate whether postoperative radiotherapy is required for FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate‐risk factor.MethodsThis was a multicenter retrospective study. The selected patients were classified into no postoperative adjuvant therapy and postoperative radiotherapy groups. The 5‐year overall survival (OS) and disease‐free survival (DFS) rates were compared.ResultsIn total, 159 patients with no postoperative adjuvant therapy and 179 patients with postoperative radiotherapy were included, with the former group showing a lower OS but no difference in DFS. No postoperative adjuvant therapy was an independent risk factor for patient mortality. Patients were also stratified by tumor diameter: 56 patients had a tumor diameter ≤2 cm, comprising 32 patients with postoperative radiotherapy and 24 patients without (no between‐group difference was found); 272 patients had a tumor diameter &gt;2 cm, comprising 122 patients with postoperative radiotherapy and 150 patients without, with the former group showing a higher OS, and no postoperative adjuvant therapy was an independent risk factor for patient mortality.ConclusionFor FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate‐risk factor and a tumor diameter &gt;2 cm, postoperative radiotherapy is likely beneficial to improve prognosis.

The Application of Real-Time Near-infrared Imaging in Gynecological Surgery

Removing in situ and metastasis lesions completely during gynecological surgery is central to reduce the recurrence and death, and the identification of lesions in traditional gynecological surgery often depends on the experience of surgeons. The identification of nerves is often needed in gynecological surgery, such as the obturator nerves in pelvic lymphadenectomy, and the pelvic autonomic nerves in nerve-sparing radical hysterectomy for cervical cancer. Nerve identification also relies heavily on the experience of surgeons. This project aims to realize the identification of lesions and nerves under the navigation of indocyanine green fluorescent imaging, and evaluate the accuracy of fluorescent imaging of lesions and the effectiveness of nerves identification by near-infrared imaging. This project may reduce the recurrence or death caused by residual lesions and postoperative dysfunction caused by nerves injury, thus, improve the survival rate and quality of life for patients with gynecological diseases.