IIA Cervical Cancer Research Articles

Clinical outcome of FIGO 2018 stage IB3/IIA2 cervical cancer treated by neoadjuvant chemotherapy followed by radical surgery due to lack of radiotherapy equipment: A retrospective comparison with concurrent chemoradiotherapy.

This study aimed to assess neoadjuvant chemotherapy's clinical outcomes such as efficacy, toxicity, and survival outcomes followed by radical hysterectomy ((NACT-RS) among women with cervical cancer stage IB3 and IIA2, by comparing concurrent chemoradiotherapy (CCRT) and NACT-RS. The study retrospectively reviewed patients with (2018 FIGO) stage IB3 and IIA2 cervical cancer who received preoperative neoadjuvant chemotherapy followed by NACT-RS or concurrent chemoradiotherapy (CCRT). The outcome measures were the 5-year survival and complication rates between the two groups. The median follow-up was 75 months. In total, 218 patients had stage IIA2, 136 patients had stage IB3, 201 patients received CCRT, and 153 patients received preoperative NACT-RS. In the CCRT group, the incidence of early complications (myelosuppression, gastrointestinal and urinary) was higher compared with that in the NACT-RS group (76.1 vs. 26.1%; p < 0.001, respectively). There was no significant difference between the two study groups concerning late complications. Five-year PFS was 79.9% and 85.5% in the NACT-RS and CCRT groups, respectively (p = 0.093). Five-year OS was 86.9% and 85.5% in the NACT-RS and CCRT groups, respectively (p = 0.97). In the multivariate clinicopathologic characteristics analysis for OS, initial tumor size > 4.3 cm (HR 5.11; p < 0.001), AC/ASC (HR 1.89; p = 0.02), histologic grade 2-3 (HR 2.25; p = 0.04), and 2018 FIGO stage IIA2 (HR 8.67; p < 0.001) were independent risk factors. The survival of patients with stage IB3 and IIA2 cervical cancer treated with NACT-RS was similar to that of patients treated with CCRT without increasing side effects.

Classifying early stages of cervical cancer with MRI-based radiomics

This study aims to establish a MRI-based classifier to distinguish early stages of cervical cancer with improved diagnostic performance to assist clinical diagnosis and treatment. 57 patients with pathological diagnosis of cervical cancer from January 2018 to May 2019 were enrolled in this study. MRI examinations, including T1-weighted image(T1WI), T2-weighted image(T2W), diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE), were performed before surgery. MR images from patients of stage Ib or IIa cervical cancer with tumor segmented were used as input. Feature extraction process extracted first-order statistics and texture and applied filters. The dimensionality of the radiomic features was reduced using the least absolute shrinkage and selection operator (LASSO). Models were trained by three machine-learning (k-nearest neighbor (KNN), support vector machine (SVM), and logistic regression (LR)) and diagnostic performance in differentiating stage Ib and stage IIa cases was evaluated. A total of 27 features were extracted to establish models, including 2 features from T1WI, 5 features from T2WI, 5 features from DWI (b = 50), 4 features from DWI (b = 800), 5 features from DCE, and 6 features from ADC. For each machine learning (ML) classifier, six sequences of training set and testing set are modeled and analyzed. Among all the models, the training set and testing set of T2WI model built by SVM classifier were the best (Area under the curve (AUC) 0.915) / (AUC 0.907). Radiomic analysis of ML-based texture features and first-order statistics features can be used to stage the early cervical cancer pre-operatively.

Clinical Study of Sentinel Lymph Node Detection to Evaluate Pelvic Lymph Node Metastasis to Determine the Prognosis of Patients with Early Cervical Cancer.

Objective Lymph node status is one of the most important prognostic factors for uterine cervical cancer. Sentinel lymph node (SLN) biopsy has emerged as a potential alternative to systematic lymphadenectomy for the lymph node mapping in such patients. However, the SLN metastasis detection via SLN biopsy in early-stage cervical cancer remains controversial. The current study is aimed at investigating the feasibility and accuracy of combined tracer method for localization of SLN in initial stages of cervical cancer and to evaluate the clinical value of SLN biopsy in replacing pelvic lymph node resection. Methods We retrospectively reviewed 348 cases who were admitted to the Department of Gynecologic Oncology, Shandong Provincial Cancer Hospital, China, between February 2003 and June 2018 with FIGO stage IA2 to IIA2 cervical cancer and undergone through SLN biopsy. Methylthioninium chloride was injected in combination with 99mtechnetium-labeled sulfur colloid prior to surgery to these patients. SLNs were identified intraoperatively, excised, and subsequently submitted to fast frozen section. The detection rates, accuracy, sensitivity, coincidence rate, false negative rate, and negative predictive values of these cases were estimated, and the follow-up outcomes were carefully observed. Chi squared test or Fisher's exact test was employed for a comparison of the categorical variables. Univariate and multivariate Cox proportional hazard models were used for estimation of relationships between overall survival (OS) and disease-free survival (DFS) and prognostic factors. Results The total detection rate of SLN was 97.1% (338/348), and identification of bilateral SLN was successful in 237 patients (70.1%). The patient's tumor size, FIGO stage, lymph node metastasis, and depth of invasion had statistically significant differences in SLN detection rates. The detection rate had inverse relation with tumors size (>4 cm), invasive depth > 2/3, lymph node positive, late staging, and preoperative radiotherapy. 117 positive SLNs were detected in 73 patients. The negative predictive value, sensitivity, false negative rate, and coincidence rate and were 97.7%, 92.4%, 7.6%, and 95.4%, respectively. In patients whose tumor size were ≦ 4 cm, the false negative rate was 4.55% (2/44), whereas it was 0 in patients with tumor size≦2 cm. The respective 1, 3, and 5-year OS was 100%, 94.8%, and 91.8%, respectively, whereas DFS rate for 1, 3, and 5 years was 96.7%, 92%, and 89.6%, respectively. The lymph node was positive, tumor size, the depth of invasion, and staging were statistically different from the recurrence rate and survival rate of patients (p < 0.05). When tumor metastasis exceeded SLN, the recurrence rate was significantly increased, and survival rate is significantly reduced (p < 0.05, p < 0.01, p < 0.05, respectively). Conclusions The identification of SLN combined with 99mtechnetium-labeled sulfur colloid and methylthioninium chloride has a good accuracy and is safe for the assessment of the status of pelvic nodes in patients with initial stage cervical cancer. Nuclide as a tracer has low dependence on objective conditions and doctors' technology and has a good detection rate. In our study, we believe that SLN biopsy is feasible when the tumor is ≦ 4 cm. Large scale clinical trials are required in China expand the sample size and validate the results of this study.

Microglandular Hyperplasia of the Cervix- A Diagnostic Challenge

We report a clinical case of a 22-years-old women manifesting otorrhagia. In the physical assessment, a suspicious exophytic bulky lesion was observed. The macroscopic appearance suggested malignancy. The first histological sampling was insufficient to rule out malignancy and magnetic resonance suggested a IIA cervical cancer. The clinical anatomopathological discrepancy demand to further study. The patient was forwarded for observation.

Laparotomic radical hysterectomy versus minimally invasive radical hysterectomy using vaginal colpotomy for the management of stage IB1 to IIA2 cervical cancer: Survival outcomes.

This study compared survival outcomes for patients with stage IB1 to IIA2 (International Federation of Gynecology and Obstetrics stage 2009) cervical cancer who underwent open radical hysterectomy (ORH) versus those who underwent minimally invasive radical hysterectomy (MIRH) using vaginal colpotomy (VC).Data for 550 patients who were diagnosed with cervical cancer at our institution during the period August 2005 to September 2018 was retrospectively reviewed. Of these, 116 patients who underwent radical hysterectomy (RH) were selected after applying the exclusion criteria. All MIRH patients underwent VC. Clinicopathological characteristics and survival outcomes between the ORH and MIRH groups were compared using appropriate statistical testing.Ninety one patients were treated with ORH and 25 with MIRH during the study period. Among the MIRH patients, 18 underwent laparoscopy-assisted radical vaginal hysterectomy and 7 underwent laparoscopic RH. Preoperative conization was performed more frequently in MIRH patients than in ORH patients (44% vs 22%, respectively, P = .028). The incidence of lymph node invasion was higher in the ORH group than in MIRH group (37.4% vs 12.0% respectively; P = .016). Following RH, ORH patients underwent adjuvant treatment more frequently than MIRH patients (71.4% vs 56.0%, respectively, P = .002). There were no significant differences between ORH and MIRH patients for either progression-free survival (PFS) (91.3% vs 78.7%, respectively; P = .220) or 5-year overall survival (OS) (96.6% vs 94.7%, respectively, P = .929). In univariate analysis, lympho-vascular space invasion was the only clinicopathological feature associated with decreased PFS. No other clinicopathological factors was significantly associated with PFS or OS in univariate and multivariate analyses.Despite a higher incidence of unfavorable prognostic factors in ORH patients, their survival outcomes were not different to those of MIRH patients with VC.

Surgical skill and oncological outcome of laparoscopic radical hysterectomy: JGOG1081s-A1, an ancillary analysis of the Japanese Gynecologic Oncology Group Study JGOG1081

ObjectivesWe investigated whether surgical skill and procedure were related to oncological outcomes in cervical cancer patients who underwent Laparoscopic Radical Hysterectomy (LRH). MethodsWe previously assessed data of LRH from 251 patients with FIGO stage (2009) IA2, IB1and IIA1 cervical cancer collected for JGOG 1081s study. 1) The JGOG 1081s cohort study was re-examined to refine the surgical details and extend the follow-up period as chart review. 2) Unedited videos for recurrent cases and matched non-recurrent control cases were newly compared by experts for various surgical skills and surgical procedures using the modified Objective Structured Assessment of Technical Skills (OSATS) tool, without awareness of the recurrence status as video review. ResultsAfter a median follow-up of 46 months, tumors had recurred in 31 of the 251 patients. The five-year Recurrence-Free Survival rate was 86.9% (81.8–90.6) and five-year Overall Survival rate was 93.7% (87.5–96.8). Multivariate analysis from chart reviews found that an experience with LRH of less than 20 cases per institution was an independent prognostic factor for recurrence (Hazard Ratio (HR) 2.49, 95%CI 1.12–5.53, p = 0.025). For the surgical video review, we compared 23 videos of recurrent cases with 23 background-matched non-recurrent controls. Lower modified OSATS scores from the video review were consistently trended to have a higher risk of recurrence. ConclusionsOur new study has found that LRH surgical experience and skill trended to have better oncological outcomes.

Chemotherapy versus chemoradiotherapy for FIGO stages IB1 and IIA1 cervical squamous cancer patients with lymphovascular space invasion: a retrospective study

PurposeTo evaluate the impact of different adjuvant therapy on IB1 and IIA1 stage cervical squamous cell cancer patients with lymphovascular space invasion. It also aimed to analyze the relationship between lymphovascular space invasion and other clinical pathological characteristics on IB1 and IIA1 stage cervical squamous cell cancer patients.MethodsThis retrospective observational study collected data of FIGO stages IB1 and IIA1 squamous cervical cancer patients at the First Affiliated Hospital of Chongqing Medical University between 2014 and 2018. A correlation analysis between lymphovascular space invasion and other clinical or pathological factors was conducted. Prognosis analysis of patients with lymphovascular space invasion were performed to assess associations between clinical-pathological characteristics and survival.ResultsA total of 357 women were identified including 110 (30.8%) with lymphovascular space invasion, 247 (69.2%) without lymphovascular space invasion. Both middle 1/3 cervical stromal invasion (p = 0.000) and deep 1/3 cervical stromal invasion (p = 0.000) were independently associated with lymphovascular space invasion. Among lymphovascular space involved women, tumor differentiation (P = 0.001) and postoperative therapy (P = 0.036) had a significant influence on disease recurrence. Multivariate analysis showed that lymph node metastasis (P = 0.017), poorer tumor differentiation (P = 0.036) and postoperative chemotherapy alone (P = 0.021) can increase the risk of tumor relapse.ConclusionOur study suggested that the presence of deep stromal invasion independently increases the risk of lymphovascular space invasion. Compared with chemotherapy, chemoradiotherapy seems to improve progression-free survival in squamous cervical cancer patients with lymphovascular space invasion.

Effect of modified no-touch laparoscopic radical hysterectomy on outcomes of early stage cervical cancer: A retrospective cohort study.

ObjectivesWe aimed to compare the prognosis of modified no‐touch laparoscopic radical hysterectomy (MLRH) and laparoscopic radical hysterectomy (LRH) on survival in patients with early stage cervical cancer.Materials and MethodsThe clinicopathological data of patients with stage IB1 and IIA1 cervical cancer, who underwent radical surgery between 2014 and 2019, were retrospectively reviewed. The 5‐year disease‐free survival (DFS) and overall survival (OS) were compared between the MLRH and LRH groups using the Kaplan–Meier method. Independent prognostic factors for 5‐year DFS and OS were identified using multivariate, forward, stepwise Cox proportional hazards regression models.ResultsA total of 223 patients with stage IB1 and IIA1 cervical cancer were included. Kaplan–Meier analysis revealed that the 5‐year DFS and OS rates in the MLRH (n = 81) group were significantly higher than those in the LRH group (n = 142) (DFS, 94.5% vs. 78.8%, p = 0.007; OS, 96.7% vs. 87.6%, p = 0.033). No significant differences were identified between the two groups in terms of operative time, blood loss, transfusion requirement, and intraoperative or postoperative complications. MLRH was an independent prognostic factor associated with increased 5‐year DFS (adjusted hazard ratio [HR], 0.202; 95% confidence interval [CI], 0.069–0.594; p = 0.004) and 5‐year OS (adjusted HR, 0.163; 95% CI, 0.035–0.748; p = 0.020).ConclusionThe oncologic outcomes were superior with MLRH than with LRH in patients with stage IB1 and IIA1 cervical cancer. Contact of cervical tumor cells with the pelvic cavity likely explains the worse prognosis associated with LRH.

Trends in Surgical Morbidity and Survival Outcomes for Radical Hysterectomy in West China: An 11-Year Retrospective Cohort Study.

ObjectivesTo vertically analyze the trend of surgical approaches, demographics, surgical morbidity, and long-term survival outcomes of early-stage cervical cancer over the past 11 years and to determine whether there have been any significant changes.MethodsA total of 851 patients with consecutive International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA–IIA cervical cancer diagnosed between January 2008 and June 2018 at a single center in China were included in this retrospective study. Trends in the rate of minimally invasive surgery (MIS), demographics, surgical morbidities, and long-term survival outcomes were determined. We categorized patients into two groups according to their year of operation. The demographics, pathological factors, surgical morbidity, and long-term survival outcomes were compared between these two groups.ResultsRegarding the surgical approach, there was a significant increase in the rate of laparoscopic radical hysterectomy (LRH) performed over the study period, from 7.8% in 2008 to 72.5% in 2018 (p < 0.0001). The mean age of patients who underwent abdominal radical hysterectomy (ARH) has increased slightly from 2008 to 2018, and those who underwent ARH in the second half of the study period (2014–2018) were significantly older (45.01 vs. 47.50 years; p = 0.001). The most impressive changes over the past 11 years have occurred in the surgical morbidity in both the ARH and LRH groups. The overall surgical morbidity decreased from 29.2% in 2008 to 11.9% in 2018, with an annual rate of 1.57%. The median estimated blood loss volume of the ARH group was 500 ml (range 50–2,000) in the first few years compared to 400 ml (30–2500) in the last few years of the study period (p < 0.0001), which in the LRH group was 350 ml (range 150–800) and 150 ml (range 5–1,000), respectively (p < 0.0001). Similarly, allogeneic blood transfusions and hospital stay have all decreased dramatically over time in both approaches. On the other hand, our study did not reveal any significant statistical changes in long-term survival outcomes over the follow-up period in either group.ConclusionsThe findings of our study demonstrate that great progress in surgically managed cervical cancer has been made over the last decade in West China. Our retrospective study demonstrated that the year of operation does not appear to influence the long-term survival, but the surgical morbidity impressively decreased over the study period in both the ARH and LRH groups, which reflects that the higher hospital surgical volume for radical hysterectomy (RH) was not associated with lower survival outcomes but related to the reduction of surgical morbidity.

Clinical Implication of Simultaneous Intensity-modulated Radiotherapy Boost to Tumor Bed for Cervical Cancer with Full-thickness Stromal Invasion.

ObjectiveThe objective of this study was to retrospectively explore the clinical implications of simultaneous intensity-modulated radiotherapy (IMRT) boost to the tumor bed in cervical cancer with full-thickness stromal invasion (FTSI).Patients and MethodsPatients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB and IIA cervical cancer with confirmed FTSI were included. Patients received pelvic IMRT from a dose of 50.4 Gy in 28 fractions with (or without) a simultaneous integrated boost (SIB) to 58.8 Gy in 28 fractions for the tumor bed. The progression-free survival (PFS), overall survival (OS), and pelvic-PFS (p-PFS) were analyzed using the Kaplan–Meier method, and independent prognostic factors were explored by Cox regression analyses.ResultsPatients without a tumor bed boost had a poor prognosis. The 5-year OS was 81.3% versus 58.3% and the 5-year PFS rates were 75.0% versus 57.6% (boost vs non-boost). The FIGO stage, pathology, adjuvant chemotherapy, and tumor bed boost were independent factors affecting both the 5-year OS and PFS. Subgroup analysis showed that the SIB group had a higher 5-year OS, PFS, and p-PFS for different stages, lymph node status, and risk groups than the non-SIB group. Recurrence occurred in 268 of 910 (29.5%) patients without SIB and 49 of 293 (16.7%) with SIB. Among patients with recurrence, 113 of 282 (40.1%) in the non-boost group compared with 14 of 51 (23.0%) patients in the boost group had a pelvic recurrence. Tumor bed boost resulted in an increase in the mean radiation dose to the intestine, rectum, and bladder, although there were no differences in the rates of acute and late toxicities between the 2 groups.ConclusionTumor bed boost by external beam radiotherapy (EBRT) is an effective and safe method for patients with FTSI and risk factors. Compared with the standard prophylactic radiation, tumor bed boost by EBRT was not associated with increased acute and late toxicities.

Roles of DWI and T2-weighted MRI volumetry in the evaluation of lymph node metastasis and lymphovascular invasion of stage IB–IIA cervical cancer

To determine whether magnetic resonance imaging volumetry on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) could be used to assess lymph node metastases (LNM) and lymphovascular invasion (LVSI) in resectable cervical cancer. Sixty-five consecutive patients with cervical cancer were enrolled retrospectively. Tumour size, including maximum transverse diameter, tumour length, and gross tumour volume (GTV), was evaluated on DWI and T2WI. Apparent diffusion coefficient (ADC) values were measured. Univariate, multivariate, and receiver operating characteristic (ROC) curve analyses were performed to determine whether tumour size and ADC could be used to assess LNM and LVSI. Tumour length on both T2WI and DWI, and T2WI-based and DWI-based GTVs could be used to assess LNM (p=0.002, 0.004, 0.001, and <0.001, respectively). Tumour length on T2WI, T2WI-based GTV, DWI-based GTV, and ADC value could be used assess LVSI (p=0.039, 0.038, 0.012, 0.039, respectively). Multivariate analyses showed both T2WI-based GTV (odds ratio [OR]=1.044; p=0.008) and DWI-based GTV (OR=1.941; p=0.019) were independent risk factors for LNM. T2WI-based GTV (OR=1.023, p=0.038) and DWI-based GTV (OR=3.275, p=0.008) were independent risk factors for LVSI. No statistically significant difference was identified between the area under the ROC curve (AUC) of the DWI-based GTV and the T2WI-based GTV (0.790 versus 0.775, p=0.113), or the tumour length on both T2WI (0.790 versus 0.734, p=0.185) and DWI (0.790 versus 0.737, p=0.333) for LNM. For LVSI, the AUC of DWI-based GTV was higher than T2WI-based GTV (0.720 versus 0.682, p=0.006). GTV on both T2WI and DWI could be used assess LNM and LVSI. DWI-based GTV might show the greatest potential for assessing LNM and LVSI in resectable cervical cancer.

Development and validation of a prognostic nomogram for 2018 FIGO stages IB1, IB2, and IIA1 cervical cancer: a large multicenter study.

BackgroundNomograms are predictive tools widely used for estimating cancer prognosis. We aimed to develop/validate a nomogram to predict the postsurgical 5-year overall survival (OS) and disease-free survival (DFS) probability for patients with stages IB1, IB2, and IIA1 cervical cancer [2018 International Federation of Gynecology and Obstetrics (FIGO 2018)].MethodsWe retrospectively enrolled cervical cancer patients at 47 hospitals with stages IB1, IB2, and IIA1 disease from the Clinical Diagnosis and Treatment for Cervical Cancer in China database. All patients were assigned to either the development or validation cohort (75% of patients used for model construction and 25% used for validation). OS and DFS were defined as the clinical endpoints. Clinicopathological variables were analyzed based on the Cox proportional hazards regression model. A nomogram was established and validated internally (with bootstrapping) and externally, and its performance was assessed according to the concordance index (C-index), receiver-operating characteristic curve, and calibration plot.ResultsIn total, 4,065 patients were enrolled and assigned to the development cohort (n=3,074) or validation cohort (n=991). The OS nomogram was constructed based on age, FIGO stage, stromal invasion, and lymphovascular space invasion (LVSI). The DFS nomogram was constructed based on the FIGO stage, histological type, stromal invasion, and LVSI. Both nomograms showed greater discrimination than the FIGO 2018 staging system in the development cohort [OS nomogram vs. FIGO 2018: C-index =0.69 vs. 0.61, area under the curve (AUC): 69.8 vs. 60.3; DFS nomogram vs. FIGO 2018: C-index =0.64 vs. 0.57, AUC: 62.6 vs. 56.9], and the same results were observed the definition in the validation cohort. Calibration plots demonstrated good agreement between the predicted and actual probabilities of 5-year OS/DFS in the development and validation cohorts. We stratified the patients into 3 subgroups with differences in OS/DFS. Each risk subgroup presented a distinct prognosis.ConclusionsWe successfully developed a robust and powerful model for predicting 5-year OS/DFS in stages IB1, IB2, and IIA1 cervical cancer (FIGO 2018) for the first time. Internal and external validation showed that the model had great prediction performance and was superior to the currently utilized FIGO staging system.

Pre-operative high-dose-rate brachytherapy in early-stage cervical cancer: long-term single-center results.

PurposeThe aim of the study was to report the outcomes of pre-operative high-dose-rate brachytherapy (pHDR-BT), followed by hysterectomy in patients with early cervical cancer.Material and methodsFrom January, 1998 to December, 2003, 113 women with IB1, IB2, and IIA1 cervical cancer (according to International Federation of Gynecology and Obstetrics [FIGO] 2018) were treated with pHDR-BT, and 6 to 8 weeks later followed by radical hysterectomy. Patients found to have positive lymph nodes, residual cervical cancer, involved parametria, or lymphovascular space invasion (LVSI) received post-operative adjuvant therapy.ResultsPost-operatively, 81.4% of patients had a complete response to pHDR-BT in the cervix, and 18.6% had residual cervical cancer. Failures occurred in 11/113 (9.7%) patients (all were stage IIA1), with pelvic recurrences in 5/113 (4.4%) and distant metastasis (DM) in 6/113 (5.3%). The 5- and 10-year disease-free survival (DFS) rates were 100% for IB1 and IB2, and 86.4% and 81.3% for IIA1, respectively. Lymph node involvement and/or residual cervical cancer correlated with worse DFS. Two vesicovaginal fistulas were observed (one in a patient treated only with pHDR-BT and one in a woman, who underwent adjuvant external-beam radiotherapy [EBRT]). Two rectovaginal fistulas and one case of proctitis were observed in patients treated with adjuvant EBRT.ConclusionspHDR-BT in early cervical cancer is well-tolerated and effective in sterilizing tumor cells in the cervix. The growing number of publications in this area may help define an optimal therapeutic scheme, but randomized trials are required to determine the best candidates for this treatment modality.In our opinion, cervical cancer patients with FIGO stage IIA1 are not good candidates for pHDR-BT, and could be given this treatment only after rigorous selection, including assessment with state-of-the-art imaging, due to higher probability of treatment failure.

Combination of Estrogen Receptor Alpha and Histological Type Helps to Predict Lymph Node Metastasis in Patients with Stage IA2 to IIA2 Cervical Cancer.

ObjectiveThis study aimed to identify a subset of patients with stage IA2 to IIA2 cervical cancer who are at low risk of lymph node metastasis (LNM) using pathological parameters including estrogen receptor alpha (ERα) and progesterone receptor (PR).MethodsThe clinical data of patients with stage IA2 to IIA2 cervical cancer who underwent radical surgery between 2014 and 2015 were retrospectively reviewed. Immunohistochemical staining was used to determine the expression of ERα and PR. A low-risk criterion for LNM was identified using logistic regression analysis, and its performance was estimated through receiver-operating characteristic curve analysis.ResultsOf 263 patients, 57 (21.7%) had pathological LNM. ERα (adjusted odds ratio [aOR], 7.582; 95% confidence interval [CI], 2.991–19.222; P < 0.001) and squamous cell carcinoma (aOR, 3.520; 95% CI, 1.887–6.568; P < 0.001) were identified as independent predictors for no LNM by multivariate logistic regression analysis, while PR had no effect on LNM. The rate of LNM was 1.4% for low-risk patients (n = 73) identified as ERα positive with squamous cell carcinoma. The 5-year disease-free survival in low-risk patients was significantly greater than in those negative for ERα and/or those with non-squamous cell carcinoma (96.9% vs 80.1%, P = 0.002).ConclusionERα positivity and squamous cell carcinoma are associated with a low risk of LNM in patients with stage IA2 to IIA2 cervical cancer. Hence, those patients without a low risk of LNM could be considered for definitive chemoradiotherapy to avoid unnecessary surgery.

Pretreatment C-Reactive Protein/Albumin Ratio is Associated With Poor Survival in Patients With 2018 FIGO Stage IB-IIA HPV-Positive Cervical Cancer.

Objectives: The present study aimed to identify the predictive value of inflammatory indexes stratified according to human papillomavirus (HPV) infection status in women with FIGO 2018 stage IB∼IIA cervical cancer. We also explored the influences of HPV infection status on the survival of cervical cancer patients. Methods: We collected data for 583 women with stage IB∼IIA cervical cancer in Sun Yat-sen University Cancer Center between 2009 and 2017. The t-test, chi-squared (χ2) test and Fisher’s exact test were applied to compare the differences of inflammatory indexes and clinicopathological features between HPV-positive and HPV-negative groups. Univariate and multivariate analyses were used to identify clinicopathological factors that were associated with the prognosis of cervical cancer patients. Results: There were no differences in overall survival (OS) and progression-free survival (PFS) between HPV-positive and HPV-negative groups. In HPV-positive group, the maximum tumor size, neoadjuvant chemotherapy and the body mass index (BMI) correlated significantly with C-reactive protein/albumin ratio (CAR). The maximum tumor size and the prognostic nutritional index (PNI) correlated significantly with the platelet-lymphocyte ratio (PLR). The maximum tumor size, neoadjuvant chemotherapy and PLR correlated significantly with PNI. Univariate and multivariate analyses showed that the depth of tumor invasion (HR: 3.651, 95% CI: 1.464–9.103, p = 0.005; HR: 2.478, 95% CI: 1.218–5.043, p = 0.012) and CAR (HR: 5.201, 95% CI: 2.080–13.004, p < 0.0001; HR: 2.769, 95% CI: 1.406–5.455, p = 0.003) were independent predictors of poor OS and PFS. PNI was an independent protective factor of OS (HR: 0.341, 95% CI: 0.156–0.745, p = 0.007). PLR was an independent factor of PFS (HR: 1.991, 95% CI: 1.018–3.894, p = 0.044). In HPV-negative group, BMI correlated significantly with CAR. Only depth of invasion (HR: 9.192, 95% CI: 1.016–83.173, p = 0.048) was the independent predictor of poor OS, and no inflammation indexes were independent predictors of prognosis. Conclusion: In patients with HPV-positive cervical cancer, depth of invasion, PNI and CAR are independent factors of OS, and depth of invasion, PLR and CAR are independent factors for PFS. For patients with HPV-negative disease, no inflammation indexes had predictive value for prognosis. The predictive value of inflammation indexes on prognosis is more significant in patients with HPV-positive cervical cancer. Stratification of HPV infection status promotes a more precise clinical application of inflammation indexes, thus improving their accuracy and feasibility.

Predictive value of hemoglobin, platelets, and D-dimer for the survival of patients with stage IA1 to IIA2 cervical cancer: a retrospective study.

ObjectiveCoagulation indexes may be useful survival biomarkers for cervical cancer. This study evaluated the ability of hemoglobin, red blood cells (RBCs), platelets, and D-dimer levels to predict post-hysterectomy survival outcomes in patients with stage IA1 to IIA2 cervical cancer.MethodsIn this retrospective study, coagulation-related indexes were compared between the anemia and non-anemia groups. Independent variables were analyzed by the Cox proportional hazards model. Survival was assessed by the Kaplan–Meier method with the log-rank test. Mortality predictions were evaluated by receiver operating characteristic curves.ResultsAmong this study’s 1088 enrolled patients, 152 had anemia. The 10-year overall survival and recurrence-free survival rates were 90.8% and 86.5%, respectively. Hemoglobin, RBC, and the rate of abnormal platelet counts were significantly lower in the anemia group. Abnormal preoperative D-dimer was an independent factor for recurrence-free survival. Receiver operating characteristic curves showed that D-dimer had area under the curve of 0.734 (cut-off value: 0.685, sensitivity: 85.7%, and specificity: 64.0%). Hemoglobin and platelets had areas under the curves of 0.487 and 0.462, respectively.ConclusionPreoperative D-dimer was the most effective prognostic predictor for patients with cervical cancer. The prognosis of patients with cervical cancer was poorer if their D-dimer levels were >0.685 mg/L.

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.

Effectiveness comparisons of various therapies for FIGO stage IB2/IIA2 cervical cancer: a Bayesian network meta-analysis

BackgroundCervical cancer is a common malignancy of the female genital tract. Treatment options for cervical cancer patients diagnosed at FIGO (2009) stage IB2 and IIA2 remains controversial.MethodsWe perform a Bayesian network meta-analysis to directly or indirectly compare various interventions for FIGO (2009) IB2 and IIA2 disease, in order to improve our understand of the optimal treatment strategy for these women. Three databases were searched for articles published between 1971 and 2020. Data on included study characteristics, outcomes, and risk of bias were abstracted by two reviewers.ResultsSeven thousand four hundred eighty-six articles were identified. Thirteen randomized controlled trials of FIGO (2009) IB2 and IIA2 cervical cancer patients were included in the final analysis. These trials used six different interventions: concomitant chemoradiotherapy (CCRT), radical surgery (RS), radical surgery following chemoradiotherapy (CCRT+RS), neoadjuvant chemotherapy followed by radical surgery (NACT+RS), adjuvant radiotherapy followed by Radical surgery (RT + RS), radiotherapy alone (RT).SUCRA ranking of OS and Relapse identified CCRT+RS and CCRT as the best interventions, respectively. Systematic clustering analysis identified the CCRT group as a unique cluster.ConclusionThese data suggest that CCRT may be the best approach for improving the clinical outcome of cervical cancer patients diagnosed at FIGO (2009) stage IB2/IIA2. Phase III randomized trials should be performed in order to robustly assess the relative efficacy of available treatment strategies in this disease context.

Health-related quality of life for early-stage cervical cancer survivors after primary radical surgery followed by radiotherapy versus radical surgery alone

This study compared the quality of life (QoL) of 265 stage IA2–IIA cervical cancer patients treated with radical surgery alone (group 1: 137 patients) versus those who underwent primary radical surgery followed by radiotherapy (group 2: 128 patients) and identified clinical characteristics that predict the poor quality of life. All participants completed quality of life questionnaires: EORTC QLQ-C30 and CMU cervical cancer QoL. For the EORTC QLQ-C30, the study groups were comparable regarding global health status/QoL scale and summary scores. Group 1 participants had better scores on the physical functioning domain and some symptom scales/items. For the CMU Cervical Cancer QoL, group 1 participants had better scores on gastrointestinal, lymphatic, and sexual/hormonal domains. In multivariable analysis, adjuvant radiation was consistently associated with poor quality of life in most domains. In general, early-stage cervical cancer survivors had a satisfactory quality of life. The clinical significance of the quality of life score differences between the study groups remains debateable. Impact statement What is already known on this subject? For women with early cervical cancer, surgery is the main treatment providing not only a good chance for a cure by total removal of the cancer but also an opportunity to preserve the hormone-producing function of the ovary as well as the flexibility of the vagina. However, radiation treatment may be indicated after surgery in some patients depending on the findings from surgery. Because of the concern about increased complications and decreased long-term quality of life following the combined treatments, some may elect to avoid surgery and receive radiation alone in the first place. In this study, we compared the quality of life of women who had surgery alone to those who had surgery followed by radiation. This information is currently lacking in the medical literature. What do the results of this study add? We found that, in general, women with early cervical cancer had a satisfactory quality of life. For a patient who is surgically fit and chooses to receive primary surgery, if radiation is subsequently required, she could still expect the acceptable long-term quality of life–although slightly less satisfactory than receiving surgery alone but not inferior to those who receive primary radiation treatment. What are the implications of these findings for clinical practice and/or further research? These findings will be useful for pre-treatment counselling and posttreatment supportive care. The information regarding disease-related and treatment-induced morbidity should be thoroughly discussed with the patients before and after treatment. Also, the use of questionnaires examining general well-being together with a cancer-specific quality of life is recommended for the systematic evaluation of cancer survivors.

Risk Stratification of Early-Stage Cervical Cancer with Intermediate-Risk Factors: Model Development and Validation Based on Machine Learning Algorithm.

BackgroundAdjuvant therapy for patients with cervical cancer (CC) with intermediate‐risk factors remains controversial. The objectives of the present study are to assess the prognoses of patients with early‐stage CC with pathological intermediate‐risk factors and to provide a reference for adjuvant therapy choice.Materials and MethodsThis retrospective study included 481 patients with stage IB–IIA CC. Cox proportional hazards regression analysis, machine learning (ML) algorithms, Kaplan‐Meier analysis, and the area under the receiver operating characteristic curve (AUC) were used to develop and validate prediction models for disease‐free survival (DFS) and overall survival (OS).ResultsA total of 35 (7.3%) patients experienced recurrence, and 20 (4.2%) patients died. Two prediction models were built for DFS and OS using clinical information, including age, lymphovascular space invasion, stromal invasion, tumor size, and adjuvant treatment. Patients were divided into high‐risk or low‐risk groups according to the risk score cutoff value. The Kaplan‐Meier analysis showed significant differences in DFS (p = .001) and OS (p = .011) between the two risk groups. In the traditional Sedlis criteria groups, there were no significant differences in DFS or OS (p > .05). In the ML‐based validation, the best AUCs of DFS at 2 and 5 years were 0.69/0.69, and the best AUCs of OS at 2 and 5 years were 0.88/0.63.ConclusionTwo prognostic assessment models were successfully established, and risk grouping stratified the prognostic risk of patients with CC with pathological intermediate‐risk factors. Evaluation of long‐term survival will be needed to corroborate these findings.Implications for PracticeThe Sedlis criteria are intermediate‐risk factors used to guide postoperative adjuvant treatment in patients with cervical cancer. However, for patients meeting the Sedlis criteria, the choice of adjuvant therapy remains controversial. This study developed two prognostic models based on pathological intermediate‐risk factors. According to the risk score obtained by the prediction model, patients can be further divided into groups with high or low risk of recurrence and death. The prognostic models developed in this study can be used in clinical practice to stratify prognostic risk and provide more individualized adjuvant therapy choices to patients with early‐stage cervical cancer.