Project description:BackgroundRadical hysterectomy is one of the standard treatments for stage Ia2 to IIa cervical cancer. Bladder dysfunction caused by disruption of the pelvic autonomic nerves is a common complication following standard radical hysterectomy and can affect quality of life significantly. Nerve-sparing radical hysterectomy is a modified radical hysterectomy, developed to permit resection of oncologically relevant tissues surrounding the cervical lesion, while preserving the pelvic autonomic nerves.ObjectivesTo evaluate the benefits and harms of nerve-sparing radical hysterectomy in women with stage Ia2 to IIa cervical cancer.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 4), MEDLINE via Ovid (1946 to May week 2, 2018), and Embase via Ovid (1980 to 2018, week 21). We also checked registers of clinical trials, grey literature, reports of conferences, citation lists of included studies, and key textbooks for potentially relevant studies.Selection criteriaWe included randomised controlled trials (RCTs) evaluating the efficacy and safety of nerve-sparing radical hysterectomy compared to standard radical hysterectomy for women with early stage cervical cancer (stage Ia2 to IIa).Data collection and analysisWe applied standard Cochrane methodology for data collection and analysis. Two review authors independently selected potentially relevant RCTs, extracted data, evaluated risk of bias of the included studies, compared results and resolved disagreements by discussion or consultation with a third review author, and assessed the certainty of evidence.Main resultsWe identified 1332 records as a result of the search (excluding duplicates). Of the 26 studies that potentially met the review criteria, we included four studies involving 205 women; most of the trials had unclear risks of bias. We identified one ongoing trial.The analysis of overall survival was not feasible, as there were no deaths reported among women allocated to standard radical hysterectomy. However, there were two deaths in among women allocated to the nerve-sparing technique. None of the included studies reported rates of intermittent self-catheterisation over one month following surgery. We could not analyse the relative effect of the two surgical techniques on quality of life due to inconsistent data reported. Nerve-sparing radical hysterectomy reduced postoperative bladder dysfunctions in terms of a shorter time to postvoid residual volume of urine ≤ 50 mL (mean difference (MD) -13.21 days; 95% confidence interval (CI) -24.02 to -2.41; 111 women; 2 studies; low-certainty evidence) and lower volume of postvoid residual urine measured one month following operation (MD -9.59 days; 95% CI -16.28 to -2.90; 58 women; 2 study; low-certainty evidence). There were no clear differences in terms of perioperative complications (RR 0.55; 95% CI 0.24 to 1.26; 180 women; 3 studies; low-certainty evidence) and disease-free survival (HR 0.63; 95% CI 0.00 to 106.95; 86 women; one study; very low-certainty evidence) between the comparison groups.Authors' conclusionsNerve-sparing radical hysterectomy may lessen the risk of postoperative bladder dysfunction compared to the standard technique, but the certainty of this evidence is low. The very low-certainty evidence for disease-free survival and lack of information for overall survival indicate that the oncological safety of nerve-sparing radical hysterectomy for women with early stage cervical cancer remains unclear. Further large, high-quality RCTs are required to determine, if clinically meaningful differences of survival exist between these two surgical treatments.
Project description:BackgroundAfter radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function.MethodsA multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function.ResultsTwo hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function.ConclusionA nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.
Project description:BACKGROUND:Minimally invasive surgery was adopted as an alternative to laparotomy (open surgery) for radical hysterectomy in patients with early-stage cervical cancer before high-quality evidence regarding its effect on survival was available. We sought to determine the effect of minimally invasive surgery on all-cause mortality among women undergoing radical hysterectomy for cervical cancer. METHODS:We performed a cohort study involving women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer during the 2010-2013 period at Commission on Cancer-accredited hospitals in the United States. The study used inverse probability of treatment propensity-score weighting. We also conducted an interrupted time-series analysis involving women who underwent radical hysterectomy for cervical cancer during the 2000-2010 period, using the Surveillance, Epidemiology, and End Results program database. RESULTS:In the primary analysis, 1225 of 2461 women (49.8%) underwent minimally invasive surgery. Women treated with minimally invasive surgery were more often white, privately insured, and from ZIP Codes with higher socioeconomic status, had smaller, lower-grade tumors, and were more likely to have received a diagnosis later in the study period than women who underwent open surgery. Over a median follow-up of 45 months, the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery (hazard ratio, 1.65; 95% confidence interval [CI], 1.22 to 2.22; P=0.002 by the log-rank test). Before the adoption of minimally invasive radical hysterectomy (i.e., in the 2000-2006 period), the 4-year relative survival rate among women who underwent radical hysterectomy for cervical cancer remained stable (annual percentage change, 0.3%; 95% CI, -0.1 to 0.6). The adoption of minimally invasive surgery coincided with a decline in the 4-year relative survival rate of 0.8% (95% CI, 0.3 to 1.4) per year after 2006 (P=0.01 for change of trend). CONCLUSIONS:In an epidemiologic study, minimally invasive radical hysterectomy was associated with shorter overall survival than open surgery among women with stage IA2 or IB1 cervical carcinoma. (Funded by the National Cancer Institute and others.).
Project description:Non-randomised studies have suggested that the postoperative complications of (Campos LS, Limberger LF, Stein AT, Kalil AN) laparoscopic radical hysterectomy are similar to those in abdominal radical hysterectomy. However, no study evaluating postoperative pain comparing both techniques has been published thus far. Our objective was to compare pain intensity and other perioperative outcomes between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in early cervical cancer.This single centre, randomised, controlled trial enrolled 30 cervical cancer patients who were clinically staged IA2 with lymph vascular invasion and IB according to the FIGO (International Federation of Gynaecology and Obstetrics) classification, and underwent LRH or ARH between late 1999 and early 2004. Postoperative pain, as measured by a 10-point numerical rate scale, was considered the primary endpoint. Postoperative pain was assessed every six hours during a patient's usual postoperative care. Perioperative outcomes were also registered. Both surgical techniques were executed by the same surgical team. Secondary outcomes included intraoperative and other postoperative surgicopathological factors and 5-year survival rates.IA2 patients with lymphatic vascular space invasion and IB cervical cancer patients were randomised to either the LRH group (16 patients) or the ARH group (14 patients). Four patients (25%) in the LRH group and 5 patients (36%) in the ARH group presented with transoperative or serious postoperative complications. All of the transoperative complications occurred in the LRH group. The relative risk of presenting with complications was 0.70; CI 95% (0.23-2.11); P?=?0.694. LRH group mean pain score was significantly lower than ARH after 36 h of observation (P?=?0.044; mean difference score: 1.42; 95% CI: 0.04-2.80). The survival results will be published elsewhere.LRH provided lower pain scores after 36 h of observation in this series. The perioperative and serious postoperative complications ratios were comparable between the groups.NCT01258413.
Project description:ObjectiveTo examine the association between surgical volume and survival of women with early-stage cervical cancer who underwent radical hysterectomy.MethodsThis is a nationwide multicenter retrospective study examining consecutive women with clinical stage IB1-IIB cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy from 2004 to 2008 (N=5,964). The surgical volume per site over the 5-year period was defined as low-volume (fewer than 32 surgeries, 46 [39.7%] institutions, n=649 [10.9%]), mid-volume (32-104 surgeries, 60 [51.7%] institutions, n=3,662 [61.4%]), and high-volume (105 surgeries or more, 10 [8.6%] institutions, n=1,653 [27.7%]). Surgical volume-specific survival was examined with multivariable analysis and propensity score matching.ResultsThe median number of surgeries per site was 44 (interquartile range, 17-65). The 5-year disease-free survival rates among stage IB1-IIB disease were 77.2%, 79.9%, and 84.5% for low-, mid-, and high-volume groups, respectively. On multivariable analysis, women in high-volume centers had a decreased risk of recurrence (adjusted hazard ratio [HR] 0.69, 95% CI 0.58-0.82, P<.001) and all-cause mortality (adjusted HR 0.73, 95% CI 0.59-0.90, P=.003) compared with those in mid-volume centers. Specifically, women in high-volume centers had a decreased risk of local recurrence (adjusted HR 0.62, 95% CI 0.49-0.78, P<.001) but not distant recurrence (adjusted HR 0.85, 95% CI 0.67-1.06, P=.142) compared with those in mid-volume centers. Among 1,700 women with clinical stage IB1 disease treated with surgery alone, surgery at high-volume centers was associated with a decreased risk of recurrence (adjusted HR 0.45, 95% CI 0.25-0.79, P=.006) and all-cause mortality (adjusted HR 0.29, 95% CI 0.11-0.76, P=.013) compared with surgery at mid-volume centers on multivariable analysis. After propensity score matching, surgery at high-volume centers remained an independent prognostic factor for decreased recurrence (adjusted HR 0.69, 95% CI 0.57-0.84, P<.001) and all-cause mortality (adjusted HR 0.75, 95% CI 0.59-0.95, P=.016) compared with surgery at mid- and low-volume centers on multivariable analysis.ConclusionHospital volume for radical hysterectomy may be a prognostic factor for early-stage cervical cancer. Surgery at high-volume centers is associated with decreased local recurrence risk and improved survival.
Project description:Cervical cancer (CC) continues to be a global burden for women, with higher incidence and mortality rates reported annually. Many countries have witnessed a dramatic reduction in the prevalence of CC due to widely accessed robotic radical hysterectomy (RRH). This network meta-analysis aims to compare intraoperative and postoperative outcomes in way of RRH, laparoscopic radical hysterectomy (LTH) and open radical hysterectomy (ORH) in the treatment of early-stage CC.A comprehensive search of PubMed, Cochrane Library and EMBASE databases was performed from inception to June 2016. Clinical controlled trials (CCTs) of above three hysterectomies in the treatment of early-stage CC were included in this study. Direct and indirect evidence were incorporated for calculating values of weighted mean difference (WMD) or odds ratio (OR), and drawing the surface under the cumulative ranking curve (SUCRA).Seventeen 17 CCTs were ultimately enrolled in this network meta-analysis. The network meta-analysis showed that patients treated by RRH and LRH had lower estimated blood loss compared to patients treated by ORH (WMD = -399.52, 95% CI = -600.64~-204.78; WMD = -277.86, 95%CI = -430.84 ~ -126.07, respectively). Patients treated by RRH and LRH had less hospital stay (days) than those by ORH (WMD = -3.49, 95% CI = -5.79~-1.24; WMD = -3.26, 95% CI = -5.04~-1.44, respectively). Compared with ORH, patients treated with RRH had lower postoperative complications (OR = 0.21, 95%CI = 0.08~0.65). Furthermore, the SUCRA value of three radical hysterectomies showed that patients receiving RRH illustrated better conditions on intraoperative blood loss, operation time, the number of resected lymph nodes, length of hospital stay and intraoperative and postoperative complications, while patients receiving ORH demonstrated relatively poorer conditions.The results of this meta-analysis confirmed that early-stage CC patients treated by RRH were superior to patients treated by LRH and ORH in intraoperative blood loss, length of hospital stay and intraoperative and postoperative complications, and RRH might be regarded as a safe and effective therapeutic procedure for the management of CC.
Project description:It is well known that tumour initiation and progression are primarily an accumulation of genetic mutations. The mutation status of a tumour may predict prognosis and enable better selection of targeted therapies. In the current study, we analysed a total of 55 surgical tumours from stage IB-IIB cervical cancer (CC) patients who had undergone radical hysterectomy including pelvic lymphadenectomy, using a cancer panel covering 50 highly mutated tumorigenesis-related genes. In 35 patients (63.6%), a total 52 mutations were detected (58.3% in squamous cell carcinoma, 73.7% in adenocarcinoma), mostly in PIK3CA (34.5%) and KRAS and TP53 (9.1%). Being mutation-positive was significantly correlated with pelvic lymph node (PLN) metastasis (P = 0.035) and tended to have a worse overall survival (P = 0.076). In particular, in the patients with squamous cell carcinoma, there was a significant association between being mutation-positive and relapse-free survival (P = 0.041). The patients with PLN metastasis had a significantly worse overall survival than those without (P = 0.006). These results indicate that somatic mutation status is a predictive biomarker for PLN metastasis in early-stage CC, and is consequently related to poor prognosis. Therefore, comprehensive genetic mutations, rather than a single genetic mutation, should be examined widely in order to identify novel genetic indicators with clinical usefulness.
Project description:The purpose of this study was to identify risk factors in patients with surgically treated node-positive IB1-IIB cervical cancer and to establish a risk model for disease-free survival (DFS) and overall survival (OS). A total of 170 patients who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment for node-positive International Federation of Gynaecology and Obstetrics (FIGO) stage IB1-IIB cervical cancer from January 2002 to December 2008 were retrospectively analyzed. Five published risk models were evaluated in this population. The variables, including common iliac lymph node metastasis and parametrial invasion, were independent predictors of outcome in a multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk) were defined using these variables. Five-year DFS rates for the low-, intermediate-, and high-risk groups were 73.7%, 60.0%, and 25.0%, respectively (P<0.001), and 5-year OS rates were 81.9%, 42.8%, and 25.0%, respectively (P<0.001). The risk model derived in this study provides a novel means for assessing prognosis of patients with node-positive stage IB1-IIB cervical cancer. Future study will focus on external validation of the model and refinement of the risk scoring systems by adding new biologic markers.
Project description:Pretherapeutic serological parameters play a predictive role in pathologic risk factors (PRF), which correlate with treatment and prognosis in cervical cancer (CC). However, the method of pre-operative prediction to PRF is limited and the clinical availability of machine learning methods remains unknown in CC. Overall, 1260 early-stage CC patients treated with radical hysterectomy (RH) were randomly split into training and test cohorts. Six machine learning classifiers, including Gradient Boosting Machine, Support Vector Machine with Gaussian kernel, Random Forest, Conditional Random Forest, Naive Bayes, and Elastic Net, were used to derive diagnostic information from nine clinical factors and 75 parameters readily available from pretreatment peripheral blood tests. The best results were obtained by RF in deep stromal infiltration prediction with an accuracy of 70.8% and AUC of 0.767. The highest accuracy and AUC for predicting lymphatic metastasis with Cforest were 64.3% and 0.620, respectively. The highest accuracy of prediction for lymphavascular space invasion with EN was 59.7% and the AUC was 0.628. Blood markers, including D-dimer and uric acid, were associated with PRF. Machine learning methods can provide critical diagnostic prediction on PRF in CC before surgical intervention. The use of predictive algorithms may facilitate individualized treatment options through diagnostic stratification.
Project description:ObjectiveTo evaluate oncologic outcomes of minimally invasive radical hysterectomy (RH) in early cervical cancer before and after the application of parametrial invasion (PMI) criterion on magnetic resonance imaging (MRI) and vaginal colpotomy (VC).MethodsA total of 216 International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer patients who underwent minimally invasive RH was identified between April 2006 and October 2018. Patients were classified into the pre-PMI intracorporeal or VC (IVC) (n=117) and post-PMI VC groups (n=99). In the pre-PMI IVC group, PMI criterion (intact stromal ring) on MRI was not applied and the patients received IVC. In the post-PMI VC group, surgical candidates were selected using the PMI criterion on MRI and all patients received VC only. Oncologic outcomes and prognostic factors associated with disease recurrence were analyzed.ResultsThe rate of positive vaginal cuff margins in the pre-PMI IVC group was higher than that in the post-PMI VC group (11.1% vs. 1.0%, p=0.003). Two-year disease-free survival was different between the 2 groups (84.5% in pre-PMI IVC vs. 98.0% in post-PMI VC groups, p=0.005). Disrupted stromal ring on MRI (hazard ratio [HR]=20.321; 95% confidence interval [CI]=4.903-84.218; p<0.001) and intracorporeal colpotomy (HR=3.059; 95% CI=1.176-7.958; p=0.022) were associated with recurrence.ConclusionThe intact cervical stromal ring on MRI might identify the low-risk group of patients in terms of PMI and lymphovascular/stromal invasion in early cervical cancer. Minimally invasive RH should be performed in optimal candidates with an intact stromal ring on MRI, using VC.