Reducing radicality in fertility-sparing surgery is associated with improved in vitro fertilization outcome in early-stage cervical cancer: A national retrospective study.

OBJECTIVE: Fertility-sparing surgery (FSS) aims to achieve oncological outcomes that are non-inferior to radical treatment while preserving fertility and optimizing reproductive results. This study assesses in vitro fertilization (IVF) outcomes in early-stage cervical cancer survivors following FSS, comparing radical and non-radical approaches. METHODS: This retrospective analysis used data from Hungary's National Health Insurance Fund (2004-2022) on patients who underwent IVF treatment following FSS for early-stage cervical cancer at ten Hungarian fertility clinics. Patients were classified into radical and non-radical surgical groups, with the uterine arteries being spared in the non-radical procedures. RStudio (R software version: 4.2.2) was used for statistical analysis. Student's t-test was used to compare group means, and Fisher's exact test was applied to assess independence and distributions between categorical variables, and to estimate odds. RESULTS: The study analyzed data from 122 IVF treatment cycles involving 36 patients. The non-radical group had a significantly higher live birth rate (83%, 5/6 compared to the radical group (17%, 5/30). Additionally, the non-radical group had a significantly higher implantation rate and cumulative live birth rate per oocyte retrieval (37%, 7/19 and 55%, 6/11 respectively) compared to the radical group (8%, 12/148 and 6%, 5/80 respectively). CONCLUSION: This is the largest study to evaluate IVF outcomes in young cervical cancer survivors who have undergone FSS. The findings suggest that less radical procedures are associated with significantly better IVF outcomes. These results emphasize the importance of considering oncological safety and reproductive outcomes together when choosing FSS for early-stage cervical cancer patients. It also highlights the reproductive benefits of performing less radical surgery.

Fertility-sparing surgery vs standard surgery for early-stage cervical cancer: difference in 5-year life expectancy by tumor size.

BACKGROUND: Cervical cancer incidence among premenopausal women is rising, and fertility-sparing surgery serves as an important option for this young population. There is a lack of evidence on what tumor size cutoff should be used to define candidacy for fertility-sparing surgery. OBJECTIVE: We sought to describe how the association between fertility-sparing surgery (compared with standard surgery) and life expectancy varies by tumor size among patients with cervical cancers measuring ≤4 cm in largest diameter. Our secondary objective was to quantify the probability of undergoing adjuvant radiotherapy among patients who underwent fertility-sparing surgery as a function of tumor size. STUDY DESIGN: We identified patients in the National Cancer Database aged ≤45 years, diagnosed with stage I cervical cancer with tumors ≤4 cm between 2006 and 2018, who received no preoperative radiation or chemotherapy, and who underwent either fertility-sparing surgery (cone or trachelectomy, either simple or radical) or standard surgery (simple or radical hysterectomy) as their primary treatment. Propensity-score matching was performed to compare patients who underwent fertility-sparing surgery with those who underwent standard surgery. A flexible parametric model was employed to quantify the difference in life expectancy within 5 years of diagnosis (restricted mean survival time) based on tumor size among patients who underwent fertility-sparing and those who underwent standard surgery. In addition, among those who underwent fertility-sparing surgery, a logistic regression model was used to explore the relationship between tumor size and the probability of receiving adjuvant radiation. RESULTS: A total of 11,946 patients met the inclusion criteria of whom 904 (7.6%) underwent fertility-sparing surgery. After propensity-score matching, 897 patients who underwent fertility-sparing surgery were matched 1:1 with those who underwent standard surgery. Although the 5-year life expectancy was similar among patients who had fertility sparing surgery and those who had standard surgery regardless of tumor sizes, the estimates of life-expectancy differences associated with fertility-sparing surgery were more precise among patients with smaller tumors (1-cm tumor: restricted mean survival time difference, -0.10 months; 95% confidence interval, -0.67 to 0.47) than among those with larger tumors (4-cm tumor: restricted mean survival time difference, -0.11 months; 95% confidence interval, -3.79 to 3.57). The probability of receiving adjuvant radiation increased with tumor size, ranging from 5.6% (95% confidence interval, 3.9-7.9) for a 1-cm tumor to 37% (95% confidence interval, 24.3-51.8) for a 4-cm tumor. CONCLUSION: Within 5 years of diagnosis, young patients with stage I cancers measuring ≤4 cm had similar survival outcomes after either fertility-sparing surgery or standard surgery. However, because few patients with tumors >2 cm underwent fertility-sparing surgery, a clinically important survival difference could not be excluded in this population.

Prediction of recurrence-related factors for patients with early-stage cervical cancer following radical hysterectomy and adjuvant radiotherapy.

OBJECTIVE: To analyze recurrent factors in patients with clinical early-stage cervical cancer (ESCC) following hysterectomy and adjuvant radiotherapy. METHODS: We collected data from patients with ESCC, staged according to the 2009 Federation International of Gynecology and Obstetrics (FIGO) staging criteria, who underwent hysterectomy followed by adjuvant radiotherapy between 2012 and 2019. These patients were subsequently restaged using the 2018 FIGO criteria. Univariable and multivariable analyses, along with nomogram analyses, were conducted to explore factors associated with recurrence-free survival (RFS). RESULTS: A total of 310 patients met the inclusion criteria, with a median follow-up time of 46 months. Among them, 126 patients with ESCC were restaged to stage III C1 or III C2 after surgery due to lymph node metastasis (LNM) based on the 2018 FIGO staging criteria. Of these, 60 (19.3%) experienced relapse. The 1-, 3-, and 5-year RFS rates were 93.9%, 82.7%, and 79.3%, respectively. Multivariate analysis revealed that the number of positive lymph nodes (LNs), tumor diameter (TD) > 4 cm, and parametrial invasion (PI) were associated with recurrence. The nomogram indicated their predictive value for 3-year and 5-year RFS. Notably, the 5-year recurrence rate (RR) increased by 30.2% in patients with LNM, particularly those with ≥ 3 positive LNs (45.5%). Patients with stage III C2 exhibited a significantly higher RR than those with IIIC1 (56.5% vs. 24.3%, p < 0.001). The 5-year RFS for patients with TD > 4 cm was 65.8%, significantly lower than for those with TD ≤ 4 cm (88.2%). Subgroup analysis revealed higher 5-year RRs in patients with stage III C2 than that in patients with III-C1 (56.5% vs. 24.3%, p < 0.001), demonstrating a significant difference in the RFS survival curve. CONCLUSION: RR in patients with clinical ESCC after hysterectomy followed by adjuvant radiotherapy is correlated with the number of positive LNs, TD > 4 cm, and PI. Emphasis should be placed on the common high-risk factor of LNM association with recurrence after radical hysterectomy in ESCC.

Development of gene panel for predicting recurrence in early-stage cervical cancer patients.

Cervical cancer (CC) is a common malignancy affecting women worldwide. Our objective was to develop a consensus-based gene panel using multi-omics data that could effectively predict recurrence in early-stage cervical cancer patients. We utilized the "Multi-Omics Consensus Integration Analysis (MOVICS)" package for consensus clustering design to integrate multiple omics datasets and improve the molecular classification landscape of early-stage CC. We identified the "resting and naive" tumor microenvironment (TME) as cancer subtype (CS) 2. Leveraging the feature genes from the CS classifier, we employed machine learning algorithms to identify a gene panel, including ALDH1A1, CLDN10, MUC13, and C10orf99, which could generate a consensus machine learning-driven score (CMLS) for each patient. Stratifying patients into high and low CMLS groups resulted in Kaplan-Meier curves demonstrating a significant difference in recurrence rates between the two groups. This difference remained significant even after adjusting for clinical features in multivariate Cox regression analysis, with the risk ratio of CMLS surpassing that of clinical characteristics. Furthermore, the TME exhibited notable differences between the different CMLS groups, suggesting that patients with low CMLS may exhibit a better response to immunotherapy. This study highlights the potential of the CMLS approach in predicting recurrence in early-stage cervical cancer patients and provides a screening model for selecting patients suitable for immunotherapy.

Survival after minimally invasive radical hysterectomy without using uterine manipulator for early-stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: Minimally invasive radical hysterectomy has been reported to increase the risk of cancer relapse and death compared with open surgery in women with early-stage cervical cancer. The use of a uterine manipulator is considered one of the risk factors. OBJECTIVES: To investigate whether women with early-stage cervical cancer treated with minimally invasive radical hysterectomy without using uterine manipulator have oncological outcomes similar to those of open surgery. SEARCH STRATEGY: Searches were performed in MEDLINE, Embase and CENTRAL from their inception until 31 March 2022. SELECTION CRITERIA: Inclusion criteria were: (1) randomised controlled trials or observational cohort studies published in English, (2) studies comparing minimally invasive radical hysterectomy without using a uterine manipulator with open radical hysterectomy in women with early-stage cervical cancer, and (3) studies comparing survival outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently conducted data extraction and assessed study quality. We calculated the hazard ratios (HR) and the 95% confidence intervals (CI) using the inverse variance approach for survival outcome. MAIN RESULTS: Six observational studies with 2150 women were included. The minimally invasive surgery group had a significantly higher risk of cancer relapse compared with open surgery group (HR 1.55, 95% CI 1.15-2.10). CONCLUSIONS: Minimally invasive radical hysterectomy without using a uterine manipulator resulted in an inferior recurrence-free survival compared with open radical hysterectomy in the treatment of women with early-stage cervical cancer.

Effect of modified radical laparoscopic hysterectomy versus open radical hysterectomy on short-term clinical outcomes in early-stage cervical cancer: a single-center, prospective, randomized controlled trial.

BACKGROUND: The long-term prognosis of minimally invasive surgery and open surgery for early cervical cancer is controversial. This study mainly discusses the feasibility and effectiveness of the endocutter in radical laparoscopic hysterectomy for early cervical cancer. METHODS: A single-center, prospective, randomized controlled trial of modified radical laparoscopic hysterectomy on patients with FIGO stage IA1 (lymphovascular invasion), IA2, and IB1 cervical cancer, between January 2020 and July 2021. Patients were randomly assigned into laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) groups. The ORH group used right-angle sealing forceps for vaginal stump closure, whereas the LRH group used endoscopic staplers. The primary outcomes included the evaluation of the patient's perioperative indicators, as well as short- and long-term complications. Recurrence and overall survival were considered secondary outcomes. RESULTS: As of July 2021, 17 patients were enrolled in the laparoscopic surgery group and 17 in the open surgery group. The hospitalization time of the laparoscopic group was significantly shorter than those of the open group (15 min vs. 9 min, P < 0.001). The vaginal stump closure time in the laparoscopic group was longer than that in the open surgery group, and the difference was statistically significant (P < 0.001). Post-operative catheter removal (P = 0.72), drainage tube removal time (P = 0.27), number of lymph node dissections (P = 0.72), and incidence of intraoperative and post-operative complications between the two groups (P > 0.05). The median blood loss in the laparoscopic group was 278 ml, and it was 350 ml in the laparotomy group. The intraoperative blood transfusion rate was lower in the laparoscopic group; however, these differences did not reach statistical significance (P = 0.175). Vaginal margin pathology and peritoneal lavage cytology were negative, and all the patient's vaginal stumps healed without infection. The median follow-up time of the laparoscopic group was 20.5 months, and it was 22 months for the open surgery group. There was no recurrence in all patients during the follow-up period. CONCLUSIONS: Modified LRH with endocutter closure of the vaginal stump is an effective approach and not inferior to ORH in treating patients with early-stage cervical cancer. TRIAL REGISTRATION: ChiCTR2000030160, date of registration February 26, 2020 ( https://www.chictr.org.cn/showprojen.aspx?proj=49809 ).

Oncologic results of fertility sparing surgery of cervical cancer: An updated systematic review.

BACKGROUND: Several techniques can be proposed as fertility sparing surgery in young patients treated for cervical cancer but uncertaincies remain concerning their outcomes. Analysis of oncological issues is then the first aim of this review in order to evaluate the best strategy. RESULTS: Data were identified from searches of MEDLINE, Current Contents, PubMed and from references in relevant articles from January 1987 to 15th of September 2021. We carry out an updated systematic review involving 5862 patients initially selected for fertility-sparing surgery in 275 series. FINDINGS: In patients having a stage IB1 disease, recurrence rate/RR in patients undergoing simple conisation/trachelectomy, radical trachelectomy/RT by laparoscopico-vaginal approach, laparotomic or laparoscopic approaches are respectively: 4.1%, 4.7%, 2.4% and 5.2%. In patients having a stage IB2 disease, RR after neoadjuvant chemotherapy or RT by laparotomy are respectively 13.2% and 4.8% (p = .0035). After neoadjuvant treatment a simple cone/trachelectomy was carried out in 91 (30%) patients and a radical one in 210 (70%) cases. But the lowest pregnancy rate is observed in patients undergoing RT by laparotomy (36%). CONCLUSIONS: The choice between these treatments should be based above all, on objective oncological data that strike a balance for each procedure between the best chances for cure and the fertility results. In patients having a stage IB1 disease, oncological results are quite similar according to the procedure used. In patients having a stage IB2 disease, RT by open approach has the lowest RR. Anyway the lowest pregnancy rate is observed in patients undergoing RT by laparotomy.

Laparo-assisted vaginal radical hysterectomy as a safe option for Minimal Invasive Surgery in early stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: Radical hysterectomy and pelvic lymphadenectomy are considered the standard treatment for early-stage cervical cancer (ECC). Minimal Invasive approach to this surgery has been debated after the publication of a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC trial). It demonstrated poorer oncological outcomes for Minimal Invasive Surgery in ECC. However, the reasons are still an open debate. Laparo-Assisted Vaginal Hysterectomy (LAVRH) seems to be a logical option to Abdominal Radical Hysterectomy (ARH). This meta-analysis has the aim to prove it. METHODS: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Pubmed database and Scopus database were systematically searched in January 2022 since early first publications. No limitation of the country was made. Only English article were considered. The studies containing data about Disease-free Survival (DFS) and/or Overall Survival (OS) and/or Recurrence Rate (RcR) were included. RESULTS: 19 studies fulfilled inclusion criteria. 9 comparative studies were enrolled in meta-analysis. Patients were analyzed concerning surgical approach (Laparo-Assisted Vaginal Radical Hysterectomy) and compared with ARH Oncological outcomes such as DFS and OS were considered. 3196 patiets were included for the review. Meta-analysis of 1988 0f them highlighted a non-statistic significant difference between LARVH and ARH (RR 0.8 [95% CI 0.55-1.16] p = 0.24; I2 = 0%; p = 0.98). OS was feasible only for 4 studies (RR 0.84 [95% CI 0.23-3.02] p = 0.79; I2 = 0 p = 0.44). Sub-analysis for tumor with a maximum diameter greater than 2 cm was performed. Data about the type of recurrences (loco-regional vs distant) were collected. CONCLUSION: LARVH does not appear to affect DFS and OS in ECC patients. The proposed results seem to be comparable with the open approach group of the LACC trial, which today represents the reference standard for the treatment of this pathology. More studies will be needed to test the safety and efficacy of LARVH in the ECC.

Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

Comparative single-center study between modified laparoscopic radical hysterectomy and open radical hysterectomy for early-stage cervical cancer.

BACKGROUND: Since the release of the LACC trial results in 2018, the safety of laparoscopic radical hysterectomy (LRH) for cervical cancer has received huge attention and heated discussion. We developed modified laparoscopic radical hysterectomy (MLRH) incorporating a series of measures to prevent tumor spillage, which has been performed in our center since 2015. OBJECTIVE: Present study retrospectively analyzed relevant indicators of MLRH and evaluated disease-free survival (DFS) primarily in the treatment of early cervical cancer compared with open surgery. METHODS: Patients with 2014 International Federation of Gynecology and Obstetrics clinical stages 1B1 and 2A1 cervical cancer who underwent radical hysterectomy in the gynecological department of our hospital from October 2015 to June 2018 were enrolled retrospectively in this study. Patients were divided into two groups based on the surgical procedure: open radical hysterectomy (ORH) group (n = 336) and MLRH group (n = 302). Clinical characteristics, surgical indices, and survival prognosis were analyzed, including 2.5-year overall survival (OS) rate, 2.5-year DFS rate, recurrence rate, and recurrence pattern. RESULTS: Compared to the ORH group, the MLRH group exhibited a longer operative time, longer normal bladder function recovery time, less intraoperative blood loss volume, and more harvested pelvic lymph nodes (P < 0.05). No significant differences were observed in postoperative complications, the 2.5-year OS, 2.5-year DFS, and recurrence rate between the two groups (P > 0.05); however, the recurrence pattern was significantly different (P < 0.05). The MLRH group mainly exhibited local single metastasis (7/11), whereas the ORH group mainly exhibited distant multiple metastases (14/16). Stratified analysis revealed that overall survival rate was higher in the MLRH group than in the ORH group in patients with stage 1B1 and middle invasion (P < 0.05). CONCLUSION: MLRH does not show a survival disadvantage in the treatment of early-stage cervical cancer when compared with open surgery. In addition, MLRH shows a survival advantage in patients with stage 1B1 and middle 1/3 invasion. Considering this is a retrospective study, further prospective study is necessary for more sufficient data support. TRIAL REGISTRATION: Present research is a retrospective study. The study had retrospectively registered on Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ), and the registered number is ChiCTR1900026306.

Association between single nucleotide polymorphisms of VEGF gene and pelvic lymph node metastasis in patients with early-stage cervical cancer.

Cervical cancer patients in early-stage cervical cancer (ECC) were divided into pelvic lymph node (PLN) metastasis and non-PLN metastasis group. Single nucleotide polymorphism (SNP) genotyping for the VEGF gene was conducted and plasma VEGF levels were measured. Multivariate analysis was performed to assess the correlation between SNPs of the VEGF gene and PLN metastasis. We found that SNP of the VEGF rs2010963 was independently associated with PLN metastasis. GG and CG genotype had increased susceptibility to PLN metastasis compared with CC genotype, and moreover, OR was higher in GG genotype than in CG genotype. Plasma VEGF levels were lowest in CC genotype, intermediate in GC genotype and highest in GG genotype. In summary, the SNP of the VEGF rs2010963 affected susceptibility to PLN metastasis in patients with ECC, and GG and CG genotype had increased susceptibility compared with CC genotype. The potential mechanism was associated with elevated plasma VEGF levels.Impact StatementWhat is already known on this subject? The positive expression of vascular endothelial growth factor (VEGF) is correlated with higher risk of lymph node metastasis among cervical cancer patients, and VEGF levels of patients with pelvic lymph node (PLN) metastasis are significantly higher than those without PLN metastasis. Additionally, single nucleotide polymorphisms (SNPs) of the VEGF gene have been indicated to be correlated with individual susceptibility to tumours and expression and protein production of VEGF.What do the results of this study add? The SNP of the VEGF rs2010963 was independently associated with PLN metastasis in patients with early-stage cervical cancer (ECC). The GG and CG genotype of the VEGF rs2010963 had increased susceptibility to PLN metastasis compared with CC genotype. Plasma VEGF levels were lowest in the CC genotype, intermediate in the GC genotype and highest in the GG genotype.What are the implications of these findings for clinical practice and/or further research? The SNP of the VEGF rs2010963 affected susceptibility to PLN metastasis in patients with ECC, and the potential mechanism was associated with elevated plasma VEGF levels.

Laparoscopic Radical Trachelectomy after Neoadjuvant Chemotherapy for Fertility Preservation in Early-Stage Bulky Cervical Cancer: A Case Report and Literature Review.

Management of early-stage cervical cancer (CC) in young women often faces challenges to preserve fertility, as well as to achieve an adequate oncological outcome. Although existing evidence supports a fertility-sparing treatment in the case of tumors <2 cm in diameter, the approach is less clear in bulky early-stage CC. In addition, the outcomes of radical trachelectomy performed by minimally invasive techniques are also highly debatable. Highlighting the high incidences of young women with early-stage CC, the lack of sufficient data raises considerable hindrances towards the proper counseling of this vulnerable patient group. In this report, a case of a young woman with bulky early-stage CC with a strong desire to preserve fertility is presented. A satisfactory oncological outcome was achieved after neoadjuvant chemotherapy followed by laparoscopic radical trachelectomy. Ongoing prospective trials are expected to provide stronger evidence on this topic.

Retrospective Comparison of Laparoscopic versus Open Radical Hysterectomy for Early-Stage Cervical Cancer in a Single Tertiary Care Institution from Lithuania between 2009 and 2019.

Background and Objectives: A great debate within the academic arena was evoked by the LACC study, giving rise to doubt regarding the oncological outcomes of the laparoscopic approach for early-stage cervical cancer. This encouraged us to conduct a retrospective analysis of CC treatment surgical approaches applied to the patients at tertiary level Vilnius University Hospital Santaros Clinics, Vilnius, Lithuania, between 2009 and 2019. Materials and Methods: The retrospective study was carried out to evaluate the outcomes after 28 laparoscopic and 62 laparotomic radical hysterectomies for early cervical cancer in a single tertiary care institution performed during the period 2009-2019. For statistical analysis of patients' parameters, SPSS v. 17.0 was applied, together with the Kaplan-Meier method with a long-rank test and the Cox proportional hazard regression model used for bi-variate analysis determining OS outcomes between MIS and open-surgery groups. Results: After computing data with the Cox regression model, there was no significant difference of the 36-months overall survival between laparoscopy and laparotomy groups, as opposed to the LACC study. Conclusions: Our tertiary institution faces a considerable challenge, and we acknowledge the limitations of the study and also feel a responsibility to follow the latest guidelines. Currently, it appears that the most substantial attention should be focused on the cessation of uterine manipulator use as well as laparoscopic technique learning curves.

The role of semiquantitative evaluation of lympho-vascular space invasion in early stage cervical cancer patients.

OBJECTIVE: Lymph vascular space involvement (LVSI) is one of the most important prognostic factors in early stage cervical cancer. Its qualitative evaluation represents a milestone for patient risk stratification and treatment choice, but a semi-quantitative analysis of LVSI may offer a more truthful risk model, as already demonstrated for endometrial cancer. The present study aims to investigate the performances of a semi-quantitative evaluation of LVSI in terms of patient risk assessment. METHODS: In this retrospective study were enrolled patients underwent surgical treatment for early cervical cancer from January 2009 to October 2018. A semi-quantitative evaluation such as the "three-tiered approach" was used to classify the LVSI pathway: negative vs. focal vs. diffuse. RESULTS: Diffuse LVSI was found to be a risk factor for lymph node metastasis (OR: 9.844, p < 0.001), and parametrial involvement (OR: 5.566, p < 0.001). Lymph nodal recurrences were more frequent in diffuse LVSI group (LVSI negative vs. focal LVSI p = 0.369; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.214); and so distant recurrences (LVSI negative vs. focal LVSI p = 0.623; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.026). Patients with diffuse LVSI showed a worse disease-free survival (DFS) than patients with focal or absent involvement (DFS LVSI negative vs. focal LVSI p = 0.938; LVSI negative vs. diffuse LVSI p < 0.001; focal LVSI vs. diffuse LVSI p = 0.036). CONCLUSION: Semi-quantitative evaluation of LVSI may be useful to identify risk patients for shorter disease-free survival and lymphatic and distant recurrences in patients with early stage.

The impact of modern preoperative high-dose-rate brachytherapy in early-stage cervical cancer.

PURPOSE: To analyze the clinical outcomes and the safety of preoperative high-dose-rate (HDR) image-guided adaptive brachytherapy (IGABT) followed by minimally invasive surgery (MIS) in the multidisciplinary management of early-stage cervical cancer. METHODS AND MATERIALS: Medical records of all consecutive patients with early-stage cervical cancer treated at our institution between 2012 and 2018 with preoperative IGABT in a multidisciplinary approach were reviewed. Treatment schedule was pelvic node dissection, preoperative IGABT followed 6-8 week later by MIS hysterectomy. RESULTS: Seventy patients with cervical cancer FIGO stages (IB1 18.6%, IB2 75.7% and IIA1 5.7%) were treated by preoperative HDR brachytherapy. With a median follow-up of 37.4 months [95% confidence interval, 32.1-39.7 months] isolated vaginal vault recurrence was not observed, 3 pelvic relapses were reported (4.3%). None of patients received postoperative radiotherapy (EBRT) or radiochemotherapy. The estimated 3-year local and pelvis relapse free survival for the entire population were respectively 98% [95% confidence interval, 89%-100%] and 90% [80%-96%]. The estimated 3-year disease-free survival (DFS) for the entire population was 88% [77-94%]. The 3-year overall survival (OS) rate was 97% [88%-99%]. Microscopic vaginal resection margin (R1) was observed in one patient ([1].4%). Lymph-vascular space invasion (LVSI) was found found in 6 (8.6%) patients. Forty-eight late complications in 36 patients (51.4%) were observed. Five (7.1%) grade 3 vaginal wound dehiscence toxicities were observed. Urinary and gastrointestinal toxicities were grade 1-2. No grade 4-5 complications were observed. CONCLUSIONS: Preoperative image-guided adaptive brachytherapy followed by minimally invasive surgery allows high local control, reduces positive surgical margins and rates of lymph-vascular space invasion avoiding adjuvants treatments. Surgical approaches must be discussed with patients including preoperative brachytherapy as a down-staging treatment.

Role of carbon nanoparticle suspension in sentinel lymph node biopsy for early-stage cervical cancer: a prospective study.

OBJECTIVE: To evaluate the clinical diagnostic validity of carbon nanoparticle suspension (CNS) in sentinel lymph node biopsy (SLNB) for assessing lymphatic spread of early-stage cervical cancer. DESIGN: A prospective study. SETTING AND POPULATION: 356 cases. METHODS: We enrolled 356 stage Ia2-IIa2 cervical cancer patients to undergo SLNB using CNS, followed by systematic pelvic lymphadenectomy. All lymph node specimens were assessed using conventional histopathologic ± pathologic ultrastaging analyses. MAIN OUTCOME MEASURES: Sentinel lymph node detection rate (DR), clinical diagnostic validity and various related factors were analysed. RESULTS: CNS identified 1456 SLNs in 325 patients. The overall SLN DR was 91.29%. A significantly higher DR was found for patients with tumours <20 mm (97.75% versus 71.91%; P < 0.001). Two patients had false-negative results. SLNB with CNS had sensitivity of 96.65%, false-negative rate (FNR) of 4.35% and negative predictive value (NPV) of 99.29%. Importantly, sensitivity (100%), NPV (100%) and FNR (0%) were improved when testing the subgroup of patients with tumours <20 mm (267 cases). There were no observed differences in DR based on pathological type or grade, stage, depth of stromal invasion, surgical approach, menopausal status or prior treatment with chemotherapy (P > 0.05). CONCLUSIONS: Sentinel lymph node biopsy with CNS results in favourable DR, sensitivity and NPV for women with early-stage cervical cancer with small tumour sizes. SLNB with CNS is safe, feasible and relatively effective for guiding precise surgical treatment of early-stage cervical cancer. TWEETABLE ABSTRACT: Sentinel lymph node biopsy with carbon nanoparticle suspension is safe and feasible for early-stage cervical cancer.

Surgery for cervical cancer: consensus & controversies.

Surgery plays an important role in the management of early-stage cervical cancer. Type III radical hysterectomy with bilateral pelvic lymph node dissection using open route is the standard surgical procedure. There is level I evidence against the use of laparoscopic/robotic approach for radical hysterectomy for cervical cancer. Emerging data support the use of sentinel lymph node biopsy and nerve sparing radical hysterectomy in carefully selected patients with early-stage disease. In locally advanced cervical cancer patients, the use of neoadjuvant chemotherapy (NACT) followed by radical surgery yields inferior disease-free survival compared to definitive concurrent chemoradiation therapy. Therefore, definitive concurrent chemoradiation is the standard treatment for locally advanced disease. Fertility preserving surgery is feasible in highly selected young patients. Role of less-radical surgical procedures in patients' with low-stage disease with good prognostic factors is under evaluation.

Laparoscopic radical hysterectomy with enclosed colpotomy without the use of uterine manipulator for early-stage cervical cancer.

BACKGROUND: We report the application of transuterine suspension sutures (TUSSs) for manipulation and vaginal closure before colpotomy in laparoscopic radical hysterectomy for early-stage cervical cancer. METHODOLOGY: Eight patients with clinical stage IB1 cervical squamous cell cancer were treated with laparoscopic radical hysterectomy between October 2019 and May 2020. The procedure was performed without a traditional uterine manipulator, and the vaginal cuff was closed with a stapler before colpotomy to prevent tumour spillage. RESULTS: All patients successfully underwent the surgery, with a median hospitalisation of 8 days (range 6-14). All drains and urethral catheters were removed after a median of 7 days (range 5-11) and 16 days (range 12-21), respectively. A median of 26 (range 20-32) pelvic lymph nodes were resected and no lymph-related complications were encountered post-operatively. With an enclosed colpotomy, no visible tumour tissues were exposed to the pelvic cavity, and all vaginal stumps healed well without complications. All pathological examinations of the vaginal margin were negative, and there were no residual lesions. At a median follow-up of 6 months, all patients were alive with no recurrence of disease. CONCLUSION: We found that laparoscopic radical hysterectomy with TUSS and vaginal closure before colpotomy is a useful and effective procedure to prevent tumour spillage for the treatment of cervical cancer.

DSG2 expression is correlated with poor prognosis and promotes early-stage cervical cancer.

BACKGROUND: The pathogenesis and developmental mechanism of early-stage (FIGO 2009 IA2-IIA2) cervical cancer (CC) remain unclear. Seeking novel molecular biomarkers based on The Cancer Genome Atlas (TCGA) will facilitate the understanding of CC pathogenesis and help evaluate early-stage CC prognosis. METHODS: To identify prognosis-related genes in early-stage CC, we analyzed TCGA mRNA-seq data and clinical data by univariate Cox and Kaplan-Meier plotter analyses. Differential expression analysis identified upregulated genes in early-stage CC. Combined with the genes correlated with unfavorable prognosis, we selected desmoglein-2 (DSG2) for further investigation. To detect DSG2 expression in early-stage CC, we used immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and western blotting. The relationship between the expression of DSG2 and clinical features was analyzed by the Chi square test. Cox analysis was applied to assess the relationship between CC overall survival (OS) and risk factors. The correlations between DSG2 expression and CC cell line proliferation and migration were investigated with Cell Counting Kit-8 (CCK-8) and migration assays. RESULTS: There were 416 prognosis-related genes in early-stage CC. DSG2, matrix metallopeptidase 1 (MMP1), carbonic anhydrase IX (CA9), homeobox A1 (HOXA1), and serine protease inhibitor B3 (SERPINB3) were upregulated in early-stage CC compared with adjacent noncancerous tissue (ANT) and correlated with unfavorable prognosis. Among them, DSG2 was most significantly correlated with patient survival. Coexpression analysis indicated that DSG2 was probably involved in cell division, positive regulation of transferase activity, positive regulation of cell migration, EGFR upregulation pathway and regulation of lymphangiogenesis. IHC, qRT-PCR and western blotting showed that DSG2 expression was higher in CC than in normal tissue. Significant correlations were identified between DSG2 expression and several aggressive clinical features, including pelvic lymph node metastasis (PLNM). Multivariate Cox analysis showed that DSG2 and PLNM were independent prognostic factors for OS. DSG2 knockdown inhibited CC cell proliferation and migration. CONCLUSIONS: DSG2 is a biomarker that promotes tumor proliferation and metastasis and is correlated with poor prognosis in early-stage CC.

Consolidation chemotherapy in early-stage cervical cancer patients with lymph node metastasis after radical hysterectomy.

OBJECTIVE: Post-operative concurrent chemoradiotherapy has become the standard treatment for patients with positive lymph nodes after radical surgery. The aim of this study was to explore the efficiency and safety of consolidation chemotherapy in early-stage cervical cancer patients with lymph node metastasis after radical hysterectomy. METHOD: We reviewed the medical records of patients with early-stage cervical cancer with lymph node metastasis after radical hysterectomy from January 2010 to January 2017. All patients underwent adjuvant concurrent chemoradiotherapy (n=49) or three cycles of platinum-based consolidation chemotherapy following concurrent chemoradiotherapy (n=89). The primary end points of the study were disease-free survival and overall survival. RESULTS: The median follow-up time was 51 months (range 10-109). No significant difference was noted in disease-free survival, overall survival, or grade 3/4 gastrointestinal disorder between the consolidation chemotherapy group (78.1% vs 83.1% vs 6.7%) and the concurrent chemoradiotherapy alone group (75.4% vs 75.3% vs 4.1%), (p=0.42, 0.26, 0.80, respectively). However, the grade 3/4 myelosuppression rate in the consolidation group was higher than in the concurrent chemoradiotherapy alone group (40.4% vs 22.4%, p=0.03). For patients with >3 positive lymph nodes or patients with >2 positive lymph nodes+lymphovascular space invasion/≥1/3 stromal invasion, disease-free survival and overall survival were superior in the consolidation chemotherapy group compared with the concurrent chemoradiotherapy alone group (p<0.05). CONCLUSION: In patients with >3 positive lymph nodes or patients with >2 positive lymph nodes, lymphovascular space invasion, and greater than 1/3 stromal invasion, disease-free survival and overall survival were superior with consolidation chemotherapy. However, consolidation chemotherapy was also associated with an increased grade 3/4 myelosuppression rate.