Rene Pareja

Response to: Correspondence on “Sentinel lymph node assessment in patients with atypical endometrial hyperplasia: a systematic review and meta-analysis” by Vieira-Serna et al and Restaino et al

Development of a surgical competency assessment tool for sentinel lymph node dissection by minimally invasive surgery for endometrial cancer

Sentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance. A Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability. Seventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; P<0.001). Internal consistency of the items was high (Cronbach α=0.88). Specific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.

Uterine transposition for fertility and ovarian function preservation after radiotherapy

To evaluate the feasibility of uterine transposition as a method of preserving fertility and ovarian function after pelvic radiation. This prospective multicenter observational study included patients with non-gynecologic pelvic cancers who underwent pelvic radiation as part of their cancer treatment between June 2017 and June 2019. For inclusion in the study, patients were required to have normal menstrual cycles and hormone levels (follicle-stimulating hormone, luteinizing hormone, and estrogen) before treatment. Uterine transposition to the upper abdomen was performed prior to irradiation. Clinical examinations and Doppler ultrasonography were used to evaluate the gonadal vasculature post-surgery. The uterus was repositioned into the pelvis 2-4 weeks after radiation therapy or at the time of rectosigmoid resection in patients with rectal cancer who had undergone neoadjuvant treatment. Cancer treatment and follow-up were performed according to standard guidelines. Eight patients (seven with rectal cancer and one with pelvic liposarcoma) underwent uterine transposition at a median age of 30.5 years (range 19-37). The uterus was successfully preserved in six patients, accompanied by normal menses, hormonal levels, and vaginal intercourse after treatment. One patient with rectal cancer died of carcinomatosis 4 months after uterine transposition. One patient presented with uterine necrosis 4 days after uterine transposition, and the uterus was removed; however, one ovary was preserved. Cervical ischemia was the most common post-surgical complication in three (37.5%) patients. Three patients attempted to conceive, and two (66%) were spontaneously successful and delivered healthy babies at 36 and 38 weeks by cesarean section without complications. Uterine transposition is a feasible procedure for preserving gonadal and uterine function in patients requiring pelvic radiotherapy for non-gynecological cancer, with the potential for achieving spontaneous pregnancy and successful delivery.

Highlights from the 24th European Congress on Gynaecological Oncology in Istanbul: an ENYGO-IJGC Fellows compilation

Sentinel lymph node assessment in patients with atypical endometrial hyperplasia: a systematic review and meta-analysis

This systematic review and meta-analysis aimed to assess the rate of sentinel lymph node (SLN) metastases in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia and endometrial cancer in hysterectomy specimens. A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and the protocol was registered in PROSPERO (CRD42023416769). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2023. The inclusion criteria were patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia undergoing hysterectomy who did or did not undergo SLN assessment. Four studies met the inclusion criteria. All studies were non-randomized studies with a total of 10 217 patients, 1044 in the SLN group and 9173 in the non-nodal assessment group. The unilateral and bilateral detection rate was 89% (I The rate of SLN metastases in patients with pre-operative atypical hyperplasia/endometrial intra-epithelial neoplasia is less than 2%, suggesting that routine SLN evaluation may not be necessary in this population.

Pelvic peritonectomy versus rectosigmoid resection in advanced epithelial ovarian cancer with Douglas pouch involvement: a systematic review and meta-analysis

To compare the oncologic outcomes in patients with advanced epithelial ovarian cancer and Douglas pouch involvement who underwent pelvic peritonectomy vs rectosigmoid resection as part of cytoreductive surgery. A systematic literature review and meta-analysis were conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses checklist. MEDLINE (through Ovid), Embase, and Cochrane Central Register of Controlled Trials were searched from inception until March 2024. We included studies with 2 arms of intervention comparing pelvic peritonectomy and rectosigmoid resection in patients diagnosed with advanced epithelial ovarian cancer (International Federation of Gynecology and Obstetrics 2014 stage IIB-IVB). Randomized controlled trials and prospective and retrospective observational studies were considered. The protocol was registered in PROSPERO (CRD42024535681). The search identified 821 articles; 598 studies were considered potentially eligible after removing duplicates, and 4 met the selection criteria, including a total of 623 patients. All 4 studies were retrospective. There was no statistically significant difference between patients undergoing pelvic peritonectomy compared to rectosigmoid resection in terms of overall recurrences (OR 0.99, 95% CI 0.53 to 1.83, I The comparison between pelvic peritonectomy and rectosigmoid resection for the treatment of Douglas pouch carcinomatosis in advanced ovarian cancer revealed no significant differences in overall and pelvic recurrence rates. Disease-free and overall survival were comparable between the 2 surgical techniques. However, pelvic peritonectomy was associated with shorter surgeries, reduced stoma formation, shorter hospital stay, and lower blood loss and transfusion requirements.

Correspondence on 'ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer – Update 2023*'

Accuracy of pre-operative tumor size assessment compared to final pathology and frequency of adjuvant treatment in patients with FIGO 2018 stage IB2 cervical cancer

The primary aim of our study was to compare tumor size assessment by pre-operative evaluation (physical examination and/or imaging) with tumor size on final pathology. As a secondary outcome, we evaluated the rate of adjuvant treatment in patients who underwent radical hysterectomy whose tumor size was ≥3 cm on final pathology. Patient details were collected from three separate databases: the University of Texas MD Anderson Cancer Center Radical Hysterectomy Database, the SUCCOR Study Group Database, and the Multi-institutional Database LATAM (encompassing Latin America and Europe). Patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer on pre-operative evaluation (physical examination or imaging) who underwent radical hysterectomy with a therapeutic intent were included. Any histological subtype, any tumor grade, and pre-operative evaluation with clinical evaluation and/or imaging (ultrasound, MRI, CT, or PET/CT) was considered. A total of 675 patients met eligibility criteria (SUCCOR=350, LATAM=250, MD Anderson=75). The median age was 46 years (range 22-82) and the median body mass index was 25.6 kg/m Our study showed that there is a high concordance between tumor size assessment by physical examination and MRI, as well as estimates of measurement by MRI and final pathology. In addition, we noted that the majority of patients with FIGO 2018 stage IB2 received adjuvant therapy after radical hysterectomy.

Adjuvant external beam radiotherapy combined with brachytherapy for intermediate-risk cervical cancer

Objective Patients with intermediate-risk cervical cancer receive external beam radiotherapy (EBRT) as adjuvant treatment. It is commonly administered with brachytherapy without proven benefits. Therefore, we evaluated the frequency of brachytherapy use, the doses for EBRT administered alone or with brachytherapy, and the overall survival impact of brachytherapy in patients with intermediate-risk, early-stage cervical cancer. Methods This retrospective cohort study was performed using data collected from the National Cancer Database. Patients diagnosed with cervical cancer from 2004 to 2019 who underwent a radical hysterectomy and lymph node staging and had disease limited to the cervix but with tumors larger than 4 cm or ranging from 2 to 4 cm with lymphovascular space invasion (LVSI) were included. Patients with distant metastasis or parametrial involvement were excluded. Patients who underwent EBRT alone were compared with those who also received brachytherapy after 2:1 propensity score matching. Results In total, 1174 patients met the inclusion criteria, and 26.7% of them received brachytherapy. After 2:1 propensity score matching, we included 620 patients in the EBRT group and 312 in the combination treatment group. Patients who received brachytherapy had higher equivalent doses than those only receiving EBRT. Overall survival did not differ between the two groups (hazard ratio (HR) 0.88 (95% confidence interval (CI), 0.62 to 1.23]; p=0.45). After stratification according to tumor histology, LVSI, and surgical approach, brachytherapy was not associated with improved overall survival. However, in patients who did not receive concomitant chemotherapy, the overall survival rate for those receiving EBRT and brachytherapy was significantly higher than that for those receiving EBRT alone (HR, 0.48 (95% CI, 0.27 to 0.86]; p=0.011). Conclusion About one-fourth of the study patients received brachytherapy and EBRT. The variability in the doses and radiotherapy techniques used highlights treatment heterogeneity. Overall survival did not differ for EBRT with and without brachytherapy. However, overall survival was longer for patients who received brachytherapy but did not receive concomitant chemotherapy.

Recurrent low-grade uterine sarcoma: a diagnostic and therapeutic challenge

Complications of HIPEC for ovarian cancer surgery: evaluation over two time periods

Cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) is being explored in the upfront, interval, and recurrent setting in patients with ovarian cancer. The objective of this systematic review was to assess the rate of complications associated with HIPEC in epithelial ovarian cancer surgery over two time periods. This study was registered in PROSPERO (CRD42022328928). A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Ovid/Medline, Ovid/Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials were searched from January 2004 to April 2022. We included studies reporting on patients with advanced primary or recurrent epithelial ovarian cancer who underwent cytoreductive surgery and HIPEC. We evaluated two different time periods: 2004-2013 and 2014-2022. A random-effects meta-analysis was used to produce an overall summary. Subgroup analyses were planned according to recruited period for each specific complication type. Heterogeneity was assessed using the I A total of 4928 patients were included from 69 studies for this systematic review; 19 published from 2004-2013, and 50 published from 2014-2022. No significant differences were found between the two time periods in terms of blood transfusions (33% vs 51%; p=0.46; I Our review showed that overall complications have not changed over time for patients undergoing HIPEC in the setting of primary or recurrent ovarian cancer. There was no decrease in the rates of ICU admissions, reoperations, or deaths.

LACC Trial: Final Analysis on Overall Survival Comparing Open Versus Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of –11.1; 95% CI, –15.8 to –6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P &lt; .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.

Vaginal radical trachelectomy: is now the end of an era?

Laparoscopic secondary cytoreductive surgery: let’s not make the same assumptions

De-escalation of surgical radicality for non-fertility preserving management in patients with early-stage cervical cancer: a systematic review

We sought to evaluate the oncologic outcomes of simple hysterectomy in patients with low-risk early-stage cervical cancer (tumors ≤2 cm with limited stromal invasion). This study was registered in PROSPERO (registration number CRD42023433840) following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) checklist. MEDLINE (through Ovid), EmMBASEbase, and Cochrane Central Register of Controlled Trials were searched from inception until June 2023. Randomized controlled trials and observational studies with two arms of comparison (simple hysterectomy with lymph node assessment vs radical hysterectomy with lymph node assessment) in patients with low-risk early-stage cervical cancer were considered. The search identified 1270 articles; eighteen studies were considered potentially eligible after removing duplicates, and four met the selection criteria. Three studies were randomized controlled trials, and the other was a retrospective cohort study. In total, 981 patients were included. There were 485 (49.4%) and 496 (50.6%) patients in the simple hysterectomy and radical hysterectomy groups, respectively. Simple hysterectomy with lymph node assessment was not associated with a higher risk of death at 5 years (RR 0.98, 95% CI: 0.31 to 3.10; I Simple hysterectomy with lymph node evaluation for low-risk early-stage cervical cancer is not associated with a detrimental effect on oncologic outcomes and has a better morbidity profile.

Gastrointestinal stromal tumor: a rare case of ovarian involvement

Hyperthermic intraperitoneal chemotherapy in epithelial ovarian cancer: current evidence-based indications

Beyond oncologic outcomes: fertility and ovarian preservation as key priorities

ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer

The objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer. From April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2-IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size 100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23-67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients-that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0-68.3). Three patients developed recurrent disease within 2 years of surgery-that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%). Our prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.

Measurement of tumor size in early cervical cancer: an ever-evolving paradigm

The major tenets in accurately assessing tumor size in patients with early stage cervical cancer currently include physical examination, imaging studies, and pathologic evaluation. It is estimated that when comparing clinical stage based on physical examination and final pathology, the concordance diminishes as stage increases: 85.4%, 77.4%, 35.3%, and 20.5% for stage IB1, IB2, IIA, and IIB, respectively. Vaginal involvement and larger tumor diameter are considered the main causes of stage inaccuracy. When considering imaging studies, magnetic resonance imaging (MRI) provides the highest level of accuracy in the assessment of cervical tumor size. Its accuracy in determining tumor location within the cervix is approximately 91% and in predicting tumor size 93%. MRI imaging is also significantly more accurate in measuring tumor size, delineating cervical tumor boundaries, and local tumor extension when compared with computed tomography (CT) scan. When comparing with pelvic ultrasound, the accuracy of both imaging techniques (MRI and pelvic ultrasound) in the assessment of tumor size in small versus large tumors is comparable. Pertaining to pathology, the depth of invasion should be measured by convention from the nearest surface epithelium, which equates to tumor thickness. In the setting where tumor is found both in the conization and hysterectomy specimen, the horizontal extent should be measured by summing the maximum horizontal measurement in the different specimens and the depth of invasion measured as the maximum depth in either specimen. A new pattern-based classification for endocervical adenocarcinomas recommends the description of patterns of invasion for human papillomavirus (HPV)-related adenocarcinomas as this is associated with differing risks of lymph node involvement.

Incidence of metastasis in circumflex iliac nodes in patients with cervical cancer: a systematic review

The circumflex iliac nodes distal to the external iliac nodes are frequently removed when bilateral pelvic lymphadenectomy is performed in patients with cervical cancer. The objective of this systematic review was to assess the incidence of metastasis in the circumflex iliac nodes in patients with cervical cancer. PubMed/Medline, ClinicalTrials, Embase, Cochrane Central Register of Controlled Trials, Scopus, and Ovid databases were searched from inception to May 2021. We included articles published in English language reporting all types of studies, except for case reports and commentaries. Abstracts and unpublished studies were excluded. The inclusion criteria were diagnosis of cervical cancer, FIGO 2009 stages IA-IIB, squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, and primary surgery including pelvic lymph node dissection. A total of 3037 articles were identified. Overall, 1165 eligible patients from four studies were included in the analysis. A total of 696 (59.7%) patients had early-stage disease (FIGO 2009 stages IA, IB1, IIA1). The median number of extracted circumflex iliac nodes, which was reported in two studies, was one (range not reported) and three (range 1-13). The positive lymph node rate for the entire population and circumflex iliac node involvement were 26.9% and 3.1%, respectively. Isolated metastases were reported for 904 patients (three studies) and in one patient nodal spread was detected (0.11%). The rate of isolated metastases in circumflex iliac nodes is small and excision of these lymph nodes as part of routine lymphadenectomy should be avoided.

Neoadjuvant chemotherapy in pregnant patients with cervical cancer: a Latin-American multicenter study

To describe oncologic and obstetric outcomes in patients diagnosed with cervical cancer during pregnancy who had a successful delivery after neoadjuvant chemotherapy. A multicenter retrospective review was conducted in 12 institutions from six Latin American countries, between January 2007 and December 2018. Data collected included clinical characteristics, neoadjuvant chemotherapy agents, treatment, obstetric and oncologic outcomes. Thirty-three patients were included. Median age was 34 years (range 31-36). Twenty (60.6%) women were diagnosed at early stage (IB), and 13 (39.4%) with locally advanced stage (IIA-IIIB) according to FIGO 2009 classification. Carboplatin and paclitaxel was the most frequent combination used (60.6%). Partial and complete response rates were 27.3% and 9.1%, respectively. Median gestational age at delivery was 35 weeks (range 34-36). All patients had live births delivered by cesarean section. Obstetric pathology: pre-term labor, placenta percreta or intra-uterine growth restriction, was documented in seven patients (21.2%). Two (6.1%) neonates had low birth weight. Definitive treatment was primary chemo-radiation in 19 (57.6%) patients, radical hysterectomy in 11 (33.3%), abandoned radical hysterectomy with para-aortic lymphadenectomy and ovarian transposition in 1 patient (3.0%), and no further treatment in 2 (6.1%) patients. After a median follow-up of 16.3 months (range 2.0-36.9), 8 (26.7%) patients had recurrent disease. Of these, four (13.3%) died due to disease. Neoadjuvant chemotherapy may be offered to patients wishing to preserve an ongoing pregnancy in order to achieve fetal maturity. Long-term consequences of chemotherapy in the child are yet to be determined.

Oncological outcomes of laparoscopic radical hysterectomy versus radical abdominal hysterectomy in patients with early-stage cervical cancer: a multicenter analysis

Recent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy. We performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models. A total of 1379 patients were included in the final analysis, with 681 (49.4%) operated by laparoscopy and 698 (50.6%) by laparotomy. There were no differences regarding the surgical approach in the rates of positive vaginal margins, deep stromal invasion, and lymphovascular space invasion. Median follow-up was 52.1 months (range, 0.8-201.2) in the laparoscopic group and 52.6 months (range, 0.4-166.6) in the laparotomy group. Women who underwent laparoscopic radical hysterectomy had a lower rate of disease-free survival compared with the laparotomy group (4-year rate, 88.7% vs 93.0%; HR for recurrence or death from cervical cancer 1.64; 95% CI 1.09-2.46; P=0.02). In sensitivity analyzes, after adjustment for adjuvant treatment, radical hysterectomy by laparoscopy compared with laparotomy was associated with increased hazards of recurrence or death from cervical cancer (HR 1.7; 95% CI 1.13 to 2.57; P=0.01) and death for any cause (HR 2.14; 95% CI 1.05-4.37; P=0.03). In this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy.

Adjuvant treatment after radical surgery for cervical cancer with intermediate risk factors: is it time for an update?

Cervical cancer is the fourth most common cancer in women worldwide. The preferred treatment for early stage cervical cancer is radical hysterectomy with pelvic lymph node assessment, and adjuvant therapy is suggested according to histopathological risk factors. A landmark study was published in 1999 that established 'intermediate risk' criteria for relapse, showing a benefit in recurrence free rate in patients that received pelvic radiotherapy. Furthermore, in the presence of parametrial, nodal, or vaginal margin involvement, another key study found that the addition of concurrent cisplatin based chemotherapy to radiation therapy improved progression free and overall survival for 'high risk' early cervical cancer. With the advancement in treatment modalities in surgery and radiotherapy, and the improved identification of prognostic histopathological factors, several authors have reconsidered the role of adjuvant therapy after radical hysterectomy in the presence of intermediate risk criteria. Here we review the literature on the evolution of adjuvant therapy for intermediate risk factors.

Surgical staging for locally-advanced cervical cancer: the answer remains ‘NO’

Outcomes of open radical hysterectomy following implementation of an enhanced recovery after surgery program

Open surgery has become the standard approach for radical hysterectomy in early stage cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2018 IA1 with lymphovascular space invasion-IIA1). Our primary objective was to compare the length of stay in patients undergoing open radical hysterectomy before and after implementation of an enhanced recovery after surgery (ERAS) program. This was a single center, retrospective, before-and-after intervention study including patients who underwent open radical hysterectomy for cervical cancer from January 2009 to December 2020. Two groups were identified based on the time of ERAS implementation: pre-ERAS group included patients who were operated on between January 2009 and October 2014; post-ERAS group included patients who underwent surgery between November 2014 and December 2020. A total of 81 patients were included, of whom 29 patients were in the pre-ERAS group and 52 patients in the post-ERAS group. Both groups had similar clinical characteristics with no differences in terms of median age (42 years (interquartile range (IQR) 35-53) in pre-ERAS group vs 41 years (IQR 35-49) in post-ERAS group; p=0.47) and body mass index (26.1 kg/m Patients undergoing open radical hysterectomy on an ERAS pathway have a shorter length of hospital stay without increasing overall complications or readmissions rates.

Fertility-sparing surgery after neo-adjuvant chemotherapy in women with cervical cancer larger than 4 cm: a systematic review

The objective of this systematic review was to assess the oncologic and fertility outcomes of patients with cervix-confined cancer >4 cm who underwent neo-adjuvant chemotherapy followed by fertility-sparing surgery. This study was registered in PROSPERO (registration number CRD42021254816). PubMed/MEDLINE, ClinicalTrials, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, and OVID databases were searched from inception to July 2021. The included patients were those with cancer confined to the cervix and tumor diameter >4 cm (International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3) with squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma who underwent intra-venous neo-adjuvant chemotherapy followed by successful fertility-sparing surgery. The initial search identified 2990 articles. A total of 40 patients from 11 studies had attempted fertility preservation surgery (conization, simple or radical trachelectomy) and in 26 patients (65%) it was successful. All patients received platinum-based chemotherapy. A complete pathological response occurred in 56% of patients and two patients (7.7%) had a recurrence. The 4.5-year disease-free survival was 92.3% and the 4.5-year overall survival rate was 100%. Of six patients who tried to conceive, four (67%) achieved at least one pregnancy and three of the five pregnancies (60%) were pre-term deliveries (all after radical trachelectomy). All patients with recurrence received cisplatin and ifosfamide instead of cisplatin and paclitaxel, underwent non-radical surgery, and had residual disease in the final specimen. Evidence for fertility-sparing surgery after neo-adjuvant chemotherapy in patients with cervical cancer and tumors >4 cm is limited, and this approach should be considered as an experimental intervention. As the use of non-radical surgery could be a risk factor, if neo-adjuvant chemotherapy is used, patients should undergo fertility-sparing radical surgery.

MILACC study: could undetected lymph node micrometastases have impacted recurrence rate in the LACC trial?

The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial. Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells). The study included 20 patients with median age of 42 (range 30-68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4-32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node. There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.

Definitive pelvic radiotherapy for patients with newly diagnosed stage IVB cervical cancer: a systematic review

The objective of this systematic review was to assess the oncologic outcomes of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IVB cervical cancer receiving definitive pelvic radiotherapy compared with systemic chemotherapy (with or without palliative pelvic radiotherapy). This study was registered in PROSPERO (registration number CRD42022333433). A systematic literature review was conducted following the MOOSE checklist. MEDLINE (through Ovid), Embase, and Cochrane Central Register of Controlled Trials were searched from inception until August 2022. The inclusion criteria were patients with metastatic FIGO 2018 stage IVB cervical cancer, a histologic subtype of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma that received definitive pelvic radiotherapy (≥45 Gy) as part of management compared with systemic chemotherapy with or without palliative (30 Gy) pelvic radiotherapy. Randomized controlled trials and observational studies with two arms of comparison were considered. The search identified 4653 articles; 26 studies were considered potentially eligible after removing duplicates, and 8 met the selection criteria. In total, 2424 patients were included. There were 1357 and 1067 patients in the definitive radiotherapy and chemotherapy groups, respectively. All included studies were retrospective cohort studies, and two were database population studies. The median overall survival reported in seven studies for the definitive radiotherapy arm versus systemic chemotherapy groups were 63.7 months versus 18.4 months (p<0.01), 14 months versus 16 months (p value not reported), 17.6 months versus 10.6 months (p<0.01), 32 months versus 24 months (p<0.01), 17.3 months versus 10 months (p<0.01), and 41.6 months versus 17.6 months (p<0.01), and not reached versus 19 months (p=0.13) respectively, favoring the groups that received definitive pelvic radiotherapy. The high clinical heterogeneity precluded the performance of meta-analysis, and all studies were at serious risk of bias. Definitive pelvic radiotherapy as part of treatment in patients with stage IVB cervical cancer may improve oncologic outcomes compared with systemic chemotherapy (with or without palliative radiotherapy); however, this is based on low-quality data. Prospective evaluation would be ideal before the adoption of this intervention in standard clinical practice.

European Society of Gynaecological Oncology resource-stratified guidelines for the management of patients with cervical cancer.

In 2023, the European Society of Gynaecological Oncology (ESGO), jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP), published evidence-based guidelines for the management of patients with cervical cancer. Acknowledging that limitations exist even in high-income countries, some of these established standards of care are not applicable in clinical practice in some areas of the world. Following a global ESGO survey involving 256 clinicians from 57 countries, which pointed out potential limitations, barriers, and missing guidelines, ESGO decided to develop alternative management strategies for situations when optimal resources are unavailable or limited. A multi-disciplinary international development group consisting of 22 experts, utilizing feedback from the survey conducted mostly in low- and middle-income regions, identified potential limitations to the standards of care as defined in the updated ESGO-ESTRO-ESP guidelines published in 2023 and suggested alternative approaches. New resource-stratified guidelines on the management of women living with the human immunodeficiency virus have been newly proposed. To ensure a global perspective, the guidelines were reviewed by 188 independent international practitioners from Asia, Africa, Europe, and South, Central, and North America. These resource-stratified guidelines focus on achieving the best patient outcomes, with alternative management strategies based on expert opinions in areas with limited evidence. They should be used as a guide for the next best alternatives in multi-disciplinary care settings such as diagnostics, pathology, surgery, radiotherapy, systemic therapy, palliative care, and follow-up management. Efforts should always focus on providing optimal available care. In the absence of key resources, the primary effort should be directed toward consulting and referring patients to other facilities that provide better conditions.

Oncological impact of pelvic vessels embolization in patients with locally advanced cervical cancer treated with concomitant chemoradiotherapy

This study aims to address the impact of pelvic vessel embolization on oncological outcomes in patients with locally advanced cervical cancer treated with concomitant chemoradiotherapy. This is a retrospective single-center cohort study including patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics 2018 stages IB3-IVA), treated between January, 2010, and December, 2020. The primary outcome was overall survival, and the secondary outcome was disease-free survival. An inverse probability of treatment weighting was applied to balance baseline characteristics between groups and generate comparable cohorts. A total of 344 patients were included, of whom 8.4% (n = 29) underwent pelvic vessel embolization before the initiation of definitive treatment with concomitant chemoradiotherapy. In the embolized group, most (75.8%, n = 22) were classified as International Federation of Gynecology and Obstetrics 2018 stage III, and 44.8% of them (n = 13) had hemoglobin levels .05). Patients with cervical cancer who underwent pelvic vessel embolization had worse overall survival in this cohort. Further studies are required to confirm this association.

Silicon dioxide, sodium selenite and citric acid vaginal gel, HPV infection, and cervical preinvasive disease: a narrative review

Cervical cancer continues to be a major public health concern, particularly in low- and middle-income countries. It is mainly caused by persistent infection with human papillomavirus (HPV). Screening has been the most effective strategy to reduce mortality, but over the last 2 decades, vaccination has emerged as an important adjunct, helping to decrease incidence and mortality. Given the natural history of HPV infection, most low-grade lesions will spontaneously resolve over time; therefore, observation is the preferred approach for low-grade squamous intraepithelial lesions. Some authors have suggested that this period without intervention may cause anxiety among patients and physicians. A vaginal gel containing 10.0 mg of silicon dioxide, 24.8 mg citric acid, and 0.25 mg selenium per dose, marketed as DeflaGyn, Deflamin, or Deflamed, has been approved in Europe, the United Arab Emirates, Uzbekistan, and Colombia. A literature search was conducted to identify all published clinical trials on DeflaGyn. As of January 2025, 6 studies have been published: 1 retrospective study, 1 randomized clinical trial (RCT) with 2 post hoc analyses, 1 prospective non-randomized trial, and 1 in vitro study. A methodological risk-of-bias assessment was performed, revealing a number of domains with high or unknown risk of bias in the RCT and its post hoc analyses. This review aims to summarize the available evidence and perform a critical analysis of the research. Current evidence is insufficient to support its use for treating HPV infection or dysplasia.

Inadvertent cervical cancer: a narrative review

Inadvertent cervical cancer, defined as infiltrative cervical carcinoma diagnosed after a simple hysterectomy for presumed benign disease, remains clinically significant yet understudied. Despite the potential for eradication of cervical carcinoma through vaccination, screening, and early treatment, disparities in health care access continue to result in preventable cases, some of which are identified only postoperatively. This condition has long been recognized, yet its management remains undefined and is supported primarily by low- or very low-quality evidence. Diagnostic failures often stem from inadequate preoperative evaluation, missed follow-up of abnormal screening results, and insufficient re-excision with conization when indicated. Social determinants of health, including race and ethnicity, socioeconomic status, and insurance status, contribute significantly to these lapses. The identification of invasive disease only postoperatively may negatively impact prognosis, even in early stages. Treatment strategies for inadvertent cervical cancer include observation, radiotherapy with or without chemotherapy, and completion surgery, such as lymph node assessment with or without parametrectomy. While retrospective studies suggest similar oncologic outcomes across some strategies (eg, additional surgery or radiotherapy), the absence of prospective trials limits definitive conclusions. Furthermore, morbidity and quality-of-life outcomes are frequently underreported. To support clinical decision-making, we propose a risk-based classification of this condition, categorizing patients as very low, low, medium, or high risk. Until stronger evidence emerges, treatment decisions should be individualized based on tumor features, surgical approach, and patient preferences. This review summarizes current evidence, highlights gaps in knowledge, and offers a pragmatic algorithm for managing this complex clinical entity.

Cervical cancer: a new era

Cervical cancer is a major global health issue, ranking as the fourth most common cancer in women worldwide. Depending on stage, histology, and patient factors, the standard management of cervical cancer is a combination of treatment approaches, including (fertility- or non-fertility-sparing) surgery, radiotherapy, platinum-based chemotherapy, and novel systemic therapies such as bevacizumab, immune checkpoint inhibitors, and antibody-drug conjugates. While ambitious global initiatives seek to eliminate cervical cancer as a public health problem, the management of cervical cancer continues to evolve with major advances in imaging modalities, surgical approaches, identification of histopathological risk factors, radiotherapy techniques, and biomarker-driven personalized therapies. In particular, the introduction of immune checkpoint inhibitors has dramatically altered the treatment of cervical cancer, leading to significant survival benefits in both locally advanced and metastatic/recurrent settings. As the landscape of cervical cancer therapies continues to evolve, the aim of the present review is to provide a comprehensive discussion of the current state and the latest practice-changing updates in cervical cancer.

Pelvic lymph node involvement and risk of recurrence in HPV‐associated endocervical adenocarcinoma stage IA2‐IB1 according to Silva's system in two Colombian cancer centers

AbstractObjectiveTo compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)‐associated endocervical adenocarcinoma stage IA2‐IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system.MethodsA retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan–Meier method was used to estimate overall survival and disease‐free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists.ResultsA total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow‐up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P &lt; 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22‐ and 4.46‐fold increased risk of relapse, respectively, compared with pattern A. The 5‐year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively.ConclusionFor patients with early‐stage HPV‐associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer

The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

Efficacy of topical treatments for high-risk human papillomavirus in preventing CIN II+ lesions: a systematic review

This study aimed to systematically review the literature regarding topical therapies for reducing the risk of cervical intra-epithelial neoplasia (CIN) grade 2 or higher (CIN II+) lesions among women with high-risk human papillomavirus (HPV) infection and histologically confirmed CIN I or either no cervical lesions. We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered the protocol in PROSPERO (CRD42024629608). We searched Ovid MEDLINE, Ovid EMBASE, Cochrane Central, and ClinicalTrials.gov from inception through December 16, 2024 for randomized controlled trials evaluating any cervical topical treatment in women with high-risk HPV and, at most, CIN I. The primary outcome was progression to histologically confirmed CIN II+. Secondary outcomes were treatment-related adverse events. Of 305 records, 19 full-text articles were reviewed. Finally, 16 trials were assessed. None met all our eligibility criteria, with some trials being excluded for multiple reasons. Twelve were excluded due to an inadequate study population (included women with CIN II+, lacked histologic confirmation of lesion grade, or lacked confirmatory high-risk HPV testing), 4 used inappropriate interventions, and 2 did not include a placebo or watchful waiting comparator. Although many studies reported HPV clearance or cytologic regression, none were powered or designed to assess progression to CIN II+. The current evidence from randomized trials is insufficient to determine whether topical cervical therapies reduce the risk of progression to CIN II+ in women with high-risk HPV infection. Future trials should prioritize histologic outcomes and adhere to current management protocols to establish the clinical utility of such therapies.

A Diagnostic Nomogram for Predicting Vaginal Invasion in Cervical Cancer

This study aims to develop a diagnostic nomogram based on clinical factors with the prediction values of vaginal invasion in cervical cancer to optimize the treatment plan and surgical procedures.

Laparoscopic Approach to Cervical Cancer

The goal of this clinical research study is to compare the long-term outcomes of different surgical methods for the treatment of cervical cancer. The long-term outcome of a total abdominal radical hysterectomy (TARH) will be compared against laparoscopy. In this study, the laparoscopy will be done with or without robotic technology.