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

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Survival after sentinel lymph node biopsy for early cervical cancers: a systematic review and meta-analysis.

BACKGROUND: Sentinel lymph node biopsy represents an alternative to pelvic lymphadenectomy for lymph node staging of early-stage cervical carcinoma, but prospective evidence on long-term oncological safety of sentinel lymph node biopsy alone versus pelvic lymphadenectomy is missing. OBJECTIVE: To investigate, with this meta-analysis, the impact of sentinel lymph node biopsy alone versus pelvic lymphadenectomy on survival for patients with early-stage cervical cancer. METHODS: A systematic literature review was performed. We excluded studies in which pelvic lymphadenectomy was systematically performed after every sentinel lymph node biopsy, including only articles where pelvic lymphadenectomy was performed because sentinel lymph node biopsy was not conclusive. A meta-analysis was carried out combining 5-year disease-free survival and overall survival rates with a random and fixed effect model. Heterogeneity was tested using the Cochran Χ2 test and quantified with Higgins information I2. RESULTS: The search of databases and registers found 927 items and six articles (two retrospective and four prospective). The median time of follow-up was 34.8 months (range 13-53). Overall common effect disease-free survival was 98% while random effect disease-free survival was 94%. Overall heterogeneity was 77%. A subgroup analysis was applied, dividing studies into one group including sentinel lymph node biopsy negative data only (common effect disease-free survival 91%; random effect disease-free survival 90%), and one group with a negative and positive sentinel lymph node biopsy (common effect disease-free survival 98%; random effect disease-free survival 96%). In the analysis of overall survival, positive and negative sentinel lymph node biopsy cases were examined together (common and random effect overall survival 99%). Ultrastaging did not affect disease-free survival (common and random effect disease-free survival 92% in the ultrastaging group vs common effect disease-free survival 99% and random effect disease-free survival 96% in the non-ultrastaging group). CONCLUSIONS: Both 5-year disease-free survival and overall survival rate after sentinel lymph node biopsy alone are higher than 90% and do not differ from pelvic lymphadenectomy survival data. Ultrastaging did not impact survival.

Management of patients with advanced epithelial ovarian cancer: a European survey.

BACKGROUND: The aim of this study was to assess current European practices in the management of patients with advanced epithelial ovarian cancer in 2021. METHODS: A 58-question electronic survey was distributed anonymously to the members of six European learned societies. Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed. RESULTS: A total of 171 participants from 17 European countries responded to emailed surveys. Most participants were experienced practitioners (superior than 15 years of experience) specializing in gynecology-obstetrics (29.8%), surgical oncology (25.1%), and oncogynecology (21.6%). According to most (64.8%) participants, less than 50% of patients were eligible for primary debulking surgery. Variations in the rate of primary debulking surgery depending on the country of origin of the practitioners were observed in this study. The LION study criteria were applied in 70.4% of cases during PDS and 27.1% after chemotherapy. In cases of BRCA1-2 mutations, olaparib was given by 75.0-84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases. CONCLUSIONS: This study sheds light on current practices and attitudes regarding the management of patients with advanced epithelial ovarian cancer in Europe in 2021.

Long-term oncological safety of sentinel lymph node biopsy in early-stage cervical cancer: A post-hoc analysis of SENTICOL I and SENTICOL II cohorts.

OBJECTIVES: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). METHODS: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. RESULTS: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. CONCLUSIONS: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

Clinical impact of low-volume lymph node metastases in early-stage cervical cancer: A comprehensive meta-analysis.

OBJECTIVE: In order to define the clinical significance of low-volume metastasis, a comprehensive meta-analysis of published data and individual data obtained from articles mentioning micrometastases (MIC) and isolated tumor cells (ITC) in cervical cancer was performed, with a follow up of at least 3 years. METHODS: We performed a systematic literature review and meta-analysis, following Cochrane's review methods guide and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was the disease-free survival (DFS), and the secondary outcome was the overall survival (OS). The hazard ratio (HR) was taken as the measure of the association between the low-volume metastases (MIC+ITC and MIC alone) and DFS or OS; it quantified the hazard of an event in the MIC (+/- ITC) group compared to the hazard in node-negative (N0) patients. A random-effect meta-analysis model using the inverse variance method was selected for pooling. Forest plots were used to display the HRs and risk differences within individual trials and overall. RESULTS: Eleven articles were finally retained for the meta-analysis. In the analysis of DFS in patients with low-volume metastasis (MIC + ITC), the HR was increased to 2.60 (1.55-4.34) in the case of low-volume metastasis vs. N0. The presence of MICs had a negative prognostic impact, with an HR of 4.10 (2.71-6.20) compared to N0. Moreover, this impact was worse than that of MIC pooled with ITCs. Concerning OS, the meta-analysis shows an HR of 5.65 (2.81-11.39) in the case of low-volume metastases vs. N0. The presence of MICs alone had a negative effect, with an HR of 6.94 (2.56-18.81). CONCLUSIONS: In conclusion, the presence of MIC seems to be associated with a negative impact on both the DFS and OS and should be treated as MAC.

Histopathologic Validation of the Sentinel Node Technique for Early-Stage Cervical Cancer Patients.

BACKGROUND: The sentinel lymph node (SLN) biopsy may be an alternative to systematic lymphadenectomy in early cervical cancer. The SLN biopsy is less morbid and has been shown to have high sensitivity for metastasis detection. However, the sensitivity of the SLN technique might be overevaluated because SLNs are examined with ultra-staging, and non-sentinel nodes usually are examined only with routine techniques. This study aimed to validate the negative predictive value (NPV) of the SLN technique by the ultra-staging of SLNs and non-sentinel nodes (NSLNs). METHODS: The SENTICOL 1 study data published in 2011 were used. All nodes (i.e., SLNs and NSLNs) were secondarily subjected to ultra-staging. The ultra-staging consisted of sectioning every 200 µm, in addition to immunohistochemistry. Moreover, the positive slides and 10% of the negative slides were reviewed. RESULTS: The study enrolled 139 patients, and SLNs were detected in 136 (97.8%) of these patiets. Bilateral SLNs were detected in 104 (76.5%) of the 136 patients. A total of 2056 NSLNs were identified (median, 13 NSLNs per patient; range 1-54). Of the 136 patients with SLNs, 23 were shown to have positive SLNs after serial sectioning and immunohistochemical staining. The NSLNs were metastatic in six patients. In the case of bilateral SLN detection, the NPV was 100%, with no false-negatives (FNs). CONCLUSIONS: The pelvic SLN technique is safe and trustworthy for determining the nodal status of patients with early-stage cervical cancer. In the case of optimal mapping with bilateral detection, the NPV was found to be 100%.

Pre-operative surgical algorithm: sentinel lymph node biopsy as predictor of parametrial involvement in early-stage cervical cancer.

INTRODUCTION: Radical hysterectomy is the gold standard in the management of early-stage cervical cancer. Parametrectomy aims to remove occult disease but is associated with significant surgical morbidity. Avoiding unnecessary parametrectomy in a subset of patients at low risk of parametrial involvement may decrease the incidence of such morbidity. The purpose of this study was to identify patients at low risk of parametrial involvement in early-stage cervical cancer potentially eligible for less radical surgery based on pre-operative criteria and sentinel lymph node (SLN) status. METHODS: We performed an ancillary analysis of data from two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I and II). Patients with International Federation of Gynecology and Obstetrics (FIGO) IA-IIA cervical cancer who underwent primary radical surgery and bilateral SLN mapping were identified between 2005 and 2012 from 25 French oncologic centers. Patients who underwent pre-operative brachytherapy or did not undergo radical surgery (simple trachelectomy, simple hysterectomy, or lymph node staging only) were excluded. RESULTS: Of 174 patients who fullfiled the inclusion criteria, 9 patients (5.2%) had parametrial involvement and 24 patients (13.8%) had positive SLN. Most patients had 2018 FIGO stage IB1 disease (86.1%) and squamous cell carcinomas (68.9%). Parametrial involvement was significantly associated with tumor size ≥20 mm on pelvic magnetic resonance imaging (MRI) (adjusted odds ratio (ORa) 9.30, 95% CI 1.71 to 50.57, p=0.01) and micrometastic or macrometastatic SLN (ORa 8.98, 95% CI 1.59 to 50.84, p=0.01). Of 114 patients with tumors <20 mm on pre-operative MRI and negative SLN after ultrastaging, only one patient had parametrial involvement (0.9%). By triaging patients with both of these criteria in a two-step surgical procedure, unjustified and contra-indicated radical hysterectomy would have been avoided in 65.5% and 8.6% of cases, respectively. CONCLUSIONS: Less radical surgery may be an option for patients with bilateral negative SLN after ultrastaging and tumors <20 mm. SLN status should be integrated into the decision-making process for tailored surgery in early-stage cervical cancer.

[Treatment of early cervical cancer : Back to the future]. / Traitement du cancer débutant du col de l'utérus : retour vers le future.

The treatment of the early-stage cervical cancer is surgical. In the last ten years we have seen a surgical de-escalation and the development of new techniques such as the sentinel node biopsy. In 2018, absolutely against the trend, the study published in the New England Journal of Medicine by Pedro Ramirez upset the world of gynecologic-oncologists by demonstrating that the open approach is superior to the minimally invasive technique in the surgical management of these cancers. A long debate arose after the publication of this article, which remains the only prospective randomized study published to date on the subject. We therefore must take a step back and return to open surgery in the treatment of early-stage cervical cancer.

Le traitement du cancer débutant du col de l'utérus est la chirurgie. Ces dix dernières années, on a assisté à une désescalade chirurgicale et au développement de nouvelles techniques comme celle du ganglion sentinelle. En 2018, en opposition avec l'évolution actuelle, l'étude publiée dans The New England Journal of Medicine par Pedro Ramirez a bouleversé le monde des gynéco-oncologues en démontrant que la chirurgie ouverte (laparotomie) est supérieure à celle mini-invasive dans la prise en charge chirurgicale de ces cancers. Un long débat est né après la publication de cet article qui reste la seule étude prospective randomisée publiée jusqu'à maintenant sur le sujet. Cependant, actuellement, il est donc impératif de faire un pas en arrière et de revenir à la chirurgie ouverte pour le traitement du cancer débutant du col de l'utérus.

Impact of micrometastasis or isolated tumor cells on recurrence and survival in patients with early cervical cancer: SENTICOL Trial.

OBJECTIVES: The aim of this study was to evaluate the impact of micrometastasis and isolated tumor cells on disease recurrence in patients with early-stage cervical cancer. METHODS: We included patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA1 with lymphvascular space invasion, stage IA2, and IB1 who participated in the SENTICOL1 trial. A centralized histologic analysis with re-reading and ultrastaging was performed 3 months after surgery and treatment was not impacted by findings from our study. Patients were followed for 3 years and outcomes were compared according to prognostic factors. RESULTS: A total of 139 patients were included and 13 recurrences were found. There were two recurrences in patients with positive sentinel lymph node (SLN) (one macrometastases and one micrometastases) and 11 recurrences in patients with negative lymph nodes (sentinel or non-sentinel). Among patients with positive SLN for micrometastases there was only one recurrence. No patient with isolated tumor cells on their lymph nodes experienced a recurrence. There was a significant decrease in disease-free survival in patients aged >50 years (p = 0.01). CONCLUSION: Evidence of micrometastasis or isolated tumor cells in the SLN of untreated patients with early cervical cancer in the SENTICOL1 trial did not impact progression-free survival.