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Objective: To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs., Methods: Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels). SLNs from each site were submitted for central quality control., Results: In the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2-4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%)., Conclusion: SLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging., Study Registration: NCT02494063 (ClinicalTrials.gov)., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer., Methods: International, multicenter, retrospective study., Inclusion Criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy ('SLN' group) or pelvic lymphadenectomy alone ('non-SLN' group)., Results: 1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5-98.5 versus 92.0 %,95 %CI:90.0-94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8-99.9 versus 96.8 %,95 %CI:95.4-98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266-0.959, p = 0.037 and HR:2.703,95 %CI:1.389-5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039)., Conclusion: Adding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Abu-Rustum received research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In cervical cancer, presence of lymph-node macrometastases (MAC) is a major prognostic factor and an indication for adjuvant treatment. However, since clinical impact of micrometastases (MIC) and isolated tumor-cells (ITC) remains controversial, we sought to identify a cut-off value for the metastasis size not associated with negative prognosis., Methods: We analyzed data from 967 cervical cancer patients (T1a1L1-T2b) registered in the SCCAN (Surveillance in Cervical CANcer) database, who underwent primary surgical treatment, including sentinel lymph-node (SLN) biopsy with pathological ultrastaging. The size of SLN metastasis was considered a continuous variable and multiple testing was performed for cut-off values of 0.01-1.0 mm. Disease-free survival (DFS) was compared between N0 and subgroups of N1 patients defined by cut-off ranges., Results: LN metastases were found in 172 (18%) patients, classified as MAC, MIC, and ITC in 79, 54, and 39 patients, respectively. DFS was shorter in patients with MAC (HR 2.20, P = 0.003) and MIC (HR 2.87, P < 0.001), while not differing between MAC/MIC (P = 0.484). DFS in the ITC subgroup was neither different from N0 (P = 0.127) nor from MIC/MAC subgroups (P = 0.449). Cut-off analysis revealed significantly shorter DFS compared to N0 in all subgroups with metastases ≥0.4 mm (HR 2.311, P = 0.04). The significance of metastases <0.4 mm could not be assessed due to limited statistical power (<80%). We did not identify any cut-off for the size of metastasis with significantly better prognosis than the rest of N1 group., Conclusions: In cervical cancer patients, the presence of LN metastases ≥0.4 mm was associated with a significant negative impact on DFS and no cut-off value for the size of metastasis with better prognosis than N1 was found. Traditional metastasis stratification based on size has no clinical implication., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest We declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN)., Methods: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences., Results: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL ( P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL., Conclusion: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL., Competing Interests: Brian SlomovitzConsulting or Advisory Role: Clovis Oncology, AstraZeneca, Genentech, Incyte, Agenus, GlaxoSmithKline, GOG Foundation, Myriad Genetics, Merck, Eisai Ignace VergoteConsulting or Advisory Role: Amgen, AstraZeneca, Clovis Oncology, Carrick Therapeutics, Deciphera, Elevar Therapeutics, Genmab, GlaxoSmithKline, Immunogen, Jazz Pharmaceuticals, Mersana, MSD, Novocure, OCTIMET Oncology NV, Oncoinvent, Sotio, Verastem, Zentalis, Roche, MillenniumResearch Funding: Roche, Genmab, Amgen, OncoinventTravel, Accommodations, Expenses: Roche, AstraZeneca, Tesaro, Amgen, MSD/Merck Mats BrännströmStock and Other Ownership Interests: EUGIN Sweden Martin WidschwendterStock and Other Ownership Interests: Sola Diagnostics, BreOva HealthPatents, Royalties, Other Intellectual Property: Patents relevant for risk prediction or diagnosis of women's cancers Paul A. DiSilvestroConsulting or Advisory Role: AstraZeneca, AgenusResearch Funding: Janssen Oncology, Tesaro, AstraZeneca, Genentech, AbbVie Robert MannelConsulting or Advisory Role: Tesaro Dorry BollResearch Funding: AstraZeneca David CibulaConsulting or Advisory Role: AstraZeneca, Sotio, Roche, GlaxoSmithKline Diane ProvencherConsulting or Advisory Role: AstraZeneca, GlaxoSmithKlineResearch Funding: AstraZeneca, AbbVie Ingo B. RunnebaumConsulting or Advisory Role: AbbVie (I), Amgen, AstraZeneca, Clovis Oncology, GlaxoSmithKline, Oncgnostics, Tesaro Preben KjølhedeResearch Funding: Leo Pharma AB Katharina E. KieserHonoraria: AstraZenecaConsulting or Advisory Role: MerckResearch Funding: AstraZeneca Nicola M. SpirtosResearch Funding: AbbVie, AstraZeneca, Genentech/Roche, Clovis Oncology, Seattle GeneticsPatents, Royalties, Other Intellectual Property: Application No. PCT/US 2019/19465 Cannabis Based Therapeutic and Method of Use Application No, US Patent 0024098766 Compounds Cannabidiol and Flavanones 63/047550 (July 1, 2020) 63/055458 (July 23, 2020) David M. O'MalleyConsulting or Advisory Role: Janssen Oncology, AstraZeneca, Clovis Oncology, Tesaro, Novocure, AbbVie, Genentech/Roche, OncoQuest, Immunogen, GOG Foundation, Translational Genomics Research Institute, Agenus, Marker Therapeutics, Eisai, Genelux, Iovance Biotherapeutics, Ambry Genetics, Tarveda Therapeutics, Leap Therapeutics, Myriad Genetics, GlaxoSmithKline, Regeneron, Sorrento Therapeutics, Rubius Therapeutics, Elevar Therapeutics, Novartis, Seagen, BBI Healthcare, Arquer Diagnostics, Toray Medical, Takeda, InxMed, Celsion, Roche Diagnostics MSAResearch Funding: Amgen, AstraZeneca, Genentech/Roche, Regeneron, Immunogen, Janssen Research & Development, Clovis Oncology, EMD Serono, Ergomed, Ajinomoto, Cerulean Pharma, PharmaMar, Array BioPharma, Bristol Myers Squibb, Agenus, Tesaro, TRACON Pharma, Genmab, Seattle Genetics, Iovance Biotherapeutics, Leap Therapeutics, Merck, AbbVie/Stemcentrx, AbbVie, Mersana, Eisai, BBI Healthcare, Sumitomo Dainippon Pharma Oncology Mario M. LeitaoHonoraria: Intuitive SurgicalConsulting or Advisory Role: Intuitive Surgical, Ethicon/Johnson & Johnson, Medtronic, TakedaResearch Funding: KCITravel, Accommodations, Expenses: Intuitive Surgical Melissa A. GellerResearch Funding: Tesaro, Genentech, FATE Therapeutics, Morphotek, Bayer Karl TamussinoOther Relationship: Medtronic Daniel H. TobiasConsulting or Advisory Role: Ethicon Jayanthi S. LeaConsulting or Advisory Role: Roche Brynhildur EyjolfsdottirOther Relationship: Intuitive Surgical Krishnansu S. TewariHonoraria: Tesaro, Clovis OncologyConsulting or Advisory Role: Roche/Genentech, Tesaro, Clovis Oncology, AstraZenecaSpeakers' Bureau: Roche/Genentech, AstraZeneca, Merck, Tesaro, Clovis OncologyResearch Funding: AbbVie, Genentech/Roche, Morphotek, Merck, RegeneronTravel, Accommodations, Expenses: Roche/Genentech Ranjit ManchandaHonoraria: AstraZeneca Linda Van LeConsulting or Advisory Role: EyePoint Pharmaceuticals, Novartis, Advarum, Neurotech, Iveric, Gemini Therapeutics, NaegisResearch Funding: GOG Partners Trial Bradley J. MonkLeadership: US OncologyHonoraria: AbbVie, Advaxis, Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoID, Clovis Oncology, Deciphera Pharmaceuticals, Eisai, Geistlich Pharma, Genmab/Seattle Genetics, ImmunoGen, Immunomedics, Incyte, Iovance Biotherapeutics, Laekna Health Care, Merck, Mersana, Myriad Pharmaceuticals, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Senti Biosciences, Takeda, Tarveda Therapeutics, Tesaro/GSK, Vavotar Life Sciences, Vascular Biogenics, Vigeo Therapeutics, GOG Foundation, Starton Therapeutics, Elevar Therapeutics, Novocure, Gradalis, Karyopharm TherapeuticsConsulting or Advisory Role: AbbVie, Advaxis, Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Clovis Oncology, Deciphera Pharmaceuticals, Eisai, Geistlich Pharma, Genmab/Seattle Genetics, GOG Foundation, ImmunoGen, Immunomedics, Incyte, Iovance Biotherapeutics, Laekna Health Care, Merck, Mersana, Myriad Pharmaceuticals, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Senti Biosciences, Takeda, Tarveda Therapeutics, Tesaro/GSK, Vavotar Life Sciences, Vascular Biogenics, Vigeo Therapeutics, Gradalis, Karyopharm Therapeutics, Sorrento Therapeutics, NovocureSpeakers' Bureau: Roche/Genentech, AstraZeneca, Clovis Oncology, Eisai, Tesaro/GSK, MerckResearch Funding: Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, Tesaro, Morphotek, Pfizer, Advaxis, AstraZeneca, Immunogen, Regeneron, Nucana Carien L. CreutzbergConsulting or Advisory Role: MerckResearch Funding: Elekta, Varian Medical SystemsNo other potential conflicts of interest were reported.

Background: In the primary treatment of apparent uterine-confined endometrial carcinoma, pelvic ± para-aortic lymphadenectomy has been considered the standard of care. Although some retrospective data suggest that the sentinel lymph node algorithm without complete lymphadenectomy can be used without jeopardizing oncologic outcome, prospective data are lacking., Primary Objectives: To assess the 36 month incidence of pelvic/non-vaginal recurrence in women with pathologically confirmed stage I intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes., Study Hypothesis: We hypothesize that patients with stage I, intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes will demonstrate a pelvic/non-vaginal recurrence rate comparable to historical estimate of stage I, intermediate-risk endometrioid endometrial carcinoma patients (estimated 2.5%)., Trial Design: This prospective multicenter single-arm observational study will follow women with stage I, intermediate risk endometrioid endometrial adenocarcinoma who have undergone successful hysterectomy, bilateral salpingo-oophorectomy, and bilateral sentinel lymph node biopsies, for recurrence. All patients will undergo lymphatic mapping using indocynanine green and will either receive no adjuvant treatment or vaginal brachytherapy only. Patients will be followed for 36 months., Major Inclusion/exclusion Criteria: Patients will be enrolled in the study cohort if all the following criteria are met: (i) at time of surgery: hysterectomy with bilateral adnexectomy, and successful bilateral pelvic sentinel lymph node mapping; (ii) on final pathology: pathologic stage I, intermediate-risk endometrioid endometrial carcinoma (grade 1 or grade 2 with ≥50% myometrial invasion, or grade 3 with <50% myometrial invasion), negative pelvic peritoneal cytology, and bilateral sentinel lymph nodes negative for malignancy; (iii) recommended adjuvant treatment: vaginal brachytherapy or no adjuvant treatment., Primary Endpoint: Incidence of pelvic/non-vaginal recurrence at 36 months., Sample Size: 182 patients for study cohort ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual will be completed in 2023 with results reported in 2026., Trial Registration: NCT04291612., Competing Interests: Competing interests: Dr Abu-Rustum reports the following, outside the submitted work: grant from Stryker/Novadaq (paid to institution); grant from Olympus (paid to institution); grant from GRAIL (paid to institution)., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology., Methods: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative., Trial Registration: ClinicalTrials.gov (NCT02494063)., Results: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases., Interpretation: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The need for radical surgery followed by adjuvant chemoradiation may be reduced by abandoning radical surgery in patients in whom lymph node involvement is detected intra-operatively., Objectives: To analyze, in a retrospective cohort study, the efficacy of the algorithm using intra-operative pathological assessment of sentinel lymph nodes., Methods: A retrospective single-institution study was carried out, which analyzed data from all consecutive patients with cervical cancer who were referred for primary surgical treatment between May 2005 and December 2015. Inclusion criteria were as follows: (1) TNM stage T1a1 with lymphovascular space invasion, T1a2, T1b, T2a, and selected T2b with incipient parametrial invasion; (2) adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma; (3) no evidence of enlarged suspicious nodes or distant metastases on pre-operative imaging; (4) primary surgery with curative intent; (5) successful detection of sentinel lymph node, at least, unilaterally. All patients had at least one sentinel lymph node detected and submitted for frozen section evaluation. When sentinel lymph node involvement was detected intra-operatively, the cervical procedure was abandoned and the patient was referred for definitive chemoradiation. Radical surgery was completed in patients with intra-operative negative sentinel lymph nodes. The reliability of intra-operative sentinel lymph node assessment was evaluated by calculating the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio., Results: The study included a total of 309 patients. Sentinel lymph nodes were detected bilaterally in 86% of the patients. Lymph node positivity was detected intra-operatively in 18 (6%) patients in whom the cervical procedure was abandoned. Adjuvant radiotherapy after completed radical surgery was given to 29 (9%) patients, including 20 patients with macrometastases (8) or micrometastases (12) reported from the final histology, eight patients with positive parametria (all ≤3 mm), and one patient with a positive vaginal resection margin. The sensitivity, specificity, positive predictive value, and negative predictive value for the intra-operative detection of lymph node positivity (macrometastases or micrometastases) was 47% (95% CI 31% to 64%), 100%, 100%, and 93% (95% CI 90% to 96%), respectively. A total of 18 (6%) patients were spared combined treatment owing to the intra-operative sentinel lymph node triage; 29 patients (9%) received combined treatment with both radical surgery and adjuvant radiotherapy CONCLUSIONS: Of 47 patients with high-risk prognostic risk factors (lymph node, parametria, or surgical margin involvement), combined treatment was successfully avoided in 18 (38%). Despite an effort to triage the patients intra-operatively, 9% received a combination of cervical procedure and adjuvant chemoradiation, mostly owing to the low sensitivity of the frozen section in the detection of micrometastases and macrometastases., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stages cervical cancer instead of systematic pelvic lymph node dissection (PLND). The aim of this article is to give a critical overview of key aspects related to this concept, such as a necessity for reliable detection of micrometastases (MIC) in SLN and the requirements for SLN pathologic ultrastaging, low accuracy of intraoperative detection of SLN involvement, and still a limited evidence of oncological safety of the replacement of PLND by SLN biopsy only in ≥IB1 tumours due to unknown risk of MIC in non-SLN pelvic lymph nodes in patients with negative SLN, and absence of any prospective evidence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To explore the factors influencing adoption of the sentinel lymph node (SLN) technique for endometrial cancer staging among gynecologic oncologists., Methods: A self-administered, web-based survey was sent via email (April 20 through May 21, 2017) to all members of European Society of Gynecologic Oncologists, International Gynecologic Cancer Society, and Society of Gynecologic Oncologists. Surgical and pathologic practices related to SLN and reasons for not adopting this technique were investigated., Results: Overall, 489 attending physicians or consultants in gynecologic oncology from 69 countries responded: 201 (41.1%), 118 (24.1%), and 117 (23.9%) from Europe, the USA, and other countries, respectively (10.8% did not report a country). SLN was adopted by 246 (50.3%) respondents, with 93.1% injecting the cervix and 62.6 % using indocyanine green dye. The National Comprehensive Cancer Network SLN algorithm was followed by 160 (65.0%) respondents (USA 74.4%, Europe 55.4%, other countries 71.4%). However, 66.7% completed a backup lymphadenectomy in high-risk patients. When SLN biopsy revealed isolated tumor cells, 13.8% of respondents recommended adjuvant therapy. This percentage increased to 52% if micrometastases were detected. Among the 243 not adopting SLN, 50.2% cited lack of evidence and 45.3% stated that inadequate instrumentation fueled their decisions., Conclusions: SLN with a cervical injection is gaining widespread acceptance for staging of endometrial cancer among gynecologic oncologists worldwide. Standardization of the surgical approach with the National Comprehensive Care Network algorithm is applied by most users. Management of isolated tumor cells and the role of backup lymphadenectomy for 'high-risk' cases remain areas of investigation., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stage cervical cancer. It appears in guidelines as an alternative option to systematic pelvic lymphadenectomy. The evidence about safety is, however, based mostly on retrospective studies, in which SLN was combined with systematic lymphadenectomy., Materials and Methods: SENTIX is a prospective multicenter trial aiming to prove that less-radical surgery with SLN is non-inferior to treatment with systematic pelvic lymphadenectomy. The primary end point is recurrence rate; the secondary end point is the prevalence of lower-leg lymphedema and symptomatic pelvic lymphocele. The reference recurrence rate was set up conservatively at 7% at 24 months after treatment. With a sample size of 300 patients treated per protocol, the trial is powered to detect a non-inferiority margin of 5% (90% power, p = 0.05) for recurrence rate, 30% reduction in the prevalence of symptomatic lymphocele or lower-leg lymphedema, with reference rates of 30% and 6% at 12 months (p = 0.025, Bonferroni correction). The patients eligible for SENTIX have stage IA1/LVSI+, IA2, IB1 (<2 cm for fertility sparing), with negative LN on pre-operative imaging. Intra-operatively, patients are excluded when there is a failure to detect SLN on both sides of the pelvis in cases of more advanced cancer (stage >IB1), or a positive intra-operative SLN assessment. The quality of SLN pathology evaluation will be assessed by central review. Three interim safety analyses are pre-planned when 30, 60, 150 patients complete 12 months' follow-up., Conclusions: The first patient was enrolled into the study in June 2016 and, by June 2018, 340 patients had been enrolled. The first analysis of secondary outcomes should be available in 2019 and the oncological outcome of 300 patients at the end of 2021. The trial is registered as a CEEGOG trial (CEEGOG CX-01), ENGOT trial (ENGOT-Cx 2), and at the ClinicalTrials.gov database (NCT02494063)., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, we aimed to describe the value of pelvic lymph node dissection (LND) after sentinel lymph node (SN) biopsy in early-stage cervical cancer.We performed a retrospective multicenter cohort study in 8 gynecological oncology departments. In total, 645 women with International Federation of Gynecology and Obstetrics stage IA to IIB cervical cancer of squamous, adeno, or adenosquamous histologic type who underwent SN biopsy followed by pelvic LND were enrolled in this study. Radioisotope tracers and blue dye were used to localize the sentinel node, and pathologic ultrastaging was performed.Among the patients with low-volume disease (micrometastases and isolated tumor cells) in the sentinel node, the overall survival was significantly better (P = 0.046) if more than 16 non-SNs were removed. No such significant difference in survival was detected in patients with negative or macrometastatic sentinel nodes.Our findings indicate that in patients with negative or macrometastatic disease in the sentinel nodes, an additional LND did not alter survival. Conversely, our data suggest that the survival of patients with low-volume disease is improved when more than 16 additional lymph nodes are removed. If in a prospective trial our data are confirmed, we would suggest a 2-stage operation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the sensitivity of sentinel node (SN) ultrastaging and to define parameters that may reduce the overall false-negative rate in women with early-stage cervical cancer. Methods: We analyzed data from a large retrospective multicenter cohort group with FIGO stages IA–IIB cervical cancer in whom at least one SN was identified and systematic pelvic lymphadenectomy was uniformly performed. All who were SN negative by initial evaluation were subjected to ultrastaging. Results: In all, 645 patients were evaluable. SN were detected bilaterally in 72% of cases and unilaterally in 28%. Patients with optimal bilateral SN detection were significantly more likely to have any metastasis detected (33.3% vs. 19.2%; P <0.001) as well as micrometastasis detected in their SN (39.6% vs. 11.4%). SN ultrastaging resulted in a low overall false-negative rate of 2.8% (whole group) and an even lower false-negative rate of 1.3% for patients with optimal bilateral mapping. Patients with false-negative SN after ultrastaging had a higher prevalence of LVSI and more frequent unilateral SN detection. Sensitivity of SN ultrastaging was 91% (95% CI: 86%–95%) for the whole group and 97% (95% CI: 91%–99%) in the subgroup with bilateral SN detection. Conclusion: These data confirm previous observations that optimal bilateral SN detection substantially decreases the false negative rate of SN ultrastaging and increases detection of micrometastasis. In patients with bilateral SN detection, the sensitivity of SN ultrastaging is not reduced in more advanced stages of the disease. SN mapping and ultrastaging should become standard practice in the surgical management of early-stage cervical cancer. [Copyright &y& Elsevier]

This work intends to present a systematic overview of data that have been published so far with regard to methods used for tissue sampling and DNA testing and with regard to the prevalence of human papillomavirus (HPV) DNA in pelvic lymph nodes (LNs) and its prognostic significance.The HPV DNA status of LN in women with cervical cancer is being explored as a potential marker of "occult" metastases. Although the presence of HPV DNA in LN usually correlates with its metastatic involvement, there is always a subgroup of HPV-positive but histologically negative LNs.The significance of HPV in negative LNs remains uncertain, although several studies have concluded that HPV is a risk factor of recurrence.A small group size and a short follow-up are the main limitations for drawing any conclusion concerning prognostic significance of the presence of HPV DNA in LNs. [ABSTRACT FROM AUTHOR]

Metastatic involvement of pelvic lymph nodes is the most important prognostic parameter in early-stage cervical cancer. Still, approximately 15% of patients with negative pelvic nodes experience recurrence, most of them in the pelvis. The presence of human papillomavirus (HPV) DNA in histologically negative pelvic nodes is considered a subclinical metastatic spread.Patients with early-stage cervical cancer referred for surgical treatment were enrolled in the study. Cytobrush technique was used for sample collection from the fresh tissue to avoid any loss of material for histology.Altogether, 49 patients were enrolled in the study. High-risk (HR) HPV DNA was identified in the tumor in 91.8% patients and in the sentinel node or other pelvic nodes in 49.9% patients. Among the 10 HR HPV genotypes detected, HPV 16 was the most frequently represented in both the tumor and the lymph nodes (66.7% and 71.4%, respectively). All metastatic lymph nodes were HR HPV positive.The presence of HR HPV DNA in a sentinel node had a 100% positive predictive value for metastatic involvement of pelvic lymph nodes in our study. This could be considered a sign of an early subclinical metastatic spread; however, the prognostic value has to be evaluated through a longer follow-up. [ABSTRACT FROM AUTHOR]