A prospective study evaluating an optimized sentinel node algorithm in early stage cervical cancer: The PROSACC-study.

OBJECTIVE: A single center prospective non-randomized study to assess a systematically developed anatomically-based sentinel lymph node (SLN) algorithm in cervical cancer. METHODS: Consecutive women with FIGO 2009 stage 1A2-2A1 cervical cancer undergoing robotic radical hysterectomy/trachelectomy between September 2014 and January 2023 had cervically injected Indocyanine Green (ICG) as a tracer for detection of pelvic SLN. An anatomically based surgical algorithm was adhered to; defining SLNs as the juxtauterine mapped nodes within the upper and lower paracervical lymphatic pathways including separate removal of the parauterine lymphovascular tissue (PULT). A completion pelvic lymphadenectomy was performed. Ultrastaging and immunohistochemistry was performed on SLNs, including the PULT. RESULTS: 181 women were included for analysis. Median histologic tumor size was 14.0 mm (range 2-80 mm). The bilateral mapping rate was 98.3%. As per protocol an interim analysis rejected H0 and inclusion stopped at 29 node positive women, all identified by at least one metastatic ICG-defined SLN. One woman awaiting histology at study-closure was node positive and included in the analysis. Sensitivity was 100% (95% CI, 88.4%-100%) and NPV 100% (95% CI, 97.6%-100%). In node positive women, the proximal obturator position harbored 46.1% of all SLN metastases representing the only position in 40% and 10% had isolated metastases in the PULT. CONCLUSIONS: Strictly adhering to an anatomically based SLN-algorithm including identification of parallell lymphatics within major pathways, partilularly the obturator compartment, assessment of the PULT, restricting nodal dissection to the removal of SLNs accurately identifies pelvic nodal metastatic disease in early-stage cervical cancer.

Similar distribution of pelvic sentinel lymph nodes and nodal metastases in cervical and endometrial cancer. A prospective study based on lymphatic anatomy.

OBJECTIVE: Comparing the anatomical distribution of metastatic and non-metastatic pelvic sentinel lymph nodes (SLN) in cervical and endometrial cancer. METHODS: Detailed SLN mapping results were prospectively retrieved in cervical (n = 145) or high-risk endometrial cancer (n = 201) patients undergoing a robotic staging procedure. Cervically injected Indocyanine Green (ICG), allowing for reinjection in case of inadequate mapping, was used as tracer. An anatomically based definition of SLNs was adhered to evaluating the upper (UPP) and lower (LPP) paracervical lymphatic pathways. The positions of SLNs were intraoperatively depicted on an anatomical chart. A completory pelvic lymphadenectomy was performed. Mapping rates and anatomical distribution of SLNs and the location of pelvic nodal metastases were compared between groups. RESULTS: The bilateral mapping rate was 97.9% and 95.0% for cervical and endometrial cancer respectively (p = .16). The proportion of typically positioned (interiliac and proximal obturator fossa) SLNs along the UPP was similar between groups (78.1% vs 82.1%, p = .09), and the rate of metastatic SLNs in the obturator fossa was 54.1% and 48.6% respectively (p = .45). All pelvic node positive women (cervical cancer n = 19, endometrial cancer n = 37) had at least one metastatic SLN. Anatomically typical positions could not be defined along the LPP. CONCLUSION: The anatomical location of SLNs and SLN metastases are similar in cervical and endometrial cancer suggesting that sensitivity results for an SLN concept in endometrial cancer and cervical cancer can be accumulated.

Long term oncologic and reproductive outcomes after robot-assisted radical trachelectomy for early-stage cervical cancer. An international multicenter study.

OBJECTIVES: Long term outcomes following fertility sparing robot-assisted radical trachelectomy (RRT). METHODS: A retrospective study of consecutive women selected for RRT between 2007 and 2019 at five referral centres. Generally used selection criteria for fertility-sparing surgery were applied. Oncologic, reproductive and long-term clinical data were analysed. RESULTS: Of the 166 included women, 149 completed a RRT. Median tumor size was 9 mm (range 3-20 mm), 111 women (75%) had FIGO 2009 stage IB1 cancer and 4.8% were node positive. At a median follow up of 58 months, 12 of all women (7.2%) and 9 of 149 women (6%) who underwent completed RRT with fertility preservation had recurred and two had died. 70 of 88 women (80%) who attempted to conceive succeeded, resulting in 81 pregnancies that progressed beyond the first trimester and 76 live births of which 54 (70%) were delivered at term and 65 (86%) delivered after gestational week 32. A short postoperative cervical length was associated with impaired fertility. A late secondary hysterectomy was necessary in four women due to persistent bleeding (n = 2), hematometra due to a cervical stenosis (n = 1) and recurrent dysplasia (n = 1). CONCLUSION: In this long-term follow-up of RRT the recurrence rate is comparable to larger individual studies of minimally invasive or vaginal radical trachelectomy with similar risk profile and follow up. The high pregnancy rate and low rate of premature delivery before 32 weeks GA may promote the use of robot-assisted approach.

Resection of the upper paracervical lymphovascular tissue should be an integral part of a pelvic sentinel lymph node algorithm in early stage cervical cancer.

OBJECTIVE: To investigate the prevalence of lymph nodes and lymph node metastases (LNMs) in the upper paracervical lymphovascular tissue (UPLT) in early stage cervical cancer. METHODS: In this prospective study consecutive women with stage IA1-IB1 cervical cancer underwent a pelvic lymphadenectomy including identification of sentinel nodes (SLNs) as part of a nodal staging procedure in conjunction with a robotic radical hysterectomy (RRH) or robotic radical trachelectomy (RRT). Indocyanine green (ICG) was used as tracer. The UPLT was separately removed and defined as "SLN-parametrium" and, as all SLN tissue, subjected to ultrastaging and immunohistochemistry. Primary endpoint was prevalence of lymph nodes and metastatic lymph nodes in the UPLT. Secondary endpoints were complications associated with removal of the UPLT. RESULTS: One hundred and forty-five women were analysed. Nineteen (13.1%) had pelvic LNMs, all identified by at least one metastatic SLN. In 76 women (52.4%) at least one UPLT lymph node was identified. Metastatic UPLT lymph nodes were identified in six women of which in three women (2.1% of all women and 15.8% of node positive women) without lateral pelvic LNMs. Thirteen women had lateral pelvic SLN LNMs with either no (n = 5) or benign (n = 8) UPLT lymph nodes. No intraoperative complications occurred due to the removal of the UPLT. CONCLUSION: Removal of the UPLT should be an integral part of the SLN concept in early stage cervical cancer.

Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists.

BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.

Combining Indocyanine Green and Tc99-nanocolloid does not increase the detection rate of sentinel lymph nodes in early stage cervical cancer compared to Indocyanine Green alone.

OBJECTIVE: To investigate whether combining two independent tracers increases the SLN-detection rate in cervical cancer. METHODS: Consecutive women with early stage cervical cancer planned for a robotic radical hysterectomy or a robotic radical trachelectomy with sentinel lymph node (SLN) detection were included. After cervical injections of Indocyanine green (ICG) and Tc99-nanocolloid (Tc99), near-infrared fluorescence imaging and a gamma probe were used to identify SLNs in the upper and lower paracervical pathways (UPP/LPP). A strict surgical algorithm was adhered to and the SLNs were defined as SLN-ICG, SLN-ICG+Tc99 or SLN-Tc99. In FIGO-stage ≥IA2 cancers a full pelvic lymph node dissection (PLND) was performed after detection of SLNs. The primary endpoint was the SLN detection rate per tracer and combination of tracers. Secondary endpoints were sensitivity and mapping rates of the SLN algorithm per tracer and combination of tracers. RESULTS: In the sixty-five analyzed women, the bilateral mapping rate was 98.5% for ICG and 60% for Tc99 (p < 0.01). Combining the tracers did not increase the bilateral detection rate. In three women (5%) Tc99 identified ICG-negative non-metastatic SLNs without impact on the bilateral detection rate. Eight women (12%) had lymph node metastases (LNMs), all had at least one metastatic SLN. Seven (35%) of the 20 metastatic SLNs were detected by ICG only and 12 (60%) were ICG and Tc99 positive. CONCLUSION: SLN detection rate was significantly higher using ICG compared with Tc99. ICG identified all patients with LNMs. Combining ICG and Tc99 did not improve the bilateral detection rate of SLNs.

Improving Double Docking for Robot-assisted Para-aortic Lymphadenectomy in Endometrial Cancer Staging: Technique and Surgical Outcomes.

Robot-assisted para-aortic lymphadenectomy (PALND) may prove to be a challenging procedure, and the ability to reach the planned anatomic landmarks is critical. In this retrospective study between 2012 and 2015, we present surgical data using a modified technique to perform infrarenal PALND for endometrial cancer using double side docking. All women with high-risk endometrial cancer scheduled for complete robotic staging including infrarenal PALND were included in the analysis. During the study period, a total of 76 women were identified. Three patients had disseminated disease and were treated with palliative hysterectomy only. The remaining 73 women underwent surgery with the intention to perform infrarenal PALND. In 7 cases, PALND was aborted because of technical inability to reach the left renal vein (10%). A median of 36 lymph nodes were harvested (pelvic n = 20, para-aortic n = 16). The median operating time (skin to skin) for patients with completed infrarenal PALND was 228 minutes (range, 181-371 minutes). Among all 76 patients, postoperative complications according to the Clavien-Dindo nomenclature were observed in 27 (36%) patients, with 6 (8%) having grade III complications. No patient died within 30 days from surgery. Our technique of double docking for robot-assisted PALND was associated with a success rate of 90%. The described technique seems to be a useful strategy to maximize the likelihood of completing the planned procedure.

A federated approach to identify women with early-stage cervical cancer at low risk of lymph node metastases.

OBJECTIVE: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection. METHODS: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion criteria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+. RESULTS: We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion>10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size ≤20 mm, and depth of invasion ≤10 mm-had a very low risk of pN+ (2.4%, 95% CI, 1.7-3.3%). CONCLUSION: Early-stage cervical cancer without LVSI, a tumour size ≤20 mm and depth of invasion ≤10 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.

Quality of life and long-term clinical outcome following robot-assisted radical trachelectomy.

Quality of Life and long-term clinical outcome following robot-assisted radical trachelectomy. OBJECTIVES: To evaluate quality of life (QoL) and long-term clinical outcome following robot-assisted radical trachelectomy (RRT). STUDY DESIGN: Prospectively retrieved clinical data were rereviewed on all women planned for a fertility sparing RRT for early stage cervical cancer at Skåne University Hospital, Sweden between 2007 and 2020. QoL was assessed using the validated questionnaires EORTC QLQ-C30, QLQ-CX24 and the Swedish LYMQOL. RESULTS: Data was analyzed from 49 women, 42 with a finalised RRT and seven with an aborted RRT due to nodal metastases (n = 3) or insufficient margins (n = 4). At a median follow-up time of 54 months one recurrence (2%) occurred (aborted RRT). According to QLQ-C30 the median global health status score was 75. The disease specific QLQ-C24 showed an impact on symptoms related to sexual function where sexual/vaginal functioning had a median score of 25 and 48% of patients reported worry that sex would cause physical pain. Despite this the functional items sexual activity and sexual enjoyment both had a median score of 66.7. Lymphoedema was reported in 45%, where 9% reported severe symptom with an impact on their QoL. No intraoperative complications and no postoperative complications ≥ Clavien Dindo grade III were observed. Twenty-two of 28 (79%) women who attempted to conceive were successful. A metronidazole/no intercourse regimen was applied between GW 15 + 0-21 + 6 in 26 of 28 pregnancies beyond first trimester resulting in a 92% term (≥GW 36 + 0) delivery rate. CONCLUSIONS: Although robot-assisted radical trachelectomy in this cohort was associated with a low recurrence rate, a high fertility rate and an exceptionally high term delivery rate, women's quality of life was affected postoperatively, particularly with regards to their sexual well-being and lymphatic side-effects.

A combination of second trimester oral metronidazole and no sexual intercourse during second and third trimester may reduce late miscarriage and premature delivery after fertility sparing radical trachelectomy.

OBJECTIVES: Women with a previous trachelectomy have an increased risk of premature delivery and second trimester miscarriage. In this study we aim to evaluate factors and regimes possibly affecting the risk for prematurity following fertility sparing robotic radical trachelectomy (RRT) in cervical cancer. METHODS: A retrospective study of the reproductive outcome following RRT with a cervical cerclage performed at one of four academic centers between 2007 and 2019. Factors possibly related to premature delivery, such as postoperative non-pregnant cervical length, previous vaginal deliveries, preservation of the uterine arteries, and the use of a second trimester oral metronidazole/no sexual intercourse regime, were assessed. RESULTS: 109 women remained for analyses after excluding recurrences before pregnancy (n = 8), secondary hysterectomy (n = 2), and women with less than six months follow up (n = 10). 74 pregnancies occurred in 52/71 women attempting to conceive, 56 of which developed past the first trimester. Two of 22 women (9%) who were prescribed an oral metronidazole regime (400 mg × 2 from gestational week 15 + 0 to 21 + 6 and abstaining from sexual intercourse for the duration of the pregnancy) had a premature delivery, compared with 13/31 (42%) where the regime was not applied (p = 0.009). The association remained after regression analyses including possible contributing factors as of above, none of which associated with prematurity at regression analyses (p = 0.001). CONCLUSIONS: The observed four-fold reduction in premature delivery indicates that an oral metronidazole/no sexual intercourse regime may reduce second trimester miscarriage and premature deliveries following an RRT. No association was observed for other investigated factors.

Increased Institutional Surgical Experience in Robot-Assisted Radical Hysterectomy for Early Stage Cervical Cancer Reduces Recurrence Rate: Results from a Nationwide Study.

The aim of this study was to evaluate the impact of institutional surgical experience on recurrence following robotic radical hysterectomy (RRH) for early stage cervical cancer. All women in Sweden who underwent an RRH for stage IA2-IB1 cervical cancer at tertiary referral centers from its implementation in December 2005 until June 2017 were identified using a Swedish nationwide register and local hospital registers. Registry data were controlled by a chart review of all women. Recurrence rates and patterns of recurrence were compared between early and late (≤50 vs. >50 procedures) institutional series. Six hundred and thirty-five women were included. Regression analysis identified a lower risk of recurrence with increased experience but without a clear cut off level. Among the 489 women who did not receive adjuvant radio chemotherapy (RC-T), the rate of recurrence was 3.6% in the experienced cohort (>50 procedures) compared to 9.3% in the introductory cohort (p < 0.05). This was also seen in tumors < 2 cm regardless of RC-T (p < 0.05), whereas no difference in recurrence was seen when analyzing all women receiving RC-T. In conclusion, the rate of recurrence following RRH for early stage cervical cancer decreased with increased institutional surgical experience, in tumors < 2 cm and in women who did not receive adjuvant RC-T.

No survival difference between robotic and open radical hysterectomy for women with early-stage cervical cancer: results from a nationwide population-based cohort study.

PURPOSE: The aim of the study was to compare overall survival (OS) and disease-free survival (DFS) after open and robotic radical hysterectomy for early-stage cervical cancer. PATIENTS AND METHODS: This was a nationwide population-based cohort study on all women with cervical cancer stage IA1-IB of squamous, adenocarcinoma or adenosquamous histological subtypes, from January 2011 to December 2017, for whom radical hysterectomy was performed. The Swedish Quality Register of Gynaecologic Cancer was used for identification. To ensure quality and conformity of data and to disclose patients not yet registered, hospital registries were reviewed and validated. Cox and propensity score regression analysis and univariable and multivariable regression analysis were performed in regard to OS and DFS. RESULTS: There were 864 women (236 open and 628 robotic) included in the study. The 5-year OS was 92% and 94% and DFS was 84% and 88% for the open and robotic cohorts, respectively. The recurrence pattern was similar in both groups. Using propensity score analysis and matched cohorts of 232 women in each surgical group, no significant differences were seen in survival: 5-year OS of 92% in both groups (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.50-2.01) and DFS of 85% vs 84% in the open and robotic cohort, respectively (HR, 1.08; 95% CI, 0.66-1.78). In univariable and multivariable analysis with OS as the end-point, no significant factors were found, and in regard to DFS, tumour size (p < 0.001) and grade 3 (p = 0.02) were found as independent significant risk factors. CONCLUSION: In a complete nationwide population-based cohort, where radical hysterectomy for early-stage cervical cancer is highly centralised, neither long-term survival nor pattern of recurrence differed significantly between open and robotic surgery.