Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial

Background: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multi centre, 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. (C) 2020 The Author(s). Published by Elsevier Ltd

Central Pathology Review in SENTIX, a Prospective Observational International Study on Sentinel Lymph Node Biopsy in Patients with Early-Stage Cervical Cancer (ENGOT-CX2)

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review

Prospective assessment of urinary and bowel symptoms, and sexual function between laparoscopic assisted vaginal radical trachelectomy and radical hysterectomy

Objective Radical trachelectomy is a valid alternative to radical hysterectomy in women with a desire to retain their fertility. Data regarding the oncological outcomes of radical trachelectomy are comparable with those of radical hysterectomy but information regarding urinary and sexual function is limited. The aim of this study was to prospectively evaluate and compare quality of life, urinary and bowel symptoms, and sexual dysfunction between patients who underwent laparoscopic assisted vaginal radical trachelectomy versus radical hysterectomy for early-stage cervical cancer. Methods Patients who underwent laparoscopic assisted vaginal radical trachelectomy or radical hysterectomy along with sentinel or systemic pelvic lymphadenectomy were included between May 2015 and January 2017. Patients were asked to complete a validated questionnaire (German pelvic symptom questionnaire) on bladder, bowel, prolapse, and sexual function, and total pelvic score, at least 48 hours before surgery and 6 months after surgery. Results A total of 51 patients were included. Of these, 26 patients (50.9%) underwent laparoscopic assisted vaginal radical trachelectomy and 25 (49.1%) underwent radical hysterectomy. No patient was converted to laparotomy. The majority of patients (76%) were diagnosed with International Federation of Gynecology and Obstetrics (FIGO 2018) stage 1B1 disease, with squamous cell carcinoma (54%) and grade II tumors (52%). Four patients (7.8 %) experienced perioperative complications (two grade II and two grade III complications according to the Clavien-Dindo classification). In the preoperative evaluation, the median scores for the four items of the questionnaire (bladder, bowel, prolapse, and sexual items) and total pelvic score were comparable between the two groups. The mean scores for radical hysterectomy and radical trachelectomy at the beginning of the study for bladder, bowel, prolapse, and sexual function were 0.93 versus 0.71, 0.71 versus 1.01, 0.12 versus 0.1, and 1.06 versus 1.0, respectively. On preoperative testing, the median scores for all four items of the questionnaire (p(bladder)=0.821, p(bowel)=0.126, p(prolapse)=0.449, p(sexual)=0.965) and the total pelvic score (p=0.756) were comparable between the two groups. The radical hysterectomy group had worse total pelvic scores at the 6 month postoperative survey compared with baseline (p=0.03). There was no difference in bladder (p=0.07) or bowel symptoms (p=0.07) in the radical hysterectomy group comparing baseline with the 6 month assessment. Women undergoing radical hysterectomy experienced more urinary morbidity than women undergoing vaginal trachelectomy at 6 weeks (p=0.025). However, the mean bladder and pelvic scores in the 6 month control were comparable between patients who had and those who had not experienced urinary morbidity (p(bladder)=0.127, p(total pelvic score)=0.480). Conclusion Patients undergoing laparoscopic assisted vaginal radical trachelectomy had similar pelvic scores in both the preoperative and postoperative periods. However, patients undergoing radical hysterectomy showed worse total pelvic scores on the postoperative assessment compared with the baseline evaluation. Urinary dysfunction in the early postoperative phase was more common in the radical hysterectomy group than in trachelectomy group

Modification of Dargent's radical vaginal trachelectomy to facilitate ureteral dissection: description of technique

Objective Radical vaginal trachelectomy is the fertility-preserving surgery for patients with early stage cervical cancer. However, it has not gained widespread approval by gynecologic oncologists because of difficulties in the dissection of the bladder pillars and identification of the ureter during the vaginal portion of the surgery. Method We describe a modification of radical vaginal trachelectomy for easier dissection of the bladder pillar. Following pelvic lymphadenectomy, the vesicovaginal space is widely opened laparoscopically. After identification of the uterine arteries, one should proceed along the course of the arteries laterally and, thus, visualize the overcrossing of the artery with the ureter. The medial aspect of the supraureteric bladder pillar is transected and the ureter marked with vessel loops on both sides close to its entry into the bladder. The lateral portion of the supraureteric bladder pillar remains intact. During the vaginal part of radical vaginal trachelectomy, the ureter may be easily found by grasping the formerly placed vessel loop and dissection of the infraureteric bladder pillar may be done without risk of ureteral injury. Results Between October 2018 and August 2019 our group has performed radical vaginal trachelectomy using this modified ureteral dissection in 12 patients. Median operation time was 239 min (range 127-290) and median blood loss was 25 mL (range 10-100). No intra- or post-operative urologic complication occurred. Median time to normal bladder function was 4 days (range 3-13). Conclusion The vaginal portion of radical vaginal trachelectomy may be simplified using this technique, especially when difficult circumstances such as endometriosis, prior operations, or unusual anatomy in nulliparous women are encountered

Laparoscopic radical hysterectomy with transvaginal closure of vaginal cuff - a multicenter analysis

Objective Laparoscopic/robotic radical hysterectomy has been historically considered oncologically equivalent to open radical hysterectomy for patients with early cervical cancer. However, a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC) has demonstrated significant inferiority of the minimally invasive approach. The aim of this study is to evaluate the oncologic outcomes of combined laparoscopic-vaginal radical hysterectomy. Methods Between August 1994 and December 2018, patients with invasive cervical cancer were treated using minimally-invasive surgery at the Universities of Jena, Charite Berlin (Campus CCM and CBF) and Cologne and Asklepios Clinic Hamburg. 389 patients with inclusion criteria identical to the LACC trial were identified. In contrast to the laparoscopic/robotic technique used in the LACC trial, all patients in our cohort underwent a combined transvaginal-laparoscopic approach without the use of any uterine manipulator. Results A total of 1952 consecutive patients with cervical cancer were included in the analysis. Initial International Federation of Gynecology and Obstetrics (FIGO) stage was IA1 lymphovascular space invasion (LVSI+), IA2 and IB1/IIA1 in 32 (8%), 43 (11%), and 314 (81%) patients, respectively, and histology was squamous cell in 263 (68%), adenocarcinoma in 117 (30%), and adenosquamous in 9 (2%) patients. Lymphovascular invasion was confirmed in 106 (27%) patients. The median number of lymph nodes was 24 (range 2-86). Lymph nodes were tumor-free in 379 (97%) patients. Following radical hysterectomy, 71 (18%) patients underwent adjuvant chemoradiation or radiation. After a median follow-up of 99 (range 1-288) months, the 3-, 4.5-, and 10-year disease-free survival rates were 96.8%, 95.8%, and 93.1 %, and the 3-, 4.5-, and 10-year overall survival rates were 98.5%, 97.8%, and 95.8%, respectively. Recurrence location was loco-regional in 50% of cases with recurrence (n=10). Interestingly, 9/20 recurrences occurred more than 39 months after surgery. Conclusion The combined laparoscopic-vaginal technique for radical hysterectomy with avoidance of spillage and manipulation of tumor cells provides excellent oncologic outcome for patients with early cervical cancer. Our retrospective data suggest that laparoscopic-vaginal surgery may be oncologically safe and should be validated in further randomized trials

Comparison of surgical and pathological parameters after laparoscopic transperitoneal pelvic/para-aortic lymphadenectomies

Objective Lymphadenectomy is an integral part of surgical staging and treatment for patients with gynecologic malignancies. Since its introduction, laparoscopic lymphadenectomy has proved feasible, safe, and oncologically adequate compared with open surgery while morbidity is lower and hospital stay considerably shorter. The aim of this study was to examine if surgical outcomes may be improved after the initial learning curve is complete. Methods An analysis of 2535 laparoscopic pelvic and/or para-aortic lymphadenectomies was performed between July 1994 and March 2018 by one team of gynecologic oncology surgeons but with the consistent supervision of a consultant surgeon. Data were collected prospectively evaluating operative time, intra-operative and post-operative complications, number of lymph nodes, and body mass index (BMI). Previously published data of 650 patients treated after introduction of the method (period 1, 1994-2003) were compared with the latter 524 patients (period 2, 2014-2018). Results The median age of the 2535 patients was 43 years (IQR 34-57). The most common indication for pelvic and/or para-aortic lymphadenectomy was cervical cancer (n=1893). Operative time for para-aortic lymph node dissection was shorter in period 2 (68 vs 100 min, p<0.001). The number of harvested lymph nodes was increased for pelvic (19.2 (range 2-52) vs 21.9 (range 4-87)) and para-aortic lymphadenectomy (10.8 (range 1-52) vs 14.4 (range 4-64)), p<0.001. BMI did not have a significant influence on node count or operative time, with BMI ranging from 14.6 to 54.1 kg/m(2). In contrast to period 1 (n=18, 2.9%), there were no intra-operative complications in period 2 (n=0, 0.0%, p<0.001) whereas post-operative complications were similar (n=35 (5.8%) in period 1; n=38 (7.6%) in period 2; p=0.32). Conclusion In this large cohort of patients who underwent laparoscopic transperitoneal lymphadenectomy, lymph node count and peri-operative complications improved after the initial learning curve