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Background Models predicting recurrence risk (RR) of cervical cancer are used to tailor adjuvant treatment after radical surgery. The goal of our study was to compare available prognostic factors and to develop a prognostic model that would be easy to standardise and use in routine clinical practice. Methods All consecutive patients with early-stage cervical cancer treated by primary surgery in a single referral centre (01/2007–12/2016) were eligible if assessed by standardised protocols for pre-operative imaging and pathology. Fifteen prognostic markers were evaluated in 379 patients, out of which 320 lymph node (LN)-negative. Results The best predictive model for the whole cohort entailed a combination of tumour-free distance (TFD) ≤ 3.5 mm and LN positivity, which separated two subgroups with a substantially distinct RR 36% and 6.5%, respectively. In LN-negative patients, a combination of TFD ≤ 3.5 mm and adenosquamous tumour type separated a group of nine patients with RR 33% from the rest of the group with 6% RR. Conclusions A newly identified prognostic marker, TFD, surpassed all traditional tumour-related markers in the RR assessment. Predictive models combining TFD, which can be easily accessed on pre-operative imaging, with LN status or tumour type can be used in daily practice and can help to identify patients with the highest RR.

Introduction/Background* SENTIX is a prospective cohort multicentric international study on sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. SLN frozen section (FS) and pathological ultrastaging were mandatory by the protocol. Samples from SLN were reviewed centrally for pathological assessment quality control. Only sites experienced in SLN biopsy technique could join the trial. Methodology In total, 47 sites from 18 countries participated in the trial. Patients with FIGO 2009 stages T1A1/LVSI+ – T1B1 ( Result(s)* Altogether 733 patients were registered until Sentix enrolment closure in October 2020, 83 patients were excluded (table 1) and 650 patients was analysed. Patients` characteristics are shown in table 1. Bilateral SLN detection rate reached 95%. FS detected macrometastases (MAC) in 44 cases and micrometastasis (MIC) in 4 cases. SLN ultrastaging found additional 9 cases with MAC, 26 with micrometastases (MIC) and all 19 cases with isolated tumor cells (ITC). Sensitivity of FS was 83.0% for the detection of MAC, 57.8% for pN1 status (MAC or MIC) and 47.1% for any type of SLN involvement (MAC, MIC, ITC). Table 2. Conclusion* High bilateral detection rate of 95% was achieved in Sentix sites experienced in the SLN biopsy technique. Intraoperative pathological assessment of SLN failed to detect majority of MIC (86.7%), all cases with ITC and 42.2% with pN1 (MIC or MAC).

Introduction/Background* Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. In studies, LLL is often assessed by calculation of limb volumes based on five circumference measurements. However, the lack of standardisation of this method hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective SENTIX trial that have implications for the standardisation of LLL assessment. Methodology In the prospective international multicentre trial SENTIX (ENGOT-cx2/CEEGOG CX-01), a group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery. Result(s)* Patient LVC substantially fluctuated in both positive and negative directions (figure 1), which were comparable in frequency up to 14% +/- LVC increments. Thirty-eight patients experienced persistent LVC increase and >10% classified as LLL, for whom median time to onset was nine months (95% CI: 7.0-11.0). Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits (figure 2). No significant correlation between LVC >10% and a patient-reported swelling was observed. Conclusion* Our study showed that lower-limb volumes after surgical treatment of cervical cancer significantly fluctuate in positive and negative directions. A diagnostic threshold for LLL should be increased to >15% LVC. Transient oedema occurs frequently, and its distinction from persistent LLL requires repeated measurements. One-third of new LLL cases were diagnosed in the second year of follow-up, highlighting the importance of a sufficient follow-up period duration. Finally, patient-reported limb swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment.

Introduction/Background* Metastatic involvement of lymph nodes (LNs) represents one of the most important prognostic parameter in cervical cancer patients. According to the stage it shortens the 5years survival rate by 25-60 %. Moreover, even in low risk group without any risk factor, a part of radicaly treated patiens suffer from relapse of the disease. Presence of HPV DNA in LNs had been therefore studied as a potential marker of unrecognized metastatic involvement. Methodology Detected were 13 genotypes of high-risk HPV in the lymphatic tissue harwested from patiens who underwent radical hysterectomy with sentinel node biopsy and pelvic lymphadnectomy or paraaortic LN staging. The cytobrush technique was used for perioperative sample collection from the tumour and fresh lymphatic tissue. Only patients with HPV positive tumours who finished their treatment were included and followed. Result(s)* Out of 119 patients who were included in the study, 93 had available data from their follow-up; 68 underwent radical surgery and 25 were treated by primary definitive radiotherapy. All 19 patients with metastaticaly involved LNs also had HPV in LNs. Another 23 patients had HPV in uninvolved LNs. After a mean follow up of 147 months 19 patients (5 early and 14 localy advanced stages) recurred and died. The majority of them (13/19) had HPV DNA in their LNs, but only 7 had metastases in the LNs at the same time. Only 6 patients (6.5%) without HPV DNA in LNs recurred – 2 early and 4 localy advanced stages. Negative predictive value for recurrence in cases with HPV negative LNs reached 87.8% in the whole cohort and 95% in early stages. Conclusion* Our pilot study shows that the presence of HPV DNA in LNs is a promising marker of occult metastatic involvement. Its prognostic value should be confirmed in a prospective trial.

Introduction/Background* The SENTIX is a prospective cohort international study on sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. The primary end point is a recurrence rate at 24 months´ follow-up after the surgery. Either magnetic resonance imaging (MRI) or expert ultrasound (EUS) was mandatory as a preoperative staging method. The aim of this study is to report the accuracy of preoperative local staging. Methodology Forty-seven sites from 18 countries participated in the study. Patients with stages T1a1/LVSI+ – T1b1 (FIGO 2009), common histological types and no suspicious lymph nodes on imaging were eligible. Patients were excluded from further study if SLN were not detected on both sides and if SLN was positive on frozen section histological evaluation. Compared were results from preoperative imaging with final pathology reports. Result(s)* From May 2016 to October 2020, 733 registered patients underwent surgery, 132 were excluded intraoperatively, data from 708 were analysed in this study. Patients’ characteristics are in table 1. Out of 90 patients clinically staged as 1A tumours, 42 (46.7%) were upstaged to IB1 (86% ≤ 2 cm, 14% 2-4cm, 0% > 4cm); 76.3% had conisation as diagnostic procedure. Fourteen out of 547 preoperatively IB1 tumours (2.6%) were upstaged to IB2 > 4cm. Analogously 33 patients (6%) with IB tumours were downstaged to IA. Preoperatively unrecognized parametrial involvement was found by pathology only in 22 out of 637 patients (3.5%). EUS and MRI were used equally in the study (53.5% vs 56.1%), both were comparable in the accuracy of tumour size measurement (2 cm size categories shift in stage IB) (p=1.000) and in the failure to detect parametrial involvement (2.9% vs 4.0%) (p=0.535). Chart 1. Conclusion* Clinical staging with EUS and MRI failed to detect positive parametria only in 3.5% of patients in the Sentix trial. Upstaging from IA tumours was frequent, mostly after previous conization. Only 2.6% of patients were upstaged to IB2 tumours >4 cm (IB3 FIGO 2018). Both EUS and MRI were equally reliable in tumour size and parametrial involvement assessment.

Introduction/Background* Lower-limb lymphedema (LLL) is a well-recognized adverse outcome of the surgical management of cervical cancer. Recently, sentinel lymph node (SLN) biopsy has emerged as an alternative procedure to systematic pelvic lymphadenectomy (PLND) aiming to decrease the risk of complications, especially LLL development. Our study represents the first prospective analysis of LLL incidence in cervical cancer patients after a uterine procedure with SLN biopsy, without systematic PLND. Methodology In a prospective international multicenter trial SENTIX, the group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy was prospectively evaluated using both objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. The characteristics of the patients are summarized in table 1. Result(s)* The cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10-19%), 9.2% for moderate LLL (LVI 20-39%), while only one patient (0.7%) developed severe LLL (LVI >40%). The median interval to LLL onset was nine months (figure 1). A transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. Conclusion* Contrary to the expectations, the replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed. Trial registration ClinicalTrials.gov: NCT02494063 Funding This work was supported by Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1) and by a grant from the Czech Health Research Council (NV19-03-00023). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Conflicts of Interest The authors declare no conflict of interest.

Background Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. However, the lack of standardisation of volumetric LLL assessment hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective trial that have implications for LLL assessment standardisation. Methods In the prospective international multicentre trial SENTIX, a group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral sentinel lymph node biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery. Results Patient LVC substantially fluctuated in both positive and negative directions, which were comparable in frequency up to ±14% change. Thirty-eight patients experienced persistent LVC increase >10% classified as LLL, with nine months median time to onset. Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits. No significant correlation between LVC >10% and a patient-reported swelling was observed. Conclusions Given that we observed comparable fluctuations of the the lower-limb volumes after surgical treatment of cervical cancer in both positive and negative direction up to ±14%, the diagnostic threshold for LLL diagnosis based on LVC should be increased to >15% LVC. The distinction of transient oedema from persistent LLL requires repeated measurements. Also, as one-third of LLL cases are diagnosed >1-year post-surgery, a sufficient follow-up duration needs to be ensured. Patient-reported swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment. Trial registration: ClinicalTrials.gov : NCT02494063

OBJECTIVE: Voiding dysfunctions represent a leading morbidity after radical hysterectomy performed in patients with early-stage cervical cancer. The aim of this study was to perform ad hoc analysis of factors influencing voiding recovery in SENTIX (SENTinel lymph node biopsy in cervIX cancer) trial. METHODS: The SENTIX trial (47 sites, 18 countries) is a prospective study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer. Overall, the data of 300 patients were analysed. Voiding recovery was defined as the number of days from surgery to bladder catheter/epicystostomy removal or to post-voiding urine residuum ≤50 mL. RESULTS: The median voiding recovery time was three days (5th-95th percentile: 0-21): 235 (78.3%) patients recovered in 30 days. In the multivariate analysis, only previous pregnancy (p = 0.033) and type of parametrectomy (p < 0.001) significantly influenced voiding recovery >7 days post-surgery. Type-B parametrectomy was associated with a higher risk of delayed voiding recovery than type-C1 (OR = 4.69; p = 0.023 vs. OR = 3.62; p = 0.052, respectively), followed by type-C2 (OR = 5.84; p = 0.011). Both previous pregnancy and type C2 parametrectomy independently prolonged time to voiding recovery by two days. CONCLUSIONS: Time to voiding recovery is significantly related to previous pregnancy and type of parametrectomy but it is not influenced by surgical approach (open vs minimally invasive), age, or BMI. Type B parametrectomy, without direct visualisation of nerves, was associated with longer recovery than nerve-sparing type C1. Importantly, voiding dysfunctions after radical surgery are temporary, and the majority of the patients recover in less than 30 days, including patients after C2 parametrectomy.

BackgroundRadical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy.Primary ObjectiveTo compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy.Study HypothesisWe hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach.Study DesignThis is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data.Inclusion CriteriaPatients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both).Exclusion CriteriaPrior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach.Primary EndpointThe primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy.Sample SizeAn estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group.

ObjectiveSentinel 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 methodsSENTIX 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 (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.ConclusionsThe 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).

Objectives The role of adjuvant radiotherapy for lymph node-negative stage IB patients with tumor-related negative prognostic factors is not uniformly accepted. It is advocated based on the GOG 92 trial, which was initiated in 1989. The aim of the current study is to report the oncological outcome of “intermediate risk” patients treated by tailored surgery without adjuvant radiotherapy. Data from two institutions that refer these patients for adjuvant radiotherapy served as a control group. Methods Included were patients with stage IB cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy, who had negative pelvic lymph nodes but a combination of negative prognostic factors adopted from the GOG 92 trial. Data were obtained from prospectively collected databases of three institutions. Radical surgery was a single-treatment modality in one of them and in the remaining two institutes it was followed by adjuvant chemoradiation. Results In 127 patients who received only radical surgery, with a median follow-up of 6.1 years, the local recurrence rate was 1.6% (2 cases), and total recurrence was 6.3% (8 cases). Disease-specific survival at 5 years was 95.7% (91.9%; 99.4%) and 91% (83.7%; 98.3%) at 10 years. The only significant factor for disease-specific survival was tumor size ≥4 cm (P = 0.032). The recurrence rate, local control or overall survival did not differ from the control group. Adjuvant radiotherapy was not a significant prognostic factor within the whole cohort. Conclusions An excellent oncological outcome, especially local control, can be achieved by both radical surgery or combined treatment in stage IB lymph node-negative cervical cancer patients with negative prognostic factors. The substantially better outcome than in the GOG 92 trial can be attributed to more accurate pre-operative and pathological staging and an improvement in surgical techniques.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005–2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20–42) years for open surgery vs 31 (18–45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0–31) mm for open surgery and 12 (0.8–40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20–16.70) years for open surgery and 3.1 years (0.02–11.10) years for minimally invasive surgery (P

BackgroundThe 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.ObjectivesTo analyze, in a retrospective cohort study, the efficacy of the algorithm using intra-operative pathological assessment of sentinel lymph nodes.MethodsA 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.ResultsThe 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 radiotherapyConclusionsOf 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.

Introduction/Background Since the risk of recurrence is low in early-stage cervical cancer, any assessment of prognostic importance of micrometastases (MIC) requires a large cohort. The aim of the study was to retrospectively analyze a large group of patients treated at a single site where sentinel lymph node (SLN) has been used in the management of cervical cancer since 2004 and which has an intensive protocol for SLN pathological ultrastaging. Methodology Patients with stage T1a - T2b cervical cancer treated by primary surgery with curative intent, who had common tumor types, at least unilateral SLN detection, and who were treated between 01/2007 - 12/2016 were included in the study. Radical surgery was abandoned if metastasis in SLN was detected by frozen section. All SLN were processed by an intensive protocol for SLN ultrastaging (entire SLN processed, 2 sections (H&E/cytokeratin) in 150 µm intervals from each block). Results The analysis included data from 234 patients (table 1). Adjuvant treatment was given to 79% of patients with macrometastasis (MAC), 77% with MIC, and 11% with isolated tumor cells (ITC). Within the median follow-up of 67 months 29 recurrences occurred. The recurrence rate of patients with negative LN, with MAC, MIC or ITC reached 9%, 29%, 35% and 22% respectively. Table 2 shows parameters significant for the risk of recurrence. Kaplan-Meier curves for PFS were significantly different for cases with MAC and MIC in comparison to LN-negative cases (figure 1). Conclusion The presence of MIC in SLN was associated with significantly decreased PFS, similar to MAC. There was a similar trend for ITC, but it did not reach significance due to low numbers. Patients with MIC and MAC should be managed identically and SLN ultrastaging should become an integral part of the management of patients with early-stage cervical cancer. Disclosure Acknowledgements This work was supported by Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1) and by a grant from the Czech Research Council (No 16-31643A). None of the authors declare any conflict of interest.

Introduction/Background The quality of pathological assessment is of pivotal importance in the management of cervical cancer patients if pelvic lymph node dissection (PLND) is to be replaced by sentinel lymph node (SLN) biopsy only. Methodology The aim was to report the results of the quality control of pathological SLN assessment in the group of 300 patients treated per protocol. All specimens and full pathology reports from at least two patients per site were reviewed centrally in Prague. SLN ultrastaging protocol included a complete processing of all SLN tissue in slices of 2 mm thickness, 2 sections in 150 µm from each block until no tissue left, one stained with H&E and second examined immunohistochemically. The findings were classified as: Minor (minor protocol deviations), Major (additional sections completed at central pathology), or Critical (deviations could not have been fixed at central pathology). In the case of Major or Critical findings, sites were requested to submit all samples from all additional patients for the second-round assessment. Results Samples from 77 cases from 36 sites with at least 1 patient treated per protocol were submitted for the central reading. Minor findings were identified in 27% of cases, Major in 30%, and Critical in 4%. Samples from 18 patients were submitted for the second control round; 9 were without deviations 7 had Minor, 2 Major, and 1 Critical findings. One site was prematurely closed due to repeated Critical findings. The most frequent deviations included incompletely processed SLN (36/95) and a lower number of immunohistochemical staining (31/95). Conclusion Major deviations from the SLN protocol were identified in 33% of sites and 31% of samples. These deviations can impact detection of small metastases and, consequently, the safety of the SLN concept. Central pathology reading allowed for substantial improvement of SLN pathological assessment during the trial. Disclosure Acknowledgements: This work was supported by a grant from the Czech Research Council (No 16-31643A). None of the authors declare a conflict of interest.

Introduction/Background SENTIX is a prospective cohort multicenter international study on sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. SLN frozen section (FS) and pathological ultrastaging were mandatory. Samples from SLN were reviewed centrally for pathological assessment quality control. Only sites experienced in SLN biopsy technique were eligible. Methodology In total, 47 sites from 18 countries participated in the study. Patients with stages T1a1/LVSI+ - T1b2 ( Results Data from 372 patients were analyzed who were pre-registered at the time when the number of cases treated per protocol reached 300. Patient characteristics are shown in table 1. Bilateral detection rate reached 91%. table 2 shows factors influencing SLN detection. Frozen section detected macrometastases (MAC) in 22 cases. SLN ultrastaging found additional 7 cases with MAC, 19 with micrometastases (MIC) and 11 with isolated tumor cells (ITC). Sensitivity of FS was 75.9% for the detection of MAC and 37.3% for any type of SLN involvement. Conclusion High bilateral detection can be achieved in sites experienced in the SLN biopsy technique. We did not confirm a higher detection rate using ICG. FS failed to detect 26/48 (54%) of cases with MIC or MAC in SLN. Disclosure This work was supported by a grant from the Czech Research Council (No 16-31643A). Conflict of interest: None of the authors declare a conflict of interest.

Introduction/Background Despite the use of nerve-sparing technique, bladder dysfunction remains the leading morbidity associated with parametrectomy (radical hysterectomy or trachelectomy). Our aim was to analyze the time to postoperative voiding recovery and the factors influencing it in the SENTIX trial cohort, in whom different types of surgical approach and parametrectomy was used. Methodology The SENTIX trial is a prospective cohort international study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer (≤4 cm or ≤2cm in fertility sparing). It entails 46 sites from 18 countries. Ad hoc analysis of data from the SENTIX trial was performed to assess factors influencing voiding recovery, which was defined as the number of days from surgery to bladder catheter or epicystostomy removal with post-voiding urine residuum Result The characteristics of the cohort of 372 patients are shown in table 1. Median (range) voiding recovery time was 3 (0–21) days; it was 1 month, only 1 case (80 days) was not associated with any severe intraoperative complication (6 cases) or adjuvant radiotherapy (3 cases). Tumor size >2 cm, open surgery, and a more extensive type of parametrectomy significantly influenced voiding recovery (figure 1). In multivariate analysis, only previous pregnancy and type of parametrectomy were significant (table 2). Conclusion Voiding recovery time is directly related to the extent of parametrectomy. It is, however, temporary and almost all patients recover within 1 month, even after a more radical procedure (C2). The higher risk associated with laparotomy reflects a tendency to be more radical with open surgery. Disclosure This work was supported by a grant from the Czech Research Council (No 16-31643A). There are no conflicts of interest.

Introduction/Background Main limitation of the majority of previous studies on prognostic markers lied in an insufficient standardisation of both clinical management and the method of assessment of individual parameters. Methodology All consecutive patients with early-stage cervical cancer treated by primary surgery in a single centre between 01/2007 and 12/2016 were eligible if they were assessed by standardized protocols for preoperative imaging and pathology. Fifteen prognostic parameters were evaluated, including age, 11 tumour-related (stage; largest tumour size; tumour size binarized; depth of stromal invasion; minimal tumour free distance (TFD); TFD binarized; lymphovascular space invasion (LVSI); tumour type; grade; parametrial invasion) and 3 lymph node (LN) status related ones (number of positive LNs; LN involvement; type of metastasis in LN). Results Data from 378 consecutive patients were analysed. Table 1 shows characteristics of the whole group (Cohort A) and LN negative patients (Cohort B). All parameters were associated with a risk of recurrence (RR), except for age and grade, in Cohort A, but only 4 remained significant in Cohort B (tumor type, grade, minimal TFD, TFD binarized). The best predictive model for Cohort A entailed a combination of TFD≤3.5 mm and LN positivity, which discriminated a subgroup of 42 patients with RR 36% versus 6.5% in the rest of the cohort (figure1). In Cohort B a combination of TFD≤3.5 mm and adenosquamous tumour type discriminated a small group of 9 patients (RR 33% versus 6% (figure 2). Conclusion TFD surpassed all other traditional tumor-related markers in the assessment of the recurrence risk in both cohorts. Predictive models combining TFD with LN status (whole cohort) or histological type (LN negative cases) can easily be used in daily practice and can identify the smallest possible group of patients with the highest risk of recurrence. Abstract P18 Table 1 Summary of demographic and clinical parameters in Cohort A (all cases) and Cohort B (LN neg) Disclosure None of the authors declare a conflict of interest. Acknowledgements This work was supported by Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1), by the project of Ministry of Health of the Czech Republic (MZ CR - RVO VFN64165) and by a grant from the Czech Research Council (No 16-31643A).

Introduction/Background The need for a combined treatment composed of radical surgery followed by adjuvant radiotherapy can be decreased by abandoning radical surgery in patients with intraoperatively detected lymph node (LN) involvement. The aim of the study was to analyze efficacy of the algorithm using intraoperative pathological assessment of sentinel LN (SLN). Methodology Cervical cancer patients were included into the study who had stage T1a - T2b squamous, adeno- or adenosquamous carcinoma, were referred for primary surgical treatment, and had at least one SLN detected and submitted for frozen section evaluation. In the case of intraoperatively detected SLN involvement, parametrectomy (radical hysterectomy or trachelectomy) was abandoned and the patient was referred for primary chemoradiation. Radical surgery was completed in patients with intraoperatively negative SLNs. Indications for postoperative adjuvant radiotherapy included LN involvement from final pathology, parametrial involvement, or positive resection margins. Results The trial included 309 patients (table 1). LN positivity was intraoperatively detected in 18 (6%) patients in whom radical hysterectomy was abandoned. Adjuvant radiotherapy after completed radical surgery was given to 29 (9%) cases, including 20 cases with macrometastases (MAC; 8) or micrometastases (MIC; 12) reported from the final histology, 8 cases with positive parametria (all ≤ 3 mm), and 1 case with a positive vaginal resection margin (figure 1). Conclusion Out of 47 (15%) patients with high-risk prognostic risk factors (LN, parametria or surgical margin involvement), in only 19 (38%) of them was a combined treatment successfully avoided. This was due to the low sensitivity of frozen section in the detection of MIC and low accuracy of clinical staging in the detection of microscopic parametrial involvement. Disclosure Nothing to disclose.

Introduction/Background To evaluate the performance of 2-dimensional (2D) ultrasound in preoperative assessment of parametria involvement in patients with cervical cancer planned for primary surgical treatment. Histopathological findings from radical hysterectomy/trachelectomy/parametrectomy were used as a reference standard. Methodology Patients with biopsy-proven cervical cancer evaluated on ultrasound and planned for primary surgery 01/2004 and 12/2017 were prospectivelly enrolled. The predefined protocol for ultrasound assessment included the presence of tumor, maximum tumor size, tumor-free distance (TFD), the parametrial involvement status, grade of parametrial infiltration and lymph node status. Results Altogether, 722 patients were included, out of them 77 patients (11%) were excluded for tumor duplicity, absence of index test or reference standard. Data of 645 patients were analysed, 555 early stage cases (T1[except T1b3], T2a1, FIGO 2018) and 90 locally advanced stage (T1b3 and higher [except T2a1], FIGO 2018). The median age was 42 years and BMI was 24.5. Sixty-two patients (10%) underwent neoadjuvant chemotherapy (NACT). The maximum tumor size was 19.5 mm. The histologically confirmed prevalence of infiltrated parametria was 3.9% (25/645), with 12 cases correctly identified by the ultrasound. Ultrasound did not detect 11 cases (1.7%) with microscopic spread ( Conclusion Ultrasound is very good method for preoperative assessment of parametrial involvement in cervical cancer with a minimal risk of failure to detect infiltration >2 mm. Disclosure This work was supported by Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1) and by a grant from the Czech Research Council (No 16-31643A). None of the authors declare any conflict of interest.

Objectives To compare disease-free survival (DFS) between patients who underwent open (ORT) versus minimally invasive (MIS) radical trachelectomy (RT) [laparoscopic (LRT) or robotic (RRT)]. Methods Eligibility criteria included 1) RT and pelvic lymphadenectomy with/without sentinel lymph node mapping, 2) 1/2005 to 12/2017 3) squamous, adenocarcinoma, or adenosquamous histology, 4) stage IA2-IB1, 5) tumors ≤2 cm, 6) 15 or more cases per center. Results A total of 698 patients [open (n=388) vs. MIS (310)] were included. The median follow-up time was 40.9 months (range, 1–179.1) [MIS 38.6 (range, Conclusions Surgical approach in radical trachelectomy for low-risk cervical cancer was not associated with differences in recurrence rates or survival. MIS had worse perioperative outcomes.

Objective A high sensitivity of sentinel lymph nodes (SLN) for pelvic lymph node (LN) staging has been repeatedly shown in patients with cervical cancer. However, since only SLN are evaluated by pathologic ultrastaging, the risk of small metastases, including small macrometastases (MAC) and micrometastases (MIC), in non-SLN is unknown. This can be a critical limitation for the oncological safety of abandoning a pelvic lymphadenectomy. Methods The patients selected for the study had cervical cancer and were at high risk for LN positivity (stage IB–IIA, biggest diameter≥3cm). The patients had no enlarged or suspicious LN on pre-operative imaging; SLNs were detected bilaterally and were negative on intra-operative pathologic evaluation. All SLNs and all other pelvic LNs were examined using an ultrastaging protocol and processed completely in intervals of 150μm. Results In all, 17 patients were enrolled into the study. The mean number of removed pelvic LNs was 30. A total of 573 pelvic LNs were examined through ultrastaging protocol (5762 slides). Metastatic involvement was detected in SLNs of 8 patients (1× MAC; 4× MIC; 3× ITC) and in non-SLNs in 2 patients (2× MIC). In both cases with positive pelvic non-SLNs, there were found MIC in ipsilateral SLNs. No metastasis in pelvic non-SLNs was found by pathologic ultrastaging in any of the patients with negative SLN Side-specific sensitivity was 100% for MAC and MIC. There was one case of ITC detected in non-SLN, negative ipsilateral SLN, but MIC in SLN on the other pelvic side. Conclusions After processing all pelvic LNs by pathologic ultrastaging, there were found no false-negative cases of positive non-SLN (MAC or MIC) and negative SLN. SLN ultrastaging reached 100% sensitivity for the presence of both MAC and MIC in pelvic LNs.

ObjectivesTo assess the survival of patients who have received an operation for recurrent cervical and endometrial cancer and to determine prognostic variables for improved oncologic outcome.MethodsA retrospective multicenter analysis of the medical records of 518 patients with cervical (N = 288) or endometrial cancer (N = 230) who underwent surgery for disease recurrence and who had completed at least 1 year of follow-up.ResultsThe median survival reached 57 months for patients with cervical cancer and 113 months for patients with endometrial cancer after surgical treatment of recurrence (p = 0.036). Histological sub-type had a significant impact on overall survival, with the best outcome in endometrial endometrioid cancer (121 months), followed by cervical squamous cell carcinoma, cervical adenocarcinoma, or other types of endometrial cancer (81 vs 35 vs 35 months; pConclusionLong-term survival can be achieved via secondary cytoreductive surgery in selected patients with recurrent cervical and endometrial cancer. An excellent outcome is possible even if the recurrence site is located in the lymph nodes. The possibility of achieving complete resection should be the main criterion for patient selection.

ObjectiveThe aim of our study was to compare the sensitivity of various methods and their combinations in the follow-up of patients with cervical cancer after fertility-sparing surgery (FSS).MethodsIncluded were women with cervical cancer in stages IA2 to IB2 who underwent FSS, which includes pelvic lymphadenectomy, sentinel lymph node biopsy, abdominal radical trachelectomy, vaginal trachelectomy, or needle conization. Follow-up visits were scheduled at 3-month intervals and included symptom-oriented discussion, gynecological and physical examination, colposcopy, Papanicolaou test, human papillomavirus (HPV) DNA test, and ultrasound examination. All cases with a recurrent disease were thoroughly analyzed, and the results of individual examinations were compared.ResultsIn total, 43 women (IA2, 8; IB1, 33; IB2, 2) were enrolled. The mean patient age was 31 years; most patients were nulliparous (68.4%, 26/38) with squamous cell cancers (26/38). Abdominal radical trachelectomy was performed in 10 women, simple vaginal trachelectomy was performed in 11 women, and conization was performed in 22 women, according to the tumor characteristics and topography. The median duration of the follow-up reached 37 months. Invasive cancer and high- and low-grade squamous intraepithelial lesions were detected in 8, 1, and 1 patients, respectively. All except 1 event were central, detected within the first year after FSS. Only 2 cases were symptomatic. Colposcopy detected 7 of 10 recurrences; 5 of them were HPV positive, and, in 2 cases, a Papanicolaou test revealed abnormalities. Papanicolaou tests were false positive in 27.7%, especially after trachelectomies.ConclusionsMost patients in whom cancer recurred after FSS reveal central or pelvic lesions, which can be successfully treated with salvage surgery or radiotherapy. The early detection of recurrence is an essential condition for a favorable oncological outcome. Colposcopy alone and in combination with HPV positivity showed the highest sensitivity for the detection of recurrent diseases, whereas other methods had limited reliability.

Ozdemir, Aykut/0000-0001-5457-3312; Basaran, Derman/0000-0002-2689-1417 WOS: 000433285800006 PubMed ID: 29770621 Objective: To evaluate the opinions of women who underwent surgery for cervical cancer (CC) and physicians who treat CC about the acceptability of increased oncological risk after less-radical surgery. Methods: One hundred eighty-two women who underwent surgery for CC and 101 physicians participated in a structured survey in 3 tertiary cancer centers in Czech Republic and Turkey. Patients and physicians were asked whether they would accept any additional oncological risks, which would be attributable to the omission of parametrectomy (radical hysterectomy/trachelectomy vs. simple hysterectomy/trachelectomy) or pelvic lymph node dissection (systematic resection vs. sentinel lymph node sampling). Results: Although 52.2% of patients reported morbidity related to their previous treatment, the majority of patients would not accept less-radical surgical treatment if it was associated with any increased risk of recurrence (50%-55%, no risk; 17%-24%, risk < 0.1%). Physicians tended to accept a significantly higher risk than patients in the Czech Republic, but not in Turkey. Patients with higher education levels, more advanced-stage of disease, or adverse events related to previous cancer treatment, and patients who received adjuvant therapy were significantly more likely to accept an increased oncological risk. Conclusion: Patients, even if they suffered from morbidity related to previous CC treatment, do not want to choose between oncological safety and a better quality of life. Physicians tend to accept the higher oncological risk associated with less-radical surgical procedures, but attitudes differ regionally. Professionals should be aware of this tendency when counselling the patients before less-radical surgery. Charles University in Prague [UNCE 204065, PROGRES-Q28/LF1]; Czech Ministry of HealthMinistry of Health, Czech Republic [MZ CR-RVO VFN64165] This work was supported by Charles University in Prague (UNCE 204065 and PROGRES-Q28/LF1) and by a project from the Czech Ministry of Health (MZ CR-RVO VFN64165).

The aim of this study was to assess the detection rate, false-negative rate and sensitivity of SLN in LN staging in tumors over 2cm on a large cohort of patients.Data from patients with stages pT1a - pT2 cervical cancer who underwent surgical treatment, including SLN biopsy followed by systematic pelvic lymphadenectomy, were retrospectively analyzed. A combined technique with blue dye and radiocolloid was modified in larger tumors to inject the tracer into the residual cervical stroma.The study included 350 patients with stages pT1a - pT2. Macrometastases, micrometastases, and isolated tumor cells were found in 10%, 8%, and 4% of cases. Bilateral detection rate was similar in subgroups with tumors2cm, 2-3.9cm, and ≥4cm (79%, 83%, 76%) (P=0.460). There were only two cases with false-negative SLN ultrastaging for pelvic LN status among those with bilateral SLN detection. The false negative rate was very low in all three subgroups of different tumor sizes (0.9%, 0.9%, and 0.0%; P=0.999). Sensitivity reached 96% in the whole group and was high in all three groups (93%, 93%, 100%; P=0.510).If the tracer application technique is adjusted in larger tumors, SLN biopsy can be equally reliable in pelvic LN staging in tumors smaller and larger than 2cm. The bilateral detection rate and false negative rate did not differ in subgroups of patients with tumors2cm, 2-3.9cm, and ≥4cm.

Objective The aim of our study was to describe oncological and obstetrical outcomes in patients who underwent less radical fertility-sparing surgical (FSS) procedures with omitted parametrectomy for cervical cancer. Methods Included were women with cervical cancer stages IA2–IB2 who were under the age of 40 and desired future pregnancy. Patients underwent pelvic lymphadenectomy and sentinel lymph node biopsy. Node-negative cases underwent subsequent cervical surgery and were further analyzed. Neoadjuvant chemotherapy (NAC) was administered in patients with tumors >2cm and/or involving >2/3 of cervical stroma. Simple vaginal trachelectomy or needle conization were performed according to tumor extent and topography. The follow-up period started once free surgical margins were reached. Results Out of 44 women enrolled, 32 women (IA2=7, IB1=23, IB2=2) successfully completed FSS. NAC was administered in 9 (28.1%) cases. A simple trachelectomy was performed in 11 patients and needle conization in 21 patients. During the follow-up, 6 out of 32 women became pregnant. Of these, 1 miscarried and 5 successfully delivered. Disease recurred in 6 patients; 5 recurrences were central and 1 recurrence presented as an ovarian mass. Invasive cervical carcinoma, high-grade squamous intraepithelial (HSIL), and low-grade squamous intraepithelial (LSIL) lesions were detected in 4, 1 and 1 patients, respectively. Three of them received NAC. All events were detected within 16months after surgery. Conclusions Nearly 27% of patients cannot complete FSS due to node positivity, progression during NAC, or involved margins. The total recurrence rate reached 18.8%, with the majority of invasive recurrences detected in patients after NAC followed by FSS. These patients represent cases at a higher risk of recurrence even if adequate free margins are reached by surgery. Nearly half of the cohort did not consider pregnancy in the near future because of personal reasons.