Gabriella Schivardi

Robotic single-port (da Vinci SP) versus multiport (da Vinci Xi) for the treatment of atypical endometrial hyperplasia and endometrial cancer: A multi-institutional comparison of surgical outcomes

The da Vinci SP robotic platform offers a novel single-port approach for minimally invasive surgery. Despite its potential, data on its safety and performance in gynecologic oncology remain limited. We aimed to compare surgical outcomes of da Vinci SP versus da Vinci Xi systems in the staging of endometrial cancer (EC). This is a multi-institutional study. Data of consecutive patients with apparent early-stage EC or atypical endometrial hyperplasia who underwent robotic surgery between January 2023-March 2025 were collected. The primary outcome was to compare the surgical outcomes between da Vinci SP and da Vinci Xi. A total of 189 patients were included: 97 (51.3 %) underwent SP surgery and 92 (48.7 %) Xi. The median (range) of operative time, estimated blood loss, and postoperative hospital stay were comparable for SP and Xi groups (140 [70-296] vs. 143 [60-297] min, p = 0.66, 40 [0-250] vs. 64 [0-1300] mL, p = 0.12, 3 [1-11] vs. 3[1-10] days, p = 1). Docking time was significantly shorter in the SP group (10 [4-31] vs. 12 [7-30] min for SP and Xi, respectively, p = 0.004). Intraoperative or post-operative complications rates were comparable (p = 0.30 and p = 0.14,respectively). The patient-reported pain score was significantly lower at 12h and 24h in the Xi group (p = 0.001), while was comparable at 48h after surgery (p = 1). The da Vinci SP system appears to be non-inferior to the multiport da Vinci Xi for surgical staging of early-stage EC. Comparable perioperative outcomes support its clinical use, although patient selection criteria and long-term results require further investigation.

Detection rate of sentinel lymph nodes in early-stage endometrial cancer according to age

Sentinel lymph node (SNL) mapping plays a crucial role in staging patients with an apparent early-stage endometrial cancer. Older age may be associated with lower detection rates due to factors such as decreased lymphatic flow; but consensus is lacking. This study aims to evaluate the impact of age on the SNL detection rate in patients undergoing minimally invasive surgical staging for endometrial cancer. This multicenter retrospective study included apparent early-stage endometrial cancer patients undergoing minimally invasive surgical staging, including SLN mapping across four ESGO-accredited centers (2020-2023). Patients were categorized into two age groups: <65 years, defined as younger adults and ≥65 years, defined as older adults. Univariate and multivariate logistic regression models were used to identify predictors of bilateral mapping. Overall, 642 patients were identified: 342 (53.3%) patients were classified as younger adults and 300 (46.7%) as older adults. The overall bilateral SLN detection rate was 89.3%, with no or unilateral detection in 10.7% of patients. Older adults had a significantly lower bilateral detection rate than younger adults (85.0% vs. 93.0%, p = 0.005). Multivariate analysis identified age ≥65 years as the only independent predictor of failed bilateral mapping (OR 2.2, 95 % CI 1.3-3.8, p = 0.003). Other clinical, surgical, and pathological factors were not associated with mapping failure. Age ≥65 is independently associated with decreased bilateral SLN detection in early-stage endometrial cancer. Nevertheless, SLN biopsy remains a feasible and reliable staging method in older adults when performed using standardized techniques by experienced surgeons.

Impact of molecular classification on recurrence risk in endometrial cancer patients with lymph node metastasis: multicenter retrospective study

To assess the distribution of molecular classes and their impact on the risk of recurrence in endometrial cancer patients with lymph node metastasis at the time of primary surgery. Endometrial cancer patients with lymph node micrometastasis or macrometastasis (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIC) after surgical staging at five referral centers worldwide from October 2013 to September 2022 who underwent molecular classification were identified. Endometrial cancers were categorized into four molecular classes: POLE mutated, mismatch repair deficient, p53 abnormal, and no specific molecular profile. Survival analyses using Kaplan-Meier and Cox models (univariate and multivariate) were conducted to evaluate the relationship between molecular class and 5-year recurrence free survival. 131 patients were included: 55 (42.0%) no specific molecular profile, 46 (35.1%) mismatch repair deficient, 1 (0.8%) POLE mutated, and 29 (22.1%) p53 abnormal. During a 5 year follow-up period, 50 (38.2%) patients experienced a recurrence with a median time of 1.2 years (interquartile range (IQR) 0.5-1.8). Median follow-up for the remaining 81 patients was 3.1 years (IQR 1.3-4.5). Survival analysis revealed a significant difference in recurrence-free survival between no specific molecular profile, mismatch repair deficient, and p53 abnormal classes (log rank p<0.01). In a model adjusted for type of lymph node metastasis and tumor grade, the molecular class did not retain significance (p=0.13), while in a model adjusted for type of lymph node metastasis and adjuvant therapy, the molecular class retained significance (p<0.01). Among patients with stage IIIC endometrial cancer, POLE mutated tumors exhibited an extremely low prevalence, with no specific molecular profile emerging as the largest molecular subgroup. Despite the significant difference in recurrence-free survival between molecular classes, conventional histopathologic parameters retained crucial prognostic value. Our findings highlight the necessity of integrating molecular classes with pathological characteristics, rather than considering them in isolation as crucial prognostic factors in stage IIIC endometrial cancer.

Determinants of adjuvant radiotherapy in early-stage cervical cancer: a retrospective analysis of the SUCCOR cohort

This study aimed to describe the patterns of adjuvant therapy use within the SUCCOR cohort, a large retrospective analysis comparing disease-free survival following minimally invasive versus open surgery in early-stage cervical cancer. Furthermore, to assess the factors associated with the indication for adjuvant radiotherapy after radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB (≤4cm) cervical cancer. A retrospective analysis was performed using the SUCCOR study database. We investigated patients with FIGO 2009 stage IB1, node-negative cervical cancer at final pathology. Univariate and multi-variable logistic regression were performed to determine factors associated with the administration of adjuvant radiation therapy. The study included a total of 572 patients. Of these, 340 patients (59.4%) did not receive adjuvant radiotherapy, including 45 (13.2%) who met the Sedlis criteria. Conversely, among the 232 patients (40.6%) who received adjuvant radiotherapy, 132 (56.9%) did not meet Sedlis criteria. In the univariate logistic regression, factors associated with adjuvant radiotherapy included tumor size >2 cm (p< .001), lymphovascular space invasion (p < .001) and a tumor grade G3 (vs G1-G2, p .01). Furthermore, the probability of receiving adjuvant radiotherapy was higher for patients with deep stromal invasion (p < .001), and with intermediate stromal invasion (p < .001) in comparison to those with superficial stromal invasion. At multiple logistic regression, open approach (odds ratio [OR] 1.63, p =.01) and G3 tumor grade (OR 1.64, p= .01) were independently associated with the administration of adjuvant radiotherapy. In addition, the presence of Sedlis criteria was associated with a 4 times higher probability of having adjuvant radiotherapy (OR 4.44, p < .001). While the Sedlis criteria should guide post-operative radiotherapy administration, we observed a significant variation in post-operative adjuvant treatment among institutions involved in the SUCCOR study. A call for a standardized recommendation of adjuvant radiation therapy is needed.

External validation of the annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer

The annual recurrence risk model (ARRM), developed by the Surveillance in Cervical Cancer consortium and endorsed by the European Society of Gynecological Oncology, predicts the annual risk of cervical cancer recurrence. However, it lacks an external validation, which we aimed to address in the current retrospective study. We included patients with pathology confirmed T1a to T2b cervical cancers who underwent radical surgery at the European Institute of Oncology, Milan from January 2010 to December 2022. Using the ARRM risk calculator, patients were assigned a score from 0 to 100 points, which allowed classification into 5 risk groups (0, 1-25, 26-50, 51-75, and 76-100 points). Differences in 5-year disease-free survival were evaluated through log-rank tests with pairwise comparisons. Annual risk of recurrence was calculated using conditional survival analysis. Overall, 411 patients with cervical cancers were included: 0 (0.0%) scored 0 points, 149 (36.3%) scored 1 to 25 points, 224 (54.5%) scored 26 to 50 points, 37 (9.0%) scored 51 to 75 points, and 1 (0.2%) scored 76 to 100 points. The patient from 76 to 100 points was excluded from further analyses. The 5-year disease-free survival rates were 96.3% (95% CI 90.0 to 98.6), 85.7% (95% CI 80.1% to 89.9%), and 66.6% (95% CI 47.3% to 80.2%) in groups 1 to 25, 26 to 50, and 51 to 75 points, respectively (p < .01). Compared with 26 to 50 and 51 to 75 points, the annual risk of recurrence was lower in the 1 to 25 points group, at around 1% from year 1 to 5. The ARRM tool confirmed its validity in stratifying cervical cancer into groups with significantly different disease-free survival rates in an independent large population from a tertiary center. The annual risk of recurrence should be carefully considered when tailoring follow-up, always taking into account the patient's perspective.

Para-aortic lymph node recurrence in surgically treated early-stage cervical cancer without para-aortic lymph node surgical staging

The standard treatment for early-stage cervical cancer includes radical hysterectomy with pelvic lymph node staging ± bilateral salpingo-oophorectomy. Para-aortic lymphadenectomy may be considered; however, its role remains controversial. The objective of this study was to assess the para-aortic lymph node recurrence rate in patients undergoing surgery for apparent early-stage cervical cancer without para-aortic lymph node surgical staging. This is a retrospective cohort study including all consecutive patients with presumed early-stage (International Federation of Gynecology and Obstetrics (FIGO) 2018 IA1-IB2, IIA1) cervical cancer who underwent radical surgery at the European Institute of Oncology, Milan, Italy. Pelvic lymph node assessment included sentinel lymph node biopsy and/or systematic pelvic lymphadenectomy. Patients who underwent para-aortic lymphadenectomy or had an indication to receive adjuvant para-aortic radiotherapy were excluded. The Kaplan-Meier method was used to estimate 5-year recurrence-free survival. Overall, 432 patients were included. The median age was 43.7 years (IQR 38.1-51.6). Sixteen (3.7%) patients were staged IA1 at diagnosis, 24 (5.6%) IA2, 208 (48.1%) IB1, 177 (41%) IB2, and 7 (1.6%) IIA1. At final pathology, the stage distribution was as follows: 36 (8.3%) stage IA1-IA2, 323 (74.8%) stage IB1-IB3, 17 (3.9%) stage II, and 56 (13%) stage IIIC1. Eighty-two patients (19%) underwent concurrent pelvic chemoradiotherapy, 20 (4.6%) radiotherapy alone, and 3 (0.7%) chemotherapy alone. Thirty-eight (8.8%) patients experienced a recurrence with a median time of 18 months (IQR 12-29). The median follow-up time for the remaining 394 (91.2%) patients was 70 months (IQR 36-98). Two patients (0.5%) had a recurrence in the para-aortic lymph nodes. The 5-year recurrence-free survival in the overall cohort was 90% (95% CI 87.4% to 93.3%). Given the low rate of para-aortic lymph node recurrence in surgically treated early-stage cervical cancer and the well-established peri-operative complications associated with para-aortic lymphadenectomy, our study aligns with recent evidence supporting the omission of this procedure in such patients.

Practice patterns and complications of hysterectomy for invasive cervical cancer after the Laparoscopic Approach to Cervical Cancer trial

After the publication of the Laparoscopic Approach to Cervical Cancer trial, the standard surgical approach for early-stage cervical cancer is open radical hysterectomy. Only limited data were available regarding whether the change to open abdominal hysterectomy observed after the Laparoscopic Approach to Cervical Cancer trial led to an increase in postoperative complication rates as a consequence of the decrease in the use of the minimally invasive approach. This study aimed to analyze whether there was a correlation between the publication of the Laparoscopic Approach to Cervical Cancer trial and an increase in the 30-day complications associated with surgical treatment of invasive cervical cancer. Data from the American College of Surgeons National Surgical Quality Improvement Program were used to compare the results in the pre-Laparoscopic Approach to Cervical Cancer period (January 2016 to December 2017) vs the results in the post-Laparoscopic Approach to Cervical Cancer period (January 2019 to December 2020). The rates of each surgical approach (open abdominal or minimally invasive) hysterectomy for invasive cervical cancer during the 2 periods were assessed. Subsequently, 30-day major complication, minor complication, unplanned hospital readmission, and intra- or postoperative transfusion rates before and after the publication of the Laparoscopic Approach to Cervical Cancer trial were compared. Overall, 3024 patients undergoing either open abdominal hysterectomy or minimally invasive hysterectomy for invasive cervical cancer were included in the study. Of the patients, 1515 (50.1%) were treated in the pre-Laparoscopic Approach to Cervical Cancer period, and 1509 (49.9%) were treated in the post-Laparoscopic Approach to Cervical Cancer period. The rate of minimally invasive approaches decreased significantly from 75.6% (1145/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 41.1% (620/1509) in the post-Laparoscopic Approach to Cervical Cancer period, whereas the rate of open abdominal approach increased from 24.4% (370/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 58.9% (889/1509) in the post-Laparoscopic Approach to Cervical Cancer period (P<.001). The overall 30-day major complications remained stable between the pre-Laparoscopic Approach to Cervical Cancer period (85/1515 [5.6%]) and the post-Laparoscopic Approach to Cervical Cancer period (74/1509 [4.9%]) (adjusted odds ratio, 0.85; 95% confidence interval, 0.61-1.17). The overall 30-day minor complications were similar in the pre-Laparoscopic Approach to Cervical Cancer period (103/1515 [6.8%]) vs the post-Laparoscopic Approach to Cervical Cancer period (120/1509 [8.0%]) (adjusted odds ratio, 1.17; 95% confidence interval, 0.89-1.55). The unplanned hospital readmission rate remained stable during the pre-Laparoscopic Approach to Cervical Cancer period (7.9% per 30 person-days) and during the post-Laparoscopic Approach to Cervical Cancer period (6.3% per 30 person-days) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.58-1.04)]. The intra- and postoperative transfusion rates increased significantly from 3.8% (58/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 6.7% (101/1509) in the post-Laparoscopic Approach to Cervical Cancer period (adjusted odds ratio, 1.79; 95% confidence interval, 1.27-2.53). This study observed a significant shift in the surgical approach for invasive cervical cancer after the publication of the Laparoscopic Approach to Cervical Cancer trial, with a reduction in the minimally invasive abdominal approach and an increase in the open abdominal approach. The change in surgical approach was not associated with an increase in the rate of 30-day major or minor complications and unplanned hospital readmission, although it was associated with an increase in the transfusion rate.

Prognostic value of isolated tumor cells in sentinel lymph nodes in intermediate-risk endometrial cancer: results from an international, multi-institutional study

This study assessed oncologic outcomes of patients with intermediate-risk endometrioid endometrial cancer and isolated tumor cells (ITC) (≤0.2 mm or ≤200 cells) in sentinel lymph nodes (SLNs). Patients with SLN-ITC diagnosed between 2012 and 2019 were identified from 19 centers worldwide, while SLN-negative patients were identified at Mayo Clinic, Rochester between 2014 and 2018. Only patients with endometrioid endometrial cancer and intermediate-risk factors (low-grade endometrioid histology and myometrial invasion ≥50%; high-grade endometrioid histology and myometrial invasion <50%) were included. Oncologic outcomes were evaluated by grouping patients according to prognostic factors: SLN-ITC and lymphovascular space invasion (LVSI). SLN-ITC patients with post-operative observation or vaginal brachytherapy (VB) alone were compared with similar node-negative patients. Of the 166 patients included, those with simultaneous presence of SLN-ITC and LVSI were at higher risk of non-vaginal recurrence (HR 3.73 [95% CI 1.17 to 11.84], p = .01) compared with patients who were node-negative with no LVSI. Among the 122 patients (28 SLN-ITC, 94 node-negative) who underwent post-operative observation or VB alone, 1 isolated vaginal recurrence was documented in a node-negative patient, while non-vaginal recurrence occurred in 3 of 28 (10.7%) SLN-ITC and 7 of 94 (7.4%) node-negative patients. The median follow-up was 2.4 years (interquartile range; 1.8-3.0) among the remaining 25 ITC patients and 2.8 years (interquartile range; 0.8-4.2) among the remaining 87 node-negative patients. There was no difference in non-vaginal recurrence-free survival (SLN-ITC: 87.3% [95% CI 74.7% to 100.0%] vs node-negative: 82.2% [95% CI 69.1% to 97.9%], p = .46) or overall survival (SLN-ITC: 76.4% [95% CI 54.3 to 100.0] vs node-negative: 84.5% [95% CI 75.0 to 95.2], p = .28) between the 2 cohorts. In patients with endometrioid endometrial cancer and intermediate-risk factors (including patients who received chemotherapy/external beam radiotherapy), the combination of SLN-ITC and LVSI was associated with worse prognosis compared with patients with no risk factors or only 1 risk factor. In the sub-group of patients who received post-operative observation or VB alone, SLN-ITC did not worsen prognosis relative to node-negative patients.

Outcomes of low-risk endometrial cancer with isolated tumor cells in the sentinel lymph nodes: a prospective, multi-center, single-arm, observational study (ENDO-ITC study)

It is unclear whether isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) adversely affect prognosis, especially in low-risk endometrial cancer. In a retrospective study, we showed a worse recurrence-free survival for low-risk endometrial cancer with ITCs than the node-negative group. Our aim is to evaluate whether the likelihood of disease recurrence differs between a prospective cohort of patients with low-risk endometrial cancer with ITCs and an historical cohort with negative SLNs. We hypothesize that patients with low-risk endometrial cancer and ITCs will have a worse recurrence-free survival than patients who are node-negative. This is a prospective, multi-center, single-arm observational study. Consecutive patients with low-risk endometrial cancer with ITCs in the SLNs will be accrued. Observation only will be suggested after surgery. We will include patients with endometrial cancer undergoing pelvic SLN biopsy and ultra-staging with the following characteristics: endometrioid histology, grades 1 to 2, <50% myometrial invasion, without substantial/extensive lympho-vascular space invasion. ITCs in SLNs are defined as tumor cell aggregates ≤0.2 mm or <200 cells. The primary end point is recurrence-free survival, measured from the date of surgery to the date of recurrence, death, or last disease evaluation. With a sample size of 132 women with low-risk endometrial cancer and ITCs, a 1-sided log-rank test achieves 85% power at a 0.05 significance level to detect an HR of 2.1. The expected number of events during the study is 17.3. The study duration will be 60 months: 24 for enrollment and 36 for follow-up. The results are expected in 2029. ClinicalTrials.gov: NCT06689956.