Nabil Manzour

An international worldwide retrospective cohort observational study comparing primary cytoreductive surgery with neoadjuvant chemotherapy and interval cytoreductive surgery in patients with carcinoma of the ovary, fallopian tubes, and peritoneum (SUROVA trial)

Currently, a lively debate exists within the scientific community regarding the most suitable procedure for treating stages IIIB-IVB carcinoma of the ovary, fallopian tubes, and peritoneum. The options under most consideration are primary cytoreductive surgery or neoadjuvant chemotherapy followed by interval cytoreductive surgery. To compare overall survival at 5 years in patients who underwent primary cytoreductive surgery versus neoadjuvant chemotherapy and interval cytoreductive surgery for stage IIIB-IVB ovarian cancer STUDY HYPOTHESIS: The treatment with primary cytoreductive surgery results in superior patient survival compared with neoadjuvant chemotherapy followed by interval cytoreductive surgery. This is a multicenter, retrospective cohort observational study. Data will be collected from patients undergoing surgery in hospitals worldwide. Two arms will be compared: primary cytoreductive surgery and neoadjuvant chemotherapy followed by interval cytoreductive surgery. Patients must have suspected or histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stages IIIB-IVB ovarian, peritoneal, or fallopian tube cancers. They must have undergone primary surgery or first course of neoadjuvant chemotherapy between January 1, 2018 and December 31, 2019. Based on all available information before the surgery (primary or interval), the patient must have been considered completely resectable. Overall survival at 5 years from the first treatment (chemotherapy in the case of neoadjuvant chemotherapy and cytoreduction in the case of primary cytoreductive surgery). An estimated total of 5000 patients will be enrolled in the study. March 2025 TRIAL REGISTRATION: NCT06223763.

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.

SUCCOR morbidity: complications in minimally invasive versus open radical hysterectomy in early cervical cancer

The aim of this study was to compare the incidence of intra-operative and post-operative complications in open and minimally invasive radical hysterectomy for patients with early-stage cervical cancer. Data were collected from the SUCCOR database of 1272 patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO), 2009) who underwent radical hysterectomy in Europe between January 2013 and December 2014. We reviewed the duration of the surgeries, estimated blood loss, length of hospital stay, intra-operative and post-operative complications. The inclusion criteria were age ≥18 years and histologic type (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma). Pelvic MRI confirming a tumor diameter ≤4 cm with no parametrial invasion and a pre-operative CT scan, MRI, or positron emission tomography CT demonstrating no extra-cervical metastatic disease were mandatory. Outcomes of interest were any grade >3 adverse events, intra-operative adverse events, post-operative adverse events, length of hospital stay, length of operation, and blood loss. The study included 1156 patients, 633 (54%) in the open surgery group and 523 (46%) in the minimally invasive surgery group. Median age was 46 years (range 18-82), median body mass index 25 kg/m Our study showed that there was no significant difference in the overall incidence of intra-operative and post-operative complications between minimally invasive radical hysterectomy and the open approach.

Ultrasound examination, MRI, or ROMA for discriminating between inconclusive adnexal masses as determined by IOTA Simple Rules: a prospective study

To determine the best second-step approach for discriminating benign from malignant adnexal masses classified as inconclusive by International Ovarian Tumour Analysis Simple Rules (IOTA-SR). Single-center prospective study comprising a consecutive series of patients diagnosed as having an adnexal mass classified as inconclusive according to IOTA-SR. All women underwent Risk of Ovarian Malignancy Algorithm (ROMA) analysis, MRI interpreted by a radiologist, and ultrasound examination by a gynecological sonologist. Cases were clinically managed according to the result of the ultrasound expert examination by either serial follow-up for at least 1 year or surgery. Reference standard was histology (patient was submitted to surgery if any of the tests was suspicious) or follow-up (masses with no signs of malignancy after 12 months were considered benign). Diagnostic performance of all three approaches was calculated and compared. Direct cost analysis of the test used was also performed. Eighty-two adnexal masses in 80 women (median age 47.6 years, range 16 to 73 years) were included. Seventeen patients (17 masses) were managed expectantly (none had diagnosis of ovarian cancer after at least 12 months of follow-up) and 63 patients (65 masses) underwent surgery and tumor removal (40 benign and 25 malignant tumors). Sensitivity and specificity for ultrasound, MRI, and ROMA were 96% and 93%, 100% and 81%, and 24% and 93%, respectively. The specificity of ultrasound was better than that for MRI (p=0.021), and the sensitivity of ultrasound was better than that for ROMA (p<0.001), sensitivity was better for MRI than for ROMA (p<0.001) and the specificity of ROMA was better than that for MRI (p<0.001). Ultrasound evaluation was the most effective and least costly method as compared with MRI and ROMA. In this study, ultrasound examination was the best second-step approach in inconclusive adnexal masses as determined by IOTA-SR, but the findings require confirmation in multicenter prospective trials.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators

Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

Intra-operative radiation therapy after a total lateral extended infralevator exenteration for recurrent cervical cancer

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer

To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

ASO Author Reflections: Will Conization Become a Standard Maneuver Before Radical Hysterectomy?

SUCCOR Risk: Design and Validation of a Recurrence Prediction Index for Early-Stage Cervical Cancer

Abstract Objective Based on the SUCCOR study database, our primary objective was to identify the independent clinical pathological variables associated with the risk of relapse in patients with stage IB1 cervical cancer who underwent a radical hysterectomy. Our secondary goal was to design and validate a risk predictive index (RPI) for classifying patients depending on the risk of recurrence. Methods Overall, 1116 women were included from January 2013 to December 2014. We randomly divided our sample into two cohorts: discovery and validation cohorts. The test group was used to identify the independent variables associated with relapse, and with these variables, we designed our RPI. The index was applied to calculate a relapse risk score for each participant in the validation group. Results A previous cone biopsy was the most significant independent variable that lowered the rate of relapse (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.17–0.60). Additionally, patients with a tumor diameter &gt;2 cm on preoperative imaging assessment (OR 2.15, 95% CI 1.33–3.5) and operated by the minimally invasive approach (OR 1.61, 95% CI 1.00–2.57) were more likely to have a recurrence. Based on these findings, patients in the validation cohort were classified according to the RPI of low, medium, or high risk of relapse, with rates of 3.4%, 9.8%, and 21.3% observed in each group, respectively. With a median follow-up of 58 months, the 5-year disease-free survival rates were 97.2% for the low-risk group, 88.0% for the medium-risk group, and 80.5% for the high-risk group (p &lt; 0.001). Conclusion Previous conization to radical hysterectomy was the most powerful protective variable of relapse. Our risk predictor index was validated to identify patients at risk of recurrence.

SUCCOR cone study: conization before radical hysterectomy

To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

SUCCOR 10 years: a decade's perspective on radical hysterectomy outcomes in cervical cancer.

Interest in long-term outcomes of radical hysterectomy for cervical cancer has increased, especially after the LACC trial findings, which showed worse outcomes for minimally invasive surgery. However, limited information is available on 10-year oncological outcomes, particularly, recurrence and survival. The primary objective of this study was to analyze the 10-year oncological outcomes of patients with International Federation of Gynecology and Obstetrics 2009 stage IB1 cervical cancer treated with radical hysterectomy performed via minimally invasive or open approaches. This retrospective, multi-center, observational study updates the data from the SUCCOR cohort. Patients diagnosed between January 2013 and December 2014 with tumors ≤4 cm without extra-cervical metastasis and treated with radical hysterectomy as the primary treatment were included, and a 10-year follow-up after surgery was successfully conducted. A total of 556 patients were analyzed. The median age was 46 years (range; 18-82). The most common final International Federation of Gynecology and Obstetrics 2009 stage was IB1, 474 patients (85%), and the most common histology was squamous carcinoma, 376 patients (67.6%). The 5-year disease-free survival was 93%, and the 10-year disease-free survival was 90%. The overall survival was 97% at 5 years and 89% at 10 years. During follow-up, 9% (n = 49) of patients experienced recurrences, 78% (n = 38) within the first 5 years. Comparing surgical approaches, 10-year disease-free survival was 92% for minimally invasive surgery and 88% for open surgery (p = .12). Similarly, 10-year overall survival was 92% for minimally invasive surgery and 88% for open surgery (p = .12). Post-recurrence disease-specific survival was 47% at 60 months and 39% at 96 months. The 2-year survival after recurrence was 80% for late recurrences (>5 years) versus 69% for early recurrences. The overall survival after radical hysterectomy at 5-years was 97% in patients with early-stage cervical cancer. The recurrence rate at 10 years was 9%. No differences in 10-year survival were observed between the surgical approaches.

SENECA study: staging endometrial cancer based on molecular classification

Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens. Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001). Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.

SUROVA - Surgery in Ovarian Cancer, Comparing Primary and Interval Cytoreductive Surgery

An international worldwide retrospective cohort observational study comparing primary cytoreductive surgery with neoadjuvant chemotherapy and interval cytoreductive surgery in patients with carcinoma of the ovary, fallopian tubes, and peritoneum.

Prognostic Value of Conization and Negative HPV After Conization in AIS and Early Stage Cervical Cancer

In women with cervical cancer -Squamous cell carcinoma, Adeno carcinoma, Adeno-squamous carcinoma or AIS we want to examine prospectively: 1. Examine if negative HR-HPV after conization to the HR-HPV the women had before conization has a high prognostic value for no residual tumor in the final pathology. 2. To examine if conization in women with cervical tumor up to Stage I B 2 (FIGO 2018) is corelated with better prognosis.