METHODS
Study design
We conducted a retrospective analysis of prospectively collected data from the STELLA-2 randomized controlled trial 23. The analysis was completed in two phases. In the first phase, we measured the agreement of sagittal abdominal diameter (SAD) and then selected the most reliable measurement. In the second phase, we evaluated its diagnostic accuracy to assess surgical morbidity (Figure 1).
Patients were not involved in the study design (only participating as study subjects). The study was carried out in three Spanish referral hospitals: Vall d’Hebron Barcelona Hospital Campus, Hospital Universitario La Paz, and Hospital General de Valencia. The study was approved by the Ethics Committee of Hospital Vall d’Hebron (protocol PR(AMI)168/2015) and by the institutional review boards of the participating hospitals.
The Guidelines for Reporting Reliability and Agreement Studies (GRRAS) and the Standards for Reporting Diagnostic accuracy studies (STARD-2015) were followed in compliance with the Equator Network recommendations. The present study did not receive any funding.
Subjects
Between 2012 and 2019, 209 patients were enrolled in the STELLA-2 trial, a randomized multicentre prospective trial comparing the transperitoneal and extraperitoneal technique for laparoscopic para-aortic lymphadenectomy in endometrial and early ovarian cancer23. All the subjects for the present study were selected from that trial.
For phase one, we randomly selected a group of patients with endometrial cancer to evaluate SAD in MRI images (Group 1). The sample size for this group was calculated to detect a minimum correlation coefficient of 0.8, with an α risk of 0.05 and a β risk of 0.05, in a two-sided test.
For phase two we included all patients from the STELLA-2 trial with high-risk endometrial cancer who underwent comprehensive surgical staging by minimally invasive surgery (Group 2). High-risk was defined in the original trial as the presence of any of the following: deep myometrial invasion (≥50% as elicited by MRI and/or transvaginal ultrasound) or stromal cervical involvement, grade 3 endometrial tumours, or non-endometrioid tumours 23. Patients with missing data were excluded. They were divided into subgroups according to the para-aortic lymphadenectomy technique and the minimally invasive approach (Figure 1).
The surgical procedures performed have been previously described24.
Measurements
Phase 1
Preoperative MRI was performed following the European Society of Gynaecological Oncology (ESGO) and the Spanish society (SEGO) guidelines, obtaining T1 and T2-weighted 5 mm axial images of the abdomen and pelvis.
SAD was measured on axial MRI images using the local software available. Measurements were made manually using the digital callipers in millimetres (mm).
We defined three anatomical references for SAD measurement (Figure 2a). Umbilical SAD had been previously described 25. We chose the left renal vein as a new anatomical landmark since it’s the superior limit of the para-aortic lymph node dissection3. During this procedure, the inferior mesenteric artery must also be carefully dissected, so we selected this as another point of reference. In our experience, these two sites reflect the areas where the procedure is most challenging and where we encounter the most complications. Two observers were selected to carry out the SAD measurements: an experienced radiologist (observer A) and an obstetrics and gynaecology first-year resident (observer B). They received written instructions and made two measurements of the three diameters, two weeks apart.
For inter-rater agreement, we evaluated the concordance between the two observers’ measurements, whereas for the intra-rater agreement we compared their first measurements with the ones carried out two weeks later (Figure 1).
Phase 2
For the second phase, the primary end-point (surgical morbidity) was a core outcome set defined as the presence of any of the following criteria: 1) need for blood transfusion, 2) Haematocrit drop > 90th percentile (>11.8% in our cohort), 3) Total operative time >90th percentile (>350 min in our cohort), 4) laparoscopic para-aortic lymphadenectomy operative time >90th percentile (>135 min in our cohort), 5) Intraoperative surgical complications ≥ grade III26 or during para-aortic lymphadenectomy, 6) Postoperative surgical complications ≥ grade III 27 or related to para-aortic lymphadenectomy, 7) uncompleted or converted laparoscopic para-aortic lymphadenectomy (Table S1).
SAD was measured preoperatively, so observers were unaware of the outcomes. We performed a multivariate logistic regression analysis including the following covariates: anthropometric measurements (SAD, BMI, waist-hip ratio, waist circumference), age-adjusted comorbidity index 28, tumour characteristics, patients’ age, and previous surgeries.
The diagnostic accuracy of SAD to predict surgical morbidity was measured using ROC curves in Group 2 and all subgroups. If the discriminatory power was adequate, we estimated the optimal cut-off point (the closest point to the top left corner in the ROC curve) and calculated sensitivity and specificity, as well as negative and positive predictive values (NPV and PPV). We also compared the diagnostic accuracy of SAD with other anthropometric measurements.
Data analysis
In phase one, we calculated Pearson’s correlation coefficient (r ) and traced concordance scatter plots. The agreement was evaluated by Bland Altman plots 29 and the concordance correlation coefficient for repeated measurements (ρc)30.
For phase two, a logistic regression analysis was modelled for the composite outcome and the covariates. DeLong’s test was used to compare two correlated ROC curves. We computed the area under the curve (AUC) confidence intervals (95% CI) and considered a clinically appropriate diagnostic power if AUC was greater than 0.70.
Statistical analysis was carried out using Stata software v13.1 (StataCorp LLC, College Station, TX, USA), R software v. 4.0 (R Core Team, GNU), and Wizard - Statistics & Analysis v.1.9 (©Evan Miller). Statistical significance was defined if p <0.05.