Impact of preoperative brachytherapy followed by radical hysterectomy in stage IB2 (FIGO 2018) cervical cancer: An analysis of SENTICOL I-II trials.

INTRODUCTION: The goal of this study was to compare the outcomes of preoperative brachytherapy followed by radical surgery versus radical surgery alone in cervical cancer with tumor between 2 and 4 cm (FIGO 2018 IB2). MATERIAL AND METHODS: SENTICOL I and SENTICOL II were two French prospective multicentric trials evaluating sentinel node biopsy in early-stage cervical cancer between 2005 and 2012. Preoperative brachytherapy (low-dose rate or pulse-dose rate at the dose of 60Gy) could be performed 6 to 8 weeks prior to the radical hysterectomy, at the discretion of each center. SENTICOL I and SENTICOL II cohorts were retrospectively analysed to compare the outcomes of preoperative brachytherapy or upfront surgery in patients with IB2 cervical tumor. RESULTS: A total of 104 patients were included: 55 underwent upfront radical hysterectomy and 49 underwent preoperative brachytherapy followed by radical hysterectomy. Patients with preoperative brachytherapy were more likely to have no residual disease (71.4% vs. 25.5%, p < 0.0001) and to be defined as low risk according to Sedlis criteria (83.3% vs. 51.2%, p < 0.0001). Adjuvant treatments were required less frequently in case of preoperative brachytherapy (14.3% vs. 54.5%, p < 0.0001). Patients with preoperative brachytherapy experienced more postoperative complications grade ≥ 3 (24.5% vs. 9.1%, p = 0.03). Patients with preoperative brachytherapy had better 5-year disease-free survival compared to patients who underwent surgery alone, 93.6% and 74.4% respectively (p = 0.04). CONCLUSION: Although preoperative brachytherapy was significantly associated with more severe postoperative complications, better pathologic features were obtained on surgical specimens and led to a better 5-year disease-free survival in IB2 cervical cancer.

Diagnostic value of frozen section examination of sentinel lymph nodes in early-stage cervical cancer at the time of ultrastaging.

OBJECTIVES: We aimed to assess the diagnostic value of frozen-section pathologic examination (FSE) of sentinel lymph nodes (SLN) in patients with early-stage cervical cancer. METHODS: Two French prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) were analysed. Patients with IA to IIA1 2018 FIGO stage, who underwent SLN biopsy with both FSE and ultrastaging examination were included. RESULTS AND DISCUSSION: Between 2005 and 2012, 313 patients from 25 centers fulfilled the inclusion criteria. Metastatic involvement of SLN was diagnosed in 52 patients (16.6%). Macrometastases, micrometastases and isolated tumor cells (ITCs) were found in 27, 12 and 13 patients respectively. Among the 928 SLNs analysed, FSE identified 23 SLNs with macrometastases in 20 patients and 5 SLNs with micrometastases in 2 patients whereas no ITCs were identified. Ultrastaging of negative SLNs by FSE found macrometastases, micrometastases and ITCs in additional 7, 11 and 17 SLNs. Ultrastaging increased significantly the rate of patients with positive SLN from 7% to 16.6% (p < 0.0001). The sensitivity and the negative predictive value of FSE were 42.3% and 89.7% respectively or 56.4% and 94.1% if ITCs were excluded. False-negative cases were more frequent with tumor size ≥ 20 mm (OR = 4.46, 95%IC = [1.45-13.66], p = 0.01) and preoperative brachytherapy (OR = 4.47, 95%IC = [1.37-14.63], p = 0.01) and less frequent with patients included in higher volume center (>5 patients/year) (OR = 0.09, 95%IC = [0.02-0.51], p = 0.01). CONCLUSIONS: FSE of SLN had a low sensitivity for detecting micrometastases and ITCs and a high negative predictive value for SLN status. Clinical impact of false-negative cases has to be assessed by further studies.

Risk factors for failure of bilateral sentinel lymph node mapping in early-stage cervical cancer.

BACKGROUND: The objective of this study was to determine clinical, tumoral and surgical factors associated with successful bilateral sentinel lymph node mapping (SBM) in early-stage cervical cancer. METHODS: We performed an ancillary work on the data of two prospective trials on SLN biopsy for FIGO IA-IIA cervical cancer (SENTICOL I & II). Patients having Sentinel lymph node (SLN) mapping for early-stage cervical cancer were included between 2005 and 2012 from 28 French oncologic centers. SLN was detected by a combined labeling technique (blue and isotopic). RESULTS: 405 patients were included for analysis: SLNs were identified on at least one side of the pelvis in 381 patients (94.1%) and bilaterally in 326 patients (80.5%). The mean age was 45.4 years [22-85 years]. Most patients had IB1 pathologic FIGO 2018 stage (81.3%) and squamous cell carcinoma (71%). Surgeries were mainly performed by minimally invasive approach (368 patients - 90.9%). By multivariate analysis, lower SBM rate was significantly associated with Age ≥70 years (ORa = 0.02, 95%CI = [0.001-0.28], p = 0.004), tumor size larger than 20 mm (ORa = 0.46,95%CI = [0.21-0.99], p = 0.048) and Body-mass index higher than 30 kg/m2 (ORa = 0.28, 95%CI = [0.12-0.65], p = 0.003). SBM rate was significantly higher in high skills centers (>5patients/year) (ORa = 8.05, 95%CI = [2.06-31.50], p = 0.003) and in SENTICOL II (2009-2012) compared to SENTICOL I (2005-2007) (ORa = 2.6, 95%CI = [1.23-5.51], p = 0.01). CONCLUSIONS: In early-stage cervical cancer, bilateral SLN detection rates is lower in patients aged more than 70years, patients with BMI≥30 kg/m2 and larger tumor ≥20 mm whereas stronger experience of SLN biopsy technique improves bilateral SLN detection.