Agnieszka Rychlik

Clinical relevance of high–intermediate risk endometrial cancer according to European risk classification

Risk models in endometrial cancer define prognosis and indicate adjuvant therapy. One of the currently used classifications was designed in 2016 in collaboration with the European Society of Medical Oncology (ESMO), the European Society of Gynecologic Oncology (ESGO), and the European Society of Radiotherapy (ESTRO). A high-intermediate risk group was introduced within the intermediate risk group. The purpose of this study was to evaluate the clinical relevance of this subclassification. A multicenter retrospective study was carried out at five international tertiary institutions. Patients diagnosed with intermediate risk endometrial cancer on the basis of definitive pathology findings were included. Patients were stratified into intermediate and high-intermediate risk groups. Incidence of nodal metastases, and disease free and overall survival were compared between the two risk groups in univariate and multivariate analysis. 477 patients were included: 325 (68%) patients were identified as intermediate and 152 (32%) as high-intermediate endometrial cancer patients. Nodal metastases were found in 18 patients (11.8%) in the high-intermediate risk endometrial cancer group and 16 patients (4.9%) in the intermediate risk group. Lymphovascular space invasion was found to be a strong predictive factor of lymph node involvement. High-intermediate risk was found to be an independent factor of disease free survival (hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.00 to 3.08; p=0.050) and overall survival (HR 1.99; 95% CI 1.10 to 3.60; p=0.022) in the multivariate analysis. The study validates the clinical significance of the intermediate risk endometrial cancer subclassification. Prognosis for high-intermediate risk endometrial cancer was significantly poorer. The prevalence of lymph node metastases was higher in this group of patients.

Effect of tumor burden and radical surgery on survival difference between upfront, early interval or delayed cytoreductive surgery in ovarian cancer

We sought to evaluate the impact on survival of tumor burden and surgical complexity in relation to the number of cycles of neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer (OC) with minimal (CC-1) or no residual disease (CC-0). This retrospective study included patients with International Federation of Gynaecology and Obstetrics IIIC-IV stage OC who underwent debulking surgery at 4 high-volume institutions between January 2008 and December 2015. We assessed the overall survival (OS) of primary debulking surgery (PDS group), early interval debulking surgery after 3-4 cycles of NACT (early IDS group) and delayed debulking surgery after 6 cycles (DDS group) with CC-0 or CC-1 according to peritoneal cancer index (PCI) and Aletti score. Five hundred forty-nine women were included: 175 (31.9%) had PDS, 224 (40.8%) early IDS and 150 (27.3%) DDS. Regardless of Aletti score, median OS after PDS was significantly higher than after early IDS or DDS, but the survival difference was higher in women with an Aletti score 10, there were no differences between PDS and early IDS, but DDS was associated with decreased OS. The benefit of complete PDS compared with NACT was maximal in patients with a low complexity score. In patients with low tumor burden, there was a survival benefit of PDS over early IDS or DDS. In women with high tumor load, DDS impaired the oncological outcome.

Adapting Radicality in Early Cervical Cancer When Quality of Life Becomes a Prominent Issue

Frozen section examination of sentinel lymph nodes can be used as a decisional tool in the surgical management of early cervical cancer

Sentinel lymph node (SLN) detection has been shown to be accurate in detecting lymph node involvement in early-stage cervical cancer. The objective of this study was to evaluate the accuracy of frozen section examination in the assessment of SLN status, with the aim of adequately driving the intra-operative decision. We designed a retrospective study including patients from two comprehensive cancer centers between January 2001 and December 2018 with early-stage cervical cancer (IA1-IB2 according to International Federation of Gynecology and Obstetrics (FIGO) 2018) undergoing SLN dissection. The SLN procedure was performed using a cervical injection with technetium-99m combined with blue dye or indocyanine green in most cases. A total of 176 patients fulfilled inclusion criteria. Bilateral mapping was detected in 153 (86.7%) of them. Nineteen of these patients (12.4%) had SLN involvement: 13 with macrometastases, three with micrometastases and three with isolated tumor cells (ITC). Macrometastatic disease was missed on frozen section in 3/13 FIGO 2018 stage IIIC patients. The three patients with ITC were also missed by frozen section examination.Considering only macrometastases as lymph node involvement, frozen section sensitivity was 76.9% (95% CI 49.7 to 91.8) and negative predictive value (NPV) was 97.9% (95% CI 94.0 to 99.3) in patients with bilateral detection. Including micrometastases, sensitivity was 81.2% (95% CI 57.0 to 93.4) and NPV remained at 97.9% (95% CI 93.9 to 99.3). With a prevalence of final-stage IIIC in patients with pre-operative early-stage cervical cancer of the order of 10% in this series, the NPV of frozen section examination of SLN is very high, with an inferior limit of the CI superior to 94%. Diagnostic accuracy remains acceptable even if micrometastases are considered. The impact of missed ITC has not been established. Frozen section examination can be incorporated in the intra-operative decision algorithm.

Radical Hysterectomy After the LACC Trial: Back to Radical Vaginal Surgery

Classical radical vaginal hysterectomy first performed by Anton Pawlik in Prague in 1888 and popularized by Frederic Schauta is now a historical technique virtually abandoned due to painful perineal incision, a high rate of urinary dysfunction, and the inability to perform lymph node assessment. However, the heritage of this approach has been still used and taught in a few centers outside their Austrian birthplace. A combined vaginal and laparoscopic approach was developed in the 1990s by French and German surgeons who designed diverse surgical techniques for which a novel classification is proposed. All these techniques are different from the so-called laparoscopically assisted radical vaginal hysterectomy (LARVH), a term widely used for laparoscopic radical hysterectomies with vaginal extraction of the specimen. Interestingly, after the publication of the LACC trial (Laparoscopic Approach to Cervical Cancer), the radical vaginal approach has found a very timely application. The creation of a vaginal cuff before performing radical laparoscopic hysterectomy described in 2007 by Leblanc as "Schautheim" operation can be used as a protective maneuver to avoid tumor spillage and potentially overturn the negative outcome of minimally invasive surgery in early-stage cervical cancer. As a result, the combination of radical vaginal and laparoscopic steps of surgery is one possible evolution after the LACC trial that needs further investigation. The forgotten vaginal surgical technique needs a specific learning curve. The creation of a vaginal cuff should be mastered by every gynecological oncologist.