Ming Yin Lin

A phase III randomized clinical trial comparing sentinel node biopsy with no retroperitoneal node dissection in apparent early-stage endometrial cancer – ENDO-3: ANZGOG trial 1911/2020

Sentinel node biopsy is a surgical technique to explore lymph nodes for surgical staging of endometrial cancer, which has replaced full retroperitoneal lymph node dissection. However, the effectiveness of sentinel node biopsy, its value to patients, and potential harms compared with no-node dissection have never been shown in a randomized trial. Stage 1 will test recovery from surgery. Stage 2 will compare disease-free survival at 4.5 years between patients randomized to sentinel node biopsy versus no retroperitoneal node dissection. The primary hypothesis for stage 1 is that treatment with sentinel node biopsy will not cause detriment to patient outcomes (lymphedema, morbidity, loss of quality of life) and will not increase treatment-related morbidity or health services costs compared with patients treated without a retroperitoneal node dissection at 12 months after surgery. The primary hypothesis for stage 2 is that disease-free survival at 4.5 years after surgery in patients without retroperitoneal node dissection is not inferior to those receiving sentinel node biopsy. This phase III, open-label, two-arm, multistage, randomized non-inferiority trial (ENDO-3) will determine the value of sentinel node biopsy for surgical management of endometrial cancer. Patients with endometrial cancer are randomized to receive: (1) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy with sentinel node biopsy or (2) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection. In stage 1, 444 patients will be enrolled to demonstrate feasibility and quality of life. If this is demonstrated, we will enroll another 316 patients in stage 2. Inclusion criteria include women aged 18 years or older with histologically confirmed endometrial cancer; clinical stage 1, who meet the criteria for laparoscopic or robotic total hysterectomy and bilateral salpingo-oophorectomy. Patients with uterine mesenchymal tumors are excluded. The endpoint for stage 1 is surgical recovery, with the proportion of patients returning to usual daily activities at 3 months post-surgery as measured with the EQ-5D. Stage 2 is disease-free survival at 4.5 years. 760 participants (both stages). Stage 1 commenced in January 2021 and is planned to be completed in December 2024 when 444 participants have completed 12 months' follow-up. Stage 2 will enroll a further 316 participants for a total of 760 patients. NCT04073706.

Survival and patterns of failure in small cell neuroendocrine carcinoma of the cervix treated with definitive chemoradiotherapy

To evaluate survival outcomes and patterns of failure in small cell neuroendocrine carcinoma of the cervix treated with curative-intent chemoradiotherapy at a tertiary referral center. Patients with International Federation of Gynecology and Obstetrics 2009 stage IB to IIIB small cell neuroendocrine carcinoma of the cervix treated between 1996 and 2017 were retrospectively reviewed. All underwent baseline magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT). Definitive chemoradiotherapy consisted of pelvic external-beam radiotherapy (45 Gy/25 fractions) with high-dose-rate brachytherapy (Equivalent Dose in 2Gy fractions (EQD2) >85 Gy) and concurrent platinum-etoposide chemotherapy, followed by 2 sequential cycles. Patients who underwent primary surgery followed by adjuvant chemoradiotherapy were analyzed separately. Survival outcomes were estimated using Kaplan-Meier analysis. Thirty-two patients were included; 26 received definitive chemoradiotherapy and 6 underwent surgery followed by adjuvant radiotherapy. Median follow-up was 48 months (interquartile range; 12-213). Five-year overall survival and progression-free survival were 54.6% and 49.7%, respectively. Pelvic control was high (88%), with no local relapses in patients with stage ≤IIA disease. Distant relapse occurred in 44% of patients, predominantly para-aortic (57%) and visceral (lung, liver, bone). Node-negative patients achieved significantly higher 5-year overall survival (70.6% vs 31.3%, p = .04) and progression-free survival (66.9% vs 22.4%, p = .01). Definitive chemoradiotherapy achieves excellent loco-regional control and durable survival in small cell neuroendocrine carcinoma of the cervix, particularly in early-stage and node-negative disease. Distant relapse remains the predominant failure pattern, highlighting the need for improved systemic approaches. These results support omission of radical surgery in well-staged early-stage patients managed with modern chemoradiotherapy.

Node-positive carcinoma of the vulva treated with curative-intent radiotherapy

This study aimed to evaluate the outcomes of patients with node-positive vulvar carcinoma treated with radiotherapy, with or without chemotherapy, administered with curative intent, focusing on patterns of first failure, locoregional control, and overall survival. Patients were eligible if they had a histologic diagnosis of node-positive vulvar cancer and were referred for curative-intent radiotherapy, with or without chemotherapy, either as the primary treatment or in the adjuvant setting following definitive surgery between January 2000 and December 2019 at our institution. Eligible patients were selected from the prospective database of the gynecology oncology unit, where clinical, histopathologic, treatment, and follow-up data were systematically collected for analysis. Out of 256 patients with vulvar cancer, 88 (34.4%) patients met the inclusion criteria. The median age was 65 years (range; 33-90). Sixty-two patients underwent surgery and adjuvant radiotherapy, of whom 57 (92%) received concomitant chemotherapy. Twenty-four patients received definitive chemoradiotherapy and 2 received definitive radiotherapy alone. The median total dose to the primary site was 54 Gy in the definitive setting and 45 Gy in the adjuvant setting. The median dose was 54 Gy (range; 45-60) to gross inguinal nodes (n = 48) and 54 Gy (range; 34-64) to gross primary disease (n = 26). The median follow-up was 5.3 years (range; 0.1-21.8). Five-year overall survival was 62% in the adjuvant group and 50% in the definitive group. Of 88 patients, 46 (52%) relapsed; 16 of 46 (35%) had failure at the primary site alone. Disease control at the primary site and nodes was 64% (95% CI; 48%-75%) in the adjuvant group and 49% (26%-68%) in the definitive group at 5 years. Locoregional control and overall survival were highest in patients treated with surgery followed by radiotherapy. Definitive chemoradiotherapy provided moderate disease control and survival outcomes in patients unfit for surgery, supporting its use as an alternative treatment strategy.

Sentinel Node Biopsy in Endometrial Cancer

Endometrial cancer (EC) is the most common gynaecological cancer. Current treatment of EC typically includes removal of the uterus and to determine the extent of the disease (removal of fallopian tubes, ovaries \& if required a lymph node dissection (surgical staging)). While lymph node dissection may be valuable to guide the need for adjuvant treatment (chemo or radiotherapy) after surgery, it has been a topic of controversy for the last 30 years. In some patients it causes morbidity, specifically lymphoedema. This recently has been replaced with sentinel node biopsy (SNB). It requires an injection of a dye into the cervix with specific equipment \& surgical dissection of the lymph node in which the dye first becomes visible. Despite this promising proposition \& similar to a lymph node dissection, the value to patients, cost effectiveness \& potential harms (e.g. lymphedema) of SNB compared to no-node dissection in EC has never been established. Aim: determine the value of SNB for patients, the healthcare system and exclude detriment to patients using a randomised approach 1:1. Stage 1 - 444 patients. Stage 2 additional 316 patients. Primary Outcome Stage 1: Proportion of participants returning to usual daily activities at 12 months from surgery using the EQ-5D which will determine when women in both groups can return to their usual activities. Primary Outcome Stage 2: Treatment non-inferiority as evaluated by disease-free survival status at 4.5 years post-surgery, as measured by the time interval between the date of randomisation and date of first recurrence. Confirmation of recurrent disease will be ascertained through clinical assessment, radiological work-up and/or histological results.