Sentinel Node Biopsy in uterine cancer – ENDO3 trial
Sentinel node biopsy for uterine (endometrial) cancer came to Australia some five years ago. In March 2018, I went to the Memorial Sloan Kettering Cancer Centre in New York to fine tune my surgical skills, and during my stay I realised that this new surgical technique is beautiful to perform but its benefit to patients (and its associated detriments) are yet to be shown.
Sometimes surgical innovations are declared standard clinical practice without high-level evidence demonstrating the pros (patient benefit) and cons (complications, cost) of the procedure.
Removal and histological assessment of lymph nodes (“surgical staging”) is such an example. Introduced in the United States of America in the 1980s, it is current standard practice in uterine cancer surgery but its benefit to patients is yet to be shown.
Nowadays surgical staging is performed through a procedure called Sentinel Node Biopsy (SNB)—it requires specific technology and takes approximately 30 to 40 minutes to complete. A tracer is injected into the cervix and gets transported via the local lymphatic channels to the pelvic nodes. After a few minutes, a laparoscopic, near infra-red camera can identify the highlighted lymph nodes. Only one node (the closest to the uterus) is excised surgically and submitted for histology assessment. If this node is negative and cancer-free, we presume all other nodes will also be negative.
Evidence demonstrates that SNB is as accurate as a full node dissection. However, the percentage of patients with positive nodes after SNB is higher because modern pathology techniques (e.g., immunohistochemical stains against cytokeratins) will detect lymph node involvement (tiny foci of tumour) that would have been missed by conventional pathology techniques. Whether the detection of such small cancer cells or small cancer clusters < 2mm actually impact on patients' survival remains unknown.
Despite being the standard treatment nationally and globally, it remains unknown if SNB does improve survival of patients requiring surgery for uterine cancer; to what degree it increases the risk of intra- or postoperative complications; to what degree it causes lymphoedema; how many more patients will be referred to radiation treatment or chemotherapy. Despite SNB being the current standard surgical treatment, it is also unknown whether SNB is cost effective and should be generally offered to patients.
For those reasons, my colleagues and I started the ENDO3 trial to determine whether patients requiring surgery for uterine cancer will actually benefit from the SNB procedure. This trial is a phase 3 randomized controlled clinical trial (RCT). Half of patients will be randomized to SNB followed by laparoscopic hysterectomy and BSO, which is the current standard treatment.
The other half of patients will only have a laparoscopic hysterectomy and BSO.
All surgeons must pass a comprehensive, independent surgical competency assessment before they can take part in this trial. Once surgeons pass accreditation and qualify for the trial, quality control will continue throughout the trial to make sure we deliver a stellar surgical procedure.
The ENDO3 trial started at RBWH, St Andrew’s Hospital, the Wesley Hospital and the Mater Hospital (all in Queensland) in 2021, and more than 100 patients have been enrolled to date. From the end of 2022 onwards, ENDO3 will also enrol patients from NSW and Victoria as well as from Singapore. Following surgery, patients are seen for follow-up as usual. A total of 760 are planned to be enrolled.
Our experience so far suggests that the quality of surgery we deliver is outstandingly high. Complication rates in both arms are low. Most patients are very willing to take part in medical research to help finding better and more effective ways to treat the next generation of women not only in Australia but worldwide.
The ENDO3 trial will enrol patients for another 3 years.