Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial)

Abstract

BackgroundGrowing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial cancer without lymphadenectomy are lacking.Primary ObjectivesThe present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes.Study HypothesisWe hypothesized that there is no survival benefit in adding systematic lymphadenectomy to sentinel node mapping for endometrial cancer staging. Additionally, we aim to evaluate morbidity and impact in quality of life (QoL) after forgoing systematic lymphadenectomy.Trial DesignThis is a collaborative, multicenter, open-label, non-inferiority, randomized trial. After total hysterectomy, bilateral salpingo-oophorectomy and SLN biopsy, patients will be randomized (1:1) into: (a) no further lymph node dissection or (b) systematic pelvic and para-aortic lymphadenectomy.Major Inclusion and Exclusion CriteriaInclusion criteria are patients with high-grade histologies (endometrioid G3, serous, clear cell, and carcinosarcoma), endometrioid G1 or G2 with imaging concerning for myometrial invasion of ≥50% or cervical invasion, clinically suitable to undergo systematic lymphadenectomy.Primary Endpoint(s)The primary objective is to compare 3-year disease-free survival and the secondary objectives are 5-year overall survival, morbidity, incidence of lower limb lymphedema, and QoL after SLN mapping ± systematic lymphadenectomy in high-intermediate and high-risk endometrial cancer.Sample size178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027.Trial Registration NumberNCT03366051.

Sentinel lymph node biopsy in high-risk endometrial cancer: performance, outcomes, and future avenues

“…Considering these complex factors, the best setting to study the survival outcome of SLN mapping in high-risk patients would be a randomized controlled study design. Notable ongoing randomized controlled trials, including ALICE [ 45 ], SELYE (clinical trial: NCT04845828), and SNEC trial [ 46 ], and the details including the inclusion criteria, primary outcome, and estimated completion date are shown in Table 2 .…”

“…If the survival outcome of SLN mapping is superior to that of complete LND, this may underscore the survival benefit of detection alone rather than resection. The recent shift in the focus on adjuvant therapy from radiotherapy to chemotherapy based on PORTEC-3 will likely bias support the survival advantage of detection, more so than resection [44]. Considering these complex factors, the best setting to study the survival outcome of SLN mapping in high-risk patients would be a randomized controlled study design.…”

“…An important research question involves finding a subset of high-risk patients with favorable prognoses, as currently defined. Although studies, such as the PORTEC-3 stated that patients with stage III disease are most likely to benefit from adjuvant chemotherapy compared to radiotherapy [44],…”

Sentinel lymph node mapping in endometrial cancer: Current evidence and practice

“…Several ongoing clinical trials are currently evaluating the oncologic outcome of SLN mapping in endometrial cancer. 20,21 ENDO-3 (ClinicalTrials.gov/NCT04073706) is evaluating progression-free survival in patients undergoing SLN mapping compared to no lymph node assessment in clinical stage I EC of all histologic subtypes. 20 The ALICE trial (ClinicalTrials.gov/ NCT03366051) is evaluating the oncologic outcomes of systematic LND after SLN mapping versus SLN mapping alone in patients with high-grade endometrial cancer or those who have deep myometrial invasion.…”

Long-term survival outcomes in high-risk endometrial cancer patients undergoing sentinel lymph node biopsy alone versus lymphadenectomy

“…However, to date international guidelines recommend sentinel lymph node biopsy for low-risk endometrial cancers, while systematic pelvic and aortic lymphadenectomy is still suggested for high-risk patients 4. The ALICE trial has been launched to clarify if sentinel lymph node biopsy can be safely offered also to high-risk endometrial cancer patients, but before its results will become available uncertainty exists around the management of such cases 11. Some authors have prospectively assessed the sentinel lymph node appropriateness in high-risk endometrial cancer cases with promising results 12–14…”