Endometrial Cancer
Conditions
Keywords
endometrial cancer, OSNA, sentinel lymph node, ultrastaging
Brief summary
Patients enrolled in the study will be randomized before surgery: in one study arm, the search for lymph node metastases in surgically removed sentinel lymph nodes will occur using the ultrastaging method (standard), while in the other arm it will be conducted using the OSNA method.
Detailed description
This is a non-inferiority randomized trial with the incidence of patients with metastatic SLN as primary endpoint. Based on recent literature, incidence of patients with metastatic SLN detected by ultrastaging has an average value of 11%. Assuming a -4% as the maximum allowable difference in detection rate to declare non-inferiority, a power of 80% and a significance level of 2.5% (one-side) a sample size of 1922 (961 per arm) is needed. Two interim analyses are planned, one after the first 640 and the second after 1280 patients. At the first interim analysis null hypothesis (inferiority of OSNA with respect to ultrastaging) will be rejected at a significance level \<0.00010 otherwise the study will go on and at the second analysis the null hypothesis will be rejected at a significance level of 0.0059. The final analysis will use 0.0189 as significance threshold. The O'Brien Fleming alpha spending function was used to define these values. The primary endpoint is defined as the proportion of patients with positive SLN over the total of randomized patients. This proportion will be reported together with the 95% confidence interval to better identify the range of inferential values. Incidence of isolated tumor cells, micro- and macro-metastasis will be calculated. Number of copies of CK19 mRNA to define volume of metastases will be adapted from previous reports. To describe the sample, quantitative variables will be summarized using median and interquartile range while categorical items will be reported as absolute counts and percentages. Patients will be described according the arm they were randomized to. A first analysis will be performed on an Intent-To-Treat basis, considering all randomized patients. A secondary analysis will be performed on the Per-Protocol population.
Interventions
DEVICEOSNA
The search for lymph node metastases in surgically removed sentinel lymph nodes will occur using the OSNA method
DEVICEUltrastaging
The search for lymph node metastases in surgically removed sentinel lymph nodes will occur using the ultrastaging method
Sponsors
Sysmex Europe GmbH
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Patients enrolled in the study will be randomized before surgery: in one study arm, the search for lymph node metastases in surgically removed sentinel lymph nodes will occur using the ultrastaging method (standard), while in the other arm it will be conducted using the OSNA method.
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed endometrial cancer * Apparent (pre-operative) FIGO stage I-II * Radical surgery * Attempt of SLN mapping
Exclusion criteria
* Uterine sarcoma (including endometrial stromal sarcoma) * Fertility sparing surgery * Dedifferentiated histology * Undifferentiated histology * Neoadjuvant therapy * Previous surgery to pelvic lymph nodes * Lymph nodes with short axis \>15 mm at pre-operative imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of SLN metastasis detected by OSNA versus ultrastaging method | From enrollment to the acquisition of the histological examination (8 weeks) | We will evaluate the number of lymph node metastases identified with both methods, in order to calculate the incidence of lymph node metastases for each group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival (measured in months) in patients with a diagnosis of lymph node metastases (identified with OSNA and ultrastaging), performing stratification by molecular class. | 3 years (a 3-year follow-up is planned) | The aim is to assess the impact of both techniques on staging, prognosis, and therapeutic strategies, optimizing patient management according to molecular subtypes. |
| 3 year disease-free survival (measured in months) in OSNA versus ultrastaging negative patients | 3 years (a 3-year follow-up is planned) | The study evaluates 3 year disease-free survival in endometrial carcinoma patients with negative sentinel lymph nodes (SLN) according to OSNA and ultrastaging. By comparing both techniques, the research aims to determine their prognostic value and potential implications for tailoring post-surgical management and follow-up strategies |
| 3 year overall survival (measured in months) in OSNA versus ultrastaging negative patients | 3 years (a 3-year follow-up is planned) | The study evaluates 3 year overall survival in endometrial carcinoma patients with negative sentinel lymph nodes (SLN) according to OSNA and ultrastaging. By comparing both techniques, the research aims to determine their prognostic value and potential implications for tailoring post-surgical management and follow-up strategies |
| 5-year disease-free survival (measured in months) in OSNA versus ultrastaging negative patients | 5 years | The study evaluates 5-year disease-free survival in endometrial carcinoma patients with negative sentinel lymph nodes (SLN) according to OSNA and ultrastaging. By comparing both techniques, the research aims to determine their prognostic value and potential implications for tailoring post-surgical management and follow-up strategies |
| Overall survival (measured in months) in patients with a diagnosis of lymph node metastases (identified with OSNA and ultrastaging), performing stratification by molecular class. | 3 years (a 3-year follow-up is planned) | The aim is to assess the impact of both techniques on staging, prognosis, and therapeutic strategies, optimizing patient management according to molecular subtypes. |
| Incidence of endosalpingiosis in ultrastaging arm | From enrollment to the acquisition of the histological examination (8 weeks) | The study investigates the incidence of endosalpingiosis in the ultrastaging arm of sentinel lymph node analysis in endometrial carcinoma. The aim is to assess its frequency, potential clinical significance, and implications for pathological interpretation and patient management. |
| Total Tumor Load (calculating by summing the number of copies of CK19 from each sentinel lymph node) and correlation with prognosis | 3 years (a 3-year follow-up is planned) | The study examines the total tumor load (TTL), defined as the sum of CK19 copies from each sentinel lymph node (SLN), and its correlation with prognosis. |
| Dimension of SLN (measured in millimeters) metastases at ultrastaging and correlation with prognosis | 3 years (a 3-year follow-up is planned) | The study analyzes the size of sentinel lymph node (SLN) metastases detected through ultrastaging and its correlation with prognosis in endometrial carcinoma. The objective is to evaluate the prognostic significance of metastasis dimensions and their potential impact on clinical management and treatment decisions. |
| 5-year overall survival (measured in months) in OSNA versus ultrastaging negative patients | 5 years | The study evaluates 5-year overall survival in endometrial carcinoma patients with negative sentinel lymph nodes (SLN) according to OSNA and ultrastaging. By comparing both techniques, the research aims to determine their prognostic value and potential implications for tailoring post-surgical management and follow-up strategies |
Countries
Italy
Contacts
Primary ContactFrancesco Fanfani, Professor
Backup ContactNicolò Bizzarri, Dr
Outcome results
None listed