The SIGMA Trial: Sentinel Lymph Node Biopsy in Gynecologic Malignancies
IntroductionLymph node involvement significantly impacts the prognosis of patients with gynecologic cancers, such as vulvar and cervical cancers. Traditional extensive lymph node dissection is associated with notable surgical complications, including infections, nerve damage, and lymphedema. However, sentinel lymph node biopsy (SNB), a minimally invasive procedure, offers an effective alternative. By identifying the first lymph nodes draining a tumor, SNB detects both micro- and macro-metastases, reducing unnecessary extensive surgeries.
SNB is commonly performed using tracers such as radiolabeled 99mTechnetium (99mTc)-based agents. These agents are cost-effective, widely available, and emit gamma rays suitable for imaging. SNB is particularly relevant for early-stage cancers, where nodal involvement is relatively low: 25–35% for vulvar cancer and 11–21% for cervical cancer.
Vulvar CancerVulvar cancer, primarily squamous cell carcinoma, accounts for approximately 6% of gynecologic cancers globally. Its primary spread is to the inguinal lymph nodes. Patients with lymph node metastasis experience significantly reduced survival rates compared to those with localized disease. SNB is recommended for small, unifocal vulvar tumors without clinical lymph node involvement, reducing surgical morbidity while maintaining diagnostic accuracy.
Cervical CancerCervical cancer ranks as the fourth most common cancer among women globally, with squamous cell carcinoma being the predominant type. Its incidence is strongly linked to human papillomavirus (HPV) infection and varies based on access to prevention and treatment. Lymphatic spread primarily occurs to pelvic nodes. For early-stage cervical cancer, SNB is a less invasive alternative to pelvic lymphadenectomy, minimizing complications while identifying nodal metastases.
Despite its benefits, SNB practices vary widely across regions due to differences in tracer availability, imaging techniques, and procedural expertise. This variability is especially pronounced in low- and middle-income countries (LMICs), where infrastructure and training constraints pose challenges.
Study ObjectivesThe SIGMA Trial, an international cooperative study led by the International Atomic Energy Agency (IAEA), seeks to standardize and evaluate SNB techniques globally. Key objectives include:
Assessing the effectiveness of radioguided SNB in vulvar and cervical cancers.
Standardizing procedures across institutions, including tracer selection, injection techniques, and imaging protocols.
Evaluating the role of advanced imaging (SPECT/CT) compared to traditional planar imaging.
Investigating discrepancies between pre-operative and intra-operative SNB findings.
Comparing outcomes based on different tracers and cancer types.
Analyzing peri- and post-operative complications and their impact on survival outcomes.
Assessing the cost-effectiveness of SNB.
Study DesignThis prospective, multicenter study will include patients with clinically and radiologically node-negative (cN0) vulvar and cervical cancers undergoing SNB. Preoperative imaging will include planar lymphoscintigraphy and SPECT/CT. The study aims to harmonize practices across diverse settings, encouraging participation from both high-income countries (HICs) and LMICs.
Eligibility Criteria: Centers in HICs must demonstrate expertise in SNB, while LMIC centers will have more flexible requirements, ensuring broader inclusion. Participating centers must adhere to standardized protocols and contribute patient data to ensure robust analysis.
Data Collection: Patient characteristics, imaging details, surgical outcomes, and histopathological findings will be prospectively recorded. Data will be uploaded to the IAEA's secure database for centralized analysis.
ConclusionThe SIGMA Trial represents a global effort to optimize and standardize SNB in gynecologic cancers, reducing surgical complications while maintaining diagnostic precision. By addressing disparities in procedural practices and resources, this study aims to improve outcomes for patients worldwide, particularly in underserved regions.