Is Lymphatic Mapping in Uterine Cancer Feasible?

Abstract

In virtually every solid tumor, the disease status of regional lymph nodes is one of the most important prognostic factors for survival as well as a significant determinant of which patients receive adjuvant chemotherapy and/or radiation. Although many readers of the Annals of Surgical Oncology are intimately familiar with lymphatic mapping and sentinel node biopsy in patients with melanoma or breast cancer, the validation and adoption of these techniques are still in their infancy in most other solid tumors. Gynecologic oncologists were among the first to begin investigating these procedures in the early 1990s. However, over 15 years later, we still do not utilize these procedures routinely as standard of care for women with cancers of the reproductive tract. In our field, application of these techniques to women with vulvar cancer has progressed furthest and certainly holds the most promise for widespread implementation in our field. Malignancies of the vulva are a seemingly ideal candidate for lymphatic mapping and sentinel node biopsy as they share many common characteristics with breast cancer and melanoma. First, the vulva is an external organ that is readily accessible for injection of mapping compounds. Second, lymphatic drainage from the vulva is highly predictable virtually always leading directly to the inguinofemoral triangle where a sentinel node can easily be found. Third, complete lymphadenectomy is associated with high morbidity, with the majority of patients experiencing lymphocyst formation, lymphedema, and/or wound separation. Finally, almost 20% of clinical stage I/II vulvar cancer will have metastatic disease to the groin nodes. However, unlike breast cancer with a predicted 184,450 new cases this year or melanoma with 62,480 new cases estimated, vulvar cancer is exceedingly rare with only 3,460 cases in the USA annually. This low incidence has been the major obstacle for validation of these techniques in women with vulvar malignancies. Multiple investigators have performed small phase II studies to evaluate the validity of these techniques in the treatment of vulvar cancer. In the entire English literature, only a total of 383 women have been reported having undergone sentinel lymph node biopsy followed by complete lymphadenectomy in an effort to determine sensitivity and negative predictive value for these procedures. For the combined group of women reported, the false-negative rate for lymphatic mapping and sentinel node biopsy for women with vulvar cancer is extremely low at 2.4%. Currently, our national collaborative consortium, the Gynecologic Oncology Group (GOG), is prospectively validating lymphatic mapping and sentinel nodes prospectively in a large phase II studywhich hopes to close accrual by the end of 2008. A recent observational study from the Netherlands prospectively followed 276 women with vulvar cancer who had a negative sentinel node biopsy and no adjuvant therapy and noted a groin recurrence rate of 2.7%. Although this technically does not qualify as a validation study, this low recurrence rate virtually matches the false-negative rate of the combined validation studies and is the best proof to date of the reliability of these techniques in this disease. Although there are almost 12 times as many cases of endometrial carcinoma annually as there are cancer of the vulva, our efforts to apply mapping techniques to women with this tumor have significantly lagged behind those in women with vulvar malignancies. However, some might argue that a reliable sentinel node identification approach in women with endometrial cancer might be even more useful than Published online May 13, 2008. Address correspondence and reprint requests to: Michael Frumovitz, MD, MPH; E-mail: Mfrumovitz@mdanderson.org