8 Therefore, their current practice is to perform surgical staging with pelvic lymphadenectomy, as well as limited intramesenteric CHIR99021 purchase paraaortic lymphadenectomy, or offer sentinel node mapping.14,15 Other data suggest para-aortic lymph node dissection may be warranted only in those with high-risk pathology. Mariani and colleagues prospectively examined 281 patients undergoing lymphadenectomy at the time of endometrial cancer staging and found 22% of patients with high-risk disease had lymph node metastases.7 Of these, 51% had both pelvic and para-aortic lymphadenopathy, 33% had positive pelvic lymph nodes only, and 16% had isolated para-aortic lymphadenopathy. In those with para-aortic lymph node involvement, 77% had metastases above the inferior mesenteric artery, and they propose systematic pelvic and extended para-aortic lymphadenectomy up to the renal vessels in patients with high-risk disease.

7,16 Conversely, they found that patients with lowgrade disease (ie, grade 1 and 2 endometrioid lesions with myometrial invasion �� 50% and tumor size �� 2 cm) had no lymphadenopathy and did not benefit from a systematic lymphadenectomy. Advantages and Potential Complications of Comprehensive Staging The advantages of comprehensive surgical staging lie in diagnosis, prognosis, and proper triage of patients for adjuvant therapy. FIGO endometrial cancer staging is based on surgical pathology, and comprehensive surgery allows for accurate definition of disease extent. GOG 33 found that 9% of clinically stage I patients had pelvic nodal metastases, 6% had para-aortic lymphadenopathy, 5% had spread to adnexa, and 6% had other extrauterine metastases at the time of surgery.

6 Patients with more advanced stage disease have poorer prognoses, which may go unrecognized without comprehensive surgical staging. Figure 1 shows the 5-year overall survival for patients with endometrial cancer based on FIGO surgical substages.17 Figure 1 Survival by International Federation of Gynecologists and Obstetricians surgical stage for endometrial cancer. Reproduced with permission from Creasman WT et al.17 In addition to defining patients with more advanced stages of endometrial cancer and their need for radiation therapy and/or chemotherapy, patients with stage I disease who should receive further treatment can be identified.

GOG 99 defined a high-intermediate risk group of early stage endometrial cancer who benefit from additional therapy in terms of progression-free survival and fewer local recurrences.18 Patients were triaged to pelvic radiation therapy based on age and pathologic factors including grade (2�C3), depth of invasion (outer third), and lymphovascular space invasion. In GOG 33, 22% Carfilzomib of clinical stage I patients had outer-third myometrial invasion, 71% were grade 2 or 3, and 15% had lymphovascular space invasion and would have been triaged to adjuvant radiation therapy based on age and the number of risk factors present.