Assessment of Prognostic Factors in Stage IIIA Endometrial Cancer 1 Andrea Mariani, M.D.,* ,2 Maurice J. Webb, M.D.,* Gary L. Keeney, M.D.,† Giacomo Aletti, M.S.,‡ and Karl C. Podratz, M.D., Ph.D.* ,3 *Department of Obstetrics and Gynecology and †Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota 55905; and ‡Department of Mathematics, University of Milano, Milan, Italy Received November 19, 2001 Objective. The objective of this study was the assessment of prognostic factors in stage IIIA endometrial cancer. Methods. Between 1984 and 1993, 51 patients with stage IIIA endometrial cancer received definitive treatment at our institution. Thirty-seven patients had positive peritoneal cytologic findings only (stage IIIA1), and 14 had adnexal or uterine serosal involve- ment (USI) (stage IIIA2). Median follow-up of surviving patients was 82.5 months. Results. The 5-year disease-related survival (DRS) and recur- rence-free survival (RFS) were 88 and 73%, respectively. RFS was 79% in patients with stage IIIA1 disease, compared with 57% in patients with stage IIIA2 disease (P  0.04). However, DRS did not significantly differ between stages IIIA1 and IIIA2. In the 37 patients with stage IIIA1 tumors, histologic grade 3, nonendo- metrioid histologic subtype, and lymphovascular invasion (LVI) significantly predicted a poor prognosis, with extraabdominal sites of failure (P < 0.05). Of the 22 patients who had stage IIIA1 disease with endometrioid histologic subtype and without LVI, none had recurrence [17 had whole abdominal irradiation (WAR) or intraperitoneal injection of 32 P, 2 had pelvic external radiother- apy (PRT)]. By contrast, of the 15 patients with either nonendo- metrioid histologic subtype orLVI, 9 (60%) had recurrence and 7 (47%) died of disease (12 had WAR or 32 P). An extraabdominal component was present in 7 of the 9 recurrences observed in this subgroup. Among the 14 patients with stage IIIA2 tumors (6 had WAR, 6 had PRT), those with USI had a 5-year DRS of 83%and a rate of extraabdominal failure of 83%, compared with 100 and 12.5% in patients without USI (P < 0.05). Conclusion. Patients with stage IIIA endometrial cancer who have endometrioid tumors, no LVI, and positive peritoneal cyto- logic findings as the only sign of extrauterine disease have an excellent prognosis. Nonendometrioid histologic subtype, LVI, and USI are strong predictors of distant failures and poor prog- nosis. Patients with either of these histologic factors should be considered candidates for systemic adjuvant therapy. © 2002 Elsevier Science (USA) Key Words: endometrial cancer, stage IIIA; prognosis; distant metastasis; adjuvant therapy; extrauterine disease; peritoneal cy- tology; uterine serosal invasion; lymphovascular invasion; histo- logic subtype. INTRODUCTION Adenocarcinoma of the endometrium is the most common malignant lesion of the female genital tract, and the endome- trium is the fourth most common cancer site, accounting for 6% of all cancers in women. During 2002, the number of new cases and deaths from endometrial cancer in the United States are estimated to approximate 39,300 and 6600, respectively [1]. Since 1988, patients with cancer cells in peritoneal wash- ings, uterine serosal invasion, or adnexal involvement have been classified as having International Federation of Obstetri- cians and Gynecologists (FIGO) stage IIIA cancer [2]. How- ever, the prognostic significance of positive results of perito- neal cytology, adnexal spread, and uterine serosal involvement continues to be debated [3]. Furthermore, the use of adjuvant therapy in patients with stage IIIA disease varies widely, from observation only to aggressive management with either pelvic or whole abdominal radiation. Unfortunately, recurrences are not uncommon, including a significant percentage at distant sites [3, 4]. In the present study, we tested the hypothesis that patients with stage IIIA disease and positive peritoneal cytologic find- ings as the only sign of extrauterine disease (stage IIIA1) have a prognosis that differs significantly from that of patients with adnexal involvement or uterine serosal invasion or both (stage IIIA2). Moreover, we assessed prognostic factors predictive of extraabdominal failures in the different stage IIIA subsets. PATIENTS AND METHODS During the period from 1984 to 1993, 612 patients with epithelial endometrial cancer were managed surgically at Mayo 1 Supported by the Mayo Cancer Center (P30CA15083) and the Rochester Research Committee, Mayo Foundation. Presented at the 12th Annual Meeting of the European Society of Gynecologic Oncologists, Venice, Italy, April 21 to 24, 2001. 2 Present address: Department of Obstetrics and Gynecology, Osp. Sacra Famiglia, Erba (CO), Italy. 3 To whom reprint requests should be addressed at Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Gynecologic Oncology 86, 38 – 44 (2002) doi:10.1006/gyno.2002.6713 38 0090-8258/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.