Predictors of vaginal relapse in stage I endometrial cancer i Andrea Mariani a , Sean C. Dowdy a , Gary L. Keeney b , Michael G. Haddock c , Timothy G. Lesnick d , Karl C. Podratz a, * a Section of Gynecologic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA b Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA c Division of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA d Division of Biostatistics, Mayo Clinic, Rochester, MN 55905, USA Received 5 November 2004 Available online 13 May 2005 Abstract Objective. To identify factors predictive of vaginal relapse in stage I endometrial cancer, thereby potentially facilitating the selection of patients who may benefit from vaginal brachytherapy. Methods. The study population included 632 patients with stage I endometrial cancer managed with hysterectomy at our institution between 1984 and 1996. Median follow-up was 73 months; 122 patients (19%) received adjuvant radiotherapy. Results. Overall, 2.9% of the stage I cohort developed vaginal relapse at 5 years. Vaginal relapse was observed in 1.7% of patients who received radiotherapy and in 3.0% of those whose treatment did not include radiotherapy (P = 0.36). Cox regression analysis (including radiotherapy) identified only grade 3 differentiation (hazard ratio = 3.83, P = 0.007) as an independent predictor of vaginal relapse. Patients with a low-grade tumor had a 5-year vaginal relapse rate of 2%, compared with 7% for those with a grade 3 tumor. When only patients who did not receive adjuvant radiotherapy were considered, both grade 3 tumor and lymphovascular invasion were significant predictors of vaginal relapse (P < 0.05). When neither variable was present, 2% of patients experienced vaginal relapse at 5 years, compared with 11% when either 1 was present (P < 0.001). Depth of myometrial invasion was not a significant predictor of vaginal recurrence. Conclusion. Histologic grade 3 tumor and lymphovascular invasion were the cogent predictors of vaginal relapse in our population. The cost and morbidity of vaginal brachytherapy should be balanced against the potential risk of vaginal relapse in this group of patients. D 2005 Elsevier Inc. All rights reserved. Keywords: Endometrial cancer; Vaginal relapse; Lymphovascular invasion Introduction Endometrial cancer is the most common malignancy of the female reproductive tract in the United States and is exceeded annually in overall frequency only by cancers of the breast, colon, and lung. It has been estimated that during calendar year 2005, 40,880 new cases of endome- trial cancer will be diagnosed and 7310 deaths will occur [1]. Vaginal relapse is a relatively common pattern of treatment failure for patients with endometrial cancer [2] and can be effectively prevented by the adminis- tration of vaginal brachytherapy [3]. Although more than 60% of isolated vaginal relapses occurring in patients with stage I disease are treated successfully at the time of recurrence [4,5], treatment-associated morbidity is significant. Traditional predictors of vaginal relapse have included the presence of deep myometrial invasion and poor tumor 0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2005.03.008 Abbreviations: FIGO, Federation of International Gynecology and Obstetrics; LVI, lymphovascular invasion. i Presented at the 34th Annual Meeting of the Society of Gynecologic Oncologists (SGO), New Orleans, Louisiana, January 31 to February 4, 2003. * Corresponding author. E-mail address: podratz.karl@mayo.edu (K.C. Podratz). Gynecologic Oncology 97 (2005) 820 – 827 www.elsevier.com/locate/ygyno