Influence of grade, histologic subtype, and timing of radiotherapy on outcome among patients with stage II carcinoma of the endometrium.

In 1988, the Federation of International Gynecologic Oncologists (FIGO) adopted a new staging system mandating preradiotherapy surgical staging in endometrial cancer. To evaluate the potential impact of this recommendation on patients with cervical involvement (stage II), an analysis of 184 consecutive patients with clinical or pathologic stage II carcinoma of the endometrium treated with definitive intent at three institutions was performed. Median follow-up time was 5.7 years. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with preoperative radiation therapy (RT) (54%), postoperative RT (37%), or both (1%); definitive RT (7%); or radical hysterectomy (1%). The median total RT dose for combined intracavitary and external beam or either alone was 70.6 Gy with a range of 32.4-105.0 Gy. The overall 5-year survival rate and disease-free survival (DFS) rate at 5 years were 70 and 79%, respectively. Of patients treated with surgery and adjuvant radiation, 13% (22/168) had infield pelvic failure (PF) and 18% (31/168) had distant metastases (DM). Patterns of failure in patients receiving preoperative and postoperative radiotherapy are presented. Univariate analysis of pretreatment and treatment factors, including histology, grade, clinical stage, extent of cervical involvement, and timing of adjuvant radiation, revealed histology and grade to be significant predictors of DFS, PF, and DM. Clinical stage was a significant predictor of DFS only in univariate analysis. Multivariate analysis found only histology (P less than 0.001) and grade (P = 0.002) to be predictors of DFS. From this review, we conclude that histology and grade are independent predictors of DFS, and more aggressive treatment should be directed at patients with stage II endometrial cancer found to have high grade adenocarcinoma or papillary serous/clear cell histologic variants. The timing of radiotherapy was not an independent predictor of outcome; therefore, preradiotherapy surgical staging should not impact on DFS and should provide surgicopathologic information to tailor treatment and predict prognosis. The FIGO clinical staging system used in this analysis was not an independent predictor of outcome, and future multivariate analyses will be necessary to test the predictive value on outcome of the new 1988 FIGO surgical staging.