Introduction Endometrial cancer patients with high grade tumours, deep myometrial invasion, or advanced stage disease have a poor prognosis. Randomized studies have demonstrated prevention of loco-regional relapses with radiotherapy with no effect on overall survival. The possible additive effect of chemotherapy remains unclear. Two randomized clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival in high-risk endometrial cancer. The two studies were pooled. Methods Patients (n=540; 534 evaluable) with operated endometrial cancer FIGO stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy. Results In the NSGO/EORTC study, combined modality treatment was associated with a 36 % reduction in the risk for relapse or death (HR 0.64, 95 % CI 0.41-0.99; P=0.04); two-sided tests were used. The result from the MaNGO-study pointed in the same direction (HR 0.61), but was not significant. In combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in overall survival. In combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P = 0.07) and cancer-specific survival was significant (HR 0.55, CI 0.35-0.88; p=0.01). Conclusion Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and high risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.

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5503 Background: Adjuvant therapy for early stage high-risk endometrial cancer remains controversial. Methods: Patients with surgical stage I, II, IIIA (positive peritoneal fluid cytology only), or IIIC (positive pelvic lymph nodes only) were eligible if they, according to departmental guidelines, had a sufficiently high risk for micrometastatic disease to qualify for adjuvant therapy. Most patients had two or more of the risk factors: grade 3, deep myometrial invasion, or DNA non-diploidy, while some patients had only one of these. Patients with serous, clear cell, or anaplastic carcinomas were eligible regardless of risk factors. Patients with para-aortic metastases were not eligible. Lymph node exploration at staging surgery was optional. Pelvic RT ± vaginal brachytherapy was given to a dose =44 Gy. CT was given before or after RT. Before August 2004 CT consisted of four courses of cisplatin =50 mg/m2 + doxorubicin 50 mg/m2 or epirubicin 75 mg/m2 (AP). Thereafter several CT regimens were allowed, of which AP, paclitaxel 175 mg/m2 + epirubicin 60 mg/m2 + carboplatin AUC 5, and paclitaxel 175 mg/m2 + carboplatin AUC 5–6 were used. Progression-free survival (PFS) was the primary end-point. The study was terminated before the aimed goal of 400 patients because of slow recruitment. We decided to make an early analysis since new studies on endometrial cancer are presently discussed. Results: 372 patients were entered between May 1996 and Oct 2006. Of 367 evaluable patients 190 were randomized to RT and 177 to RT+CT. Risk factors were well balanced between the randomization arms. The median follow-up time was 3.5 years. The hazard ratio for PFS was 0.58 in favor of RT+CT (95 % confidence interval (CI) 0.34 - 0.99; p=0.046). This translates to an estimated 7 % absolute difference in 5-year PFS from 75 % (95 % CI 67 % - 82 %) to 82 % (95 % CI 73 % - 88 %). Conclusion: RT+CT was better than RT alone. Next question is if RT+CT is better than CT alone. No significant financial relationships to disclose.

The prognostic impact of DNA ploidy, MIB-1 and p53 was evaluated in relation to clinical and histopathological features in surgical stage I endometrial carcinoma (n = 284) and in the histopathological endometrioid subgroup (n = 257). Tumour material from 284 consecutive patients was analysed regarding image cytometric DNA ploidy and the immunohistochemical MIB-1 and p53 expression. Twenty-four tumours relapsed. In univariate analysis, histopathological subgroup (endometrioid vs. non-endometrioid), grade, DNA ploidy and p53 were highly significant prognostic factors (p < or = 0.001). MIB-1 was also significant (p = 0.039). In the endometrioid subgroup only DNA ploidy and p53 were significant (p < 0.001). In multivariate analysis of the entire material, ploidy and histopathological subgroup retained their significance (p = 0.001, p = 0.004), whereas only ploidy was significant in the endometrioid subgroup (p = 0.001). DNA ploidy was the strongest predictor of relapse-free survival and the only independent prognostic factor in the endometrioid subgroup.