Surgically Staged High-Risk Endometrial Cancer: Randomized Study of Adjuvant Radiotherapy Alone vs. Sequential Chemo-Radiotherapy

Abstract

Abstract Objective Our purpose was to establish whether platinum-based chemotherapy combined with standard surgery and radiotherapy will improve overall and disease-free survival and lower the recurrence rate in patients with high-risk endometrial cancer. Study design A total of 156 patients with Stage IA–B Grade 3 ( n =28), or Stage IC–IIIA Grade 1–3 ( n =128) were postoperatively randomized to receive radiotherapy (56 Gy) only (Group A, n =72) or radiotherapy combined with three courses of cisplatin (50 mg/m 2 ), epirubicin (60 mg/m 2 ) and cyclophosphamide (500 mg/m 2 ) (Group B, n =84). Results The disease-specific overall five-year survival was in Group A 84.7% vs. 82.1% in Group B ( p =0.148). The median disease-free survival in A was 18 (range 9–36) months and 25 (range 12–49) months in B ( p =0.134), respectively. During a five-year follow-up 32 patients relapsed. Of the recurrences 5 were local and 20 distant, while 7 were combined. As calculated from the operation, the median time to recurrence was 15 (range 6–37) months in Group A, and 20 (range 8–60) months in Group B, respectively ( p =0.170). Twenty-six patients died of the disease during the five-year follow-up, 11 in A and 15 in B. The patients succumbing in A lived a median 23 (range 15–44) months as compared to 37 (range 13–50) months in B ( p =0.148). Chemotherapy was associated with an acceptable rate of acute toxicity. Less than 8% of the patients complained of Grade 3/4 nausea. The rate of Grade 3/4 leucopenia was at the highest at 16.6% during the third cycle but only 6.2% of the patients had Grade 3 infection. A total of 10 patients developed intestinal complications demanding surgery, 2 in Group A (2.7%) and 8 (9.5%) in Group B, respectively. Conclusion Adjuvant chemotherapy with cisplatin, epirubicin and cyclophosphamide failed to improve overall survival or lower the recurrence rate in patients operated on and radiated for high-risk endometrial carcinoma. Chemotherapy was associated with a low rate of acute toxicity but appeared to increase the risk of bowel complications.