Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial.

PURPOSE: Stage IC, grade 3 endometrial cancer is regarded as a high-risk category. Stage IC, grade 3 patients were not eligible for the randomized Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial, but were registered and received postoperative radiotherapy. PATIENTS AND METHODS: The PORTEC trial included 715 patients with stage IC, grade 1 or 2, and stage IB, grade 2 or 3 endometrial cancer. Patients were randomly assigned after surgery to receive pelvic radiotherapy (RT) or no further treatment. A total of 104 patients with stage IC, grade 3 endometrial cancer were registered, of whom 99 could be evaluated. Patterns of relapse and survival were compared with PORTEC patients receiving RT. Median follow-up was 83 months. RESULTS: The actuarial 5-year rates of locoregional relapse were 1% to 3% for PORTEC patients who received RT, compared with 14% for stage IC, grade 3 patients. Five-year distant metastases rates were 3% to 8% for grade 1 and 2 tumors; 20% for stage IB, grade 3 tumors; and 31% for stage IC, grade 3 tumors. Overall survival rates were 83% to 85% for grades 1 and 2; 74% for stage IB, grade 3; and 58% for stage IC, grade 3 patients (P <.001). In multivariate analysis grade 3 was the most important adverse prognostic factor for relapse and death as a result of endometrial cancer (hazard ratios, 5.4 and 5.5; P <.0001). CONCLUSION: Patients with stage IC, grade 3 endometrial carcinoma are at high risk of early distant spread and endometrial carcinoma-related death. Novel strategies for adjuvant therapy should be explored to improve survival for this patient group.

Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review.

PURPOSE: In 2000, the results of the multicenter Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial were published. This trial included 714 Stage I endometrial carcinoma patients randomly assigned to postoperative pelvic radiotherapy (RT) or no further treatment, excluding those with Stage IC, Grade 3, or Stage IB, Grade 1 lesions. Radiotherapy significantly decreased the risk of locoregional recurrence (4% vs. 14%), without affecting overall survival. In this report the long-term outcome and results with central pathology review are presented. METHODS AND MATERIALS: The slides of 569 patients (80%) could be obtained for pathology review. Median follow-up for patients alive was 97 months. Analysis was done according to the intention-to-treat principle. The primary study endpoints were locoregional recurrence and death. RESULTS: Ten-year locoregional relapse rates were 5% (RT) and 14% (controls; p < 0.0001), and 10-year overall survival was 66% and 73%, respectively (p = 0.09). Endometrial cancer related death rates were 11% (RT) and 9% (controls; p = 0.47). Pathology review showed a substantial shift from Grade 2 to Grade 1, but no significant difference for Grade 3. When cases diagnosed at review as Grade 1 with superficial myometrial invasion were excluded from the analysis, the results remained essentially the same, with 10-year locoregional recurrence rates of 5% (RT) and 17% (controls; p < 0.0001). CONCLUSIONS: In view of the significant locoregional control benefit, radiotherapy remains indicated in Stage I endometrial carcinoma patients with high-risk features for locoregional relapse.

[Computer-assisted cervical screening]. / Computerondersteunde cervixscreening.

As a result of the transition from obtaining cervical smears for diagnostic purposes only to obtaining them for preventive health screening, it became clear that automated imaging and evaluation would be inevitable; screening entails many more preparations needing to be assessed along with an anticipated reduction in the identification of abnormal findings. A uniform method of preparing specimens facilitates scanning and organising. Instead of the usual smearing of cervical specimens, a method has since been devised for creating thin-layer specimens. Current techniques for automated imaging allow by computer-assisted screening a preselection of deviant cells and cell groups that are later visually assessed by an analyst. There are two compact ('bench top') systems available that have similar features; their use generally corresponds to the way conventional cervical smears are processed. Computer-assisted screening saves laboratories time. Interpreting the cell groups preselected by the computer remains a human task.

Prognostic significance and interobserver variability of histologic grading systems for endometrial carcinoma.

BACKGROUND: The most widely used histologic grading system for endometrial carcinoma is the three-tiered International Federation of Gynecology and Obstetrics (FIGO) system. Although FIGO grading has significant predictive value, the reproducibility of Grade 2 is limited. Recently, a binary grading system was proposed based on the amount of solid growth, the pattern of myometrial invasion, and the presence of tumor cell necrosis. The authors analyzed and compared the prognostic significance and the interobserver variability of both grading systems and of the three criteria for the binary grading system. METHODS: Eight hundred patients with Stage I-III endometrioid endometrial carcinoma were reviewed and graded independently by two pathologists according to the three-tiered FIGO grading system and the novel binary grading system. RESULTS: The interobserver agreement for both systems was moderate, with 70% and 73% agreement rates for the FIGO (kappa = 0.41) and binary (kappa = 0.39) grading systems, respectively. When converting the FIGO grading system into an artificial, 2-tiered grading system (Grade 3 vs. Grades 1-2), the agreement was much better (agreement rate, 85%; kappa = 0.58). Of the 3 criteria for the binary grading system, amount of solid growth (< or = 50% vs. > 50%) had the greatest reproducibility (agreement rate, 80%; kappa = 0.50). Both the 2-tiered FIGO grading system and the binary grading system were significant predictors of local recurrence, distant recurrence, and disease-specific survival (hazard ratios [HRs]: 1.7, 2.5, and 2.6, respectively, for FIGO and 2.1, 4.1, and 3.8, respectively, for the binary grading system). The amount of solid growth also was a strong prognostic factor for these three endpoints (HRs: 2.4, 3.9, and 3.8, respectively). CONCLUSIONS: Both the binary grading system and the FIGO grading system had strong prognostic significance. Their reproducibility, however, was limited. A simple architectural binary grading system that divided tumors into low-grade lesions and high-grade lesions based on the proportion of solid growth (< or = 50% or > 50%) had superior prognostic power and greater reproducibility.

Survival after relapse in patients with endometrial cancer: results from a randomized trial.

OBJECTIVE: The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. METHODS: The PORTEC trial included 715 patients with stage 1 endometrial cancer, either grade 1 or 2 with deep (>50%) myometrial invasion or grade 2 or 3 with <50% invasion. In all cases an abdominal hysterectomy was performed, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy) or no further treatment. RESULTS: The analysis was done by intention-to-treat. A total of 714 patients were evaluated. At a median follow-up of 73 months, 8-year actuarial locoregional recurrence rates were 4% in the RT group and 15% in the control group (P < 0.0001). The 8-year actuarial overall survival rates were 71 (RT group) and 77% (control group, P = 0.18). Eight-year rates of distant metastases were 10 and 6% (P = 0.20). The majority of the locoregional relapses were located in the vagina, mainly in the vaginal vault. Of the 39 patients with isolated vaginal relapse, 35 (87%) were treated with curative intent, usually with external RT and brachytherapy, and surgery in some. A complete remission (CR) was obtained in 31 of the 35 patients (89%), and 24 patients (77%) were still in CR after further follow-up. Five patients subsequently developed distant metastases, and 2 had a second vaginal recurrence. The 3-year survival after first relapse was 51% for patients in the control group and 19% in the RT group (P = 0.004). The 3-year survival after vaginal relapse was 73%, in contrast to 8 and 14% after pelvic and distant relapse (P < 0.001). At 5 years, the survival after vaginal relapse was 65% in the control group compared to 43% in the RT group. CONCLUSION: Survival after relapse was significantly better in the patient group without previous RT. Treatment for vaginal relapse was effective, with 89% CR and 65% 5-year survival in the control group, while there was no difference in survival between patients with pelvic relapse and those with distant metastases. As pelvic RT was shown to improve locoregional control significantly, but without a survival benefit, its use should be limited to those patients at sufficiently high risk (15% or over) for recurrence in order to maximize local control and relapse-free survival.