Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancerPORTEC Study Grp, Feb-2018, In : Annals of Oncology. 29, 2, p. 424-430 7 p.
Research output: Contribution to journal › Article › Academic › peer-review
Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m(2) in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m(2)). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.
Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (j).
Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (j = 0.72), lymph-vascular space invasion (j = 0.72) and histological grade (j = 0.70).
Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over-or undertreatment, especially when treatment modalities with substantial toxicity are involved.
This study is registered with ISRCTN (ISRCTN14387080, www. controlled-trials. com) and with ClinicalTrials. gov (NCT00411138).
|Number of pages||7|
|Journal||Annals of Oncology|
|Publication status||Published - Feb-2018|
- endometrial carcinoma, randomised trial, radiation therapy, chemotherapy, pathology review, high risk, EXTERNAL-BEAM RADIOTHERAPY, RADIATION-THERAPY, POSTOPERATIVE RADIOTHERAPY, INTEROBSERVER VARIABILITY, GRADING SYSTEMS, OPEN-LABEL, STAGE-I, CARCINOMA, REPRODUCIBILITY, DIAGNOSIS