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/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). 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 (κ). 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 (κ = 0.72), lymph-vascular space invasion (κ = 0.72) and histological grade (κ = 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).

中文翻译：

---

PORTEC-3随机试验对高危子宫内膜癌的前期病理学检查的临床结果。

背景在PORTEC-3试验中，患有高危子宫内膜癌（HR-EC）的妇女被随机分配接受盆腔放疗（RT），伴或不伴并发和辅助化疗（在第1和第4周进行两个周期的顺铂50 mg / m2疗程） RT，随后进行四个周期的卡铂AUC5和紫杉醇175 mg / m2。入组前需要进行病理检查。该分析的目的是评估随机分组之前中央病理学检查的作用。患者和方法在荷兰（n = 395）和英国（n = 900）总共对1295例患者进行了病理学检查，以确认HR-EC，并有1226/1295（95％）病例进行了匹配的检查和原始报告。总共有329名患者参加了PORTEC-3试验：荷兰为145名，英国为184名，占PORTEC-3总数686名参与者的48％。评估差异区域，并通过计算kappa值（κ）评估原始意见与评论意见之间的观察员之间的一致性。结果在1226份病理学检查中，有6356项选择的项目可评估原始病理学和评价病理学。在43％的病例中，至少一项病理项目在复查后发生了变化。对于102例患者（8％），这种差异导致不符合PORTEC-3试验的资格，最常见的原因是组织学类型（34％），宫颈内膜间质受累（27％）和组织学分级（19％）的评估存在差异。观察者之间的最低共识是组织学类型（κ= 0.72），淋巴管间隙侵犯（κ= 0.72）和组织学分级（κ= 0.70）。结论由专家妇科病理学家进行的中央病理学检查改变了43％HR-EC妇女的组织学类型，等级或其他项目，导致8％的患者不符合PORTEC-3试验的资格。前期病理学检查对于确保目标人群的入组，避免过度治疗或治疗不足至关重要，特别是在涉及具有重大毒性的治疗方式时。该研究已在ISRCTN（ISRCTN14387080，www.control-trials.com）和ClinicalTrials.gov（NCT00411138）进行了注册。